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1. Using Explicit Instruction and Video Modeling to Teach Rational Number Skills to Students with Learning Disabilities

Author: Jared R. Morris, Elizabeth M. Hughes, and David Lee
Abstract: The purpose of this study was to examine the effects of utilizing explicit instruction, point-of-view video modeling, and augmented reality technology to teach mathematics to students with disabilities. A multiple probe single-case research design was used. Three students with Learning Disabilities (LD) who were receiving special education services in mathematics participated in the study. The results were analyzed using visual analysis of trend, level, and variability and demonstrated a functional relation between the intervention and the students' performance on three rational number mathematics skills. Maintenance and generalization of the rational number skills were measured with variable findings. The intervention was determined to be socially valid by the participants and teachers.
Published: 2024

2. Targeting osteoclasts for treatment of high-risk B-cell acute lymphoblastic leukemia

Author: Rishi S. Kotecha, Sarah M. Trinder, Anastasia M. Hughes, Benjamin H. Mullin, Sarah Rashid, Jinbo Yuan, Jiake Xu, Owen Duncan, Patrycja Skut, Grace-Alyssa Chua, Sajla Singh, Joyce Oommen, Richard B. Lock, Ursula R. Kees, Sebastien Malinge, Vincent Kuek, and Laurence C. Cheung
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2025
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3. Urinary metabolite model to predict the dying process in lung cancer patients

Author: Séamus Coyle, Elinor Chapman, David M. Hughes, James Baker, Rachael Slater, Andrew S. Davison, Brendan P. Norman, Ivayla Roberts, Amara C. Nwosu, James A. Gallagher, Lakshminarayan R. Ranganath, Mark T. Boyd, Catriona R. Mayland, Douglas B. Kell, Stephen Mason, John Ellershaw, and Chris Probert
Subjects: Medicine
Abstract: Abstract Background Accurately recognizing that a person may be dying is central to improving their experience of care at the end-of-life. However, predicting dying is frequently inaccurate and often occurs only hours or a few days before death. Methods We performed urinary metabolomics analysis on patients with lung cancer to create a metabolite model to predict dying over the last 30 days of life. Results Here we show a model, using only 7 metabolites, has excellent accuracy in the Training cohort n = 112 (AUC = 0·85, 0·85, 0·88 and 0·86 on days 5, 10, 20 and 30) and Validation cohort n = 49 (AUC = 0·86, 0·83, 0·90, 0·86 on days 5, 10, 20 and 30). These results are more accurate than existing validated prognostic tools, and uniquely give accurate predictions over a range of time points in the last 30 days of life. Additionally, we present changes in 125 metabolites during the final four weeks of life, with the majority exhibiting statistically significant changes within the last week before death. Conclusions These metabolites identified offer insights into previously undocumented pathways involved in or affected by the dying process. They not only imply cancer’s influence on the body but also illustrate the dying process. Given the similar dying trajectory observed in individuals with cancer, our findings likely apply to other cancer types. Prognostic tests, based on the metabolites we identified, could aid clinicians in the early recognition of people who may be dying and thereby influence clinical practice and improve the care of dying patients.
Published: 2025
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4. Spatial interaction mapping of PD-1/PD-L1 in head and neck cancer reveals the role of macrophage-tumour barriers associated with immunotherapy response

Author: Vahid Yaghoubi Naei, Rafael Tubelleza, James Monkman, Habib Sadeghirad, Meg L. Donovan, Tony Blick, Agata Wicher, Sara Bodbin, Amelie Viratham, Robert Stad, Subham Basu, Caroline Cooper, Catherine Barnett, Ken O’Byrne, Rahul Ladwa, Majid Ebrahimi Warkiani, Brett G. M. Hughes, and Arutha Kulasinghe
Subjects: Head and neck cancer, Proximity ligation assay, Immunotherapy, Macrophages, Cellular interactions, PD-L1 interactions, Medicine
Abstract: Abstract Background Mucosal head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage, where the prognosis is poor due to the high rates of recurrence and metastasis. With approximately one million new cases projected in 2024, worldwide mortality of HNSCC is estimated to reach 50% of detected cases the same year. Patients with early-stage tumours showed a 50–60% five-year survival rate in the US. Immune checkpoint inhibitors (ICIs) have shown promising results in prolonging survival in a subset of patients with recurrent or metastatic disease. However, challenges remain, particularly the limited efficacy of PD-1/PD-L1 blockade therapies. PD-L1 protein expression has been shown to be limited in its predictive power for ICI therapies. Emerging evidence shows that intricate characterisation of the tumour microenvironment (TME) is fundamental to understand interacting cells. This study aims to bridge the gap in understanding the tumor microenvironment by identifying distinct spatial patterns of PD-1/PD-L1 interactions and their association with immunotherapy responses in head and neck squamous cell carcinoma (HNSCC). Methods In this study, we sought to apply a more nuanced approach to understanding cellular interactions by mapping PD-1/PD-L1 interactions across whole-slide HNSCC tissue samples collected prior to ICI therapy. We used a combination of spatial proteomics (Akoya Biosciences) and an in situ proximity ligation assay (isPLA, Navinci Diagnostics) to visualise PD-1/PD-L1 interactions across cell types and cellular neighbourhoods within the tumour TME. Results Our findings indicate the existence of isPLA+ PD-1/PD-L1 interactions between macrophages/CD3 T cell-enriched neighbourhoods and tumour cells at the tumour-stroma boundaries in ICI-resistant tumours. The presence of these dense macrophage-tumour layers, which are either absent or dispersed in responders, indicates a barrier that may restrict immune cell infiltration and promote immune escape mechanisms. In contrast, responders had abundant B and T cell aggregates, predominantly around the tumour edges linked to enhanced immune responses to ICI therapy and better clinical outcomes. Conclusion This study highlights the utility of isPLA in detecting distinct tumour-immune interactions within the TME, offering new cellular interaction metrics for stratifying and optimising immunotherapy strategies.
Published: 2025
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5. Exploration of an SRSD Writing Strategy on Students' Written Expressions of Math Reasoning and Sensemaking

Author: Elizabeth M. Hughes, Paul J. Riccomini, Joo-Young Lee, Michelle J. Cook, and Kaleena A. Selfridge
Abstract: This exploratory study evaluated the effects of self-regulated strategy development (SRSD) on students' written expression when asked to solve a word problem and explain reasoning. A secondary question evaluated potential for differential effects based on determination of having mathematics difficulty (MD). We implemented a quasi-experimental design with 163 students with and without MD in grade 4. Results indicated that students in the treatment group (n = 83) significantly outperformed students in the comparison group (n = 80) on measures of mathematical writing involving subtraction and division word problems. For the subtraction problems, students in the treatment group improved their overall written expression of mathematics scores (g = 0.688), yielding a medium effect. The intervention differentially benefited students without MD. Our findings call for greater integration of systematic writing opportunities in mathematics and highlight the importance of explicitly teaching students how to approach the written expression of their mathematical reasoning.
Published: 2024
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6. Pediatric Mental Health Care and Scope-of-Practice Expansions

