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  1. Article ; Online: How good are we at reporting the socioeconomic position, ethnicity, race, religion and main language of research participants? A review of the quality of reporting in palliative care intervention studies.

    Selvakumaran, Keerthika / Sleeman, Katherine E / Davies, Joanna M

    Palliative medicine

    2024  Volume 38, Issue 3, Page(s) 396–399

    MeSH term(s) Humans ; Palliative Care ; Ethnicity ; Socioeconomic Factors ; Social Class ; Religion
    Language English
    Publishing date 2024-02-08
    Publishing country England
    Document type Review ; Letter
    ZDB-ID 639247-7
    ISSN 1477-030X ; 0269-2163
    ISSN (online) 1477-030X
    ISSN 0269-2163
    DOI 10.1177/02692163231224154
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    Zs.A 2285: Show issues Location:
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  2. Article ; Online: Destabilisation of T cell-dependent humoral immunity in sepsis.

    Davies, Kate / McLaren, James E

    Clinical science (London, England : 1979)

    2024  Volume 138, Issue 1, Page(s) 65–85

    Abstract: Sepsis is a heterogeneous condition defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For some, sepsis presents as a predominantly suppressive disorder, whilst others experience a pro-inflammatory ... ...

    Abstract Sepsis is a heterogeneous condition defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For some, sepsis presents as a predominantly suppressive disorder, whilst others experience a pro-inflammatory condition which can culminate in a 'cytokine storm'. Frequently, patients experience signs of concurrent hyper-inflammation and immunosuppression, underpinning the difficulty in directing effective treatment. Although intensive care unit mortality rates have improved in recent years, one-third of discharged patients die within the following year. Half of post-sepsis deaths are due to exacerbation of pre-existing conditions, whilst half are due to complications arising from a deteriorated immune system. It has been suggested that the intense and dysregulated response to infection may induce irreversible metabolic reprogramming in immune cells. As a critical arm of immune protection in vertebrates, alterations to the adaptive immune system can have devastating repercussions. Indeed, a marked depletion of lymphocytes is observed in sepsis, correlating with increased rates of mortality. Such sepsis-induced lymphopenia has profound consequences on how T cells respond to infection but equally on the humoral immune response that is both elicited by B cells and supported by distinct CD4+ T follicular helper (TFH) cell subsets. The immunosuppressive state is further exacerbated by functional impairments to the remaining lymphocyte population, including the presence of cells expressing dysfunctional or exhausted phenotypes. This review will specifically focus on how sepsis destabilises the adaptive immune system, with a closer examination on how B cells and CD4+ TFH cells are affected by sepsis and the corresponding impact on humoral immunity.
    MeSH term(s) Animals ; Humans ; Immunity, Humoral ; T-Lymphocytes ; B-Lymphocytes ; Sepsis ; Immunosuppressive Agents
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2024-01-09
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20230517
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    Ua VI Zs.220: Show issues Location:
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  3. Article ; Online: Targeting CD20-expressing malignant melanoma cells augments BRAF inhibitor killing.

    Mukhtar, Abdullahi B / Morgan, Huw J / Gibbs, Alex / Davies, Gemma E / Lovatt, Charlotte / Patel, Girish K

    The British journal of dermatology

    2024  Volume 190, Issue 5, Page(s) 729–739

    Abstract: Background: Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however, high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease ... ...

