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  1. Article ; Online: Cancer: Context Is Key for E-cadherin in Invasion and Metastasis.

    Fearon, Eric R

    Current biology : CB

    2019  Volume 29, Issue 21, Page(s) R1140–R1142

    Abstract: ... of the E-cadherin tumor suppressor protein enhanced cell invasion, but inhibited multiple steps ...

    Abstract A recent paper demonstrates how tissue context impacts the breast cancer cell phenotype. Loss of the E-cadherin tumor suppressor protein enhanced cell invasion, but inhibited multiple steps in metastatic spread due to the accumulation of reactive oxygen species and induction of apoptosis.
    MeSH term(s) Apoptosis ; Breast Neoplasms ; Cadherins ; Humans ; Neoplasm Invasiveness ; Tumor Suppressor Proteins
    Chemical Substances Cadherins ; Tumor Suppressor Proteins
    Language English
    Publishing date 2019-11-05
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2019.09.054
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3208: Show issues Location:
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  2. Article: Treatment of Apathy in Parkinson's Disease and Implications for Underlying Pathophysiology.

    Maher, Senan / Donlon, Eoghan / Mullane, Gerard / Walsh, Richard / Lynch, Tim / Fearon, Conor

    Journal of clinical medicine

    2024  Volume 13, Issue 8

    Abstract: Apathy is a prevalent and highly debilitating non-motor symptom of Parkinson's disease (PD) that is often overlooked in clinical practice due to its subtle nature. This review aims to provide a comprehensive overview of the current evidence for the ... ...

    Abstract Apathy is a prevalent and highly debilitating non-motor symptom of Parkinson's disease (PD) that is often overlooked in clinical practice due to its subtle nature. This review aims to provide a comprehensive overview of the current evidence for the treatment of apathy in PD, highlighting recent advancements and emerging therapeutic avenues. In this review, we analyse a diverse array of treatment strategies for apathy in PD, including pharmacological interventions, non-pharmacological approaches, and emerging neuromodulation techniques. We evaluate the efficacy, safety, and limitations of established pharmacotherapies, such as dopaminergic agents, antidepressants, and cognitive enhancers. Additionally, we examine the promising role of non-pharmacological interventions, encompassing psychotherapies and behavioural interventions, in ameliorating apathetic symptoms. Furthermore, this review explores the effects of neuromodulation techniques on apathy, including the modulation of apathy via deep brain stimulation and emerging data on the potential influence of transcranial magnetic stimulation (TMS) on apathy in PD. Ultimately, a deeper understanding of effective treatment strategies for apathy has the potential to significantly improve the quality of life and overall well-being of individuals living with PD.
    Language English
    Publishing date 2024-04-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm13082216
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  3. Article ; Online: Arm Swing while Walking and Running: A New Clinical Feature to Separate Parkinson's Disease from Functional Parkinsonism.

    Fearon, Conor / Bhowmick, Suvorit S / Tosserams, Anouk / Di Luca, Daniel G / Liao, Jane / Nonnekes, Jorik / Bloem, Bastiaan R / Lang, Anthony E

    Movement disorders clinical practice

    2024  Volume 11, Issue 2, Page(s) 166–170

    Abstract: Background: Functional parkinsonism is an important differential diagnosis of Parkinson's disease (PD). Based on anecdotal experience, we hypothesized that arm swing while walking and running could differentiate these two conditions, but this assumption ...

    Abstract Background: Functional parkinsonism is an important differential diagnosis of Parkinson's disease (PD). Based on anecdotal experience, we hypothesized that arm swing while walking and running could differentiate these two conditions, but this assumption has not been previously explored systematically.
    Objectives: To examine differences in arm swing while walking and running between patients with PD and functional parkinsonism.
    Methods: We analyzed blinded video assessments of arm swing and other gait parameters in patients with asymmetrical PD (n = 81) and functional parkinsonism (n = 8) while walking and running. The groups were matched for age, sex and disease duration.
    Results: In contrast to those with PD, patients with functional parkinsonism (i) were more likely to have a marked asymmetry in arm swing while walking (5/8 vs. 25/81; P = 0.06), (ii) were less likely to improve arm swing while running with full effort (3/8 vs. 72/81; P < 0.001) and (iii) demonstrated normal passive arm swing even when asymmetry of arm swing was marked during running/walking (6/6 vs. 9/33; P = 0.002).
    Conclusions: Assessment of arm swing while walking and running and passive arm swing could be important differentiating clinical features between functional parkinsonism and PD.
    MeSH term(s) Humans ; Arm ; Gait ; Parkinson Disease/diagnosis ; Running ; Walking ; Male ; Female
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article
    ISSN 2330-1619
    ISSN (online) 2330-1619
    DOI 10.1002/mdc3.13952
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  4. Article ; Online: Parental sensitivity and child behavioral problems: A meta-analytic review.