Author: Phillip M. Hughes, Genevieve Graaf, Kristin H. Gigli, Neal A. deJong, Robert E. McGrath, and Kathleen C. Thomas
Abstract: To examine the association between psychologist and nurse practitioner scope-of-practice (SoP) regulations and pediatric mental health service access. A nationally representative sample of children with mental health needs was identified using 5 years of National Survey of Children's Health (2016-2020). Utilization was measured in two ways: (1) unmet mental health care needs and (2) receipt of mental health medication. Expanded SoP for psychologists and nurse practitioners was measured based on the child's state of residence and the year of the survey. The associations between both SoP expansion and both outcomes were assessed using logistic regression models adjusted for multiple covariates. The probability of having unmet mental health needs was 5.4 percentage points lower (95% CI - 0.102, - 0.006) for children living in a state with psychologist SoP expansion; however, there was no significant difference in unmet mental health needs between states with and without NP SoP expansion. The probability of receiving a mental health medication was 2.0 percentage points higher (95% CI 0.007, 0.034) for children living in a state with psychologist SoP expansion. Conversely, the probability of receiving a mental health medication was 1.5 percentage points lower (95% CI - 0.023, - 0.007) for children living in a state with NP SoP expansion. Expanded SoP for psychologists is associated with improved access to pediatric mental health care in terms of both unmet need and receiving medication. Expanded SoP for NPs, however, was not associated with unmet need and lower receipt of medication.
Published: 2024
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7. Music, Muscle, and Masterful Arts: Black and Indigenous Performers of the Circus Age

Author: Sakina M. Hughes
Published: 2025

8. Revalidation of Proactive Gastrostomy Tube Placement Guidelines for Head and Neck Cancer Patients Receiving Helical Intensity-Modulated Radiotherapy

Author: Teresa E. Brown, Angela Byrnes, Aaron C. Chan, Kathleen Dwyer, Anna Edwards, Claire L. Blake, Merrilyn D. Banks, Brett G. M. Hughes, Charles Y. Lin, Lizbeth M. Kenny, Ann-Louise Spurgin, and Judith D. Bauer
Subjects: head and neck cancer, radiotherapy, gastrostomy, enteral feeding, nutrition, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: The Royal Brisbane and Women’s Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement. Data were collected on guideline adherence, gastrostomy tube insertions, the duration of enteral tube use and weight change. Sensitivity, specificity and positive predictive and negative predictive values were calculated and compared with the historical cohort. Overall guideline adherence was 84%, with 60% and 96% adherence to the high-risk and low-risk pathways, respectively. Seventy patients underwent proactive gastrostomy tube placement (n = 62 high-risk; n = 8 low-risk). Validation outcomes were sensitivity 73% (compared to 72%) and specificity 86% (compared to 96%). The guidelines yielded a high sensitivity and specificity, remaining valid in a cohort of patients treated with H-IMRT. Further studies are recommended to improve the sensitivity and understand the decrease in specificity in order to make ongoing guideline improvements.
Published: 2024
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9. Personalised antimicrobial susceptibility testing with clinical prediction modelling informs appropriate antibiotic use

Author: Alex Howard, David M. Hughes, Peter L. Green, Anoop Velluva, Alessandro Gerada, Simon Maskell, Iain E. Buchan, and William Hope
Subjects: Science
Abstract: Abstract Antimicrobial susceptibility testing is a key weapon against antimicrobial resistance. Diagnostic microbiology laboratories use one-size-fits-all testing approaches that are often imprecise, inefficient, and inequitable. Here, we report a personalised approach that adapts laboratory testing for urinary tract infection to maximise the number of appropriate treatment options for each patient. We develop and assess susceptibility prediction models for 12 antibiotics on real-world healthcare data using an individual-level simulation study. When combined with decision thresholds that prioritise selection of World Health Organisation Access category antibiotics (those least likely to induce antimicrobial resistance), the personalised approach delivers more susceptible results (results that encourage prescription of that antibiotic) per specimen for Access category antibiotics than a standard testing approach, without compromising provision of susceptible results overall. Here, we show that personalised antimicrobial susceptibility testing could help tackle antimicrobial resistance by safely providing more Access category antibiotic treatment options to clinicians managing urinary tract infection.
Published: 2024
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10. Can self-testing be enhanced to hasten safe return of healthcare workers in pandemics? Random order, open label trial using two manufacturers’ SARS-CoV-2 lateral flow devices concurrently and nested viral culture study

Author: Xingna Zhang, Christopher P. Cheyne, Christopher Jones, Michael Humann, Gary Leeming, Claire Smith, David M. Hughes, Girvan Burnside, Susanna Dodd, Rebekah Penrice-Randal, Xiaofeng Dong, Malcolm G. Semple, Tim Neal, Sarah Tunkel, Tom Fowler, Lance Turtle, Marta García-Fiñana, and Iain E. Buchan
Subjects: Covid-19, SARS-CoV-2, Lateral flow test, Healthcare worker, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Covid-19 healthcare worker testing, isolation and quarantine policies had to balance risks to patients from the virus and from staff absence. The emergence of the Omicron variant led to dangerous levels of key-worker absence globally. We evaluated whether using two manufacturers’ lateral flow tests (LFTs) concurrently improved SARS-CoV-2 Omicron detection significantly and was acceptable to hospital staff. In a nested study, to understand risks of return to work after a 5-day isolation/quarantine period, we examined virus culture 5–7 days after positive test or significant exposure. Methods Fully-vaccinated Liverpool (UK) University Hospitals staff participated (February-May 2022) in a random-order, open-label trial testing whether dual LFTs improved SARS-CoV-2 detection, and whether dual swabbing was acceptable to users. Participants used nose-throat swab Innova and nose-only swab Orient Gene LFTs in daily randomised order for 10 days. A user-experience questionnaire was administered on exit. Selected participants gave swabs for viral culture on days 5–7 after symptom onset or first positive test. Cultures were considered positive if cytopathic effect was apparent or SARS-CoV-2 N gene sub-genomic RNA was detected. Results Two hundred and twenty-six individuals reported 1466 pairs of LFT results. Tests disagreed in 127 cases (8.7%). Orient Gene was more likely (78 cf. 49; OR: 2.1, 1.1–4.1; P = 0.03) to be positive. If Innova was swabbed second, it was less likely to agree with a positive Orient Gene result (OR: 2.7, 1.3–5.2; P = 0.005); swabbing first with Innova made no significant difference (OR: 1.1, 0.5–2.3; P = 0.85). Orient Gene positive Innova negative result-pairs became more frequent over time (OR: 1.2, 1.1–1.3; P
Published: 2024
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11. Exploring dysfunctional barrier phenotypes associated with glaucoma using a human pluripotent stem cell-based model of the neurovascular unit

Author: Sailee S. Lavekar, Jason M. Hughes, Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Scott G. Canfield, and Jason S. Meyer
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Glaucoma is a neurodegenerative disease that results in the degeneration of retinal ganglion cells (RGCs) and subsequent loss of vision. While RGCs are the primary cell type affected in glaucoma, neighboring cell types selectively modulate RGCs to maintain overall homeostasis. Among these neighboring cell types, astrocytes, microvascular endothelial cells (MVECs), and pericytes coordinate with neurons to form the neurovascular unit that provides a physical barrier to limit the passage of toxic materials from the blood into neural tissue. Previous studies have demonstrated that these barrier properties may be compromised in the progression of glaucoma, yet mechanisms by which this happens have remained incompletely understood. Thus, the goals of this study were to adapt a human pluripotent stem cell (hPSC)-based model of the neurovascular unit to the study of barrier integrity relevant to glaucoma. To achieve this, hPSCs were differentiated into the cell types that contribute to this barrier, including RGCs, astrocytes, and MVECs, then assembled into an established Transwell®-insert model. The ability of these cell types to contribute to an in vitro barrier model was tested for their ability to recapitulate characteristic barrier properties. Results revealed that barrier properties of MVECs were enhanced when cultured in the presence of RGCs and astrocytes compared to MVECs cultured alone. Conversely, the versatility of this system to model aspects of barrier dysfunction relevant to glaucoma was tested using an hPSC line with a glaucoma-specific Optineurin (E50K) mutation as well as a paired isogenic control, where MVECs then exhibited reduced barrier integrity. To identify factors that could result in barrier dysfunction, results revealed an increased expression of TGFβ2 in glaucoma-associated OPTN(E50K) astrocytes, indicating a potential role for TGFβ2 in disease manifestation. To test this hypothesis, we explored the ability to modulate exogenous TGFβ2 in both isogenic control and OPTN(E50K) experimental conditions. Collectively, the results of this study indicated that the repurposing of this in vitro barrier model for glaucoma reliably mimicked some aspects of barrier dysfunction, and may serve as a platform for drug discovery, as well as a powerful in vitro model to test the consequences of barrier dysfunction upon RGCs in glaucoma.
Published: 2024
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12. Churning the tides of care: when nurse turnover makes waves in patient access to primary care

