Author: "Dent OF" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

4,113 results on '"Dent OF"'

1. Derivation and validation of the Ottawa weight loss prediction model for patients on a low-calorie diet

Author: Robert R. M. Dent and Carl van Walraven
Subjects: Weight loss, Prediction, Longitudinal regression, Medicine, Science
Abstract: Abstract Accurate weight predictions are essential for weight management program patients. The freely available National Institutes of Health Body Weight Planner (NIH-BWP) returns expected weights over time but overestimates weight when patients consume a low-calorie diet. This study sought to increase the accuracy of NIH-BWP predicted weights for people on low-calorie diets. People enrolled in a weight management program were included if they received meal replacements with defined caloric content for the 3 months of the weight loss phase of the program. The Ottawa Weight Loss Prediction Model (OWL-PM) modelled the relative difference between observed and NIH-BWP predicted weights using longitudinal analysis methods based on patient factors. OWL-PM was externally validated. 1761 people were included (mean age 46 years, 73.3% women) with a mean (SD) baseline weight in pounds and body mass index of 271.9 (55.6) and 43.9 (7.4), respectively. At the end of the program’s weight loss phase, people lost a median (IQR) of 17.1% (14.8–19.5) of their baseline weight. Observed weight relative to NIH-BWP predicted weights had a median value of − 4.9% but ranged from − 32.1% to + 28.5%. After adjustment, weight overestimation by NIH-BWP was most pronounced in male patients, people without diabetes and with increased observation time. OWL-PM returned expected weights at 3 months that were significantly more accurate than those from NIH-BWP alone (mean difference observed vs. expected [95% CI] 6.7lbs [6.4–7.0] vs. 12.6lbs [12.1–13.0]). In the external validation cohort (n = 106), OWL-PM was significantly more accurate than NIH-BWP (mean squared error 24.3 vs. 40.0, p = 0.0018). OWL-PM incorporated patient-level covariates to significantly increase weight prediction accuracy of NIH-BWP in patients consuming a low-calorie diet.
Published: 2024
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2. Actin networks modulate heterogeneous NF-κB dynamics in response to TNFα

Author: Francesca Butera, Julia E Sero, Lucas G Dent, and Chris Bakal
Subjects: actin, NF-κB, RELA, PDAC, single-cell dynamics, TNF, Medicine, Science, Biology (General), QH301-705.5
Abstract: The canonical NF-κB transcription factor RELA is a master regulator of immune and stress responses and is upregulated in pancreatic ductal adenocardinoma (PDAC) tumours. In this study, we characterised previously unexplored endogenous RELA-GFP dynamics in PDAC cell lines through live single-cell imaging. Our observations revealed that TNFα stimulation induces rapid, sustained, and non-oscillatory nuclear translocation of RELA. Through Bayesian analysis of single-cell datasets with variation in nuclear RELA, we predicted that RELA heterogeneity in PDAC cell lines is dependent on F-actin dynamics. RNA-seq analysis identified distinct clusters of RELA-regulated gene expression in PDAC cells, including TNFα-induced RELA upregulation of the actin regulators NUAK2 and ARHGAP31. Further, siRNA-mediated depletion of ARHGAP31 and NUAK2 altered TNFα-stimulated nuclear RELA dynamics in PDAC cells, establishing a novel negative feedback loop that regulates RELA activation by TNFα. Additionally, we characterised the NF-κB pathway in PDAC cells, identifying how NF-κB/IκB proteins genetically and physically interact with RELA in the absence or presence of TNFα. Taken together, we provide computational and experimental support for interdependence between the F-actin network and the NF-κB pathway with RELA translocation dynamics in PDAC.
Published: 2024
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3. Impact of a Health Coach–Led, Text-Based Digital Behavior Change Intervention on Weight Loss and Psychological Well-Being in Patients Receiving a Procedureless Intragastric Balloon Program: Prospective Single-Arm Study

Author: Paul M Sacher, Emily Fulton, Victoria Rogers, Julia Wilson, Marco Gramatica, Jennifer E Dent, Edo O Aarts, David Eccleston, Jan Willem Greve, Inge Palm-Meinders, and Ram Chuttani
Subjects: Medicine
Abstract: BackgroundDigital health interventions show promise for weight management. However, few text-based behavior change interventions have been designed to support patients receiving intragastric balloons, and none have simultaneously evaluated weight loss, psychological well-being, and behavior change despite the crucial interplay of these factors in weight management. ObjectiveThis study aims to assess whether a health coach–led, asynchronous, text-based digital behavior change coaching intervention (DBCCI) delivered to participants receiving an intragastric balloon and its aftercare program was feasible and acceptable to participants and supported improved outcomes, including weight loss, psychological well-being, and lifestyle behavior change conducive to weight loss maintenance. MethodsThis 12-month, single-arm prospective study enrolled adults aged 21 to 65 years with BMI ≥27 kg/m2 receiving a procedureless intragastric balloon (PIGB) at 5 bariatric clinics in the United Kingdom and the Netherlands. Participants received the DBCCI and the clinic-led PIGB aftercare program (remotely delivered) for 6 months after PIGB placement and then no intervention for an additional 6 months. The DBCCI was an evidence-based, personalized intervention wherein health coaches supported participants via exchanged asynchronous in-app text-based messages. Over the 12-month study, we assessed percentage of total body weight loss and psychological well-being via self-administered validated questionnaires (Warwick-Edinburgh Mental Wellbeing Scale, Generalized Anxiety Disorder Scale, Impact of Weight on Quality of Life–Lite–Clinical Trials Version, Loss of Control Over Eating Scale–Brief, Weight Efficacy Lifestyle Questionnaire–Short Form, and Barriers to Being Active Quiz). Participant engagement with and acceptability of the intervention were assessed via self-reported surveys. ResultsOverall, 107 participants (n=96, 89.7% female; mean baseline BMI 35.4, SD 5.4 kg/m2) were included in the analysis. Mean total body weight loss was 13.5% (SEM 2.3%) at the end of the DBCCI and 11.22% (SEM 2.3%) at the 12-month follow-up (P
Published: 2024
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4. Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome

Author: Josephina A. N. Meester, Anne Hebert, Maaike Bastiaansen, Laura Rabaut, Jarl Bastianen, Nele Boeckx, Kathryn Ashcroft, Paldeep S. Atwal, Antoine Benichou, Clarisse Billon, Jan D. Blankensteijn, Paul Brennan, Stephanie A. Bucks, Ian M. Campbell, Solène Conrad, Stephanie L. Curtis, Majed Dasouki, Carolyn L. Dent, James Eden, Himanshu Goel, Verity Hartill, Arjan C. Houweling, Bertrand Isidor, Nicola Jackson, Pieter Koopman, Anita Korpioja, Minna Kraatari-Tiri, Liina Kuulavainen, Kelvin Lee, Karen J. Low, Alan C. Lu, Morgan L. McManus, Stephen P. Oakley, James Oliver, Nicole M. Organ, Eline Overwater, Nicole Revencu, Alison H. Trainer, Bhavya Trivedi, Claire L. S. Turner, Rebecca Whittington, Andreas Zankl, Dominica Zentner, Lut Van Laer, Aline Verstraeten, and Bart L. Loeys
Subjects: Medicine, Genetics, QH426-470
Abstract: Abstract Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5’ untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.
Published: 2024
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5. Validity of two weight prediction models for community-living patients participating in a weight loss program

Author: Robert Dent, Neil Harris, and Carl van Walraven
Subjects: Medicine, Science
Abstract: Abstract Models predicting individual body weights over time clarify patient expectations in weight loss programs. The accuracy of two commonly used weight prediction models in community living people is unclear. All eligible people entering a weight management program between 1992 and 2015 were included. Patients’ diet was 1200 kcal/day for week 0 followed by 900 kcal/day for weeks 1–7 and were excluded from the analysis if they were nonadherent. We generated expected weights using the National Institutes of Health Body Weight Planner (NIH-BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC-WLP). 3703 adherent people were included (mean age 46 years, 72.6% women, mean [SD] weight 262.3 pounds [54.2], mean [SD] BMI 42.4 [7.6]). Mean (SD) relative body weight differences (100*[observed−expected]/expected) for NIH-BWP and PBRC-WLP models was − 1.5% (3.8) and − 2.9% (3.2), respectively. At week 7, mean squared error with NIH-BWP (98.8, 83%CI 89.7–108.8) was significantly lower than that with PBRC-WLP (117.7, 83%CI 112.4–123.4). Notable variation in relative weight difference were seen (for NIH-BWP, 5th–95th percentile was − 6.2%, + 3.7%; Δ 9.9%). During the first 7 weeks of a weight loss program, both weight prediction models returned expected weights that were very close to observed values with the NIH-BWP being more accurate. However, notable variability between expected and observed weights in individual patients were seen. Clinicians can monitor patients in weight loss programs by comparing their progress with these data.
Published: 2023
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6. O20: Beyond the genome: RNA sequencing resolves unique diagnostic challenges

Author: Robert Lewis, Makenzie Fulmer, Jian Zhao, Lucilla Pizzo, Ting Wen, John O'Shea, Thomas Nicholas, Steven Boyden, David Viskochil, Nicola Longo, Ashley Andrews, Erin Baldwin, Matt Velinder, Russell Butterfield, Karin Dent, Kourtney Santucci, Austin Larson, Rong Mao, Lorenzo Botto, and Pinar Bayrak-Toydemir
Subjects: Genetics, QH426-470, Medicine
Published: 2024
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7. USP22 overexpression fails to augment tumor formation in MMTV-ERBB2 mice but loss of function impacts MMTV promoter activity

Author: Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J. Muller, Sharon Y. R. Dent, and Evangelia Koutelou
Subjects: Medicine, Science
Published: 2024

8. IMPAACT: IMproving the PArticipAtion of older people in policy decision-making on common health CondiTions – a study protocol

Author: Simon Stewart, Michael Lawless, Renuka Visvanathan, Danielle Taylor, Mandy Archibald, Hannah M O'Rourke, Matthew J Leach, Mark Thompson, Justin Beilby, Rachel C Ambagtsheer, Kathy Williams, Annette Braunack-Mayer, Victoria Cornell, Catherine J Hurley, Elsa Dent, Lyn Whiteway, and Agnieszka Chudecka
Subjects: Medicine
Abstract: Introduction Rapid population ageing is a demographic trend being experienced and documented worldwide. While increased health screening and assessment may help mitigate the burden of illness in older people, issues such as misdiagnosis may affect access to interventions. This study aims to elicit the values and preferences of evidence-informed older people living in the community on early screening for common health conditions (cardiovascular disease, diabetes, dementia and frailty). The study will proceed in three Phases: (1) generating recommendations of older people through a series of Citizens’ Juries; (2) obtaining feedback from a diverse range of stakeholder groups on the jury findings; and (3) co-designing a set of Knowledge Translation resources to facilitate implementation into research, policy and practice. Conditions were chosen to reflect common health conditions characterised by increasing prevalence with age, but which have been underexamined through a Citizens’ Jury methodology.Methods and analysis This study will be conducted in three Phases—(1) Citizens’ Juries, (2) Policy Roundtables and (3) Production of Knowledge Translation resources. First, older people aged 50+ (n=80), including those from traditionally hard-to-reach and diverse groups, will be purposively recruited to four Citizen Juries. Second, representatives from a range of key stakeholder groups, including consumers and carers, health and aged care policymakers, general practitioners, practice nurses, geriatricians, allied health practitioners, pharmaceutical companies, private health insurers and community and aged care providers (n=40) will be purposively recruited for two Policy Roundtables. Finally, two researchers and six purposively recruited consumers will co-design Knowledge Translation resources. Thematic analysis will be performed on documentation and transcripts.Ethics and dissemination Ethical approval has been obtained through the Torrens University Human Research Ethics Committee. Participants will give written informed consent. Findings will be disseminated through development of a policy brief and lay summary, peer-reviewed publications, conference presentations and seminars.
Published: 2024
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9. Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2–, PIK3CA-mutated breast cancers