    Abstract Background: Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however, high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease recurrence and mortality. As MM recurrence during targeted therapy can present with the simultaneous occurrence of multiple tumour nodules at the original body sites, we hypothesized the presence of an intrinsically resistant MM cell subpopulation.
    Objectives: To identify an MM cell subpopulation that is intrinsically resistant to targeted therapy and possibly responsible for MM recurrence.
    Methods: Using melanoma cell lines, we defined culture conditions for the reproducible three-dimensional growth of melanospheres to investigate putative cancer stem cell populations. We undertook RNA sequencing and bioinformatic analysis to characterize cell populations between adherent and nonadherent culture, and cells expressing or not expressing CD20. Furthermore, we defined an in vitro assay to evaluate the killing of melanoma cancer stem cells as a therapeutic test using combination therapies targeting driver mutation and CD20.
    Results: We described the culture conditions that promote MM cells to form melanospheres with a reproducible colony-forming efficiency rate of 0.3-1.3%. RNA sequencing of melanosphere vs. conventional MM cell cultures (n = 6), irrespective of the BRAF mutation status, showed that melanosphere formation was associated with growth and differentiation transcriptional signatures resembling MM tumours. Importantly, melanosphere formation also led to the emergence of a CD20+ MM cell subpopulation, similar to that observed in primary human MM tumours. CD20+ MM cells were resistant to BRAF inhibitor therapy and, consistent with this finding, demonstrated a Forkhead box protein M1 transcriptomic profile (n = 6). Combining BRAF inhibitor and anti-CD20 antibody treatment led to the additional killing of previously resistant CD20+  BRAF mutant MM cells.
    Conclusions: In patients with MM that harbour a CD20+ subpopulation, combined therapy with BRAF inhibitor and anti-CD20 antibody could potentially kill residual MM cells and prevent disease recurrence.
    MeSH term(s) Humans ; Melanoma/pathology ; Proto-Oncogene Proteins B-raf/genetics ; Neoplasm Recurrence, Local ; Protein Kinase Inhibitors/pharmacology ; Mutation ; Cell Line, Tumor
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Protein Kinase Inhibitors ; BRAF protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2024-02-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 80076-4
    ISSN 1365-2133 ; 0007-0963
    ISSN (online) 1365-2133
    ISSN 0007-0963
    DOI 10.1093/bjd/ljad502
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  4. Article ; Online: Highway to HHGE: An Interview with Dame Kay E. Davies.

    Davies, Kevin / Davies, Kay E

    The CRISPR journal

    2020  Volume 3, Issue 5, Page(s) 325–331

    MeSH term(s) Gene Editing/ethics ; Gene Editing/history ; Genetic Diseases, Inborn/genetics ; Genetic Diseases, Inborn/history ; Genetic Diseases, Inborn/therapy ; Genome, Human ; History, 20th Century ; Humans ; Research Report/history
    Language English
    Publishing date 2020-10-23
    Publishing country United States
    Document type Autobiography ; Historical Article ; Interview
    ZDB-ID 3017891-5
    ISSN 2573-1602 ; 2573-1599
    ISSN (online) 2573-1602
    ISSN 2573-1599
    DOI 10.1089/crispr.2020.29104.kda
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    Zs.A 7195: Show issues Location:
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  5. Article: Umbilical Cord Stem Cell Lysate: A New Biologic Injectate for the Putative Treatment of Acute Temporomandibular Joint Inflammation.

    Ward, Christopher K / Gill, Rita G / Liddell, Robert S / Davies, John E

    Journal of inflammation research

    2023  Volume 16, Page(s) 4287–4300

    Abstract: Objective: To compare in vivo, the acute anti-inflammatory effects of a lysate derived from human umbilical perivascular mesenchymal cells with the cells themselves in both an established hind-paw model of carrageenan-induced inflammation and also in ... ...

    Abstract Objective: To compare in vivo, the acute anti-inflammatory effects of a lysate derived from human umbilical perivascular mesenchymal cells with the cells themselves in both an established hind-paw model of carrageenan-induced inflammation and also in the inflamed temporomandibular joint.
    Study design: Human umbilical cord perivascular cells were harvested and cultured in xeno- and serum-free conditions to P3. In addition, P3 cells were used to prepare a proprietary 0.22 micron filtered lysate. First, CD1 immunocompetent mice underwent unilateral hind-paw injections of carrageenan for induction of inflammation, followed immediately by treatment with saline (negative control), 1% cell lysate, or viable cells. The contralateral paw remained un-injected with carrageenan. Paw circumference was measured prior to injections and 48 hr later and myeloperoxidase and TNF-alpha concentrations were measured post-sacrifice in excised tissue. Second, immunocompetent Male Wistar rats underwent unilateral intra-articular temporomandibular (TMJ) injections from the same treatment groups and were sacrificed at 4 and 48 hr post-injection. The contralateral TMJ remained un-injected with carrageenan. Articular tissue and synovial aspirates, from the treated TMJ were obtained for histologic and leukocyte infiltration analyses.
    Results: The lysate and cell-treated hind-paw demonstrated reduced tissue edema, and significantly lower concentrations of myeloperoxidase and TNF-alpha at 48 hr compared to untreated controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium compared to controls and histologic evidence, in the peri-articular tissue, of reduced inflammation.
    Conclusion: In this preliminary study, both the human umbilical perivascular cells and a highly diluted lysate produced therefrom were anti-inflammatory.
    Language English
    Publishing date 2023-09-27
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494878-0
    ISSN 1178-7031
    ISSN 1178-7031
    DOI 10.2147/JIR.S420741
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  6. Article: The Dental Health of Looked After Children in the UK and Dental Care Pathways: A Scoping Review.