Author: Kelley Arredondo, Ashley M. Hughes, Houston F. Lester, Trang N.D. Pham, Laura A. Petersen, LeChauncy Woodard, Richard SoRelle, Cheng (Rebecca) Jiang, Frederick L. Oswald, Daniel R. Murphy, Hilary N. Touchett, Joshua Hamer, and Sylvia J. Hysong
Subjects: Registered nurses, RN, Staffing stability, Primary care teams, Patient aligned care teams, PACT, Nursing, RT1-120
Abstract: Abstract Background Team-based primary care (PC) enhances the quality of and access to health care. The Veterans Health Administration (VHA) implements team-based care through Patient Aligned Care Teams (PACTs), consisting of four core members: a primary care provider, registered nurse (RN) care manager, licensed vocational nurse, and scheduling clerk. RNs play a central role: they coordinate patient care, manage operational needs, and serve as a patient point of contact. Currently, it is not known how varying levels of RN staffing on primary care teams impact patient outcomes. Objective This study aims to empirically assess how the stability of RN staffing within team-based primary care affects patient access to care. Methods A retrospective database review using clinical and administrative data from the VHA over 24 months. Participants included 5,897 PC PACTs across 152 VHA healthcare facilities in the United States and its territories. The stability of personnel in the RN role was categorized as: RN continuous churn, RN staffing instability and RN vacancy. All 3 categories were compared to teams with RN stability (i.e., same person in the role for the entire 24-month period). Access measures included: average third-next-available appointment, established patient average wait time in days, urgent care utilization, emergency room utilization, and total inbound-to-outbound PC secure messages ratio. Results RN continuous churn within PACTs had a significant impact on third-next-available appointment (b = 3.70, p
Published: 2024
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13. Defining, Measuring, and Teaching Mathematical Flexibility: A Content Analysis of Extant Research

Author: Sarah K. Cox, Matthew K. Burns, Elizabeth M. Hughes, Taryn Wade, and Michelle Brown
Abstract: Mathematical flexibility is thought to be a critical component of mathematical proficiency, and the term "mathematical flexibility" has been used by teachers, researchers, and policy makers for more than 2 decades. Although there seems to be consensus on the importance of mathematical flexibility as a construct, the way it is defined and described is inconsistent. Without a clear and consistent definition of mathematical flexibility, it is impossible to develop accurate measures of the construct or to improve instructional strategies to promote its use. Therefore, this systematic literature review examines the way mathematical flexibility has been defined, taught, and measured. Using a combination of descriptive statistics and qualitative content analysis, articles were coded for themes around definitions, instruction, and measurement. Finally, we looked at connectivity between authorship to examine relationships between citations of how mathematical flexibility was defined.
Published: 2024
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14. Parental Education and Children's Depression, Anxiety, and ADHD Traits, a Within-Family Study in MoBa

Author: Amanda M. Hughes, Fartein Ask Torvik, Elsje van Bergen, Laurie J. Hannigan, Elizabeth C. Corfield, Ole A. Andreassen, Eivind Ystrom, Helga Ask, George Davey Smith, Neil M. Davies, and Alexandra Havdahl
Abstract: Children born to parents with fewer years of education are more likely to have depression, anxiety, and attention-deficit hyperactivity disorder (ADHD), but it is unclear to what extent these associations are causal. We estimated the effect of parents' educational attainment on children's depressive, anxiety, and ADHD traits at age 8 years, in a sample of 40,879 Norwegian children born in 1998-2009 and their parents. We used within-family Mendelian randomization, which employs genetic variants as instrumental variables, and controlled for direct genetic effects by adjusting for children's polygenic indexes. We found little evidence that mothers' or fathers' educational attainment independently affected children's depressive, anxiety, or ADHD traits. However, children's own polygenic scores for educational attainment were independently and negatively associated with these traits. Results suggest that differences in these traits according to parents' education may reflect direct genetic effects more than genetic nurture. Consequences of social disadvantage for children's mental health may however be more visible in samples with more socioeconomic variation, or contexts with larger socioeconomic disparities than present-day Norway. Further research is required in populations with more educational and economic inequality and in other age groups.
Published: 2024
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15. Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trialResearch in context

