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  1. Article ; Online: New twists to the ALTernative endings at telomeres.

    Bhargava, Ragini / Lynskey, Michelle Lee / O'Sullivan, Roderick J

    DNA repair

    2022  Volume 115, Page(s) 103342

    Abstract: Activation of a telomere maintenance mechanism is key to achieving replicative immortality. Alternative Lengthening of Telomeres (ALT) is a telomerase-independent pathway that hijacks the homologous recombination pathways to elongate telomeres. ... ...

    Abstract Activation of a telomere maintenance mechanism is key to achieving replicative immortality. Alternative Lengthening of Telomeres (ALT) is a telomerase-independent pathway that hijacks the homologous recombination pathways to elongate telomeres. Commitment to ALT is often associated with several hallmarks including long telomeres of heterogenous lengths, mutations in histone H3.3 or the ATRX/DAXX histone chaperone complex, and incorporation of non-canonical telomere sequences. The consequences of these genetic and epigenetic changes include enhanced replication stress and the presence of transcriptionally permissive chromatin, which can result in replication-associated DNA damage. Here, we detail the molecular mechanisms that are critical to repairing DNA damage at ALT telomeres, including the BLM Helicase, which acts at several steps in the ALT process. Furthermore, we discuss the emerging findings related to the telomere-associated RNA, TERRA, and its roles in maintaining telomeric integrity. Finally, we review new evidence for therapeutic interventions for ALT-positive cancers which are rooted in understanding the molecular underpinnings of this process.
    MeSH term(s) Chromatin ; Histones/genetics ; Telomerase/metabolism ; Telomere/metabolism ; Telomere Homeostasis
    Chemical Substances Chromatin ; Histones ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2022-05-13
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2071608-4
    ISSN 1568-7856 ; 1568-7864
    ISSN (online) 1568-7856
    ISSN 1568-7864
    DOI 10.1016/j.dnarep.2022.103342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Do mixed-species groups of capuchin (

    Daoudi-Simison, Sophia / O'Sullivan, Eoin / Moat, Genevieve / Lee, Phyllis C / Buchanan-Smith, Hannah M

    Philosophical transactions of the Royal Society of London. Series B, Biological sciences

    2023  Volume 378, Issue 1878, Page(s) 20220111

    Abstract: In the wild, coordinated behaviour across group members is essential for maintaining spatial coherence, with potential implications for individual fitness. Such coordination often leads to behavioural synchrony (performing the same behaviour at the same ... ...

    Abstract In the wild, coordinated behaviour across group members is essential for maintaining spatial coherence, with potential implications for individual fitness. Such coordination often leads to behavioural synchrony (performing the same behaviour at the same time). Tufted capuchins (
    MeSH term(s) Animals ; Behavior, Animal ; Cebus ; Saimiri ; Sapajus apella ; Social Behavior
    Language English
    Publishing date 2023-04-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208382-6
    ISSN 1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
    ISSN (online) 1471-2970
    ISSN 0080-4622 ; 0264-3839 ; 0962-8436
    DOI 10.1098/rstb.2022.0111
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Pareidolias are a function of visuoperceptual impairment.

    McCann, Emily / Lee, Soohyun / Coleman, Felicia / O'Sullivan, John D / Nestor, Peter J

    PloS one

    2023  Volume 18, Issue 11, Page(s) e0293942

    Abstract: Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are ... ...

    Abstract Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are included as a core clinical feature in Dementia with Lewy Bodies (DLB). A newly developed Noise Pareidolia Test (NPT) was proposed as a possible surrogate marker for VH in DLB patients as increased pareidolic responses correlated with informant-corroborated accounts of VH. This association could, however, be mediated by visuoperceptual impairment. To understand the drivers of performance on the NPT, we contrasted performances in patient groups that varied both in terms of visuoperceptual ability and rates of VH. N = 43 patients were studied of whom n = 13 had DLB or PD with Dementia (PDD); n = 13 had PD; n = 12 had typical, memory-onset Alzheimer's Disease (tAD); and n = 5 had Posterior Cortical Atrophy (PCA) due to Alzheimer's disease. All patient groups reported pareidolias. Within the Lewy body disorders (PD, DLB, PDD), there was no significant difference in pareidolic response rates between hallucinating and non-hallucinating patients. Visuoperceptual deficits and pareidolic responses were most frequent in the PCA group-none of whom reported VH. Regression analyses in the entire patient cohort indicated that pareidolias were strongly predicted by visuoperceptual impairment but not by the presence of VH. These findings suggest that pareidolias reflect the underlying visuoperceptual impairment of Lewy body disorders, rather than being a direct marker for VH.
    MeSH term(s) Humans ; Lewy Body Disease ; Alzheimer Disease ; Parkinson Disease ; Hallucinations ; Illusions/physiology
    Language English
    Publishing date 2023-11-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0293942
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Copper-mediated oxidation of imidazopyrazinones inhibits marine luciferase activity.