    Hurry, K J / Ridsdale, L / Davies, J / Muirhead, V E

    Community dental health

    2023  Volume 40, Issue 3, Page(s) 154–161

    Abstract: Background: There has been a 37% increase in the number of Looked After Children (LAC) in England over the past decade. Although LAC have more health and social problems than their peers, little is known about their dental needs, barriers to dental care, ...

    Abstract Background: There has been a 37% increase in the number of Looked After Children (LAC) in England over the past decade. Although LAC have more health and social problems than their peers, little is known about their dental needs, barriers to dental care, and pathways used to access it.
    Objectives: This scoping review assessed the evidence on the dental health needs of LAC in the UK and their different dental care pathways.
    Methods: Embase, MedLine(R), Scopus, Web of Science, PubMed and CINAHL, grey literature databases and third-sector organisation websites were searched up to February 2022. Included studies were any study type involving UK resident LAC aged 0-18 with no limits placed on time in care/placement. Thematic analysis identified access barriers and dental care pathways.
    Results: Twenty-eight articles were included (nine publications, 11 abstracts and 8 grey literature). Oral health surveys, population linkages studies and service evaluations described the poor oral health of LAC and their unmet needs. Barriers included the lack of dental care and irregular attendance; the lack of integrated working between health and social care teams, lack of self-care and oral health promotion, and psychological issues complicating dental treatment. Four dental care pathway models were identified: care navigation, facilitated access, nurse-led triage and referral, and signposting to local dentist with multi-agency information sharing.
    Conclusion: LAC are a vulnerable group with barriers to care suggesting the need for integrated working between health and social care teams, specialist services and an evaluation of pathways to identify best practice.
    MeSH term(s) Humans ; Child ; Critical Pathways ; Oral Health ; Health Promotion ; Dental Health Surveys ; United Kingdom
    Language English
    Publishing date 2023-08-31
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 631156-8
    ISSN 0265-539X
    ISSN 0265-539X
    DOI 10.1922/CDH_00252Hurry08
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    Zs.A 2169: Show issues Location:
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  7. Article ; Online: Chilling injury in human kidney tubule cells after subzero storage is not mitigated by antifreeze protein addition.

    Tomalty, Heather E / Graham, Laurie A / Walker, Virginia K / Davies, Peter L

    Cryobiology

    2023  Volume 111, Page(s) 113–120

    Abstract: By preventing freezing, antifreeze proteins (AFPs) can permit cells and organs to be stored at subzero temperatures. As metabolic rates decrease with decreasing temperature, subzero static cold storage (SZ-SCS) could provide more time for tissue matching ...

