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  1. Article ; Online: Insights into platelet pharmacology from a cryo-EM structure of the ABCC4 transporter.

    Sharda, Anish V / Gu, Sean X / Hwa, John

    Nature cardiovascular research

    2023  Volume 2, Issue 7, Page(s) 606–608

    Abstract: Structural determination of the ABCC4 transporter is a major first step in providing crucial molecular insights into the transport of platelet substrates into granules, as well as drug transport from platelets. The findings provide a framework for ... ...

    Abstract Structural determination of the ABCC4 transporter is a major first step in providing crucial molecular insights into the transport of platelet substrates into granules, as well as drug transport from platelets. The findings provide a framework for understanding platelet interactions and potential design of specific platelet antagonists.
    Language English
    Publishing date 2023-06-19
    Publishing country England
    Document type Journal Article
    ISSN 2731-0590
    ISSN (online) 2731-0590
    DOI 10.1038/s44161-023-00293-z
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  2. Article ; Online: SOD2 in platelets: with age comes responsibility.

    Jain, Kanika / Gu, Sean X / Hwa, John

    Journal of thrombosis and haemostasis : JTH

    2023  Volume 21, Issue 5, Page(s) 1077–1081

    MeSH term(s) Humans ; Animals ; Mice ; Blood Platelets/metabolism ; Oxidative Stress ; Mitochondria/metabolism ; Superoxide Dismutase/metabolism ; Mice, Knockout
    Chemical Substances Superoxide Dismutase (EC 1.15.1.1)
    Language English
    Publishing date 2023-01-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2023.01.016
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    Zs.A 5805: Show issues Location:
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  3. Article ; Online: Fishing for "complements" with vascular organoid models of microvascular disease.

    Gu, Sean X / Yarovinsky, Timur O / Hwa, John

    Cell stem cell

    2023  Volume 30, Issue 10, Page(s) 1285–1286

    Abstract: In this issue of Cell Stem Cell, Kawakami et al. develop a SARS-CoV-2 infection-competent, progenitor-derived, human vascular organoid model and uncover a role for complement factor D (CFD) in mediating microvascular immunothrombosis. This model may be ... ...

    Abstract In this issue of Cell Stem Cell, Kawakami et al. develop a SARS-CoV-2 infection-competent, progenitor-derived, human vascular organoid model and uncover a role for complement factor D (CFD) in mediating microvascular immunothrombosis. This model may be applied to conditions where microvascular disease plays a major pathogenic role.
    MeSH term(s) Humans ; COVID-19 ; Organoids
    Language English
    Publishing date 2023-10-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2023.09.004
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  4. Article: Redox Mechanisms of Platelet Activation in Aging.

    Gu, Sean X / Dayal, Sanjana

    Antioxidants (Basel, Switzerland)

    2022  Volume 11, Issue 5

    Abstract: Aging is intrinsically linked with physiologic decline and is a major risk factor for a broad range of diseases. The deleterious effects of advancing age on the vascular system are evidenced by the high incidence and prevalence of cardiovascular disease ... ...

    Abstract Aging is intrinsically linked with physiologic decline and is a major risk factor for a broad range of diseases. The deleterious effects of advancing age on the vascular system are evidenced by the high incidence and prevalence of cardiovascular disease in the elderly. Reactive oxygen species are critical mediators of normal vascular physiology and have been shown to gradually increase in the vasculature with age. There is a growing appreciation for the complexity of oxidant and antioxidant systems at the cellular and molecular levels, and accumulating evidence indicates a causal association between oxidative stress and age-related vascular disease. Herein, we review the current understanding of mechanistic links between oxidative stress and thrombotic vascular disease and the changes that occur with aging. While several vascular cells are key contributors, we focus on oxidative changes that occur in platelets and their mediation in disease progression. Additionally, we discuss the impact of comorbid conditions (i.e., diabetes, atherosclerosis, obesity, cancer, etc.) that have been associated with platelet redox dysregulation and vascular disease pathogenesis. As we continue to unravel the fundamental redox mechanisms of the vascular system, we will be able to develop more targeted therapeutic strategies for the prevention and management of age-associated vascular disease.
    Language English
    Publishing date 2022-05-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11050995
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  5. Article ; Online: Inflammation mediated platelet hyperactivity in aging.