Author: O. Abani, A. Abbas, F. Abbas, J. Abbas, K. Abbas, M. Abbas, S. Abbasi, H. Abbass, A. Abbott, N. Abdallah, A. Abdelaziz, M. Abdelfattah, B. Abdelqader, A. Abdul, B. Abdul, S. Abdul, A. Abdul Rasheed, A. Abdulakeem, R. Abdul-Kadir, A. Abdullah, A. Abdulmumeen, R. Abdul-Raheem, N. Abdulshukkoor, K. Abdusamad, Y. Abed El Khaleq, M. Abedalla, A. Abeer Ul Amna, L. Abel, K. Abernethy, M. Abeywickrema, C. Abhinaya, A. Abidin, A. Aboaba, A. Aboagye-Odei, C. Aboah, H. Aboelela, H. Abo-Leyah, K. Abouelela, A. Abou-Haggar, M. Abouibrahim, A. Abousamra, M. Abouzaid, M. Abraham, T. Abraham, A. Abraheem, J. Abrams, R. Abrams, H.J. Abu, A. Abu-Arafeh, S.M. Abubacker, A. Abung, Y. Abusamra, Y. Aceampong, A. Achara, D. Acharya, F. Acheampong, P. Acheampong, S. Acheampong, J. Acheson, S. Achieng, A. Acosta, R. Acquah, C. Acton, J. Adabie-Ankrah, P. Adair, A.S. Adam, F. Adam, M. Adam, H. Adamali, M. Adamczyk, C. Adams, D. Adams, K. Adams, L. Adams, N. Adams, R. Adams, T. Adams, L. Adamu-Ikeme, K. Adatia, K. Adcock, L. Addai-Boampong, A. Addo, O. Adeagbo, A. Adebiyi, O. Adedeji, Y. Adegeye, K. Adegoke, V. Adell, S. Adenwalla, F.W. Adeoye, O.A. Adesemoye, E.O. Adewunmi, A. Adeyanju, J. Adeyemi, T. Adeyemo, B. Adhikari, S.A. Adhikari, R. Adhikary, A. Aditya, P. Adjepong, G. Adkins, A. Adnan, M. Adriaanse, J. Aeron-Thomas, D. Affleck, C. Afnan, M. Afridi, P. Afrim, F.A. Afriyie, Z.A. Aftab, A. Afum-Adjei Awuah, M. Agarwal, P.N. Agasiya, R. Agbeko, C. Agbo, S. Aggarwal, A. Aghababaie, L. Aguilar Jimenez, J.A. Agyekum, K. Agyen, E.K. Ahadome, S. Ahamed Sadiq, M.H. Ahammed Nazeer, M. Ahmad, S. Ahmad, A. Ahmed, B.A.R. Ahmed, B. Ahmed, F. Ahmed, H. Ahmed, I. Ahmed, K. Ahmed, L. Ahmed, M. Ahmed, M.C. Ahmed, M.S. Ahmed, N. Ahmed, O. Ahmed, R.A. Ahmed, R. Ahmed, S. Ahmed, S.G. Ahmed, S.H. Ahmed, R. Ahmed Ali, B. Ahmed Mohamud, S. Ahmer, A. Ahonia, C. Aidoo, C. Aiken, D. Ail, M. Ainsworth, M. Aissa, L. Aitken, B. Ajay, A. Ajibode, A. Ajmi, N. Akhtar, S. Akili, B. Akinbiyi, O. Akindolie, Y. Akinfenwa, O. Akinkugbe, I. Akinpelu, M. Akram, O. Aktinade, U. Akudi, A.S.A.R. Al Aaraj, A. Al Balushi, M. Al Dakhola, A. Al Swaifi, E. Al-Abadi, A. Alabi, N. Aladangady, M. Alafifi, A. Alam, S. Alam, A. Al-Asadi, K. Alatzoglou, P. Albert, A. Albertus, L. Albon, A. Alcala, G. Alcorn, S. Alcorn, A. Aldana, D. Alderdice, A. Aldesouki, R. Aldouri, J. Aldridge, N. Aldridge, R. Ale, R.M. Ale, A. Alegria, A. Alexander, C. Alexander, J. Alexander, P.D.G. Alexander, J. Al-fori, L. Alghazawi, O. Alhabsha, B. Al-Hakim, R. Alhameed, M. Al-Hayali, S. Al-Hity, A. Ali, F.R. Ali, J. Ali, M. Ali, M.S. Ali, N. Ali, O. Ali, R. Ali, S. Ali, E. Aliberti, J. Alin, A. Alina, A. Alipustain, B. Alisjahbana, F. Aliyuda, K. Alizadeh, M. Al-Jibury, S. Al-Juboori, M. Al-Khalil, A. Alkhudhayri, M. Alkhusheh, F. Allan, N. Allan, A. Allanson, R. Allcock, E. Allen, J. Allen, K. Allen, L. Allen, P. Allen, R. Allen, S. Allen, T. Allen, A. Alli, K. Allison, B. Allman, H.K. Allsop, L. Allsop, D. Allsup, A.F.T. Almahroos, H. Al-Moasseb, M. Al-Obaidi, L. Alomari, A. Al-Rabahi, B. Al-Ramadhani, Z. Al-Saadi, R. Al-Sammarraie, I. Alshaer, R. Al-Shahi Salman, W. Al-Shamkhani, F. Alsheikh, B. Al-Sheklly, S. Altaf, A. Alty, M. Alvarez, M. Alvarez Corral, E. Alveyn, M. Alzetani, S. Amamou, N. Amar, S. Ambalavanan, R. Ambrogetti, C. Ambrose, A. Ameen, A. Amelia Ganefianty, K. Ames, M.R. Amezaga, A. Amin, K. Amin, S. Amin, T. Amin, B. Amit, A. Amjad, N. Amjad, J. Amoah-Dankwa, A. Amoako-Adusei, V. Amosun, M. Amsal, K. Amsha, J. Amuasi, N. Amutio Martin, P. Amy, A. Anada, A. Anand, S. Anandappa, S.D. Anantapatnaikuni, N.K.N. Andari, E. Anderson, J. Anderson, L. Anderson, M. Anderson, N. Anderson, R. Anderson, S. Anderson, W. Anderson, P. Andreou, A. Andrews, J. Andrews, K. Aneke, A. Ang, W.W. Ang, T. Angel, A. Angela, P. Angelini, L. Anguvaa, O. Anichtchik, M. Anim-Somuah, K. Aniruddhan, J. Annett, L. Anning, M. Ansah, P.J. Anstey, R. Anstey, A. Anthony, A. Anthony-Pillai, P. Antill, Z. Antonina, V. Anu, M. Anwar, S. Anwar, E. Apetri, A. Apostolopoulos, S. Appleby, D. Appleyard, M.F. Aquino, B. Araba, S. Aransiola, M. Araujo, A. Archer, D. Archer, S. Archer, D. Arcoria, C. Ardley, G. Arhin-Sam, A.-M. Arias, O. Aribike, R. Arimoto, N.L.P.E. Arisanti, C. Arkley, C. Armah, I. Armata, J. Armistead, A. Armitage, C. Armstrong, M. Armstrong, S. Armstrong, W. Armstrong, P. Armtrong, H. Arndt, C. Arnison-Newgass, D. Arnold, R. Arnold, A. Arnott, D. Arora, K. Arora, P. Arora, R. Arora, A. Arter, A. Arthur, N.M. Artini, A. Arumaithurai, A. Arya, R. Arya, D. Aryal, D. Asandei, G.A. Asare, A. Asghar, M. Asghar, A. Ashab, C. Ashbrook-Raby, H. Ashby, J. Ashcroft, S. Ashcroft, G. Asher, Z. Ashfak, A. Ashfaq, H.A. Asiamah, A. Ashish, D. Ashley, S. Ashman-Flavell, S. Ashok, A.-E.-A. Ashour, M.Z. Ashraf, S. Ashraf, M.B. Ashraq, D. Ashton, S. Ashton, A. Ashworth, F.J. Ashworth, R. Ashworth, A. Aslam, I. Aslam, S. Aslam, L. Aslett, H. Asogan, A. Asrar, O. Assaf, R. Astin-Chamberlain, Y.E. Atabudzi, P. Athavale, D. Athorne, B. Atkins, C. Atkins, S. Atkins, J. Atkinson, V. Atkinson, A. Atomode, B. Atraskiewicz, A.A. Attia, E. Attubato, M. Attwood, P. Aubrey, Z. Auer, A. Aujayeb, A.T. Aung, H. Aung, H.W.W. Aung, K.K. Aung, K.T. Aung, N. Aung, Y. Aung, Z.M. Aung, E. Austin, K. Austin, A. Auwal, M. Avari, M. Avery, N. Aveyard, J. Avis, G. Aviss, C. Avram, P. Avram, A. Awadelkareem, G. Awadzi, M. Awaly, A. Awan, S. Awisi, A. Aya, E. Ayaz, J.M. Ayerh, A. Ayers, J. Azam, A. Azeem, M. Azharuddin, A. Aziz, G. Aziz, I. Aziz, N. Aziz, A. Azkoul, A. Azman Shah, G. Azzopardi, H. Azzoug, F. Babatunde, M. Babi, B. Babiker, G. Babington, M. Babirecki, M. Babores, A.O. Babs-Osibodu, T. Bac, S. Bacciarelli, R. Bachar, M.-E. Bachour, A. Bachti, G. Bacon, J. Bacon, B. Badal, A. Badat, M. Bader, G.R. Badhan, S. Badhrinarayanan, J.P. Bae, A. Baggaley, A. Baggott, G. Bagley, D. Bagmane, L. Bagshaw, K. Bahadori, Y. Bahurupi, A. Bailey, J. Bailey, K. Bailey, L. Bailey, M.A. Bailey, M. 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Vass, K. Vassell, V. Vasu, V. Vasudevan, M. Vatish, S. Vaughan, H. Vayalaman, D. Vayapooree, C. Vaz, N. Veale, S. Veerasamy, S. Velankar, L. Velauthar, N. Veli, N. Vella, A. Velugupati, A. Velusamy, I. Venables, M. Venditti, R. Venkataramakrishnan, R. Venn, M. Venter, L. Ventilacion, J. Vere, M. Veres, S. Vergnano, W. Verling, A. Verma, R. Vernall, B. Vernon, M. Vertue, L. Verueco, J. Verula, A. Veterini, N. Vethanayagam, S. Vettikumaran, L. Veys, C. Vickers, S. Victor, S. Victoria, C. Vidaillic, C.P. Vidaillac, J. Vidler, B. Vijayakumar, V.W. Vijayaraghavan Nalini, B. Vilcinskaite, A. Vileito, N. Vilimiene, L. Vinall, S. Vinay, L. Vinayakarao, O. Vincent, R. Vincent, N.Q. Vinh, P. Virdee, E. Virgilio, A.M. Virk, E. Visentin, M. Vitaglione, K. Vithian, S. Vittoria, S. Vivekananthan, E. Vlad, B. Vlies, L. von Oven, C. Vooght, K.T. Vu Thai, K. Vutipongsatorn, A. Vuylsteke, E. Vyras, R. Wach, B. Wadams, S. Wadd, N. Waddington, P. Wade, J. Wadsley, K. Wadsworth, S.E.I. Wafa, D. Wagstaff, L. Wagstaff, D. Wahab, Z. Wahbi, A. Waheed Adigun, S. Waidyanatha, A. Waite, R. Wake, A. Wakefield, W. Wakeford, F. Wakinshaw, E. Waldeck, A. Walden, L. Walding, A. Waldron, J. Waldron, E. Wales, B. Wali, D. Walker, G. Walker, H. Walker, I. Walker, K. Walker, L. Walker, O. Walker, R. Walker, S. Walker, G. Wallace, R. Wallbutton, J. Wallen, K. Wallendszus, A. Waller, R. Waller, G. Wallis, L. Wallis, M. Wallis, E. Walmsley, D. Walsh, E. Walsh, L. Walsh, D. Walstow, D. Walter, A. Walters, H. Walters, J. Walters, E. Walton, L. Walton, M. Walton, O. Walton, S. Walton, M. Wan, J. Wanda, M. Wands, R. Wane, F. Wang, N. Wang, R. Wang, S. Wang, D. Warbrick, S. Warburton, C. Ward, D. Ward, E. Ward, H. Ward, J. Ward, L. Ward, N. Ward, R. Ward, T. Ward, S.A. Warden, G. Wardere, S. Wardle, H. Wardy, G. Waring, S. Waring, J. Warmington, B. Warner, C. Warner, L. Warnock, S. Warran, J. Warren, L. Warren, R. Warren, Y. Warren, D. Warrender, H. Warren-Miell, A. Warris, G. Warwick, H. Wassall, S. Wasserman, E. Wasson, H.J. Watchorn, H. Waterfall, A. Waters, D. Waters, M. Waterstone, A. Watkin, C. Watkins, E. Watkins, K. Watkins, L. Watkins, A. Watson, A.J.R. Watson, E. Watson, F. Watson, J.G.R. Watson, L. Watson, P. Watson, R. Watson, K. Watson, M. Watters, D. Watterson, K. Wattimena, D. Watts, J. Watts, M. Watts, V. Waugh, E. Wayman, M. Wayman, A. Wazir, M. Weatherhead, N. Weatherly, C. Webb, H. Webb, K. Webb, S. Webb, C. Websdale, D. Webster, I. Webster, J. Webster, T. Webster, J. Wedlin, L. Wee, R. Weerakoon, T. Weerasinghe, J. Weeratunga, M. Weetman, S. Wei, I. Weichert, E. Welch, H. Welch, J. Welch, L. Welch, S. Welch, B. Welham, S. Weller, L. Wellings, B. Wells, S. Wellstead, B. Welsh, R. Welsh, I. Welters, R. Welton, V. Wenn, L. Wentworth, J. Wesonga, K. Wesseldine, J. West, M. West, R. West, S. West, L. Western, R. Westhead, H. Weston, A. Westwood, K. Westwood, S. Westwood, B. Wetherill, S. Wheaver, H. Wheeler, B. Whelan, M. Whelband, A. Whileman, A. Whitcher, A. White, B. White, C. White, D. White, J. White, K. White, M. White, N. White, S. White, T. White, C. Whitehead, K. Whitehorn, A. Whitehouse, C. Whitehouse, T. Whitehouse, J. Whiteley, L. Whiteley, S. Whiteley, R. Whitham, G. Whitlingum, D. Whitmore, E. Whittaker, L. Whittam, A. Whittington, H. Whittle, R. Whittle, E. Wiafe, L. Wiblin, O. Wickens, J. Widdrington, J. Wieboldt, H. Wieringa, C. Wiesender, L. Wiffen, A. Wight, A. Wignall, C. Wignall, A. Wilce, D. Wilcock, E. Wilcock, L. Wilcox, B. Wild, L. Wild, S. Wild, M. Wilde, L. Wilding, P. Wilding, T. Wildsmith, J. Wileman, J. Wiles, K. Wiles, E. Wilhelmsen, T. Wiliams, J. Wilkie, D. Wilkin, H. Wilkins, J. Wilkins, S. Wilkins, I. Wilkinson, L. Wilkinson, N. Wilkinson, S. Wilkinson, T. Wilkinson, S. Willetts, A. Williams, C. Williams, C.V. Williams, D. Williams, E. Williams, G. Williams, H. Williams, J. Williams, K. Williams, M. Williams, P. Williams, R. Williams, S. Williams, T. Williams, A. Williamson, C. Williamson, D. Williamson, J. Williamson, J.D. Williamson, R. Williamson, H. Williamson, E. Willis, H. Willis, J. Willis, L. Wills, L. Willsher, C. Willshire, F. Willson, J. Willson, A. Wilson, B. Wilson, D. Wilson, I. Wilson, J. Wilson, K. Wilson, K.-A. Wilson, L. Wilson, M. Wilson, S. Wilson, T. Wilson, K.L.Y. Win, M. Win, T. Win, T.T. Win, W.Y.W. Win, L. Winckworth, L. Winder, P. Winder, S. Winearl, H. Winmill, S. Winn, C. Winpenny, H. Winslow, H. Winter, J. Winter, B. Winter-Goodwin, J. Winterton, H. Winwood, J. Wischhusen, S. Wisdom, M. Wise, M. Wiselka, R. Wiseman, S. Wiseman, S. Wishart, T. WIshlade, E. Witele, N. Withers, J. Wittes, D. Wixted, T. Wodehouse, W. Wolf, N. Wolff, K. Wolffsohn, R. Wolf-Roberts, E. Wolodimeroff, A. Wolstencroft, A. Wong, C. Wong, C.-H. Wong, C.-M. Wong, E. Wong, J.S.Y. Wong, K.Y. Wong, M.Y. Wong, N. Wong, S. Wong, T. Wong, A.A. Wongkyezeng, A. Wood, C. Wood, D. Wood, F. Wood, G. Wood, H. Wood, J. Wood, L. Wood, M. Wood, S. Wood, T. Wood, K. Woodall, R. Woodfield, C. Woodford, E. Woodford, J. Woodford, L. Woodhead, T. Woodhead, P. Woodland, M. Woodman, S. Woodmansey, C. Woods, J. Woods, K. Woods, S. Woods, Z. Woodward, M. Woolcock, G. Wooldridge, R. Woolf, C. Woollard, L. Woollen, E. Woolley, J. Woolley, D. Woosey, D. Wootton, J. Wootton, D. Worley, S. Worton, J. Wraight, M. Wray, K. Wren, L. Wren, C. Wrey Brown, C. Wright, D. Wright, F. Wright, H. Wright, I. Wright, L. Wright, R. Wright, S. Wright, T. Wright, C. Wroe, H. Wroe, H. Wu, P. Wu, J. Wubetu, F. Wulandari, R. Wulandari, S. Wurie, C. Wyatt, F. Wyn-Griffiths, I. Wynter, B. Xavier, A. Xhikola, B.E. Xia, Z. Xia, E. Yacoba, S. Yadav, M. Yakubi, M. Yan, Y. Yanagisawa, F. Yang, Y. Yang, M. Yanney, W.L. Yap, N. Yaqoob, S. Yasmin, B. Yates, D. Yates, E. Yates, H. Yates, T. Yates, M. Yates, J. Ye, C. Yearwood Martin, K. Yein, F. Yelnoorkar, L. Yen, L.M. Yen, A. Yeoh, C.Y. Yeung, P. Yew, D. Yewatkar, L. Ylquimiche Melly, I. Ynter, H. Yong, J. Yorke, J. Youens, A. Younes Ibrahim, E. Young, G. Young, L. Young, A. Yousafzar, S. Youssouf, A. Yousuf, H. Yovita, C. Yu, J.S.J. Yuan, N. Yufaniaputri, B. Yung, D. Yusef, S. Yusef, I. Yusuf, A.-S. Zafar, S. Zagalo, S. Zaher, A. Zahoor, M. Zainab, T. Zak, K. Zaki, N. Zakir, K. Zalewska, A. Zamalloa, M. Zaman, S. Zaman, J. Zamikula, L. Zammit, M. Zammit-Mangion, M. Zawadzka, M. Zayed, E. Zebracki, D. Zehnder, L. Zeidan, D. Zeinali, J. Zhang, X. Zhao, D. Zheng, D. Zhu, M. Zia, O. Zibdeh, R. Zill-E-Huma, E.T. Zin, E. Zincone, G. Zindoga, E. Zinkin, V. Zinyemba, C. Zipitis, L. Zitter, A. Zmierczak, G. Zubikarai, A. Zubir, N. Zuhra, R. Zulaikha, S. Zulfikar, C. Zullo, and A. Zuriaga-Alvaro
Subjects: COVID-19, Corticosteroid, Dexamethasone, Mortality, Clinical trial, Medicine (General), R5-920
Abstract: Summary: Background: Low dose corticosteroids (e.g., 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with clinical hypoxia but not receiving ventilatory support (the combination of non-invasive mechanical ventilation, including high-flow nasal oxygen, continuous positive airway pressure and bilevel positive airway pressure ventilation, and invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain. Methods: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) assessed multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients receiving ventilatory support were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. Recruitment closed on 31 March 2024 when funding for the trial ended. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 25 May 2021 and 9 January 2024, 477 COVID-19 patients receiving ventilatory support were randomly allocated to receive usual care plus higher dose corticosteroids vs. usual care alone (of whom 99% received corticosteroids during the follow-up period). Of those randomised, 221 (46%) were in Asia, 245 (51%) in the UK and 11 (2%) in Africa. 143 (30%) had diabetes mellitus. Overall, 86 (35%) of 246 patients allocated to higher dose corticosteroids vs. 86 (37%) of 231 patients allocated to usual care died within 28 days (rate ratio [RR] 0.87; 95% CI 0.64–1.18; p = 0.37). There was no significant difference in the proportion of patients discharged from hospital alive within 28 days (128 [52%] in the higher dose corticosteroids group vs. 120 [52%] in the usual care group; RR 1.04, 0.81–1.33]; p = 0.78). Among those not on invasive mechanical ventilation at baseline, there was no clear reduction in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (76 [37%] of 206 vs. 93 [45%] of 205; RR 0.79 [95% CI 0.63–1.00]; p = 0.05). Interpretation: In patients hospitalised for COVID-19 receiving ventilatory support, we found no evidence that higher dose corticosteroids reduced the risk of death compared to usual care, which included low dose corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute for Health Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).
Published: 2025
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16. Kidney Function and Incident Stroke and Dementia Using an Updated Estimated Glomerular Filtration Rate Equation Without Race: The Multi-Ethnic Study of Atherosclerosis