Author: Katherine E. Hutchinson, Jessica W. Chen, Heidi M. Savage, Thomas J. Stout, Frauke Schimmoller, Javier Cortés, Susan Dent, Nadia Harbeck, William Jacot, Ian Krop, Sally E. Trabucco, Smruthy Sivakumar, Ethan S. Sokol, and Timothy R. Wilson
Subjects: PIK3CA, Double PIK3CA mutation, Clonal, Taselisib, PI3K inhibitor, Breast cancer, Medicine, Genetics, QH426-470
Abstract: Abstract Background Mutations in the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), encoded by the PIK3CA gene, cause dysregulation of the PI3K pathway in 35–40% of patients with HR+/HER2– breast cancer. Preclinically, cancer cells harboring double or multiple PIK3CA mutations (mut) elicit hyperactivation of the PI3K pathway leading to enhanced sensitivity to p110α inhibitors. Methods To understand the role of multiple PIK3CAmut in predicting response to p110α inhibition, we estimated the clonality of multiple PIK3CAmut in circulating tumor DNA (ctDNA) from patients with HR+/HER2– metastatic breast cancer enrolled to a prospectively registered clinical trial of fulvestrant ± taselisib, and analyzed the subgroups against co-altered genes, pathways, and outcomes. Results ctDNA samples with clonal multiple PIK3CAmut had fewer co-alterations in receptor tyrosine kinase (RTK) or non-PIK3CA PI3K pathway genes compared to samples with subclonal multiple PIK3CAmut indicating a strong reliance on the PI3K pathway. This was validated in an independent cohort of breast cancer tumor specimens that underwent comprehensive genomic profiling. Furthermore, patients whose ctDNA harbored clonal multiple PIK3CAmut exhibited a significantly higher response rate and longer progression-free survival vs subclonal multiple PIK3CAmut. Conclusions Our study establishes clonal multiple PIK3CAmut as an important molecular determinant of response to p110α inhibition and provides rationale for further clinical investigation of p110α inhibitors alone or with rationally-selected therapies in breast cancer and potentially other solid tumor types.
Published: 2023
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10. Characterization and utility of two monoclonal antibodies to cholera toxin B subunit

Author: Noel Verjan Garcia, Ian Carlosalberto Santisteban Celis, Matthew Dent, and Nobuyuki Matoba
Subjects: Medicine, Science
Abstract: Abstract Cholera toxin B subunit (CTB) is a potent immunomodulator exploitable in mucosal vaccine and immunotherapeutic development. To aid in the characterization of pleiotropic biological functions of CTB and its variants, we generated a panel of anti-CTB monoclonal antibodies (mAbs). By ELISA and surface plasmon resonance, two mAbs, 7A12B3 and 9F9C7, were analyzed for their binding affinities to cholera holotoxin (CTX), CTB, and EPICERTIN: a recombinant CTB variant possessing mucosal healing activity. Both 7A12B3 and 9F9C7 bound efficiently to CTX, CTB, and EPICERTIN with equilibrium dissociation constants at low to sub-nanomolar concentrations but bound weakly, if at all, to Escherichia coli heat-labile enterotoxin B subunit. In a cyclic adenosine monophosphate assay using Caco2 human colon epithelial cells, the 7A12B3 mAb was found to be a potent inhibitor of CTX, whereas 9F9C7 had relatively weak inhibitory activity. Meanwhile, the 9F9C7 mAb effectively detected CTB and EPICERTIN bound to the surface of Caco2 cells and mouse spleen leukocytes by flow cytometry. Using 9F9C7 in immunohistochemistry, we confirmed the preferential localization of EPICERTIN in colon crypts following oral administration of the protein in mice. Collectively, these mAbs provide valuable tools to investigate the biological functions and preclinical development of CTB variants.
Published: 2023
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11. Trajectories, Transitions, and Trends in Frailty among Older Adults: A Review

Author: Emiel O. Hoogendijk and Elsa Dent
Subjects: frail older adults, frailty, aging, longitudinal studies, trends, Medicine, Geriatrics, RC952-954.6
Abstract: Frailty is an age-related clinical state associated with deterioration across multiple physiological systems and a leading cause of morbidity and mortality later in life. To understand how frailty develops and what causes its progression, longitudinal data with repeated frailty measurements are required. This review summarizes evidence from longitudinal studies on frailty trajectories, transitions, and trends. We identified several consistent findings: frailty increases with aging and is a dynamic condition, and more recent generations of older adults have higher frailty levels. These findings have both clinical and public health relevance, including the provision of healthcare and aged care services in the coming years. Further studies are required, particularly those conducted in low- and middle-income countries and those investigating factors associated with changes in frailty. The latter may help develop better-targeted interventions to reverse or slow the progression of frailty.
Published: 2022
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12. Retrospective comparison of traditional and artificial intelligence-based heart failure phenotyping in a US health system to enable real-world evidence

Author: Arthur Reshad Garan, Keri L Monda, Ricardo E Dent-Acosta, Daniel J Riskin, and Ty J Gluckman
Subjects: Medicine
Abstract: Objective Quantitatively evaluate the quality of data underlying real-world evidence (RWE) in heart failure (HF).Design Retrospective comparison of accuracy in identifying patients with HF and phenotypic information was made using traditional (ie, structured query language applied to structured electronic health record (EHR) data) and advanced (ie, artificial intelligence (AI) applied to unstructured EHR data) RWE approaches. The performance of each approach was measured by the harmonic mean of precision and recall (F1 score) using manual annotation of medical records as a reference standard.Setting EHR data from a large academic healthcare system in North America between 2015 and 2019, with an expected catchment of approximately 5 00 000 patients.Population 4288 encounters for 1155 patients aged 18–85 years, with 472 patients identified as having HF.Outcome measures HF and associated concepts, such as comorbidities, left ventricular ejection fraction, and selected medications.Results The average F1 scores across 19 HF-specific concepts were 49.0% and 94.1% for the traditional and advanced approaches, respectively (p
Published: 2023
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13. Neratinib as a Potential Therapeutic for Mutant RAS and Osimertinib-Resistant Tumours

Author: Paul Dent, Laurence Booth, Andrew Poklepovic, and John F. Hancock
Subjects: Medicine
Abstract: Neratinib was developed as an irreversible catalytic inhibitor of ERBB2, which also acts to inhibit ERBB1 and ERBB4. Neratinib is U.S. Food and Drug Administration (FDA)-approved as a neo-adjuvant therapy for use in HER2+ breast cancer. More recently, chemical biology analyses and the authors’ own bench work have demonstrated that neratinib has additional targets, which open up the possibility of using the drug in cell types that either lack ERBB receptor family expression or who rely on survival signalling downstream of growth factor receptors. Neratinib rapidly disrupted mutant RAS nanoclustering, which was followed by mutant rat sarcoma virus proteins translocating via LC3-associated phagocytosis into the cytosol where they were degraded by macroautophagy. Neratinib catalytically inhibited the MAP4K mammalian STE20-like protein kinase 4 and also caused its degradation via macroautophagy. This resulted in ezrin dephosphorylation and the plasma membrane becoming flaccid. Neratinib disrupted the nanoclustering of RAC1, which was associated with dephosphorylation of PAK1 and Merlin, and with increased phosphorylation of the Merlin binding partners large tumour suppressor kinase 1/2, YAP, and TAZ. YAP and TAZ exited the nucleus. Neratinib retained its anti-tumour efficacy against NSCLC cells made resistant to either afatinib or to osimertinib. Collectively, these findings argue that the possibilities for the further development of neratinib as cancer therapeutic in malignancies that do not express or over-express members of the ERBB receptor family are potentially wide-ranging.
Published: 2022
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14. Vertebrate growth plasticity in response to variation in a mutualistic interaction

Author: Theresa Rueger, Anjali Kristina Bhardwaj, Emily Turner, Tina Adria Barbasch, Isabela Trumble, Brianne Dent, and Peter Michael Buston
Subjects: Medicine, Science
Abstract: Abstract Vertebrate growth can be phenotypically plastic in response to predator–prey and competitive interactions. It is unknown however, if it can be plastic in response to mutualistic interactions. Here we investigate plasticity of vertebrate growth in response to variation in mutualistic interactions, using clown anemonefish and their anemone hosts. In the wild, there is a positive correlation between the size of the fish and the size of the anemone, but the cause of this correlation is unknown. Plausible hypotheses are that fish exhibit growth plasticity in response to variation in food or space provided by the host. In the lab, we pair individuals with real anemones of various sizes and show that fish on larger anemones grow faster than fish on smaller anemones. By feeding the fish a constant food ration, we exclude variation in food availability as a cause. By pairing juveniles with artificial anemones of various sizes, we exclude variation in space availability as a single cause. We argue that variation in space availability in conjunction with host cues cause the variability in fish growth. By adjusting their growth, anemonefish likely maximize their reproductive value given their anemone context. More generally, we demonstrate vertebrate growth plasticity in response to variation in mutualistic interactions.
Published: 2022
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15. Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells

Author: Fang Ke, Zachary L Benet, Mitra P Maz, Jianhua Liu, Alexander L Dent, Joanne Michelle Kahlenberg, and Irina L Grigorova
Subjects: follicular regulatory T cells, germinal center b cells, immunologic tolerance, nuclear proteins, Medicine, Science, Biology (General), QH301-705.5
Abstract: Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.
Published: 2023
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16. P499: RNA-sequencing positional gene enrichment is a useful tool in resolving cases of X chromosome copy number variation

Author: Robert Lewis, David Viskochil, Ashley Andrews, Karin Dent, Rong Mao, Lorenzo Botto, and Pinar Bayrak-Toydemir
Subjects: Genetics, QH426-470, Medicine
Published: 2023
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17. Combining viral genomics and clinical data to assess risk factors for severe COVID-19 (mortality, ICU admission, or intubation) amongst hospital patients in a large acute UK NHS hospital Trust.

Author: Max Foxley-Marrable, Leon D'Cruz, Paul Meredith, Sharon Glaysher, Angela H Beckett, Salman Goudarzi, Christopher Fearn, Kate F Cook, Katie F Loveson, Hannah Dent, Hannah Paul, Scott Elliott, Sarah Wyllie, Allyson Lloyd, Kelly Bicknell, Sally Lumley, James McNicholas, David Prytherch, COVID-19 Genomics UK (COG-UK) consortium, Andrew Lundgren, Or Graur, Anoop J Chauhan, and Samuel C Robson
Subjects: Medicine, Science
Abstract: Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.
Published: 2023
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18. Understanding actions and challenges in protecting older people during covid-19 pandemic in indonesia: A qualitative study with female caregivers

Author: Gregorius Abanit Asa, Nelsensius Klau Fauk, Melkianus Ratu, Elsa Dent, and Paul Russell Ward
Subjects: Medicine, Science
Abstract: COVID-19 has rapidly impacted societies on a global scale, with older people among the most affected. To care for older people living in their own homes, female family caregivers play a pivotal role. The current study aimed to explore the actions of female family caregivers and the challenges they faced in taking care of older people living at homes during the COVID-19 pandemic in Belu district, Indonesia. This qualitative study involved twenty female family caregivers, who were recruited using a combination of purposive and snowball sampling techniques. Findings were grouped into two main categories: (i) actions of female family caregivers in taking care of older adults during the COVID-19 pandemic. These included limiting both visitations of extended family members and older adults’ activities outside homes; explaining the virus to older adults and controlling their access to news, social media and smartphones; providing nutrition, supplement and maintaining daily diets; and (ii) challenges they faced in taking care of older adults included excessive fear of contracting COVID-19 and possibility of transmitting it to older people; feeling stressed; tired and overburdened. The study highlights the significant role family caregivers played to protect older people living at home. The findings can inform government to develop intervention programs that address and support the needs of both family caregivers and older people living at home.
Published: 2023

19. Cell-free and alkylated hemoproteins improve survival in mouse models of carbon monoxide poisoning

Author: Qinzi Xu, Jason J. Rose, Xiukai Chen, Ling Wang, Anthony W. DeMartino, Matthew R. Dent, Sagarika Tiwari, Kaitlin Bocian, Xueyin N. Huang, Qin Tong, Charles F. McTiernan, Lanping Guo, Elmira Alipour, Trevor C. Jones, K. Burak Ucer, Daniel B. Kim-Shapiro, Jesús Tejero, and Mark T. Gladwin
Subjects: Pulmonology, Therapeutics, Medicine
Abstract: I.v. administration of a high-affinity carbon monoxide–binding (CO-binding) molecule, recombinant neuroglobin, can improve survival in CO poisoning mouse models. The current study aims to discover how biochemical variables of the scavenger determine the CO removal from the RBCs by evaluating 3 readily available hemoproteins, 2,3-diphosphoglycerate stripped human hemoglobin (StHb); N-ethylmaleimide modified hemoglobin (NEMHb); and equine myoglobin (Mb). These molecules efficiently sequester CO from hemoglobin in erythrocytes in vitro. A kinetic model was developed to predict the CO binding efficacy for hemoproteins, based on their measured in vitro oxygen and CO binding affinities, suggesting that the therapeutic efficacy of hemoproteins for CO poisoning relates to a high M value, which is the binding affinity for CO relative to oxygen (KA,CO/KA,O2). In a lethal CO poisoning mouse model, StHb, NEMHb, and Mb improved survival by 100%, 100%, and 60%, respectively, compared with saline controls and were well tolerated in 48-hour toxicology assessments. In conclusion, both StHb and NEMHb have high CO binding affinities and M values, and they scavenge CO efficiently in vitro and in vivo, highlighting their therapeutic potential for point-of-care antidotal therapy of CO poisoning.
Published: 2022
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20. Optimizing treatment selection, and sequencing decisions for Management of HR-Positive, HER2-Negative advanced breast cancer – Proceedings from breast cancer expert group meeting