    Gu, Sean X / Dayal, Sanjana

    Annals of blood

    2020  Volume 5

    Language English
    Publishing date 2020-03-25
    Publishing country China
    Document type Journal Article ; Comment
    ISSN 2521-361X
    ISSN (online) 2521-361X
    DOI 10.21037/aob.2020.03.01
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  6. Article ; Online: Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach: A clinicopathologic analysis.

    Gu, Sean X / Siddon, Alexa J / Huntington, Scott F / Jain, Dhanpat

    American journal of clinical pathology

    2023  Volume 160, Issue 6, Page(s) 612–619

    Abstract: Objectives: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The ... ...

    Abstract Objectives: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The clinicopathologic features have not been well studied, and optimal management strategies remain unclear.
    Methods: The pathology database was searched for primary gastric MALT lymphomas diagnosed from 2000 to 2017. The clinical data and the slides were reviewed. The cases were divided for analysis into those with a background of chronic gastritis with HP, chronic gastritis without HP, and without either a background of chronic gastritis or HP.
    Results: Of 70 gastric MALT lymphoma cases identified, 26 (37% of total) had chronic gastritis and were positive for HP histologically (n = 23) or were HP positive by additional laboratory testing (n = 3). The remaining 44 (63% of total) cases were HP negative by histology. Within the HP-negative cases, 5 (11% of HP-negative cases) showed histologic gastritis while 39 (89% of HP-negative cases) did not have sufficient evidence of gastritis through review of slides (n = 18) or based on available pathology reports (n = 21). The HP-negative cases without gastritis had higher propensities to show a mass lesion on endoscopy compared with HP-positive cases (37.5% vs 11.1%, P = .02) at the initial diagnosis. The immunophenotype and rate of positive B-cell gene rearrangement were not significantly different between the 2 groups. While all HP-positive patients received antibiotics for HP eradication, treatment in the HP-negative group varied among antibiotics, radiation, rituximab, or chemotherapy. Among HP-negative patients with available follow-up, 13 (39%) showed disease recurrence, similar to the recurrence rate in HP-positive patients; however, no individual from either group has died of the disease thus far.
    Conclusions: The incidence of HP-negative MALT lymphoma is increasing, and in our practice, it is currently more common than HP-associated MALT lymphomas. The pathophysiology of HP-negative MALT lymphoma without chronic gastritis remains unclear. Follow-up data in our study suggest that the prognosis of these cases is excellent despite varied management modalities.
    MeSH term(s) Humans ; Lymphoma, B-Cell, Marginal Zone/pathology ; Helicobacter pylori/physiology ; Neoplasm Recurrence, Local ; Helicobacter Infections/diagnosis ; Stomach Neoplasms/pathology ; Gastritis/pathology ; Anti-Bacterial Agents/therapeutic use ; Gastritis, Atrophic ; Lymphoid Tissue/pathology ; Mucous Membrane/pathology
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2023-08-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2944-0
    ISSN 1943-7722 ; 0002-9173
    ISSN (online) 1943-7722
    ISSN 0002-9173
    DOI 10.1093/ajcp/aqad088
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  7. Article: Thinking outside the cavity: Effusion lymphoma primary to bone marrow.

    Gu, Sean X / Pan, Zenggang / Xu, Mina L

    Clinical case reports

    2021  Volume 9, Issue 5, Page(s) e04100

    Abstract: This case illustrates a rare and aggressive entity in AIDS-related lymphoproliferative disorders and highlights the importance and challenges of recognizing PEL outside of cavitary lesions. ...

    Abstract This case illustrates a rare and aggressive entity in AIDS-related lymphoproliferative disorders and highlights the importance and challenges of recognizing PEL outside of cavitary lesions.
    Language English
    Publishing date 2021-05-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2740234-4
    ISSN 2050-0904
    ISSN 2050-0904
    DOI 10.1002/ccr3.4100
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  8. Article ; Online: Thinking outside the cavity

    Sean X. Gu / Zenggang Pan / Mina L. Xu

    Clinical Case Reports, Vol 9, Iss 5, Pp n/a-n/a (2021)

    Effusion lymphoma primary to bone marrow

    2021  

    Abstract: Abstract This case illustrates a rare and aggressive entity in AIDS‐related lymphoproliferative disorders and highlights the importance and challenges of recognizing PEL outside of cavitary lesions. ...