Author: Samuel R. Moen, Jeffrey R. Misialek, Timothy M. Hughes, Craig W. Johnson, Mark J. Sarnak, Sarah N. Forrester, W.T. Longstreth, Jr., Mercedes R. Carnethon, James S. Pankow, and Sanaz Sedaghat
Subjects: Dementia, glomerular filtration rate, kidney, longitudinal, stroke, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Rationale & Objective: Equations for estimated glomerular filtration rate (eGFR) have previously included a coefficient for African American race. We evaluated and compared risk of incident stroke and dementia between old and new equations of eGFR for African American and non-African American participants. Study Design: Prospective observational study. Setting & Participants: Baseline values were collected from 6,814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort between 2000 and 2002. Participants were followed up until 2018. The analytic sample consisted of 6,646 participants (mean [SD] age 62 [10] years; 53% female; 39% White, 27% African American, 12% Chinese American, and 22% Hispanic/Latino). Exposure: eGFR equation from 2021 based on serum creatinine and cystatin C levels without race. Outcome: Incident stroke and dementia. Analytical Approach: Cox proportional regression adjusting for demographic, lifestyle, and clinical variables was performed to estimate associations between different eGFR measures and risk of incident stroke and dementia. Results: During a median follow-up period of 17 years, 349 (5.3%) participants experienced an incident stroke event, and 574 (8.6%) participants experienced incident dementia. In the fully adjusted model, overall participants with eGFR 90 mL/min/1.73 m2 were at significantly increased risk of dementia (HR, 95% CI: 1.73, 1.21-2.45). A lower eGFR was not significantly associated with incident stroke (1.30, 0.75-2.24). African American participants tended to be reclassified to a lower group of eGFR in the new equations, whereas non-African American participants were reclassified to a higher group of eGFR. When comparing older versus newer equations of eGFR in African American and non-African American participants in association with incident stroke and dementia, differences were minimal. Limitations: Incident dementia was ascertained through International Classification of Diseases (Ninth and Tenth Revisions) codes. Conclusions: Our findings illustrate participants with 2021 eGFR 90 mL/min/1.73 m2 have higher risk of dementia in both African American and non-African American participants, but not of stroke. Plain Language Summary: Existing research has established that declined kidney function is associated with stroke and dementia. Kidney function is commonly estimated using inputs of blood proteins alongside demographic inputs of age, sex at birth, and race. Inclusion of race to estimate kidney function has gained increased scrutiny given its problematic nature of being a societal construct rather than an inherent biological trait that affects function of the kidneys. Recommendations were recently made to remove race from this estimation, and data were lacking on the relationship between new estimates of kidney function with outcomes such as stroke and dementia. Our research provides updated risk estimates for stroke and dementia using the new estimation for kidney function in a large multiethnic cohort.
Published: 2025
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17. Forecasting Asparaginase Need and Cost for Childhood Cancer Using ACCESS FORxECAST