    Cooke, Jessica E / Deneault, Audrey-Ann / Devereux, Chloe / Eirich, Rachel / Fearon, R M Pasco / Madigan, Sheri

    Child development

    2022  Volume 93, Issue 5, Page(s) 1231–1248

    Abstract: ... Sensitivity significantly related to internalizing (k = 69 studies; N = 14,729; r = -.08, 95% CI [-.12, -.05 ... and externalizing (k = 94; N = 25,418; r = -.14, 95% CI [-.17, -.11]) problems, with stronger ...

    Abstract Meta-analytic associations between observed parental sensitivity and child behavioral problems were examined (children aged 0-17 years). Studies (k = 108, N = 28,114) contained sociodemographically diverse samples, primarily from North America and Europe, reporting on parent-child dyads (95% mothers; 54% boys). Sensitivity significantly related to internalizing (k = 69 studies; N = 14,729; r = -.08, 95% CI [-.12, -.05]) and externalizing (k = 94; N = 25,418; r = -.14, 95% CI [-.17, -.11]) problems, with stronger associations found for externalizing. For internalizing problems, associations were significantly stronger among samples with low socioeconomic status (SES) versus mid-high SES, in peer-reviewed versus unpublished dissertations, and in studies using composite versus single scale sensitivity measures. No other moderators emerged as significant.
    MeSH term(s) Europe ; Female ; Humans ; Male ; Mothers ; Parents ; Problem Behavior
    Language English
    Publishing date 2022-03-31
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 215602-7
    ISSN 1467-8624 ; 0009-3920
    ISSN (online) 1467-8624
    ISSN 0009-3920
    DOI 10.1111/cdev.13764
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  5. Article: Human MAIT Cells Respond to

    Cooper, Andrew J R / Clegg, Jonah / Cassidy, Féaron C / Hogan, Andrew E / McLoughlin, Rachel M

    Microorganisms

    2022  Volume 10, Issue 1

    Abstract: Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT ... ...

    Abstract Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT cells is to defend against
    Language English
    Publishing date 2022-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms10010148
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  6. Article ; Online: Early-Onset Neurodevelopmental Movement Disorder Secondary to Novel Mutation in KCNN2.

    Fearon, Conor / Grippe, Talyta Cortez / Chen, Robert / Lang, Anthony E

    Movement disorders clinical practice

    2022  Volume 9, Issue Suppl 2, Page(s) S9–S12

    Language English
    Publishing date 2022-09-11
    Publishing country United States
    Document type Case Reports
    ISSN 2330-1619
    ISSN (online) 2330-1619
    DOI 10.1002/mdc3.13535
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  7. Article ; Online: The providential randomisation of genotypes.

    Pingault, Jean-Baptiste / Fearon, Pasco / Viding, Essi / Davies, Neil / Munafò, Marcus R / Davey Smith, George

    The Behavioral and brain sciences

    2023  Volume 46, Page(s) e197

    Abstract: When building causal knowledge in behavioural genetics, the natural randomisation of genotypes at conception (approximately analogous to the artificial randomisation occurring in randomised controlled trials) facilitates the discovery of genetic causes. ... ...

    Abstract When building causal knowledge in behavioural genetics, the natural randomisation of genotypes at conception (approximately analogous to the artificial randomisation occurring in randomised controlled trials) facilitates the discovery of genetic causes. More importantly, the randomisation of genetic material within families also enables a better identification of (environmental) risk factors and aetiological pathways to diseases and behaviours.
    MeSH term(s) Humans ; Genotype ; Random Allocation ; Genetics, Behavioral
    Language English
    Publishing date 2023-09-11
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 423721-3
    ISSN 1469-1825 ; 0140-525X
    ISSN (online) 1469-1825
    ISSN 0140-525X
    DOI 10.1017/S0140525X2200214X
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    Zs.A 1470: Show issues Location:
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  8. Article ; Online: An Open-Label, Randomized, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers.

    Goldenson, Nicholas I / Fearon, Ian M / Buchhalter, August R / Henningfield, Jack E

    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

    2021  Volume 23, Issue 6, Page(s) 947–955

    Abstract: Introduction: This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes ... ...