    O'Sullivan, Justin J / Lee, Vanessa J / Heffern, Marie C

    Luminescence : the journal of biological and chemical luminescence

    2022  Volume 38, Issue 2, Page(s) 216–220

    Abstract: The development of bioluminescence-based tools has seen steady growth in the field of chemical biology over the past few decades ranging in uses from reporter genes to assay development and targeted imaging. More recently, coelenterazine-utilizing ... ...

    Abstract The development of bioluminescence-based tools has seen steady growth in the field of chemical biology over the past few decades ranging in uses from reporter genes to assay development and targeted imaging. More recently, coelenterazine-utilizing luciferases such as Gaussia, Renilla, and the engineered nano-luciferases have been utilized due to their intense luminescence relative to firefly luciferin/luciferase. The emerging importance of these systems warrants investigations into the components that affect their light production. Previous work has reported that one marine luciferase, Gaussia, is potently inhibited by copper salt. The mechanism for inhibition was not elucidated but was hypothesized to occur via binding to the enzyme. In this study, we provide the first report of a group of nonhomologous marine luciferases also exhibiting marked decreases in light emission in the presence of copper (II). We investigate the mechanism of action behind this inhibition and demonstrate that the observed copper inhibition does not stem from a luciferase interaction but rather the chemical oxidation of imidazopyrazinone luciferins generating inert, dehydrated luciferins.
    MeSH term(s) Copper/pharmacology ; Luciferases/genetics ; Oxidation-Reduction ; Luciferases, Firefly/metabolism ; Firefly Luciferin ; Luminescent Measurements/methods ; Luminescence
    Chemical Substances Copper (789U1901C5) ; Luciferases (EC 1.13.12.-) ; Luciferases, Firefly (EC 1.13.12.7) ; Firefly Luciferin (5TBB02N29K)
    Language English
    Publishing date 2022-12-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 1470995-8
    ISSN 1522-7243 ; 1522-7235 ; 1099-1271
    ISSN (online) 1522-7243
    ISSN 1522-7235 ; 1099-1271
    DOI 10.1002/bio.4415
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Cognitive Load of Inpatient Consults: A Convergent Parallel Mixed Methods Study Using the Consult Cognitive Load Instrument.

    Brondfield, Sam / Lee, Kewchang / O'Sullivan, Patricia S

    Academic medicine : journal of the Association of American Medical Colleges

    2021  Volume 96, Issue 11S, Page(s) S119–S125

    Abstract: Purpose: Consultation is crucial for patient care and a primary responsibility of fellows. Understanding the cognitive load associated with the complex skill of consultation would enhance fellow learning. The authors aimed to determine themes describing ...

    Abstract Purpose: Consultation is crucial for patient care and a primary responsibility of fellows. Understanding the cognitive load associated with the complex skill of consultation would enhance fellow learning. The authors aimed to determine themes describing the fellow experience during inpatient consults specifically, align these themes with Consult Cognitive Load (CCL) scores, and identify strategies to manage cognitive load to enhance fellow education and performance, and, consequently, patient care.
    Method: The authors studied 16 fellows using mixed methods. Fellows who accepted an invitation completed an inpatient consult followed by the CCL, a measure of cognitive load during consults, and an interview. Three authors conducted a thematic analysis. Member checks and triangulation supported theme trustworthiness. Subsequently, 3 authors rated the extent and cognitive demand of each theme expressed in each transcript. The authors measured interrater reliability and used Spearman correlation to describe the association of these ratings with CCL scores. The authors examined themes to identify strategies that educators might use.
    Results: Analysis revealed 4 themes: "nature and scope," which conceptually aligned with intrinsic load (IL); "leveraging resources," which had elements of both IL and extraneous load (EL); "extraneous factors," which aligned with EL; and "drivers," which aligned with germane load (GL). Interrater reliability for extent and demand ratings ranged from 0.57 to 0.79. The correlation between "nature and scope" and IL was 0.37, "extraneous factors" and EL 0.71, and "drivers" and GL 0.32. "Leveraging resources" did not correlate with IL (0.06) or EL (-0.09). Potential strategies based on themes included offering level-appropriate assistance to match IL, focusing the fellow's attention to reduce EL, and providing succinct teaching to promote GL.
    Conclusions: This study provided deep insight into the fellow consult experience and suggested strategies for educators to guide consult learning. The theme "leveraging resources" merits further exploration.
    MeSH term(s) Adult ; Cognition ; Female ; Humans ; Inpatients ; Male ; Physician-Patient Relations ; Physicians/psychology ; Referral and Consultation
    Language English
    Publishing date 2021-08-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 96192-9
    ISSN 1938-808X ; 1040-2446
    ISSN (online) 1938-808X
    ISSN 1040-2446
    DOI 10.1097/ACM.0000000000004265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Extrachromosomal Telomeres Derived from Excessive Strand Displacements.