Author: Terence M. Hughes, Nitin Shrivastava, Lewis B. Silverman, A. Lindsay Frazier, Sumit Gupta, and Avram Denburg
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: PURPOSEAsparaginase (ASN) is a critical component of pediatric ALL protocols. Until recently, ASN was available in three formulations: native Escherichia coli, PEGylated E. coli (PEG), and Erwinase, with native E. coli typically more accessible in low- and middle-income countries (LMICs). Short shelf lives, intermittent availability, and concern for substandard formulations in LMICs have created a need for proactive ASN demand estimates.METHODSWe adapted FORxECAST, a pediatric cancer drug forecasting model, to focus on ASN for pediatric ALL. The model is adaptable to user data and defaults to best available public data where local data are unavailable. We forecast ASN quantity and cost in three case study countries for four scenarios using two regimens—base regimen (BR) and intensified regimen (IR)—outlining how quantity and costs vary on the basis of ASN formulation, dose, and second-line availability.RESULTSNative E. coli is cheaper than PEG for first-line treatment across all scenarios. Regimen intensification from BR to IR requires a substantially higher cost when PEG is used relative to native E. coli. The cost of treating ASN hypersensitivity with Erwinase for BR in Burundi, Ghana, and Turkmenistan is $19,660 in US dollars (USD), $24,800 USD, and $15,246 USD, respectively.CONCLUSIONTreatment intensification requires a cost increase that should be accessible for most LMICs, but PEG utilization is substantially more costly, suggesting that prioritizing investment in intensifying treatment using native E. coli is the least costly approach to maximize treatment availability. Cost savings associated with native E. coli utilization may liberate funds for Erwinase procurement for patients with ASN hypersensitivity. Future analyses needed include an evaluation of costs associated with preventing abandonment due to compliance complexity with native E. coli given increased administration frequency compared with PEG.
Published: 2025
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18. Striving for consistency in a national lake assessment: Defining reference status and littoral macroinvertebrate condition in lakes across the conterminous United States