    Abstract Abstract This case illustrates a rare and aggressive entity in AIDS‐related lymphoproliferative disorders and highlights the importance and challenges of recognizing PEL outside of cavitary lesions.
    Keywords AIDS‐related lymphoma ; extracavitary ; primary effusion lymphoma ; Medicine ; R ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Fibrin films: overlooked hemostatic barriers against microbial infiltration.

    Gu, Sean X / Lentz, Steven R

    The Journal of clinical investigation

    2018  Volume 128, Issue 8, Page(s) 3243–3245

    Abstract: The hemostatic response to vascular injury culminates in a fibrin clot network that forms an initial barrier to blood loss and also contributes to microbial host defense. Fibrinogen is cleaved by thrombin into fibrin monomers that spontaneously ... ...

    Abstract The hemostatic response to vascular injury culminates in a fibrin clot network that forms an initial barrier to blood loss and also contributes to microbial host defense. Fibrinogen is cleaved by thrombin into fibrin monomers that spontaneously polymerize into protofibrils and form the extensive fiber networks characteristic of blood clots. In this issue of the JCI, Macrae and colleagues characterize an alternative fibrin structure in which fibrinogen and fibrin assemble into a continuous 2D film at the exterior face of the fibrin clot network. Fibrin films connect to the underlying fiber network through tethering fibers and provide a protective barrier to microbial infiltration. These findings shed new light on a previously overlooked mechanism of fibrin assembly at the clot surface and provide a link between hemostasis and innate immunity.
    MeSH term(s) Biofilms ; Fibrin ; Fibrinogen ; Hemostasis ; Hemostatics ; Humans ; Thrombin ; Thrombosis
    Chemical Substances Hemostatics ; Fibrin (9001-31-4) ; Fibrinogen (9001-32-5) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2018-06-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI121858
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  10. Article: Speaker-turn aware diarization for speech-based cognitive assessments.

    Xu, Sean Shensheng / Ke, Xiaoquan / Mak, Man-Wai / Wong, Ka Ho / Meng, Helen / Kwok, Timothy C Y / Gu, Jason / Zhang, Jian / Tao, Wei / Chang, Chunqi

    Frontiers in neuroscience

    2024  Volume 17, Page(s) 1351848

    Abstract: ... to a diarization system that outperforms the conventional x-vector/PLDA systems under language-, age-, and ...

    Abstract Introduction: Speaker diarization is an essential preprocessing step for diagnosing cognitive impairments from speech-based Montreal cognitive assessments (MoCA).
    Methods: This paper proposes three enhancements to the conventional speaker diarization methods for such assessments. The enhancements tackle the challenges of diarizing MoCA recordings on two fronts. First, multi-scale channel interdependence speaker embedding is used as the front-end speaker representation for overcoming the acoustic mismatch caused by far-field microphones. Specifically, a squeeze-and-excitation (SE) unit and channel-dependent attention are added to Res2Net blocks for multi-scale feature aggregation. Second, a sequence comparison approach with a holistic view of the whole conversation is applied to measure the similarity of short speech segments in the conversation, which results in a speaker-turn aware scoring matrix for the subsequent clustering step. Third, to further enhance the diarization performance, we propose incorporating a pairwise similarity measure so that the speaker-turn aware scoring matrix contains both local and global information across the segments.
    Results: Evaluations on an interactive MoCA dataset show that the proposed enhancements lead to a diarization system that outperforms the conventional x-vector/PLDA systems under language-, age-, and microphone-mismatch scenarios.
    Discussion: The results also show that the proposed enhancements can help hypothesize the speaker-turn timestamps, making the diarization method amendable to datasets without timestamp information.
    Language English
    Publishing date 2024-01-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1351848
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