    Abstract By preventing freezing, antifreeze proteins (AFPs) can permit cells and organs to be stored at subzero temperatures. As metabolic rates decrease with decreasing temperature, subzero static cold storage (SZ-SCS) could provide more time for tissue matching and potentially lead to fewer discarded organs. Human kidneys are generally stored for under 24 h and the tubule epithelium is known to be particularly sensitive to static cold storage (SCS). Here, telomerase-immortalized proximal-tubule epithelial cells from humans, which closely resemble their progenitors, were used as a proxy to assess the potential benefit of SZ-SCS for kidneys. The effects of hyperactive AFPs from a beetle and Cryostasis Storage Solution were compared to University of Wisconsin Solution at standard SCS temperatures (4 °C) and at -6 °C for up to six days. Although the AFPs helped guard against freezing, lower storage temperatures under these conditions were not beneficial. Compared to cells at 4 °C, those stored at -6 °C showed decreased viability as well as increased lactate dehydrogenase release and apoptosis. This suggests that this kidney cell type might be prone to chilling injury and that the addition of AFPs to enable SZ-SCS may not be effective for increasing storage times.
    MeSH term(s) Humans ; Cryopreservation/methods ; Antifreeze Proteins/metabolism ; Organ Preservation Solutions ; Kidney Tubules/metabolism
    Chemical Substances University of Wisconsin-lactobionate solution ; Antifreeze Proteins ; Organ Preservation Solutions
    Language English
    Publishing date 2023-05-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80098-3
    ISSN 1090-2392 ; 0011-2240
    ISSN (online) 1090-2392
    ISSN 0011-2240
    DOI 10.1016/j.cryobiol.2023.05.002
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    Zs.A 528: Show issues Location:
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  8. Article ; Online: Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

    Davies, K L / Miles, J / Camm, E J / Smith, D J / Barker, P / Taylor, K / Forhead, A J / Fowden, A L

    The Journal of endocrinology

    2024  Volume 260, Issue 3

    Abstract: Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause ... ...

    Abstract Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.
    MeSH term(s) Female ; Pregnancy ; Animals ; Sheep ; Hydrocortisone/metabolism ; Adrenocorticotropic Hormone/metabolism ; Fetus/metabolism ; Adrenal Glands/metabolism ; Glucose/metabolism ; Insulin/metabolism ; Gestational Age
    Chemical Substances Hydrocortisone (WI4X0X7BPJ) ; Adrenocorticotropic Hormone (9002-60-2) ; Glucose (IY9XDZ35W2) ; Insulin
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-23-0326
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    Uh III Zs.133: Show issues Location:
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  9. Article ; Online: Contextualizing Children's Caregiving Responses to Interparental Conflict: Advancing Assessment of Parentification.

    Nuttall, Amy K / Valentino, Kristin / Mark Cummings, E / Davies, Patrick T

    Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)

    2022  Volume 35, Issue 3, Page(s) 276–287

    Abstract: ... caregiving at the family level (i.e., within parent-child relationships) proved most informative ...

    Abstract Parentification is a parent-child dynamic in which children assume caregiving responsibilities while parents fail to support and reciprocate children's roles. There is a gap between empirical research, which typically operationalizes parentification as the occurrence of children's caregiving behaviors, and theory, which emphasizes consideration of the family context in which children engage in caregiving as well as adjustment. The present study (N=235) considered multiple operationalizations of the construct by assessing kindergarten-aged children's caregiving reactions to interparental conflict in a standardized paradigm and additionally contextualizing caregiving reactions within family context and child adjustment over time through mixture modeling approaches. Although 88% of children endorsed caregiving, contextualizing caregiving resulted in lower estimates of this phenomenon (conservatively, 30%). Moreover, contextualizing children's caregiving at the family level (i.e., within parent-child relationships) proved most informative in identifying between-family differences in within-family experiences of parentification. Despite identifying a pattern of parentification at the family level (high children's caregiving reactions in conjunction with
    MeSH term(s) Aged ; Child, Preschool ; Family Conflict/psychology ; Humans ; Parent-Child Relations ; Parents/psychology ; Social Behavior
    Language English
    Publishing date 2022-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 619328-6
    ISSN 1939-1293 ; 0893-3200
    ISSN (online) 1939-1293
    ISSN 0893-3200
    DOI 10.1037/fam0000646
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  10. Article ; Online: Tetramine Aspect Ratio and Flexibility Determine Framework Symmetry for Zn

    Davies, Jack A / Tarzia, Andrew / Ronson, Tanya K / Auras, Florian / Jelfs, Kim E / Nitschke, Jonathan R

    Angewandte Chemie (International ed. in English)

    2023  Volume 62, Issue 10, Page(s) e202217987

    Abstract: We derive design principles for the assembly of rectangular tetramines into ... ...

    Abstract We derive design principles for the assembly of rectangular tetramines into Zn
    Language English
    Publishing date 2023-02-01
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202217987
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