Author: Richard M. Mitchell, Alan T. Herlihy, and Robert M. Hughes
Subjects: Ecology, QH540-549.5
Abstract: Benthic macroinvertebrates are widely used for assessing lotic ecosystems, however, their use in assessing lake condition has been more limited—especially at large, continental extents. We used data collected during the U.S. EPA’s National Lake Assessment between 2007–2022 to develop and validate a national macroinvertebrate multi-metric index (MMI) of lake condition across the conterminous U.S. As part of that process, we identified least-disturbed ecoregional reference lakes by filtering all sampled lakes by using specific physical, chemical, and disturbance variables to remove disturbed lakes. To account for natural variability, different criteria values were used for each of the nine national ecoregions. This allowed for a regionally explicit and reproducible definitions of lake reference condition for current and future analyses. Because of insufficient reference lake numbers in some of the nine ecoregions, macroinvertebrate MMI development was done independently for each of five aggregate national ecoregions. All 126 candidate macroinvertebrate metrics were screened for reproducibility, responsiveness, and redundancy to identify the best metric in each of six group types: composition, diversity, feeding group, habit, richness, and pollution tolerance for each ecoregion. The six chosen metrics were summed to calculate the MMI. Condition benchmarks (good/fair/poor) for assessing biological condition were defined for each ecoregion based on reference lake MMI percentiles. Using these five MMIs with the 2022 survey data, an estimated 44% of the lakes were in good condition, whereas 27% were in poor condition. Our MMIs offer managers valuable tools for assessing lakes at large ecoregional and continental extents.
Published: 2025
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19. A qualitative interview study of care home managers’ experiences of medicines optimisation for residents with dementia during the COVID-19 pandemic

Author: Carmel M Hughes, Heather E Barry, and Nawaf Alsulami
Subjects: Medicine
Abstract: Objectives To explore care home managers’ views and experiences of optimising medicines use for residents with dementia during the COVID-19 pandemic.Design, setting and participants A descriptive exploratory qualitative study using semistructured interviews (conducted via telephone or online videoconferencing platform), with care home managers across Northern Ireland, purposively sampled from care homes that provided care for residents with dementia. Care home managers were asked to describe their experiences of accessing primary healthcare services (such as those provided by general practitioners and community pharmacists), how medicines use by residents with dementia was affected by the pandemic, and what they had learnt from their experiences. Data were analysed using inductive thematic analysis.Results Fourteen interviews were conducted between January and July 2022. Four themes, ‘isolation’, ‘burden’, ‘disruption’ and ‘connection and communication’, were identified; isolation was a cross-cutting theme that permeated the other themes. Care home managers described feeling isolated from healthcare professionals, healthcare services and residents’ family members. This isolation placed additional burden on care home staff and residents with dementia by increasing staff workload and negatively affecting residents’ well-being. Participants reported that disruption to primary healthcare service provision, particularly services provided by general practices, had significant impact on residents with dementia. Participants described a lack of face-to-face contact with healthcare professionals, and medication reviews often ceased to take place. The connection and communication between key stakeholders were perceived to be important when optimising medicines for residents with dementia.Conclusions This study has highlighted the challenges and initial impact of the COVID-19 pandemic on medicines optimisation for care home residents with dementia, which was characterised by isolation. Further research is needed to determine the extent of the long-term impact of the COVID-19 pandemic on this resident population. In future public health crises, better communication is needed between healthcare professionals and care homes.
Published: 2025
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20. The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

Author: Ann M. Mc Cartney, Giulio Formenti, Alice Mouton, Diego De Panis, Luísa S. Marins, Henrique G. Leitão, Genevieve Diedericks, Joseph Kirangwa, Marco Morselli, Judit Salces-Ortiz, Nuria Escudero, Alessio Iannucci, Chiara Natali, Hannes Svardal, Rosa Fernández, Tim De Pooter, Geert Joris, Mojca Strazisar, Jonathan M. D. Wood, Katie E. Herron, Ole Seehausen, Phillip C. Watts, Felix Shaw, Robert P. Davey, Alice Minotto, José M. Fernández, Astrid Böhne, Carla Alegria, Tyler Alioto, Paulo C. Alves, Isabel R. Amorim, Jean-Marc Aury, Niclas Backstrom, Petr Baldrian, Laima Baltrunaite, Endre Barta, Bertrand BedHom, Caroline Belser, Johannes Bergsten, Laurie Bertrand, Helena Bilandija, Mahesh Binzer-Panchal, Iliana Bista, Mark Blaxter, Paulo A. V. Borges, Guilherme Borges Dias, Mirte Bosse, Tom Brown, Rémy Bruggmann, Elena Buena-Atienza, Josephine Burgin, Elena Buzan, Alessia Cariani, Nicolas Casadei, Matteo Chiara, Sergio Chozas, Fedor Čiampor, Angelica Crottini, Corinne Cruaud, Fernando Cruz, Love Dalen, Alessio De Biase, Javier del Campo, Teo Delic, Alice B. Dennis, Martijn F. L. Derks, Maria Angela Diroma, Mihajla Djan, Simone Duprat, Klara Eleftheriadi, Philine G. D. Feulner, Jean-François Flot, Giobbe Forni, Bruno Fosso, Pascal Fournier, Christine Fournier-Chambrillon, Toni Gabaldon, Shilpa Garg, Carmela Gissi, Luca Giupponi, Jessica Gomez-Garrido, Josefa González, Miguel L. Grilo, Björn Grüning, Thomas Guerin, Nadege Guiglielmoni, Marta Gut, Marcel P. Haesler, Christoph Hahn, Balint Halpern, Peter W. Harrison, Julia Heintz, Maris Hindrikson, Jacob Höglund, Kerstin Howe, Graham M. Hughes, Benjamin Istace, Mark J. Cock, Franc Janžekovič, Zophonias O. Jonsson, Sagane Joye-Dind, Janne J. Koskimäki, Boris Krystufek, Justyna Kubacka, Heiner Kuhl, Szilvia Kusza, Karine Labadie, Meri Lähteenaro, Henrik Lantz, Anton Lavrinienko, Lucas Leclère, Ricardo Jorge Lopes, Ole Madsen, Ghislaine Magdelenat, Giulia Magoga, Tereza Manousaki, Tapio Mappes, Joao Pedro Marques, Gemma I. Martinez Redondo, Florian Maumus, Shane A. McCarthy, Hendrik-Jan Megens, Jose Melo-Ferreira, Sofia L. Mendes, Matteo Montagna, Joao Moreno, Mai-Britt Mosbech, Mónica Moura, Zuzana Musilova, Eugene Myers, Will J. Nash, Alexander Nater, Pamela Nicholson, Manuel Niell, Reindert Nijland, Benjamin Noel, Karin Noren, Pedro H. Oliveira, Remi-Andre Olsen, Lino Ometto, Rebekah A. Oomen, Stephan Ossowski, Vaidas Palinauskas, Snaebjorn Palsson, Jerome P. Panibe, Joana Pauperio, Martina Pavlek, Emilie Payen, Julia Pawlowska, Jaume Pellicer, Graziano Pesole, Joao Pimenta, Martin Pippel, Anna Maria Pirttilä, Nikos Poulakakis, Jeena Rajan, Rúben M.C. Rego, Roberto Resendes, Philipp Resl, Ana Riesgo, Patrik Rodin-Morch, Andre E. R. Soares, Carlos Rodriguez Fernandes, Maria M. Romeiras, Guilherme Roxo, Lukas Rüber, Maria Jose Ruiz-Lopez, Urmas Saarma, Luis P. da Silva, Manuela Sim-Sim, Lucile Soler, Vitor C. Sousa, Carla Sousa Santos, Alberto Spada, Milomir Stefanovic, Viktor Steger, Josefin Stiller, Matthias Stöck, Torsten H. Struck, Hiranya Sudasinghe, Riikka Tapanainen, Christian Tellgren-Roth, Helena Trindade, Yevhen Tukalenko, Ilenia Urso, Benoit Vacherie, Steven M. Van Belleghem, Kees Van Oers, Carlos Vargas-Chavez, Nevena Velickovic, Noel Vella, Adriana Vella, Cristiano Vernesi, Sara Vicente, Sara Villa, Olga Vinnere Pettersson, Filip A. M. Volckaert, Judit Voros, Patrick Wincker, Sylke Winkler, Claudio Ciofi, Robert M. Waterhouse, and Camila J. Mazzoni
Subjects: General. Including nature conservation, geographical distribution, QH1-199.5
Abstract: Abstract A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.
Published: 2024
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21. Tropical peat composition may provide a negative feedback on fire occurrence and severity

