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  • 1
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 7 ( 2019-07-01), p. 1194-1201
    Abstract: This study assessed longitudinal change in depression symptoms over ≥4 years in adults with type 1 diabetes and examined the association between change in depression symptom status and glycemia. RESEARCH DESIGN AND METHODS Adults in the T1D Exchange registry with HbA1c and Patient Health Questionnaire (PHQ-8) at 1 year (baseline) and 5 years post-enrollment (follow-up; n = 2,744, mean age, 42 years; 57% female, 92% white; mean HbA1c, 7.6% [58 mmol/mol]) were included. Depression status was defined as Persistent Elevated Depression Symptoms (EDS) (EDS at baseline and follow-up), Resolved EDS (EDS at baseline, no EDS at follow-up), New Onset EDS (no EDS at baseline, EDS at follow-up), and Not Depressed (no EDS at baseline or follow-up). RESULTS Overall, 131 (5%) had Persistent EDS, 122 (4%) had Resolved EDS, 168 (6%) had New Onset EDS, and 2,323 (85%) were Not Depressed. Of those with EDS (PHQ ≥ 10) at baseline, 53% had EDS at follow-up; of those not depressed at baseline, 7% had EDS at follow-up. An increase in PHQ-8 was associated with an increase in HbA1c (P & lt; 0.001). Although HbA1c increased in all groups, the increase was less in the Resolved EDS and Not Depressed groups (P = 0.001). Persistent EDS and New Onset EDS groups were more likely to experience diabetic ketoacidosis (DKA) (P & lt; 0.001). CONCLUSIONS T1D Exchange registry data provide evidence for relationships over time between persistently, and newly developing EDSs and worsening glycemic control, and suggest relationships between depression symptoms and the occurrence of severe hypoglycemia and DKA. Successful treatment of depression symptoms may lead to better long-term diabetes outcomes.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: To assess change in depression over ≥4 years in adults with type 1 diabetes (T1D) and the association between change in depression and glycemic outcomes, we examined PHQ-8 data in adults in the T1D Exchange Clinic Registry with T1D duration ≥ 1 year (N= 2547; 57% female, 92% non-Hispanic white, year 1 age 43±16 years). PHQ-8 score ≥10 defined “depressed.” Linear regression was used to assess association of continuous outcomes and depression; logistic regression was used for categorical outcomes. At year 1/year 5, 9%/11% were depressed. In this sample, 126 (5%) had Persistent Depression (depressed at year 1 and year 5), 112 (4%) Resolved Depression (depressed at year 1, not at year 5), 148 (6%) New Year 5 Depression (not depressed at year 1, depressed at year 5), and 2161 (85%) Not Depressed at year 1/year 5. Of those depressed at year 1, 53% were depressed at year 5; of those not depressed at year 1, 6% were depressed at year 5. Participants with persistent depression/new year 5 depression had a significant increase (↑) in A1c [adj mean ↑ 0.5± 0.2/0.5± 0.2; adj mean 8.1±0.1 for both; adj P’s=0.001]; those not depressed at year 1/year 5 showed a trend in ↑A1c [0.3±0.1; adj mean 7.8±0.1; adj P=0.04] . Those with resolved depression did not show change in A1c [0.2±0.2; adj mean 7.7±0.2; adj P=0.28]. Those with persistent depression/new year 5 depression were more likely to report new year 5 DKA (DKA year 5 | no DKA year 1) than those not depressed at year 1/year 5 (adj P’s=0.03/0.04). There were trends for those with persistent depression to be more likely to report new year 5 severe hypoglycemia (SH) than those not depressed (11.1% vs. 4.8%); and for those with resolved depression to be less likely to report new year 5 SH (3.6 vs. 4.8%, adj P’s=0.09/0.11). Depression category was not associated with change in BMI (adj P=0.80). As a continuous variable, ↑in PHQ-8 was associated with ↑ in A1c (adj P & lt;0.001), but not with new year 5 SH or BMI change (adj P & gt;0.50). Depression (persistent or new year 5) has a negative impact on glycemic control over time. Adults with T1D should be screened and treated for depression. Disclosure P.M. Trief: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. N.C. Foster: None. N. Chaytor: None. M.E. Hilliard: None. J. Kittelsrud: None. S. Jaser: None. S. Majidi: None. S. Corathers: None. S. Bzdick: None. D. Adkins: None. R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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  • 3
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs. Methods We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs. Results ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.59; 95%CI: 0.45–0.77) and severe anaemia (OR: 0.55; 95%CI: 0.33–0.90), and experience of pain for more than 4 days a week (OR: 0.50; 95%CI: 0.30–0.83), while it increased the likelihood of mild neutropenia (OR: 1.73; 95%CI: 1.27–2.35). It also reduced the cost of chemotherapy by 12% (95%CI: 3–31) or £9765, the cost of non-elective hospitalisation by 23% (95%CI: 8–36) or £2331, and the cost of critical care by 21% (95%CI: 2–36) or £1219 per patient. For the DPYD variant associated with critical risk of toxicity (rs3918290), the improved non-elective hospital costs were  〉  £20,000, whereas variants associated with hand-foot syndrome toxicity had no detectable cost improvement. Conclusion Upfront testing of DPYD variants appears to reduce the toxicity burden of Capecitabine and 5-FU in cancer patients and can lead to substantial hospital cost savings, only if the dose management of the drugs in response to variants detected is standardised and regulated.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041352-X