Author: Shaheenah Dawood, Maria Konstantionva, Rebecca Dent, Florencia Perazzo, Sung-Bae Kim, Cynthia Villarreal-Garza, Sandra Franco, Ming-Shen Dai, and Sergio Simon
Subjects: Cyclin-dependent kinase 4/6 inhibitor, Endocrine therapy, Hormone receptor-positive, Human epidermal growth factor receptor 2 negative, Metastatic breast cancer PI3K/mTOR inhibitor, Registry, Medicine, Science
Abstract: Abstract Purpose The therapeutic landscape of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents and their combinations with endocrine therapies. In this scenario, optimizing treatment selection and sequencing is daunting for clinicians. The purpose of this review is to provide evidence-based answers to key clinical questions on treatment selection and sequencing for the management of HR + HER2 − mBC. Design A panel of nine key opinion leaders from Argentina, Brazil, Colombia, Mexico, Moscow, Singapore, South Korea, Taiwan, and UAE convened in October 2018. They reviewed the literature and formulated answers to clinical questions on optimizing the management of HR + HER2 − mBC. Results Evidence-based answers were formulated for: (1) optimal initial treatment choice; (2) ovarian function suppression, optimal endocrine partner, and role of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (in premenopausal women); (3) better first-line standard of care than aromatase inhibitors; (4) preferred second-line treatment; (5) treatment of oligometastatic disease; (6) factors influencing first-line single-agent endocrine therapy choice; (7) influence of endocrine resistance on treatment selection; (8) optimal maintenance regimen in visceral crisis; and (9) need for a breast cancer registry for patients with HR + HER2 − mBC. The panel also proposed a treatment-sequencing algorithm for the management of HR + HER2 − mBC. Conclusion The current article will serve as a comprehensive guide for optimizing the management of HR + HER2 − mBC. The proposed breast cancer registry will help identify unmet needs and develop strategic regional policies to help improve access to optimized care for HR + HER2 − mBC.
Published: 2021
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21. SARS-CoV-2 Seroprevalence before Delta Variant Surge, Chattogram, Bangladesh, March–June 2021

Author: Taufiqur Rahman Bhuiyan, Juan Dent Hulse, Sonia T. Hegde, Marjahan Akhtar, Taufiqul Islam, Zahid Hasan Khan, Ishtiakul Islam Khan, Shakeel Ahmed, Mamunur Rashid, Rumana Rashid, Emily S. Gurley, Tahmina Shirin, Ashraful Islam Khan, Andrew S. Azman, and Firdausi Qadri
Subjects: COVID-19, Delta variant, coronavirus disease, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, seroepidemiologic studies, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: A March–June 2021 representative serosurvey among Sitakunda subdistrict (Chattogram, Bangladesh) residents found an adjusted prevalence of severe acute respiratory syndrome coronavirus 2 antibodies of 64.1% (95% credible interval 60.0%–68.1%). Before the Delta variant surge, most residents had been infected, although cumulative confirmed coronavirus disease incidence was low.
Published: 2022
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22. Lymphocyte crosstalk is required for monocyte-intrinsic trained immunity to Plasmodium falciparum

Author: Juliet N. Crabtree, Daniel R. Caffrey, Leandro de Souza Silva, Evelyn A. Kurt-Jones, Katherine Dobbs, Arlene Dent, Katherine A. Fitzgerald, and Douglas T. Golenbock
Subjects: Immunology, Infectious disease, Medicine
Abstract: Plasmodium falciparum (P. falciparum) induces trained innate immune responses in vitro, where initial stimulation of adherent PBMCs with P. falciparum–infected RBCs (iRBCs) results in hyperresponsiveness to subsequent ligation of TLR2. This response correlates with the presence of T and B lymphocytes in adherent PBMCs, suggesting that innate immune training is partially due to adaptive immunity. We found that T cell–depleted PBMCs and purified monocytes alone did not elicit hyperproduction of IL-6 and TNF-α under training conditions. Analysis of P. falciparum–trained PBMCs showed that DCs did not develop under control conditions, and IL-6 and TNF-α were primarily produced by monocytes and DCs. Transwell experiments isolating purified monocytes from either PBMCs or purified CD4+ T cells, but allowing diffusion of secreted proteins, enabled monocytes trained with iRBCs to hyperproduce IL-6 and TNF-α after TLR restimulation. Purified monocytes stimulated with IFN-γ hyperproduced IL-6 and TNF-α, whereas blockade of IFN-γ in P. falciparum–trained PBMCs inhibited trained responses. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) on monocytes from patients with malaria showed persistently open chromatin at genes that appeared to be trained in vitro. Together, these findings indicate that the trained immune response of monocytes to P. falciparum is not completely cell intrinsic but depends on soluble signals from lymphocytes.
Published: 2022
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23. Projected resurgence of COVID-19 in the United States in July—December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination

Author: Shaun Truelove, Claire P Smith, Michelle Qin, Luke C Mullany, Rebecca K Borchering, Justin Lessler, Katriona Shea, Emily Howerton, Lucie Contamin, John Levander, Jessica Kerr, Harry Hochheiser, Matt Kinsey, Kate Tallaksen, Shelby Wilson, Lauren Shin, Kaitlin Rainwater-Lovett, Joseph C Lemairtre, Juan Dent, Joshua Kaminsky, Elizabeth C Lee, Javier Perez-Saez, Alison Hill, Dean Karlen, Matteo Chinazzi, Jessica T Davis, Kunpeng Mu, Xinyue Xiong, Ana Pastore y Piontti, Alessandro Vespignani, Ajitesh Srivastava, Przemyslaw Porebski, Srinivasan Venkatramanan, Aniruddha Adiga, Bryan Lewis, Brian Klahn, Joseph Outten, Mark Orr, Galen Harrison, Benjamin Hurt, Jiangzhuo Chen, Anil Vullikanti, Madhav Marathe, Stefan Hoops, Parantapa Bhattacharya, Dustin Machi, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Marta Galanti, Teresa K Yamana, Sen Pei, Jeffrey L Shaman, Jessica M Healy, Rachel B Slayton, Matthew Biggerstaff, Michael A Johansson, Michael C Runge, and Cecile Viboud
Subjects: pandemic, disease modeling, COVID-19, SARS-CoV-2, Delta variant, scenario projection, Medicine, Science, Biology (General), QH301-705.5
Abstract: In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July–December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July–December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July–December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.
Published: 2022
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24. High Infection Attack Rate after SARS-CoV-2 Delta Surge, Chattogram, Bangladesh

Author: Sonia T. Hegde, Taufiqur Rahman Bhuiyan, Marjahan Akhtar, Taufiqul Islam, Juan Dent Hulse, Zahid Hasan Khan, Ishtiakul Islam Khan, Shakeel Ahmed, Mamunur Rashid, Rumana Rashid, Emily S. Gurley, Tahmina Shirin, Ashraful Islam Khan, Andrew S. Azman, and Firdausi Qadri
Subjects: COVID-19, Delta variant, coronavirus disease, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, attack rate, Medicine, Infectious and parasitic diseases, RC109-216
Published: 2022
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25. Accurate GFR in obesity—protocol for a systematic review

Author: Sriram Sriperumbuduri, Robert Dent, Janine Malcolm, Swapnil Hiremath, Ran Klein, Christine A. White, Pierre Antoine Brown, and Ayub Akbari
Subjects: Obesity, eGFR, CKD, Systematic review, Meta-analysis, Medicine
Abstract: Abstract Background Obesity is increasing globally. Chronic kidney disease (CKD) is strongly associated with obesity. Kidney function is commonly estimated with equations using creatinine (such as CKD-EPI equation) which is a product of muscle metabolism. Decisions about categorizing CKD, planning modality of renal replacement therapies, and adjusting dosages of medications excreted by the kidneys are done using these equations. However, it is not well appreciated that creatinine-based equations may not accurately estimate kidney function in obese individuals. We plan a systematic review of diagnostic studies which will compare estimating equations to actual measured kidney function. Methods We will systematically search electronic bibliographic databases including MEDLINE, EMBASE, and the Cochrane Library with no restrictions on language or specific dates. The search terms will be adapted for the different databases using a combination of Medical Subject Heading and relevant keywords contained in titles and abstracts. Our preliminary search strategy using Cochrane, MEDLINE, and EMBASE databases have identified 190, 1246, and 1660 citations, respectively. For all studies selected, we will extract information on general study characteristics, study participant (age, sex, ethnicity, weight, height, BMI, BSA), type and protocol of reference standard utilized, the index test studied, the methodology of measurement of index test, categories of GFR, the proportion of eGFR within 10, 20, 30, 40, and 50% of measured GFR, and bias between eGFR and measured GFR. If the quality of methods and risk of bias are adequate, we will perform a meta-analysis. We will assess the heterogeneity using the χ 2 and the I 2 statistics to examine whether the estimates from studies included could be pooled. Sensitivity and multivariate meta-regression analyses will be performed to assess the effects of clinical factors and socio-demographic characteristics reported in included studies on the meta-analytic estimates. All analysis will be performed using the Comprehensive Meta-analysis software. Discussion This systematic review might help to inform clinicians on the best equation to use in patients with obesity and CKD for staging of CKD and for medication dosing. If no equation is deemed suitable, this review will form a basis for future studies of GFR in obese individuals. Systematic review registration PROSPERO CRD42018104345
Published: 2019
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26. 28 Trusting who knows best when managing long-term conditions in dementia: Findings from a qualitative study of stakeholder perspectives

Author: C Cooper, J Rees, A Burton, K Walters, M Leverton, P Rapaport, R Herat-Gunaratne, and J Beresford-Dent
Subjects: Medicine
Published: 2021
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27. Cohort profile: The Singapore Breast Cancer Cohort (SGBCC), a multi-center breast cancer cohort for evaluation of phenotypic risk factors and genetic markers.

Author: Peh Joo Ho, Yen Shing Yeoh, Hui Miao, Swee Ho Lim, Ern Yu Tan, Benita Kiat Tee Tan, Veronique Kiak Mien Tan, Su Ming Tan, Wei Sean Yong, Fuh Yong Wong, Preetha Madhukumar, Ching Wan Chan, Philip Tsau Choong Iau, Soo Chin Lee, Thomas Putti, Shaik Ahmad Buhari, Jin Yee Lee, Geok Hoon Lim, Evan Woo, Zhiyan Yan, Patrick Mun Yew Chan, Juliana Jia Chuan Chen, Sarah Qinghui Lu, Rebecca Dent, Wai Peng Lee, Chi Wei Mok, Jaime Chin Mui Seah, Xueling Sim, Rob Martinus van Dam, Kee Seng Chia, Jingmei Li, and Mikael Hartman
Subjects: Medicine, Science
Abstract: This article aims to provide a detailed description of the Singapore Breast Cancer Cohort (SGBCC), an ongoing multi-ethnic cohort established with the overarching goal to identify genetic markers for breast cancer risk, prognosis and treatment response, as well as to understand the ethnic differences in disease risk and outcome in an Asian setting. The cohort comprises of breast cancer patients aged 21 years and above from six public hospitals which diagnose and treat nearly 76% breast cancer cases in Singapore. Self-reported data on sociodemographic and lifestyle, reproductive risk factors, medical history and family history of breast or ovarian cancer is collected using a structured questionnaire. Clinical data on tumour characteristics, and treatment modalities are obtained through medical record. Bio-specimens (blood or saliva) is collected at recruitment. Follow-up on survival information is done through routine linkage with the Registry of Births and Deaths. As of 31 December 2016, 7,768 subjects have been recruited to the study with 76% subjects contributed bio-specimens. The SGBCC provides a valuable platform which offers a unique, large and rich resource for new research ideas on breast cancer related phenotypic risk factors and genetic markers.
Published: 2021
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28. The effect of music on body sway when standing in a moving virtual environment.