    Lee, Junyeop / Lee, Jina / Sohn, Eric J / Taglialatela, Angelo / O'Sullivan, Roderick J / Ciccia, Alberto / Min, Jaewon

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Alternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication (BIR), evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular ... ...

    Abstract Alternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication (BIR), evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), unique to ALT cells, are considered potential precursors of C-circles, their generation process remains undefined. Here, we introduce a highly sensitive method to detect single stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear C-rich ssDNA accumulation may indeed precede C-circle formation. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a new model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.
    Language English
    Publishing date 2023-10-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.31.551186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Pareidolias are a function of visuoperceptual impairment

    Emily McCann / Soohyun Lee / Felicia Coleman / John D. O’Sullivan / Peter J. Nestor

    PLoS ONE, Vol 18, Iss

    2023  Volume 11

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Investigating the influence of Taekwondo body protectors size on shock absorption.

    Jeong, Hee Seong / Lee, Sae Yong / Noh, Hyung Jun / O'Sullivan, David Michael / Lee, Young Rim

    Technology and health care : official journal of the European Society for Engineering and Medicine

    2021  Volume 29, Issue 4, Page(s) 667–675

    Abstract: Objective: This study aims to compare and analyze the difference of impact force attenuation according to size and impact location on a Taekwondo body protector.: Methods: Body protectors sized 1 to 5, were impact tested by equipment based on the ... ...

    Abstract Objective: This study aims to compare and analyze the difference of impact force attenuation according to size and impact location on a Taekwondo body protector.
    Methods: Body protectors sized 1 to 5, were impact tested by equipment based on the specifications in the European standard manual (EN 13277-1, 3). The impactor release heights were set to match impact energies of 3 and 15 J. The impactor was made from a 2.5 kg cylindrically cut piece of aluminum. Each body protector was impacted 10 times at the two impact energies and two locations. The differences in performance for each body protector size were compared using a two-way analysis of variance with a significance level of p< 005. The effect sizes were investigated using a partial eta squared value (η2).
    Results: The significant mean differences between the body protector size and impact area (p< 005) and the average impact time of impact strengths 3 and 15 J were 0.0017 and 0.0012 s, respectively In addition, when an impact strength of 15 J was applied, the maximum resulting impact force exceeded 2000 N for both locations on all sizes. Furthermore, at an impact strength of 3 J size 3 significantly reduced the impact force more than the other sizes; however, size 1 showed the greatest shock absorption at an impact of 15 J.
    Conclusion: The results of this study show that the shock absorption of body protectors does not increase according to size; i.e., a larger body protector does not reduce the impact load more effectively. To improve safety performance, we recommend a maximum impact force of 2000 N or less for all body protectors.
    MeSH term(s) Humans ; Martial Arts
    Language English
    Publishing date 2021-01-11
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1159961-3
    ISSN 1878-7401 ; 0928-7329
    ISSN (online) 1878-7401
    ISSN 0928-7329
    DOI 10.3233/THC-202598
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Arterial and venous thromboembolic complications of COVID-19 detected by CT angiogram and venous duplex ultrasound.

    Lee, Edison / Krajewski, Adam / Clarke, Cynthia / O'Sullivan, David / Herbst, Timothy / Lee, Steven

    Emergency radiology

    2021  Volume 28, Issue 3, Page(s) 469–476

    Abstract: Objective: To investigate the incidence of thromboembolic events, specifically pulmonary embolism (PE), deep vein thrombosis (DVT), and cerebrovascular accidents (CVA), in patients who tested positive for COVID-19 through RT-PCR in a regional healthcare ...