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  • 4
    In: Developmental Cell, Elsevier BV, Vol. 58, No. 19 ( 2023-10), p. 1967-1982.e8
    Type of Medium: Online Resource
    ISSN: 1534-5807
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2053870-4
    SSG: 12
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  • 5
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 4 ( 2016-02-17)
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2016
    detail.hit.zdb_id: 2711781-9
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Sustainability Vol. 2 ( 2021-7-29)
    In: Frontiers in Sustainability, Frontiers Media SA, Vol. 2 ( 2021-7-29)
    Abstract: In leadership positions at UCL, we have spent more than a decade seeking to fulfil our university's founding commitment—inspired almost two centuries ago by the utilitarian philosopher Jeremy Bentham—to innovation, accessibility, and relevance for the benefit of humanity. Our guiding principle has been to make our institution and its activities greater than the sum of its parts. To enable us to have most impact in “sustainable human progress,” we have focused our approach on cross-disciplinarity—by which we mean collaboration between experts in different disciplines that transcends subject boundaries—because the problems faced by society cannot be solved by research from one discipline alone. In recent years we have come to understand the boundaries between disciplines to be a subset of the many types of barriers—such as those between communities (disciplinary, academic and otherwise) and between different kinds of activity—that can inhibit the fulfilment of our vision to maximise our public benefit. In order to address crucial challenges—from the local to the global—we need to form collaborations across society that increase our mutual knowledge and engagement. We need to understand how the translation and application of knowledge will change in different settings and according to different practicalities. And we need to better reflect and enhance our role as convenors of different stakeholders to promote greater shared dialogue, co-creation and action.
    Type of Medium: Online Resource
    ISSN: 2673-4524
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 3035410-9
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-10-3)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-10-3)
    Abstract: Neuroblastoma is believed to arise from sympathetic neuroblast precursors that fail to engage the neuronal differentiation programme, but instead become locked in a pro-proliferative developmental state. Achaete-scute homolog 1 (ASCL1) is a proneural master regulator of transcription which modulates both proliferation and differentiation of sympathetic neuroblast precursor cells during development, while its expression has been implicated in the maintenance of an oncogenic programme in MYCN-amplified neuroblastoma. However, the role of ASCL1 expression in neuroblastoma is not clear, especially as its levels vary considerably in different neuroblastoma cell lines. Here, we have investigated the role of ASCL1 in maintaining proliferation and controlling differentiation in both MYCN amplified and Anaplastic Lymphoma Kinase (ALK)-driven neuroblastoma cells. Using CRISPR deletion, we generated neuroblastoma cell lines lacking ASCL1 expression, and these grew more slowly than parental cells, indicating that ASCL1 contributes to rapid proliferation of MYCN amplified and non-amplified neuroblastoma cells. Genome-wide analysis after ASCL1 deletion revealed reduced expression of genes associated with neuronal differentiation, while chromatin accessibility at regulatory regions associated with differentiation genes was also attenuated by ASCL1 knock-out. In neuroblastoma, ASCL1 has been described as part of a core regulatory circuit of developmental regulators whose high expression is maintained by mutual cross-activation of a network of super enhancers and is further augmented by the activity of MYC/MYCN. Surprisingly, ASCL1 deletion had little effect on the transcription of CRC gene transcripts in these neuroblastoma cell lines, but the ability of MYC/MYCN and CRC component proteins, PHOX2B and GATA3, to bind to chromatin was compromised. Taken together, our results demonstrate several roles for endogenous ASCL1 in neuroblastoma cells: maintaining a highly proliferative phenotype, regulating DNA binding of the core regulatory circuit genes to chromatin, while also controlling accessibility and transcription of differentiation targets. Thus, we propose a model where ASCL1, a key developmental regulator of sympathetic neurogenesis, plays a pivotal role in maintaining proliferation while simultaneously priming cells for differentiation in neuroblastoma.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 8
    Online Resource
    Online Resource
    The Physiological Society ; 2018
    In:  Physiology News , No. Autumn 2018 ( 2018-9-1), p. 16-17
    In: Physiology News, The Physiological Society, , No. Autumn 2018 ( 2018-9-1), p. 16-17
    Type of Medium: Online Resource
    URL: Issue
    Language: English
    Publisher: The Physiological Society
    Publication Date: 2018
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  • 9
    In: The Lancet, Elsevier BV, Vol. 386, No. 10006 ( 2015-11), p. 1861-1914
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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