Author: Shaquitta Dent, Kelley Burger, Skyler Stevens, Benjamin D Smith, and Jefferson W Streepey
Subjects: Medicine, Science
Abstract: Movement of the visual environment presented through virtual reality (VR) has been shown to invoke postural adjustments measured by increased body sway. The effect of auditory information on body sway seems to be dependent on context with sounds such as white noise, tones, and music being used to amplify or suppress sway. This study aims to show that music manipulated to match VR motion further increases body sway. Twenty-eight subjects stood on a force plate and experienced combinations of 3 visual conditions (VR translation in the AP direction at 0.1 Hz, no translation, and eyes closed) and 4 music conditions (Mozart's Jupiter Symphony modified to scale volume at 0.1 Hz and 0.25 Hz, unmodified music, and no music) Body sway was assessed by measuring center of pressure (COP) velocities and RMS. Cross-coherence between the body sway and the 0.1 Hz and 0.25 Hz stimuli was also determined. VR translations at 0.1 Hz matched with 0.1Hz shifts in music volume did not lead to more body sway than observed in the no music and unmodified music conditions. Researchers and clinicians may consider manipulating sound to enhance VR induced body sway, but findings from this study would not suggest using volume to do so.
Published: 2021
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29. Exploring how people with dementia can be best supported to manage long-term conditions: a qualitative study of stakeholder perspectives

Author: Kate R Walters, Julie Beresford-Dent, Jessica Laura Rees, Alexandra Burton, Monica Leverton, Penny Rapaport, Ruminda Herat Gunaratne, and Claudia Cooper
Subjects: Medicine
Abstract: Objectives To explore how the self-management of comorbid long-term conditions is experienced and negotiated by people with dementia and their carers.Design Secondary thematic analysis of 82 semi-structured interviews.Setting Community settings across the United Kingdom.Participants 11 people with dementia, 22 family carers, 19 health professionals and 30 homecare staff.Results We identified three overarching themes: (1) The process of substituting self-management: stakeholders balanced the wishes of people with dementia to retain autonomy with the risks of lower adherence to medical treatments. The task of helping a person with dementia to take medication was perceived as intermediate between a personal care and a medical activity; rules about which professionals could perform this activity sometimes caused conflict. (2) Communication in the care network: family carers often communicated with services and made decisions about how to implement medical advice. In situations where family carers or homecare workers were not substituting self-management, it could be challenging for general practitioners to identify changes in self-management and decide when to intervene. (3) Impact of physical health on and from dementia: healthcare professionals acknowledged the inter-relatedness of physical health and cognition to adapt care accordingly. Some treatments prescribed for long-term conditions were perceived as unhelpful when not adapted to the context of dementia. Healthcare professionals and homecare workers sometimes felt that family carers were unable to accept that available treatments may not be helpful to people with dementia and that this sometimes led to the continuation of treatments of questionable benefit.Conclusion The process of substituting self-management evolves with advancement of dementia symptoms and relies on communication in the care network, while considering the impact on and from dementia to achieve holistic physical health management. Care decisions must consider people with dementia as a whole, and be based on realistic outcomes and best interests.
Published: 2020
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30. Attention capture in birds performing an auditory streaming task.

Author: Huaizhen Cai and Micheal L Dent
Subjects: Medicine, Science
Abstract: Numerous animal models have been used to investigate the neural mechanisms of auditory processing in complex acoustic environments, but it is unclear whether an animal's auditory attention is functionally similar to a human's in processing competing auditory scenes. Here we investigated the effects of attention capture in birds performing an objective auditory streaming paradigm. The classical ABAB… patterned pure tone sequences were modified and used for the task. We trained the birds to selectively attend to a target stream and only respond to the deviant appearing in the target stream, even though their attention may be captured by a deviant in the background stream. When no deviant appeared in the background stream, the birds experience the buildup of streaming process in a qualitatively similar way as they did in a subjective paradigm. Although the birds were trained to selectively attend to the target stream, they failed to avoid the involuntary attention switch caused by the background deviant, especially when the background deviant was sequentially unpredictable. Their global performance deteriorated more with increasingly salient background deviants, where the buildup process was reset by the background distractor. Moreover, sequential predictability of the background deviant facilitated the recovery of the buildup process after attention capture. This is the first study that addresses the perceptual consequences of the joint effects of top-down and bottom-up attention in behaving animals.
Published: 2020
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31. Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children

Author: Liriye Kurtovic, Marije C. Behet, Gaoqian Feng, Linda Reiling, Kiprotich Chelimo, Arlene E. Dent, Ivo Mueller, James W. Kazura, Robert W. Sauerwein, Freya J. I. Fowkes, and James G. Beeson
Subjects: Antibodies, Circumsporozoite protein, Sporozoite, Complement, Malaria, Plasmodium falciparum, Medicine
Abstract: Abstract Background Antibodies targeting Plasmodium falciparum sporozoites play a key role in human immunity to malaria. However, antibody mechanisms that neutralize sporozoites are poorly understood. This has been a major constraint in developing highly efficacious vaccines, as we lack strong correlates of protective immunity. Methods We quantified the ability of human antibodies from malaria-exposed populations to interact with human complement, examined the functional effects of complement activity against P. falciparum sporozoites in vitro, and identified targets of functional antibodies. In children and adults from malaria-endemic regions, we determined the acquisition of complement-fixing antibodies to sporozoites and their relationship with antibody isotypes and subclasses. We also investigated associations with protective immunity in a longitudinal cohort of children (n = 206) residing in a malaria-endemic region. Results We found that antibodies to the major sporozoite surface antigen, circumsporozoite protein (CSP), were predominately IgG1, IgG3, and IgM, and could interact with complement through recruitment of C1q and activation of the classical pathway. The central repeat region of CSP, included in leading vaccines, was a key target of complement-fixing antibodies. We show that antibodies activate human complement on P. falciparum sporozoites, which consequently inhibited hepatocyte cell traversal that is essential for establishing liver-stage infection, and led to sporozoite death in vitro. The natural acquisition of complement-fixing antibodies in malaria-exposed populations was age-dependent, and was acquired more slowly to sporozoite antigens than to merozoite antigens. In a longitudinal cohort of children, high levels of complement-fixing antibodies were significantly associated with protection against clinical malaria. Conclusions These novel findings point to complement activation by antibodies as an important mechanism of anti-sporozoite human immunity, thereby enabling new strategies for developing highly efficacious malaria vaccines. We also present evidence that complement-fixing antibodies may be a valuable correlate of protective immunity in humans.
Published: 2018
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32. Assessing personality disorder through storymaking : a reliability and validity study of the 6-Part Story Method

Author: Dent-Brown, Kim and Wang, Michael
Subjects: 616.8581075, Medicine
Abstract: The 6-Part Story Method (6PSM) involves the participant creating and telling a fictional story which is then discussed with the interviewer. Stories were recorded from NHS mental health clinicians, and from adult mental health patients with and without a diagnosis of Borderline Personality Disorder (BPD). Statements describing the stories could be reliably scored by raters who were blind to the authorship of the stories. It was possible to use these statements to assemble a scale with good internal consistency, inter-rater reliability and test- retest reliability over a one-month period. The scale statements all related to the degree of negativity and failure expressed in the story. Ratings on this negativity scale given to stories from patients with a cluster B personality disorder diagnosis were significantly higher than the ratings given to stories from other participants. The text of the story transcriptions was analysed using computerised text analysis programs, which detected some patterns of language use that appeared to distinguish reliably between stories from participants with BPD and other stories. Participants were asked for their reactions to the 6PSM process, and their responses analysed using a Grounded Theory approach. This suggested that for most participants, the 6PSM works through increasingly close emotional identification with an initially distant and metaphorical main character.
Published: 2004

33. The biochemistry of synovial fluid from injured knees

Author: Dent, Colin Michael
Subjects: 616, Medicine
Published: 2002

34. Sero-catalytic and Antibody Acquisition Models to Estimate Differing Malaria Transmission Intensities in Western Kenya

Author: Grace E. Weber, Michael T. White, Anna Babakhanyan, Peter Odada Sumba, John Vulule, Dylan Ely, Chandy John, Evelina Angov, David Lanar, Sheetij Dutta, David L. Narum, Toshihiro Horii, Alan Cowman, James Beeson, Joseph Smith, James W. Kazura, and Arlene E. Dent
Subjects: Medicine, Science
Abstract: Abstract We sought to identify a subset of Plasmodium falciparum antibody targets that would inform monitoring efforts needed to eliminate malaria in high transmission settings. IgG antibodies to 28 recombinant Pf antigens were measured in residents of two communities in western Kenya examined in 2003 and 2013, when the respective prevalence of asymptomatic parasitemia among children was 81 and 15 percent by microscopy. Annual seroconversion rates based on a sero-catalytic model that dichotomised antibody values to negative versus positive showed that rates were higher in 2003 than 2013 for 1 pre-erythrocytic and 7 blood-stage antigens. Antibody acquisition models that considered antibody levels as continuous variables showed that age-related antibody levels to Circumsporozoite Protein and 10 merozoite proteins increased at different rates with age in 2003 versus 2013. Both models found that antibodies to 5 proteins of the Merozoite Surface Protein 1 complex were differentially acquired between the cohorts, and that changes in antibody levels to Apical Membrane Antigen 1 suggested a decrease in transmission that occurred ~10 years before 2013. Further studies evaluating antibodies to this subset of Pf antigens as biomarkers of malaria exposure and naturally acquired immunity are warranted in endemic settings where transmission has been reduced but persists.
Published: 2017
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35. Proceedings of the 16th Annual UT-KBRIN Bioinformatics Summit 2016: proceedings

Author: L. Leon Dent, Sammed N. Mandape, Siddharth Pratap, Jianan Dong, Jamaine Davis, Jennifer A. Gaddy, Kofi Amoah, Steve Damo, Dana R. Marshall, Jacob Jones, Toni Brandt, Gilberto Diaz, Qingguo Wang, Todd Gary, Ashwini Yenamandra, Marina Z. Ghattas, Marwa Elrakaiby, Ramy K. Aziz, Hamdallah H. Zedan, Moamen Elmassry, Marwa ElRakaiby, Mariam Lotfy, Jarrad Marcel, Rania A. Khattab, Maha M. Abdelfattah, Jack A. Gilbert, Pouya Dini, Shavahn C. Loux, Kirsten E. Scoggin, Alejandro Esteller-Vico, Edward L. Squires, Mats H. T. Troedsson, Peter Daels, Barry A. Ball, Kalpani De Silva, Ernest Bailey, Joel C. Stephens, Theodore S. Kalbfleisch, Christine E. Dolin, Lauren G. Poole, Daniel W. Wilkey, Eric C. Rouchka, Gavin E. Arteel, Michelle T. Barati, Michael L. Merchant, Richard M. Higashi, Teresa W-M Fan, Hunter Moseley, and Andrew N Lane
Subjects: Medicine, Science
Published: 2017
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36. Resistance exercise initiates mechanistic target of rapamycin (mTOR) translocation and protein complex co-localisation in human skeletal muscle

Author: Zhe Song, Daniel R. Moore, Nathan Hodson, Carl Ward, Jessica R. Dent, Mary F. O’Leary, Andrew M. Shaw, D. Lee Hamilton, Sovan Sarkar, Yann-Gaël Gangloff, Troy A. Hornberger, Lawrence L. Spriet, George J. Heigenhauser, and Andrew Philp
Subjects: Medicine, Science
Abstract: Abstract The mechanistic target of rapamycin (mTOR) is a central mediator of protein synthesis in skeletal muscle. We utilized immunofluorescence approaches to study mTOR cellular distribution and protein-protein co-localisation in human skeletal muscle in the basal state as well as immediately, 1 and 3 h after an acute bout of resistance exercise in a fed (FED; 20 g Protein/40 g carbohydrate/1 g fat) or energy-free control (CON) state. mTOR and the lysosomal protein LAMP2 were highly co-localised in basal samples. Resistance exercise resulted in rapid translocation of mTOR/LAMP2 towards the cell membrane. Concurrently, resistance exercise led to the dissociation of TSC2 from Rheb and increased in the co-localisation of mTOR and Rheb post exercise in both FED and CON. In addition, mTOR co-localised with Eukaryotic translation initiation factor 3 subunit F (eIF3F) at the cell membrane post-exercise in both groups, with the response significantly greater at 1 h of recovery in the FED compared to CON. Collectively our data demonstrate that cellular trafficking of mTOR occurs in human muscle in response to an anabolic stimulus, events that appear to be primarily influenced by muscle contraction. The translocation and association of mTOR with positive regulators (i.e. Rheb and eIF3F) is consistent with an enhanced mRNA translational capacity after resistance exercise.
Published: 2017
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37. Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

Author: Muneer G. Hasham, Nicoleta Baxan, Daniel J. Stuckey, Jane Branca, Bryant Perkins, Oliver Dent, Ted Duffy, Tolani S. Hameed, Sarah E. Stella, Mohammed Bellahcene, Michael D. Schneider, Sian E. Harding, Nadia Rosenthal, and Susanne Sattler
Subjects: Autoimmunity, Dilated cardiomyopathy, Heart disease, Myocarditis, Model, Resiquimod, Toll-like receptor 7/8, Medicine, Pathology, RB1-214
Abstract: Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.
Published: 2017
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38. Study protocol for a randomised controlled trial assessing the clinical and cost-effectiveness of the Journeying through Dementia (JtD) intervention compared to usual care