    Abstract Introduction: This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes in 24 adult smokers.
    Methods: At five study visits, subjects used either the JS in 59 mg/mL, JS 18 mg/mL (two visits), and JS 9 mg/mL (all tobacco-flavored) or smoked their UB cigarette first during a controlled puffing sequence (CPS) and then ad libitum (5 min) use sessions. Blood samples were taken at specified timepoints for 60 min in each session. The modified Product Evaluation Scale assessed subjective effects 30-min post-use in the CPS session.
    Results: Maximum plasma nicotine concentration (Cmax-BL), total nicotine exposure (AUC0-60-BL), and rate of plasma nicotine rise were significantly lower for all JS products compared to subjects' UB cigarette in CPS and ad libitum use sessions. In both use sessions these PK parameters were significantly higher for JS 59 mg/mL compared to 18 and 9 mg/mL. Subjective measures of cigarette craving relief and "Enough Nicotine" for JS 59 mg/mL did not differ significantly from UB cigarettes, but JS 18 and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes.
    Conclusions: Nicotine exposure and subjective relief were directly related to JS nicotine concentration: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving. Heavier and more dependent smokers may require the greater nicotine delivery of JS 59 mg/mL to successfully transition away from cigarettes.
    Implications: It has been suggested that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes may facilitate smokers transitioning away from cigarettes. We examined nicotine PK and subjective effects of JUUL System (JS) ENDS with three nicotine concentrations (59, 18 and 9 mg/mL) compared to combustible cigarettes. Nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. These findings suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes.
    MeSH term(s) Adult ; Cross-Over Studies ; Electronic Nicotine Delivery Systems ; Humans ; Nicotine/pharmacokinetics ; Smokers ; Tobacco Products
    Chemical Substances Nicotine (6M3C89ZY6R)
    Language English
    Publishing date 2021-01-22
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1452315-2
    ISSN 1469-994X ; 1462-2203
    ISSN (online) 1469-994X
    ISSN 1462-2203
    DOI 10.1093/ntr/ntab001
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    Zs.A 5789: Show issues Location:
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  9. Article ; Online: Editorial: Making clinical trials smarter (and more interesting).

    Fearon, R M Pasco

    Journal of child psychology and psychiatry, and allied disciplines

    2017  Volume 58, Issue 2, Page(s) 113–115

    Abstract: ... difficulties when they arise. While there have been some successes (e.g. stimulant medication for ADHD, parent ...

    Abstract At its heart, the field of child psychology and psychiatry is geared towards using science to develop interventions that promote children's healthy development and treat behavioural and emotional difficulties when they arise. While there have been some successes (e.g. stimulant medication for ADHD, parent training for child conduct problems, Fonagy et al., ) serious challenges lie ahead if we are to achieve reliable and lasting improvements for a larger number of children, and for a broader spectrum of problems.
    MeSH term(s) Child Psychiatry/standards ; Clinical Trials as Topic/standards ; Humans ; Psychology, Child/standards ; Research Design/standards
    Language English
    Publishing date 2017-01-19
    Publishing country England
    Document type Editorial
    ZDB-ID 218136-8
    ISSN 1469-7610 ; 0021-9630 ; 0373-8086
    ISSN (online) 1469-7610
    ISSN 0021-9630 ; 0373-8086
    DOI 10.1111/jcpp.12696
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  10. Article ; Online: Human MAIT Cells Respond to Staphylococcus aureus with Enhanced Anti-Bacterial Activity

    Andrew J. R. Cooper / Jonah Clegg / Féaron C. Cassidy / Andrew E. Hogan / Rachel M. McLoughlin

    Microorganisms, Vol 10, Iss 148, p

    2022  Volume 148

    Abstract: Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT ... ...

    Abstract Mucosal-Associated Invariant T (MAIT) cells have been shown to play protective roles during infection with diverse pathogens through their propensity for rapid innate-like cytokine production and cytotoxicity. Among the potential applications for MAIT cells is to defend against Staphylococcus aureus , a pathogen of serious clinical significance. However, it is unknown how MAIT cell responses to S. aureus are elicited, nor has it been investigated whether MAIT cell cytotoxicity is mobilized against intracellular S. aureus . In this study, we investigate the capacity of human MAIT cells to respond directly to S. aureus . MAIT cells co-cultured with dendritic cells (DCs) infected with S. aureus rapidly upregulate CD69, express IFNγ and Granzyme B and degranulate. DC secretion of IL-12, but not IL-18, was implicated in this immune response, while TCR binding of MR1 is required to commence cytokine production. MAIT cell cytotoxicity resulted in apoptosis of S. aureus -infected cells, and reduced intracellular persistence of S. aureus . These findings implicate these unconventional T cells in important, rapid anti- S. aureus responses that may be of great relevance to the ongoing development of novel anti- S. aureus treatments.
    Keywords Staphylococcus aureus ; MAIT cell ; vaccines ; cell mediated immunity ; IFNγ ; dendritic cell ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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