    Abstract Objective: To investigate the incidence of thromboembolic events, specifically pulmonary embolism (PE), deep vein thrombosis (DVT), and cerebrovascular accidents (CVA), in patients who tested positive for COVID-19 through RT-PCR in a regional healthcare system in Connecticut.
    Materials and methods: All CT angiogram (CTA) and venous duplex extremity ultrasound (US) examinations performed on 192 consecutively documented cases of COVID-19 were retrospectively reviewed at a multi-centered healthcare system. Clinical characteristics and patient outcomes were evaluated and compared between two groups based on the presence or absence of acute thromboembolic events.
    Results: Of the 16,264 patients tested for COVID-19, 3727 (23%) were positive. Out of those, 192 patients underwent 245 vascular imaging studies including chest CTA (86), venous duplex ultrasound (134), and CTA head and neck (25). Among those who underwent imaging, 49 (26%) demonstrated acute thromboembolic events which included 13/86 (15%) with PE, 34/134 (25%) with DVT, and 6/25 (24%) with CVA. One patient had positive results on all 3 examinations, and 2 patients had positive results on both chest CTA and venous duplex US. Males were more likely to have a thromboembolic event than females (33/103 (34%) vs. 14/89 (16%), p = 0.009). No significant difference was observed with respect to age, cardiopulmonary comorbidities, malignancy history, diabetes, or dialysis.
    Conclusion: Approximately 26% of COVID-19 patients with positive testing who underwent vascular imaging with CTA or venous duplex ultrasound had thromboembolic events including PE, DVT, and CVA. This indicates that COVID-19 patients are at increased risk for thromboembolic complications.
    MeSH term(s) Aged ; COVID-19/complications ; COVID-19/epidemiology ; Computed Tomography Angiography/methods ; Connecticut/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; Thromboembolism/diagnostic imaging ; Thromboembolism/epidemiology ; Thromboembolism/virology ; Ultrasonography, Doppler, Duplex/methods
    Language English
    Publishing date 2021-01-11
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 1425144-9
    ISSN 1438-1435 ; 1070-3004
    ISSN (online) 1438-1435
    ISSN 1070-3004
    DOI 10.1007/s10140-020-01884-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: 'Long-term outcomes after endoscopic submucosal dissection for relative indication early gastric cancer in non-surgical candidates'.

    Wang, Hunter / Nguyen, Melinda / Gupta, Sunil / Sidhu, Mayenaaz / Cronin, Oliver / O'Sullivan, Timothy / Whitfield, Anthony / Lee, Eric Y T / Burgess, Nicholas G / Bourke, Michael J

    Gastrointestinal endoscopy

    2024  

    Abstract: Background and aims: Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). It's role in the comorbid with more advanced disease is unknown. We sought to evaluate this in a large Western cohort.: Methods: ... ...

    Abstract Background and aims: Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). It's role in the comorbid with more advanced disease is unknown. We sought to evaluate this in a large Western cohort.
    Methods: Consecutive patients who underwent ESD for EGC in a single tertiary Western endoscopy centre over 10 years were prospectively analyzed. The primary outcomes were long term overall survival (OS) and disease-free survival (DFS) up to 5 years. Secondary outcomes were efficacy and serious adverse events (SAE).
    Results: ESD for 157 EGC in 149 patients were performed in an elderly and comorbid cohort with mean age 73.7 years and age-adjusted Charleson Comorbidity Index 4.2. Over a median follow-up period of 51.6 months, there was no significant difference in 5-year OS (88.9% vs 77.9%, P = 0.290) and DFS (83.2% vs 75.1%, P = 0.593) between absolute indication (AI) EGC and relative indication (RI) EGC. AI EGC cohort achieved higher en bloc (96.3% vs 87.5%, P = 0.069) and R0 resection rate (93.6% vs 62.5%, P <0.001) when compared to RI EGC. There were no significant differences in SAE (7.3% vs 12.5%, P = 0.363). No mortality or surgical resection ensued from ESD complications.
    Conclusion: ESD safely confers DFS in poor surgical candidates with RI EGC in a large Western cohort. Patients who are elderly and comorbid or decline surgical resection may benefit from ESD and avoid the risks of surgery and its long-term sequelae.
    Language English
    Publishing date 2024-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 391583-9
    ISSN 1097-6779 ; 0016-5107
    ISSN (online) 1097-6779
    ISSN 0016-5107
    DOI 10.1016/j.gie.2024.03.032
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