Author: Tom Dening, Jessica Wright, Gail Mountain, Kirsty Sprange, Cindy Cooper, Ellen Lee, Stephen Walters, Alexis Foster, Katherine Berry, Esme Moniz-Cook, Amanda Loban, Tracey Anne Young, Claire Craig, Julie Beresford-Dent, Benjamin John Thompson, Emma Young, and Benjamin David Thomas
Subjects: Medicine
Abstract: Introduction Services are being encouraged to provide postdiagnostic treatment to those with dementia but the availability of evidence-based interventions following diagnosis has not kept pace with increase in demand. To address this need, the Journeying through Dementia (JtD) intervention was created. A randomised controlled trial (RCT), based on a pilot study, is in progress.Methods and analysis The RCT is a pragmatic, two-arm, parallel group trial designed to test the clinical and cost-effectiveness of JtD compared with usual care. Recruitment will be through NHS services, third sector organisations and Join Dementia Research. The sample size is 486 randomised (243 to usual care and 243 to the intervention usual care). Participants can choose to ask a friend or relative (supporter) to become involved in the study. The primary outcome measure for participants is Dementia-Related Quality of Life (DEMQOL), collected at baseline and at 8 months’ postrandomisation. Secondary outcome measures will be collected from participants and supporters at those visits. Participants will also be followed up at 12 months’ postrandomisation with a reduced set of measures. A process evaluation will be conducted through qualitative and fidelity substudies. Analyses will compare the two arms of the trial on an intention to treat as allocated basis. The primary analyses will compare the mean DEMQOL scores of the participants at 8 months between the two study arms. A cost-effectiveness analysis will consider the incremental cost per Quality Adjusted Life Years of the intervention compared with usual care. Qualitative and fidelity substudies will be analysed through framework analysis and fidelity assessment tools respectively.Ethics and dissemination REC and HRA approval were obtained. A Data Monitoring and Ethics Committee has been constituted. Dissemination will be via publications, conferences and social media. Intervention materials will be made open access.Trial registration number ISRCTN17993825.
Published: 2019
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39. Mechanism of completion of peptidyltransferase centre assembly in eukaryotes

Author: Vasileios Kargas, Pablo Castro-Hartmann, Norberto Escudero-Urquijo, Kyle Dent, Christine Hilcenko, Carolin Sailer, Gertrude Zisser, Maria J Marques-Carvalho, Simone Pellegrino, Leszek Wawiórka, Stefan MV Freund, Jane L Wagstaff, Antonina Andreeva, Alexandre Faille, Edwin Chen, Florian Stengel, Helmut Bergler, and Alan John Warren
Subjects: ribosome, cryo-EM, Shwachman-Diamond syndrome, ribosomopathy, leukaemia, SBDS, Medicine, Science, Biology (General), QH301-705.5
Abstract: During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large ribosomal subunits. Here, we present the mechanism of peptidyltransferase centre (PTC) completion that explains how integration of the last ribosomal proteins is coupled to release of the nuclear export adaptor Nmd3. Single-particle cryo-EM reveals that eL40 recruitment stabilises helix 89 to form the uL16 binding site. The loading of uL16 unhooks helix 38 from Nmd3 to adopt its mature conformation. In turn, partial retraction of the L1 stalk is coupled to a conformational switch in Nmd3 that allows the uL16 P-site loop to fully accommodate into the PTC where it competes with Nmd3 for an overlapping binding site (base A2971). Our data reveal how the central functional site of the ribosome is sculpted and suggest how the formation of translation-competent 60S subunits is disrupted in leukaemia-associated ribosomopathies.
Published: 2019
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40. Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial

Author: Rebecca Dent, Sung-Bae Kim, Matthew Wongchenko, Nicholas C. Turner, Zbigniew Nowecki, Carlos H. Barrios, Igor Bondarenko, Shigehira Saji, Mafalda Oliveira, Steven J. Isakoff, Bruno Kovic, Joyce O'Shaughnessy, Heather Hinton, Sarah-Jayne Reilly, Qinshu Lian, Aruna Mani, Institut Català de la Salut, [Turner N] Breast Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK. Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK. [Dent RA] Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore. [O'Shaughnessy J] Department of Medical Oncology, Texas Oncology, Baylor University Medical Center, US Oncology, Dallas, TX, USA. [Kim SB] Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [Isakoff SJ] Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA. [Barrios C] Latin American Cooperative Oncology Group, Oncology Research Service, Hospital São Lucas, PUCRS, Porto Alegre, RS, Brazil. [Oliveira M] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, medicine.medical_specialty, Paclitaxel, Class I Phosphatidylinositol 3-Kinases, Receptor, ErbB-2, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], medicine.medical_treatment, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Breast Neoplasms, Neutropenia, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], Gastroenterology, Piperazines, Medicaments antineoplàstics - Efectes secundaris, Phosphatidylinositol 3-Kinases, Breast cancer, Double-Blind Method, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Other subheadings::Other subheadings::/adverse effects [Other subheadings], Clinical endpoint, Humans, Medicine, Adverse effect, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Chemotherapy, Taxane, business.industry, Hazard ratio, PTEN Phosphohydrolase, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.disease, Metastatic breast cancer, Hormones, Pyrimidines, Oncology, Mama - Càncer - Tractament, Female, Neoplasm Recurrence, Local, business, Proto-Oncogene Proteins c-akt
Abstract: Purpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse 2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). Conclusion Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects. Trial registration NCT03337724.
Published: 2021
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41. Social isolation produces no effect on ultrasonic vocalization production in adult female CBA/CaJ mice.

Author: Laurel A Screven and Micheal L Dent
Subjects: Medicine, Science
Abstract: Mice produce ultrasonic vocalizations (USVs) in a wide variety of social contexts, including courtship, investigation, and territorial defense. Despite the belief that mouse USVs are innate, social experience may be necessary for mice to learn the appropriate situation to emit USVs. Mouse USVs have been divided into categories based on their spectrotemporal parameters, but it is currently unclear if social experience changes these parameters (e.g., frequency and duration) or the proportion of calls from each category produced. Social isolation has been found to influence USV production in male mice. To investigate the influence of social isolation on vocal behavior in female mice, recordings were made of USVs emitted to unfamiliar male and female mice by subjects with one of three types of social experience. Twenty-four adult female CBA/CaJ mice either lived alone, lived with other females only, or lived with other females and had limited access to a male. Mice were recorded while in isolation, ensuring all recorded USVs were from the female of interest. Vocalizations were separated into nine categories and peak frequency, duration, and bandwidth were measured for every call. Socially isolated mice did not produce significantly more USVs or USV types than socially experienced mice. Social isolation did not have a significant effect on the features of USVs, suggesting production of USVs may not be learned in female mice.
Published: 2019
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42. Age targeting and scale-up of voluntary medical male circumcision in Mozambique.

Author: Juan Dent, Nuno Gaspar, Emmanuel Njeuhmeli, and Katharine Kripke
Subjects: Medicine, Science
Abstract: BackgroundThe voluntary medical male circumcision (VMMC) program in Mozambique aimed to increase male circumcision (MC) coverage to 80 percent among males ages 10 to 49 by 2018. Given the difficulty in attracting adult men over age 20 for circumcision, Mozambique became interested in assessing its age-targeting strategy and progress at the provincial level to inform program planning.MethodsWe examined the impact and cost-effectiveness of circumcising different age groups of men using the Decision Makers' Program Planning Toolkit, Version 2.1 (DMPPT 2). We also applied the model to assess the scale-up efforts through the end of September 2017 and project their impact on HIV incidence through 2030. The DMPPT 2 is a compartmental Excel-based model that analyzes the effects of age at circumcision on program impact and cost-effectiveness. The model tracks changes in age-specific MC coverage due to VMMC program circumcisions. Baseline MC prevalence was based on data from the 2011 Demographic and Health Survey. The DMPPT 2 was populated with HIV incidence projections from Spectrum/Goals under an assumption that Mozambique would reach its national targets for HIV treatment and prevention by 2022.ResultsWe estimate the VMMC program increased MC coverage among males ages 10 to 49 from 27 percent in 2009 to 48 percent by end of September 2017. Coverage increased primarily in males ages 10 to 29. VMMCs conducted in the national program through the end of September 2017 are projected to avert 67,076 HIV infections from 2010 to 2030. Scaling up circumcisions in males ages 20 to 29 will have the most immediate impact on HIV incidence, while the greatest impact over a 15-year period is obtained by circumcising males ages 15 to 24 in the majority of priority provinces. Circumcising 80 percent of males ages 10 to 29 can achieve 77 percent of the impact through 2030 compared with circumcising 80 percent of males ages 10 to 49.ConclusionThe VMMC program in Mozambique has made great strides in increasing MC coverage, particularly for males ages 10 to 29. Scaling up and maintaining MC coverage in this age group offers an attainable and cost-effective target for VMMC in Mozambique.
Published: 2019
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43. Sex differences in auditory brainstem response audiograms from vasopressin-deficient Brattleboro and wild-type Long-Evans rats.

Author: Payton E Charlton, Kelcie C Schatz, Kali Burke, Matthew J Paul, and Micheal L Dent
Subjects: Medicine, Science
Abstract: Rats are highly social creatures that produce ultrasonic vocalizations (USVs) during social interactions. Brattleboro rats, a Long-Evans derived rat that lacks vasopressin (AVP) due to a mutation in the Avp gene, exhibit atypical social behavior, including fewer USVs with altered spectrotemporal characteristics during social interactions. It is unclear why Brattleboro rats produce atypical USVs, but one factor could be differences in auditory acuity between them and wild-type Long Evans rats with functional vasopressin. Previous studies have suggested a link between increased levels of AVP and auditory processing. Additionally, few studies have investigated sex differences in auditory perception by Long-Evans rats. Sex differences in auditory acuity have been found throughout the animal kingdom, but have not yet been demonstrated in rat audiograms. This study aimed to measure auditory brainstem response (ABR) derived audiograms for frequencies ranging from 1 to 64 kHz in male and female homozygous Brattleboro (Hom), heterozygous Brattleboro (Het), and wild-type (WT) Long-Evans rats to better understand the role of AVP and sex differences in auditory processing by these rats. We failed to detect significant differences between the ABR audiograms of Hom, Het, and WT Long-Evans rats, suggesting that varying levels of AVP do not affect auditory processing. Interestingly, males and females of all genotypes did differ in their ABR thresholds, with males exhibiting higher thresholds than females. The sex differences in auditory acuity were significant at the lowest and highest frequencies, possibly affecting the perception of USVs. These are the first known sex differences in rat audiograms.
Published: 2019
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44. Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform.

Author: Yoon-Sim Yap, Man Chun Leong, Yong Wei Chua, Kiley Wei Jen Loh, Guek Eng Lee, Elaine Hsuen Lim, Rebecca Dent, Raymond Chee Hui Ng, John Heng-Chi Lim, Garima Singh, Angela Tan, Guofeng Guan, Andrew Wu, Yi Fang Lee, Ali Asgar S Bhagat, and Darren Wan-Teck Lim
Subjects: Medicine, Science
Abstract: ObjectivesWe aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC).Materials and methodsPeripheral blood samples were collected from 108 BC patients before starting a new line of treatment ("baseline"), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses.ResultsThe detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS.ConclusionsThis work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.
Published: 2019
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45. Dichotomous effects of cellular expression of STAT3 on tumor growth of HNSCC

Author: Benjamin Van Court, Jacob Gadwa, Diemmy Nguyen, Shiv Bhuvane, Thomas E. Bickett, Laurel L. Lenz, Shilpa Bhatia, Laurel B. Darragh, Ayman Oweida, Alexander L. Dent, Michael W. Knitz, Miles Piper, Andy Phan, Sana D. Karam, Tiffany T. Pham, and Sophia Corbo
Subjects: STAT3 Transcription Factor, medicine.medical_treatment, Cell, Biology, T-Lymphocytes, Regulatory, Mice, Immune system, Drug Discovery, Tumor Microenvironment, Genetics, medicine, Animals, Antigen-presenting cell, Molecular Biology, Mice, Knockout, Pharmacology, Tumor microenvironment, Squamous Cell Carcinoma of Head and Neck, medicine.disease, Head and neck squamous-cell carcinoma, medicine.anatomical_structure, Cytokine, Head and Neck Neoplasms, Cancer cell, Knockout mouse, Cancer research, Molecular Medicine, Original Article
Abstract: STAT3 signaling has been shown to regulate cellular function and cytokine production in the tumor microenvironment (TME). Within the head and neck squamous cell carcinoma (HNSCC) TME, we previously showed that therapeutic targeting of STAT3 in combination with radiation resulted in improved tumor growth delay. However, given the independent regulatory effects STAT3 has on anti-tumor immunity, we aimed to decipher the effects of individually targeting STAT3 in the cancer cell, regulatory T cells (Tregs), and natural killer (NK) cell compartments in driving tumor growth and resistance to therapy in HNSCCs. We utilized a CRISPR knockout system for genetic deletion of STAT3 within the cancer cell as well as two genetic knockout mouse models, FoxP3-Cre/STAT3 fl and NKp46-Cre/STAT3 fl, for Tregs and NK cell targeting, respectively. Our data revealed differences in development of resistance to treatment with STAT3 CRISPR knockout in the cancer cell, driven by differential recruitment of immune cells. Knockout of STAT3 in Tregs overcomes this resistance and results in Treg reprogramming and recruitment and activation of antigen-presenting cells. In contrast, knockout of STAT3 in the NK cell compartment results in NK cell inactivation and acceleration of tumor growth. These data underscore the complex interplay between the cancer cell and the immune TME and carry significant implications for drug targeting and design of combination approaches in HNSCCs.
Published: 2022
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46. Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial

Author: Seth Toback, Eva Galiza, Catherine Cosgrove, James Galloway, Anna L Goodman, Pauline A Swift, Sankarasubramanian Rajaram, Alison Graves-Jones, Jonathan Edelman, Fiona Burns, Angela M Minassian, Iksung Cho, Lakshmi Kumar, Joyce S Plested, E Joy Rivers, Andreana Robertson, Filip Dubovsky, Greg Glenn, Paul T Heath, Roy L. Soiza, Robin Brittain-Long, Chiara Scicluna, Carole Edwards, Lynn Mackay, Mariella D'Allesandro, Amy Nicol, Karen Norris, Sandra Mann, Heather Lawrence, Ruth Valentine, Marianne Elizabeth Viljoen, Carol H. Pretswell, Helen Nicholls, Imrozia Munsoor, Agnieszka Meyrick, Christina Kyriakidou, Shalini Iyengar, Arham Jamal, Nick Richards, Helen Price, Bridie Rowbotham, Danielle Bird, Karen Smith, Olga Littler, Kirsty Fielding, Anna Townsend-Rose, Karen Miller, Jessica Davis, Alison Elliot-Garwood, Lauren Trottier, Paul Edwards, Margaret McFarland, Orod Osanlou, Laura Longshaw, Jane Stockport, Lynne Grundy, Katharine Lucy Broad, Karen Regan, Kim Storton, Declan Ryan-Wakeling, Brad Wilson, Malathy Munisamy, John Wright, Anil Shenoy, Beverley English, Lucy Brear, Paola Cicconi, Marta Boffito, Ana Milinkovic, Ruth Byrne, Roya Movahedi, Rosalie Housman, Naveed Kara, Ellen Brown, Andrea Cipriani, Mary-Jane Attenburrow, Katharine A. Smith, Jonathan Packham, Geoff Sparrow, Richard Smith, Josephine M. Rosier, Khalid Saja, Nyasha Nago, Brian Camilleri, Anita Immanuel, Mike Hamblin, Rawlings Osagie, Mahalakshmi Mohan, Hilary Floyd, Suzanne Goddard, Sanjay Mutgi, John Evans, Sean McKeon, Neringa Vilimiene, Rosavic Chicano, Rachel Hayre, Alice Pandaan, Catherine Henshall, Sonia Serrano, Andrea Mazzella, Thurkka Rajeswaran, Moncy Mathew, Karen Bisnauthsing, Laura Bremner, Henry Fok, Franca Morselli, Paola Cinardo, Blair Merrick, Lucy Sowole, Samantha Broadhead, Natalie Palmer, Jessica Cordle, Jaimie Wilson Goldsmith, Enya Cooney, Beth Jackson, Thilina Jayatilleke, Zelda Cheng, Toby Helliwell, Adrian Chudyk, Rafaela Giemza, John Lord Villajin, Noah Yogo, Esther Makanju, Pearl Dulawan, Deepak Nagra, April Buazon, Alice Russell, Georgie Bird, Amardeep Heer, Rex Sarmiento, Balraj Sanghera, Melanie Mullin, Adam Champion, Aisling Bevan, Kinzah Iqbal, Alshia Johnson, Rebecca Clark, Sarah Shaw, Steven Shaw, Amanda Chalk, Martin Lovatt, Caroline Lillicrap, Angela Parker, Jan Hansel, Zhi Wong, Galvin Gan, Eyad Tuma, Jane Minton, Jennifer Murira, Razan Saman, Alistair Hall, Kyra Holliday, Zara Khan, James Calderwood, George Twigg, Helena Baker, Julie Corrigan, Katy Houseman, Subhra Raguvanshi, Dominic Heining, Jake Weddell, Liz Glaves, Kim Thompson, Francis Davies, Ruth Lambley Burke, Emma C. Thomson, Dinesh Saralaya, Lisa Berry, Nancy Hopewell, Leigh Gerdes, Mihaela Pacurar, Saul N. Faust, Jeremy Turner, Christopher Jeanes, Adele Cooper, Jocelyn Keshet-Price, Lou Coke, Melissa Cambell-Kelly, Ketan Dhatariya, Claire Williams, Georgina Marks, James Sudbury, Lisa Rodolico, Judy Bradley, Sharon Carr, Roisin Martin, Angelina Madden, Paul Biagioni, Sonia McKenna, Alison Clinton, Maurice O'Kane, Justin Carter, Matthew Dewhurst, Bill Wetherill, Thandiwe Hoggarth, Katrina Lennon Collins, Marie Chowdhury, Adil Nathoo, Anna Heinen, Orla MacDonald, Claudia Hurducas, Liliana Cifuentes, Harjeevan Gill, Andy Gibson, Raha West, Jane Ewing, Rachel Blacow, John Haughney, Jonathan MacDonald, John Paul Seenan, Stewart Webb, Colin O'Leary, Scott Muir, Beth White, Neil Ritchie, Daniel F. McAuley, Jonathan Stewart, Mariella D'Alessandro, Nicki Lakeman, Laura Purandare, Duncan Browne, David Tucker, Peter Luck, Angharad Everden, Lisa Trembath, Michael Visick, Nick Morley, Laura Reid, Helen Chenoweth, Kirsty Maclean, Ray P. Sheridan, Tom Burden, Craig Francis Lunt, Shirley Todd, Stephanie Estcourt, Jasmine Marie Pearce, Suzanne Wilkins, Cathryn Love-Rouse, Eva Torok-Pollok, Mike Youle, Sara Madge, Danielle Solomon, Aarti Nandani, Janet M. North, Nargis Hemat, Rachel Newport, Philip A. Kalra, Chukwuma Chukwu, Olivia Wickens, Vikki O'Loughlin, Hema Mistry, Louise Harrison, Robert Oliver, Anne-Marie Peers, Jess Zadik, Katie Doyle, David R. Chadwick, Kerry Colling, Caroline Wroe, Marie Branch, Alison Chilvers, Sarah Essex, Mark Stone, Alberto San Francisco Ramos, Emily Beales, Olivia Bird, Zsofia Danos, Hazel Fofie, Cecilia Hultin, Sabina Ikram, Fran Mabesa, Aoife Mescall, Josyanne Pereira, Jennifer Pearce, Natalina Sutton, Emma Snashall, David Neil Baxter, Sara Bennett, Debbie Suggitt, Kerry Hughes, Wiesia Woodyatt, Lynsey Beacon, Alissa Kent, Chris Cooper, Milan Rudic, Simon Tunstall, Matthew Jackson, Claire Hombersley, Patrick Moore, Rebecca Cutts, Andrew Higham, Marwan Bukhari, Mohamed Elnaggar, Michelle Glover, Fiona Richardson, Alexandra Dent, Shahzeb Mirza, Rajiv Ark, Jennie Han, Suzy V. Hope, Philip J. Mitchelmore, Rostam Osanlou, Andrew Freedman, Alison Cooper, Katherine Burton, Kashyap Katechia, Michael Barrett, Jo Salkeld, Natalie Hill, Nathaniel Lee, Jon Perkins, and Polly Fox
Subjects: Adult, Pulmonary and Respiratory Medicine, Trivalent influenza vaccine, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, Influenza vaccine, Population, Placebo, Young Adult, Immunogenicity, Vaccine, Double-Blind Method, Internal medicine, Humans, Medicine, education, Adverse effect, Aged, education.field_of_study, Reactogenicity, SARS-CoV-2, business.industry, COVID-19, Articles, Middle Aged, Vaccine efficacy, Vaccination, Influenza Vaccines, Seasons, business
Abstract: Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to
Published: 2022
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47. The Influence of the Doctor of Nursing Practice on West Texas Health Care

Author: Joyce Batcheller, Brandon 'Kit' Bredimus, Bob Dent, and Carol Boswell
Subjects: Officer, medicine.medical_specialty, Doctor of Nursing Practice, Nursing, Leadership and Management, business.industry, Acute care, Health care, medicine, Leadership team, business, Psychology, Qualitative research
Abstract: This case study reflects the journey taken by multiple individuals as they considered the doctor of nursing practice (DNP) evolution within one suburban acute care setting. The DNP education that the chief nursing officer (CNO) experienced led to a major change for all the nursing leaders in the organization. Two CNOs provide their unique path and insights to building a leadership team composed primarily of DNP-prepared leaders, sustaining the momentum, and fostering further growth in an isolated area of West Texas. Findings from a qualitative study on the perceived impact of the DNP education and actionable steps are shared.
Published: 2022
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48. The 40-year debate: a meta-review on what works for juvenile offenders

Author: Laceé N. Pappas and Amy L. Dent
Subjects: Youth Violence, medicine.medical_treatment, Criminology, Corrections, Article, Intervention (counseling), medicine, Juvenile delinquency, 0501 psychology and cognitive sciences, Violence Research, Pediatric, Juvenile offenders, Peace, Rehabilitation, Modalities, Recidivism, 050901 criminology, 05 social sciences, Justice and Strong Institutions, What works, Meta-analysis, Systematic review, 0509 other social sciences, Reentry, Law, 050104 developmental & child psychology, Criminal justice, Clinical psychology
Abstract: Objectives This meta-review integrates the findings of meta-analyses and systematic reviews to explore the effect of intervention programs on recidivism for juvenile offenders. Methods The systematic literature search gathered 48 meta-analyses and systematic reviews from 53 research reports, contributing 56 independent effect sizes for analysis. These effect sizes were statistically integrated, and five moderators of theoretical and methodological importance were tested using meta-regression. Results On average, intervention programs are associated with a significant reduction in recidivism (rΦ = −0.09, p < 0.001) for juvenile offenders who participate in a program compared to those who do not. However, reductions in recidivism significantly vary between the levels of criminal justice system, characteristics of juvenile offenders, types of program modalities, and methodological quality. Conclusions Results indicate that intervention programs can be an effective approach to reducing recidivism for juvenile offenders, especially when combined with a rehabilitative program modality.
Published: 2023

49. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Nabeel Abdallah, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, David Abdo, Basir Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Amina Abdulle, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Ul Amna Abeer Ul Amna, Katrina Abernethy, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Sarah Acheampong, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Sara Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Charlotte Adams, Kate Adams, Lisa Adams, Richard Adams, Tim Adams, Kirsty Adcock, Jemaimah Addai, Ade Adebiyi, Ken Adegoke, Vicki Adell, Debo Ademokun, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Rina Adhikary, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Debbie Affleck, Dominic Affron, Carmel Afnan, Muhammad Afridi, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Penny Agent, Sunil Aggarwal, Arameh Aghababaie, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Humayun Ahmad, Mohammad Ahmad, Syed Ahmad, Asim Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Iram Ahmed, Irshad Ahmed, Khaled Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Sophia Ahmed, Syed Ahmed, Syed Haris Ahmed, Roa Ahmed Ali, Sana Ahmed, Sana Ahmer, Dhiraj Ail, Mark Ainsworth, Giulia Airoldi, Myriam Aissa, Lindianne Aitken, Bini Ajay, Francis Ajeneye, Abdulakeem Ajibode, Ayesha Ajmi, Tahir Akbar, Naim Akhtar, Nasim Akhtar, Nauman Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Olajide Akinwumiju, Olugbenro Aktinade, Ahmad Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Narendra Aladangady, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Karina Al-Asadi, Kyriaki Alatzoglou, Manaf Al-Bayati, Paul Albert, Lorraine Albon, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter D G Alexander, Charlotte Alford, Julyan Al-Fori, Laith Alghazawi, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Asad Ali, Fawzia R Ali, Hoodo Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Nayab Ali, Oudai Ali, Sabira Ali, Sakina Ali, Syed Ali, Abid Alina, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Moutaz Alkhusheh, Allameddine Allameddine, Fiona Allan, Rachel Allan, Alison Allanson, Robert Allcock, Beverley Allen, Eireann Allen, Jess Allen, Kerry Allen, Laura Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Sara Altaf, Mary Alvarez, Balaal Alyas, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Kenneth Amenyah, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Amjad Amjad, Neelma Amjad, Mariam Ammoun, Victoria Amosun, Khaled Amsha, Pugh Amy, Atul Anand, Rekha Anand, Samantha Anandappa, Julie Anderson, Kevin Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Susan Andrews, Gregory Andrikopoulos, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, George Apostolides, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia Far Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Emily Arbon, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Sylvia Armstrong-Fisher, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Sarah Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Andrea Arroyo, Arslam Arter, Ayush Arya, Rita Arya, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Glen Ashby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Deborah Asher, Ayesha Ashfaq, Ben Ashford, Suhail Ashgar, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Arshia Aslam, Harshini Asogan, Abigail Asquith, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Richard Athay-Hunt, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Brygitta Atraskiewicz, Claire Atterbury, Abdul Ahmad Attia, Rita Atugonza, Paula Aubrey, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Kyaw Thu Aung, Ni Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Miriam Avery, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Gabriel Awadzi, Atia Awan, Aszad Aya, Eman Ayaz, Amanda Ayers, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Sibel Bafekr Mishamandani, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Stephen Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Sanchia Baines, Vikram Bains, Aimi Baird, David Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Charles Baker, Emma Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Nauman Bakhtiar, Panos Bakoulas, Julie Balaam, Niranjan Balachandran, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Rebekah Baldwin-Jones, James Balfour, Gagan Bali, Sonya Balkee, Ceri Ball, Kasia Ballard, Amy Ballinger, Ismael Balluz, Craig Balmforth, Emese Balogh, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Tanya Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Millie Banerjee, Ritwik Banerjee, Harrison Banks, Lauren Banks, Luke Banks, Paul Banks, Oliver Bannister, Bharat Bansal, Robert Banthorpe, Laura Banton, Mariamma Baptist, Tanya Baqai, Ananya Mouli Baral, Desislava Baramova, Alex Barber, Russel Barber, Emma Barbon, Miriam Barbosa, Monica Barbosa, Jamie Barbour, Alexander Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Amy Barker, Debbie Barker, Helen Barker, Joseph Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, 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Mika Burgess, Paula Burgess, Richard Burgess, Sophia Burgess, Paula Burgett, Adrian Burman, Sara Burnard, Caroline Burnett, John Burnett, Amanda Burns, Amy Burns, Collette Burns, James Burns, Karen Burns, Samuel Burns, Sarah Burns, Daniel Burrage, Sadie Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Matthew Burton, Angela Busby, Deborah Butcher, Aaron Butler, Jessica Butler, Joanne Butler, Joshua Butler, Lesley Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Mohammad M Butt, Sophia Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Eleanor Byworth, Amanda Cabandugama, Ruth Cade, Anthony Cadwgan, Donna Cairney, James Calderwood, Darren Caldow, Moira Caldwell, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sarah Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Ana Canabarro, Lisa Canclini, Shaula Mae Candido, Janie Candlish, Cielito Caneja, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Anne Capps-Jenner, Thomas Capstick, Ishmael Carboo, Nuria Cardenas, Mary Cardwell, Rachel Carey, Simon Carley, Tammy Carlin, Andrew Carlton, Samantha Carmichael, Mandy Carnahan, Rebecca Carnegie, Charlotte Caroline, Emily Carpenter, Jodi Carpenter, David Carr, Sharon Carr, Anna Carrasco, Samantha Carrington, Zoe Carrington, Paul Carroll, Caroline Carron, Anne Carstairs, Jonathan Carter, Michael Carter, Moira Carter, Paul Carter, Penny Carter, Steven Carter, Simon 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Eric Chiang, Angela Chiapparino, Rosavic Chicano, Zviedzo A Chikwanha, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Karen Chinn, Vashira Chiroma, Heather Chisem, Claire Chisenga, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Vandana Choudhary, Sarah Choudhury, Bing-Lun Chow, Fateha Chowdhury, Mahibbur Chowdhury, Shahid Chowdhury, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Shabs Chucha, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael E Chukwu, Izu Chukwulobelu, Chi Y Chung, Ben Church, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Nick Ciccone, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, 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Davies, Ffyon Davies, Helen Davies, James Davies, Jane Davies, Jeni Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Louisa Davies, Mark Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sarah Davies, Simon Davies, Alison Davis, Gwyneth Davis, Illinos Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Alexander Davison, Sophia Davison, Mark Davy, Christine Dawe, H Dawe, Mark Dawkins, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Susan Dawson, Tom Dawson, Andrew Daxter, Andrew Day, Helena Day, Jacob Day, Jeremy Day, Lynn Day, Jamie D'Costa, Parijat De, Duneesha de Fonseka, Toni de Freitas, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Anthony de Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie 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Abrar Gani, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Jill Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Justin Garner, Lucie Garner, Zoe Garner, Kimberley Garnett, Robert Garney, Rosaline Garr, Michael Garstka, Peter Gartan, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Noha Gasmalseed, Michaela Gaspar, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Alison Geddis, Ian Gedge, Sarah Gee, Minerva Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Susan Gent, Natalie Geoghegan, Chloe George, Sam George, Tina George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Hisham Ghanayem, Amardeep Ghattaoraya, Anca Gherman, Alison Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Andrew Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Cat Gilbert, Jeanette Gilbert, Joanne Gilbert, Kayleigh Gilbert, Sean Gilchrist, Benjamin Giles, Mandy Gill, Rose Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Matt Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Theodora Giokanini-Royal, Anna Gipson, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Ana Glennon, John Glover, Kyle Glover, Jan Glover Bengtsson, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Gillian Godding, Emma Godson, Gerry Gogarty, Sukanya Gogoi, Aiky Goh, Rebeca Goiriz, Sriya Gokaraju, Philip Gold, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel 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Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, Emily Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Sandra Harlow, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Fiona Harper, Heather Harper, Melanie Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Naomi Harris, Nichola Harris, Sophie Harris, Alex Harrison, David Harrison, Julie Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Heli Harvala, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Sarah Haskins, Zena Haslam, Adil 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Susie Holt, Alexandra Holyome, Marie Home, Toni Home, Renate Homewood, Kate Hong, Laura Hontoria del Hoyo, Clare Hooper, Sarah Hoosdally, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Daniel Hornan, Nicola Hornby, Zoey Horne, Latoya Horsford, Megan Horsford, Mark Horsford, Valana Horsham, Alexander Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Nicola Horton-Turner, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Leanne Hostler, Maxine Hough, Sarah Hough, Brittany Houghton, Catherine Houghton, Iain Houghton, Kathryn Houghton, Rebecca Houlihan, Angela Houston, Hamish Houston, Tawedzegwa Hove, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Alison Howarth, Diane Howarth, Serena Howe, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Joanne Hoyle, Josh Hrycaiczuk, Naing Zaya Htoon, Su Htwe, Ying Hu, Chiang Ooi Huah Huah, Abby 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Mohammed Hussam El-Din, Raheem Hussein, Rebecca Hussey, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Mazen Ibraheim, Abdalla Ibrahim, Ahmed Ibrahim, Asil Ibrahim, Mohamed Ibrahim, Monzeer Ibrahim, Wadah Ibrahim, Adetokunbo I Idowu, Muhammad Idrees, Hina Iftikhar, Mawara Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Mary Ilsley, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Alison Imtiaz, Haider Imtiaz, Claire Ingall, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Jennifer Inglis, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Ilian P Iordanov, Anil Ipe, Adil Iqbal, Madiha Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Jane Ireland, Robert Irons, Mohannad Irshad, Muhammad S Irshad, Janice Irvine, Val Irvine, Pamela Irving, Robert Irving, Mina Ishak, Erica Isherwood, Aminul Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, Caroline Ison, M'hamedi Israa, Sharon Isralls, Ali Issa, Monica Ivan, Catrina Ivel, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Menaka Iyer, Mia Iyer, Calum Jack, Amanda Jackson, Anthony Jackson, Ben Jackson, Beth Jackson, Douglas Jackson, Ella Jackson, Hayley Jackson, Helen Jackson, Jane Jackson, Julie Jackson, Karin Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Sharon Jackson, Nikita Jacob, Patricia Jacob, Reni Jacob, Nicola Jacques, Terri-Lisa Jacques-Brown, Anisa Jafar, Daniel Jafferji, Ali Jaffery, Chandrashekar Jagadish, Vijay Jagannathan, Sam Jaggard, Mandeep Jagpal, Fernandez R Jaime, Neemisha Jain, Seema Jain, Susan Jain, Sanjay Jaiswal, Danyal Jajbhay, Thomas Jaki, Bintou Jallow, Yusuf Jaly, Sabine Jamal, Zeba Jamal, Yasmin Jameel, Albie James, Christie James, Kate James, Lee James, Linda James, Mark James, Nicholas James, Olivia James, Rebecca James, Ruth James, Tracy James, Jack Jameson, Aaron Jamison, Phoebe Jane, Azara Janmohamed, Sabrina Jansz, Deepa Japp, Lorraine Jappy, Victor Jardim, Catherine Jardine, Emma Jarnell, Ellie Jarvie, Ann Jarvis, Claire Jarvis, Lisa Jarvis, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Mays Jawad, Lona Jawaheer, Kauky Jawaid, Anu Jayachandran, Dinakaran Jayachandran, Angelina Jayakumar, Deepak Jayaram, Ravi Jayaram, Geeshath Jayasekera, Thilina Jayatilleke, Abi Jayebalan, Saman Jeddi, Vandana Jeebun, Mohammad S Jeelani, Zeynab Jeewa, Emma Jefferson, Katie Jeffery, Helen Jeffrey, Jenni Jeffrey, Rachel Jeffrey, Sue Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, Christopher Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Jacqui Jennings, Louise Jennings, Rebecca Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge Antonio Jesus Silva, Champa Jetha, Kishan Jethwa, Jeby Jeyachandran, Visuvanathan Jeyakumar, Dharshana Jeyapalan, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Laura Jimenez, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Navin John, Sarah John, Emma Johns, Margaret Johns, Anne-Marie Johnson, Antoinette Johnson, David Johnson, Emma Johnson, Gillian Johnson, Kathryn Johnson, Katie Johnson, Luke Johnson, Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Rachel Johnson, Tracy Johnson, Zoe Johnson, Claire Johnston, Janet Johnston, Laura Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Hazel Jones, Jac Jones, James Jones, Jamie Jones, Jessica Jones, Jonathon Jones, Julie Jones, Karen Jones, Kate E Jones, Kevin Jones, Laura Jones, Laura M Jones, Lorna Jones, Louise Jones, Mathew Jones, Nicola Jones, Paul Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Taya Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Annette Jose, Sanal Jose, Anna Joseph, Joseph Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Revati Joshi, Benz Josiah, Tiffany Joyce, Adriel Ju Wen Kwek, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Katarina Kacinova, Nikhil Kadam, Rebecca Kahari, Gail Kakoullis, Azad Kala Bhushan, Richard JK Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Seika Kalsoom, Elisa Kam, John Kamara, Mohamed Kamara, Ajay Kamath, Prakash Kamath, Ravindra Kamath, Siddharth Arun Kamerkar, Nick Kametas, Musaiwale Kamfose, Arul Kandaswamy, Leia Kane, Osei Kankam, Thogulava Kannan, Abhinav Kant, Vikas Kapil, Ritoo Kapoor, Sonal Kapoor, Sourjya Kar, Janaka Kara, Vasita Kara, Marina Karakantza, Rona Kark, Nicholas Karunaratne, Natashja Kasianczuk, Vidya Kasipandian, Rizwan Kassam, Janarth Kathirgamachelvam, Victoria Katsande, Kulbinder Kaul, Daljit Kaur, Dervinder Kaur, Jasmin Kaur, Jaspreet Kaur, Satvinder Kaur, Zunaira Kausar, Mohammad AA Kawser, Andrea Kay, Sarah Kay, Jossy N Kayappurathu, Callum Kaye, Ahemd Kazeem, Naved Kazi, Sharon Kaznica, Samantha Kearley, Rachel Kearns, Nichola Kearsley, Joanne Keating, John Keating, Liza Keating, Elizabeth Keddie-Gray, Katie Keen, Natalie Keenan, Jonathan Kefas, Stephen Kegg, Laura Keith, Uzoamaka Keke, Tosin Kelani, Joanne Kellett, Jeremy Kellington, Alison Kelly, Conor Kelly, David Kelly, Diane Kelly, Dominic Kelly, Emma Kelly, Laura Kelly, Martin Kelly, Michael Kelly, Rosalind Kelly, Sinead Kelly, Stephen Kelly, Thomas Kelly, Mary Kelly-Baxter, Marketa Keltos, Timothy Kemp, Kelly Kemsley, Alexandra Kendall-Smith, Sarah Kennard, Ann Kennedy, Caroline Kennedy, James Kennedy, Sophie Kennedy-Hay, Julia 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Michelle Lake, Nicki Lakeman, David Lalloo, Fiona Lalloo, Alison Lam, Fiona Lamb, Lucy Lamb, Thomas Lamb, Nick Lambe, Pauline Lambert, Claudia Lameirinhas, Mohammed KG Lami, Abigail Lamikanra, Holly Lamont, Michal Lamparski, Djillali Lamrani, Christine Lanaghan, Rebecca Lanaway, Ivone Lancona-Malcolm, Julia Lancut, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Alidih Lang, Stephen Lang, Daniel Langer, Margaret Langley, Charles Langoya, Emily Langthorne, Taiya Large, Wojciech Lason, Anna Last, Scott Latham, John Latham-Mollart, Afzal Latheef, Darren Latimer, Nang Latt, Carly-Jane Lattimore, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jennifer Law, Jessica Law, Penny Law, Richard Law, Colin Lawler, Mark Lawley, Emma Lawrence, Jo Lawrence, Neil Lawrence, Ryan Lawrie, Jemima Lawson, Joanne Lawson, Louise Lawson, Rebecca Lawton, Michael Lay, Christine Laycock, Reina Layug, Maria Lazo, Vietland Le, Amelia Lea, William Lea, Ian Leadbitter, Thomas Leahy, Richard Lean, Lorna Leandro, Darren Leaning, Sandra Leason, Christina Leaver, Marie Anne Ledingham, Emma Lee, Hannah Lee, Irish Lee, Judith Lee, Sam Lee, Shi Han Lee, Simon Lee, Sindy Lee, Stephanie Lee, Tracey Lee, Xiang Lee, Diana Lees, Jennifer Lees, Helen Legge, Julian Leggett, Katie Leigh-Ellis, Kevan Leighton, Nicky Leitch, Eleni Lekoudis, Petula Lemessy, Nicholas Lemoine, Joana Lemos, Irina Lenchuk, Katy Leng, Katrina Lennon, Liz Lennon, Isabel Lentell, Kelly Leonard, Wen Leong, Nicky Leopold, Oskar Lepiarczyk, Isla Leslie, Eleni Lester, Joe Leung, Ullrich Leuschner, Emma Levell, Chris Levett, Alice Lewin, Michaela Lewin, Alison Lewis, David Lewis, Dee Lewis, Georgina Lewis, Gillian Lewis, Joanne Lewis, Joseph Lewis, Kathryn Lewis, Keir Lewis, Leon Lewis, Lisa Lewis, Marissa Lewis, Rob Lewis, Robert Lewis, Catherine Lewis-Clarke, Lorraine Lewis-Prosser, Katherine Lewiston, Adam Lewszuk, Penny Lewthwaite, Samantha Ley, Anna Li, Jenny Li, Angela Liao, Victoria Licence, David Lieberman, Susan 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Nisbett, Aksinya Nisha James, Sabaahat Nishat, Tomoko Nishiyama, Sara Nix, Jennifer Nixon, Maxine Nixon, Khwaja Nizam Ud Din, Maria Nizami, Josephine Nnadi, Lyrics Noba, Harriet Noble, Hsu Noe, Jerry Nolan, Zahid Noor, Zaid Noori, Jamie Norgrave, Louis Norman, Rachel Norman, Karen Norris, Lillian Norris, Sally Ann Nortcliffe, Fiona North, Julie North, Thomas North, Julie Northcote, John Northfield, Samantha Northover, Jurgens Nortje, Donna Norton, Rowen Norton, Holly Notman, Khalid Nourein, Timea Novak, Tony Noyce, Alan Noyon, Arlene Nubi, Mohamed Nugdallah, Anne Marie Nugent, Justine Nugent, Kribashnie Nundlall, Kieran Nunn, Michelle Nunn, Jane Nunnick, Yvonne Nupa, Zubeir Nurgat, Kelly Nwankiti, Eugenia Nweje, Godfrey Nyamugunduru, Maggie Nyirenda, Kerry Nyland, Daire O Shea, Ruth O'Donnell, Chloe O'Hara, Kevin O'Reilly, William O'Rourke, Caroline Oakley, Begho Obale, Clements Oboh, Andrew O'Brien, Clare O'Brien, Julie O'Brien, Kirsty O'Brien, Linda O'Brien, Marese O'Brien, Neale 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O'Neill, Lauran O'Neill, Chon Sum Ong, Chidera Onyeagor, Huah C Ooi, Amin Oomatia, Maria Opena, Richard Oram, Chloe Orchard, Christy Ord, Jonathan Ord, Charlotte O'Reilly, Lola Orekoya, Devaki O'Riordan, Sean O'Riordan, Amy Orme, Hannah Orme, Dave Ormrod, Charlotte Orr, Sarah Orr, Christopher Orton, Anna Osadcow, Rawlings Osagie, Rostam Osanlou, Lynn Osborne, Nigel Osborne, Rebecca Osborne, Wendy Osborne, William Osborne, Charles Osbourne, Jennifer Osei-Bobie, Mandy O'Shea, Joseph Osman, Wa'el Osman, Bashir Osman, G Osoata, Marlies Ostermann, Eoin O'Sullivan, Susan O'Sullivan, Noor Otey, Otheroro K. 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Tanaraj Perinpanathan, Lakshmi Periyasamy, Francesca Perkins, Rachel Perkins, Elizabeth Perritt, Alison Perry, Emily Perry, Meghan Perry, Terrie Perry, Thomas M Perumpral, Guilherme Pessoa-Amorim, Ruth Petch, Lionel Peter, Cecilia Peters, Craig Peters, Jayne Peters, Mark Peters, Steve Peters, Tim Peters, Remy Petersen, Alexandra Peterson, Leon Peto, Iulia Petras, Ilianna Petrou, Boyanka Petrova, Mirela Petrova, Paul Pfeffer, Mysore Phanish, Paul Phelan, Christopher Philbey, Jennifer Philbin, Neil Philips, Alex Phillips, Danielle Phillips, Dylan Phillips, Karen Phillips, Pat Phillips, Rachael Phillips, Katherine Philpott, Marie Phipps, Virach Phongsathorn, Mandeep Phull, Masroor M Phulpoto, Myat TT PI, Sara Pick, James Pickard, Charlotte Pickering, Gillian Pickering, Thomas Pickett, Hayleah Pickford, Joanna Pickles, Benjamin Pickwell-Smith, Natalia Pieniazek, Charlie Piercy, Angelo Pieris, Samia Pilgrim, Paul Anthony Pillai, Zoe Pilsworth, Heather Pinches, Stacey Pinches, Julia Pinder, 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Anand Shah, Bhavni Shah, Momin Shah, Neil Shah, Pallav Shah, Priyank Shah, Qasim Shah, Sarfaraz H Shah, Snehal Shah, Suraj Shah, Syed Shah, Wajid Shah, Saarma Shahad, Sousan Shahi, Sipan Shahnazari, Muhammad Shahzeb, Aisha Shaibu, Zara Shaida, Amina Y Shaikh, Maliha Shaikh, Rajit Shail, Mariya Shaji, Muhammad Shakeel, Korah Shalan, Nadia Shamim, Kazi Shams, Alison Shanahan, Thomas Shanahan, Shaminie Shanmugaranjan, Hamed Sharaf, Muhammad Sharafat, Asir Sharif, Ajay Sharma, Akhilesh Sharma, Ash Sharma, Bhawna Sharma, Mona Sharma, Ojasvi Sharma, Poonam Sharma, Rajeev Sharma, Sanjeev Sharma, Sarkhara Sharma, Shriv Sharma, Sonal Sharma, Alexander Sharp, Charles Sharp, Gemma Sharp, Paula Sharratt, Phoebe Sharratt, Katherine Sharrocks, Emma Sharrod, Christopher Shaw, Daisy Shaw, David Shaw, Deborah Shaw, Joanne Shaw, Jonathan Shaw, Lisa Shaw, Tomos G Shaw, Anna Shawcross, Jill Shawe, Lou Shayler, Khuram Shazad, Sophy Shedwell, Jonathan Sheffield, Zak Shehata, Arshiya Sheik, Asif Sheikh, 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Jyoti Singh, Lokeshwar Singh, Manjeet Singh, Nadira Singh, Pankaj Singh, Prabhsimran Singh, Salil Singh, Saurabh Singh, Parag Singhal, Bryan Singizi, Manas Sinha, Utkarsh Sinha, Guy Sisson, Sarah Sithiravel, Karthikadevi Sivakumar, Shanmugasundaram Sivakumar, Darsh Sivakumran, Sivanthi Sivanadarajah, Pasupathy-Rajah Sivasothy, Rebecca Sivers, Alison Sivyer, Nicole Skehan, Robert Skelly, Orlagh Skelton, Imogen Skene, Michael J Skill, Denise Skinner, Tabitha Skinner, Victoria Skinner, Agnieszka Skorko, Iwona Skorupinska, Mariola Skorupinska, Amy Slack, Katie Slack, Wendy Slack, Heather Slade, Helen Slade, Mark Slade, Helen Slater, Lynda Slater, Nicola Slawson, Andrew Sloan, Brendan Sloan, Derek Sloan, Geraldine Sloane, Benjamin Small, Ellen Small, Emma Small, Samuel Small, Karen D Smallshaw, Andy Smallwood, Carien Smit, Aileen Smith, Alex Smith, Amanda Smith, Amy Smith, Andrew Smith, Anna Smith, Camilla Smith, Catherine Smith, Chris Smith, Christopher Smith, Dominic Smith, Eleanor Smith, Harriet Smith, Hazel Smith, Helen Smith, Jacky Smith, Janice Smith, Jessica Smith, Juliet Smith, Karen Smith, Kate Smith, Kathryn Smith, Katie Smith, Kelly Smith, Kerry Smith, Lara Smith, Linda Smith, Lisa Smith, Loren Smith, Maria Smith, Mel Smith, Oliver Smith, Rachel Smith, Rebecca Smith, Richard Smith, Ruth Smith, Sally Smith, Samantha Smith, Stacey Smith, Stephanie Smith, Susan Smith, Imogen Smith, John Smith, Gemma Smithson, Sue Smolen, Sara Smuts, Naoise Smyth, Annette Snell, David Snell, Luke Snell, Beng So, Michelle Soan, Toluleyi Sobande, Alberto Sobrino Diaz, Basit Sohail, Bina Sohail, Herminder Sohal, Roy Soiza, Mary Sokolowski, Olajumoke Solademi, Krishma Solanki, Babak Soleimani, Amanda Solesbury, Reanne Solly, Louise Solomon, Subash Somalanka, Chandrashekaraiah Somashekar, Raj Sonia, Shiu-Ching Soo, Deepti Sood, Pavandeep Soor, Germanda Soothill, Jennifer Soren, Youssef Sorour, Apina Sothinathan, Pragalathan Sothirajah, Najwa Soussi, Donna Southam, David Southern, Iain 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Yates, David Yates, Edward Yates, Helen Yates, Julie Yates, Mark Yates, Charlotte Yearwood Martin, Andrew Yeatman, Khin Yein, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Richard Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Raisa Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Lynn Zarb, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Marian Zelman, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Veronica Zindonda, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Roslin Zuha, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, Will Zuurbier, Sheba Zyengi, and University of St Andrews. School of Medicine
Subjects: Male, Convalescent plasma, medicine.medical_treatment, 030204 cardiovascular system & hematology, Antibodies, Viral, Rate ratio, 0302 clinical medicine, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Medicine, Hospital Mortality, 030212 general & internal medicine, 11 Medical and Health Sciences, Aged, 80 and over, Medicine(all), Mortality rate, Covid19, Articles, 3rd-DAS, General Medicine, Middle Aged, Hospitals, Treatment Outcome, Female, Open label, Coronavirus Infections, Life Sciences & Biomedicine, RM, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, Humans, In patient, Pandemics, COVID-19 Serotherapy, Aged, Mechanical ventilation, Science & Technology, SARS-CoV-2, business.industry, Significant difference, Immunization, Passive, COVID-19, Length of Stay, NIS, R1, Respiration, Artificial, United Kingdom, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, business
Abstract: Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Published: 2021
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50. SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program

Author: Madara Ratnadiwakara, Stuart K Archer, Craig I Dent, Igor Ruiz De Los Mozos, Traude H Beilharz, Anja S Knaupp, Christian M Nefzger, Jose M Polo, and Minna-Liisa Anko
Subjects: SR protein, RNA processing, pluripotent, reprogramming, mRNA export, alternative splicing, Medicine, Science, Biology (General), QH301-705.5
Abstract: The establishment and maintenance of pluripotency depend on precise coordination of gene expression. We establish serine-arginine-rich splicing factor 3 (SRSF3) as an essential regulator of RNAs encoding key components of the mouse pluripotency circuitry, SRSF3 ablation resulting in the loss of pluripotency and its overexpression enhancing reprogramming. Strikingly, SRSF3 binds to the core pluripotency transcription factor Nanog mRNA to facilitate its nucleo-cytoplasmic export independent of splicing. In the absence of SRSF3 binding, Nanog mRNA is sequestered in the nucleus and protein levels are severely downregulated. Moreover, SRSF3 controls the alternative splicing of the export factor Nxf1 and RNA regulators with established roles in pluripotency, and the steady-state levels of mRNAs encoding chromatin modifiers. Our investigation links molecular events to cellular functions by demonstrating how SRSF3 regulates the pluripotency genes and uncovers SRSF3-RNA interactions as a critical means to coordinate gene expression during reprogramming, stem cell self-renewal and early development.
Published: 2018
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