Author: Alastair J. Crawford, Claire M. Belcher, Stacey New, Angela Gallego-Sala, Graeme T. Swindles, Susan Page, Tatiana A. Blyakharchuk, Hinsby Cadillo-Quiroz, Dan J. Charman, Mariusz Gałka, Paul D. M. Hughes, Outi Lähteenoja, Dmitri Mauquoy, Thomas P. Roland, and Minna Väliranta
Subjects: Science
Abstract: Abstract Loss of peat through increased burning will have major impacts on the global carbon cycle. In a normal hydrological state, the risk of fire propagation is largely controlled by peat bulk density and moisture content. However, where humans have interfered with the moisture status of peat either via drainage, or indirectly via climate change, we hypothesise that its botanical composition will become important to flammability, such that peats from different latitudes might have different compositionally-driven susceptibility to ignition. We use pyrolysis combustion flow calorimetry to determine the temperature of maximum thermal decomposition (T max) of peats from different latitudes, and couple this to a botanical composition analysis. We find that tropical peat has higher T max than other regions, likely on account of its higher wood content which appears to convey a greater resistance to ignition. This resistance also increases with depth, which means that loss of surface peat in tropical regions may lead to a reduction in the subsequent ignitability of deeper peat layers as they are exposed, potentially resulting in a negative feedback on increased fire occurrence and severity.
Published: 2024
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22. More than sleep problems? Testing five key health behaviors as reasons for quality of life issues among shift workers

Author: Yuxin Chen, Kaiyi Deng, Ian M. Hughes, Claire E. Smith, Hongdao Meng, Minh Quan Le, Min Sun, Xianyan Zhang, and Danping Liu
Subjects: Shift work, Quality of life, Health behaviors, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Abstract Background The shift work schedule is a common work arrangement that can disrupt typical sleep-wake rhythms and lead to negative health consequences. The present study aims to examine the effect of shift work on health-related quality of life (QoL) and explore potential behaviorial mediators (i.e., sleep, eating, exercise, smoking, drinking). Methods A cross-sectional survey was conducted among 4,449 petroleum workers in southwest China. Data on shift work status, health behaviors, and physical and mental health QoL were collected. We tested our model using path analysis and the Monte Carlo approach among 2,129 included participants. Results After adjusting for covariates, shift work did not exhibit a significant direct association with QoL. However, shift work indirectly related to poorer physical health quality of life via less frequent healthy food consumption; shift work also indirectly related to poorer mental health QoL via both less frequent healthy food consumption and physical exercise. No significant indirect effects were found via sleeping, smoking, or drinking. Conclusions Results suggest that shift work presents a challenge for QoL among Chinese petroleum workers due to their lesser engagement in two specific health behaviors: healthy eating and physical exercise. Healthy eating and exercise may present an even more prominent threat to shift workers’ QoL than sleep and substance use. Strategies targeting shift work schedule as well as eating and exercise behaviors may help protect against poor QoL and adverse physical and mental health outcomes in this vulnerable group.
Published: 2024
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23. Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge

Author: Daniel Malouli, Meenakshi Tiwary, Roxanne M. Gilbride, David W. Morrow, Colette M. Hughes, Andrea Selseth, Toni Penney, Priscila Castanha, Megan Wallace, Yulia Yeung, Morgan Midgett, Connor Williams, Jason Reed, Yun Yu, Lina Gao, Gabin Yun, Luke Treaster, Amanda Laughlin, Jeneveve Lundy, Jennifer Tisoncik-Go, Leanne S. Whitmore, Pyone P. Aye, Faith Schiro, Jason P. Dufour, Courtney R. Papen, Husam Taher, Louis J. Picker, Klaus Früh, Michael Gale, Nicholas J. Maness, Scott G. Hansen, Simon Barratt-Boyes, Douglas S. Reed, and Jonah B. Sacha
Subjects: Science
Abstract: Abstract An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.
Published: 2024
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24. Pembrolizumab plus epacadostat in patients with recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-669/ECHO-304): a phase 3, randomized, open-label study

Author: Byoung Chul Cho, Irene Braña, Beatriz Cirauqui, Sercan Aksoy, Felix Couture, Ruey-Long Hong, Wilson H. Miller, Manuel Chaves-Conde, Margarida Teixeira, Lance Leopold, Mihaela Munteanu, Joy Yang Ge, Ramona F. Swaby, and Brett G. M. Hughes
Subjects: Pembrolizumab, PD-1, Immunotherapy, EXTREME, Cetuximab, Head and neck squamous cell carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Advanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial. Methods KEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019. Results Between December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%–49%) for pembrolizumab plus epacadostat, 21% (6%–46%) for pembrolizumab monotherapy, and 34% (19%–52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3–4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects. Conclusions Pembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC. Trial registration NCT03358472. Date of trial registration: November 30, 2017.
Published: 2024
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25. Acupuncture in the emergency department (ACUITY): Results from a BraveNet multi-center feasibility randomized controlled trial

Author: Jeffery A. Dusek, Gene A. Kallenberg, Alan B. Storrow, Robert M. Hughes, Christopher J. Coyne, David R. Vago, Arya Nielsen, Alison Karasz, Ryung S. Kim, Jessica Surdam, Tracy Segall, Kiran A. Faryar, Natalie L. Dyer, Bruce A. Barton, and M. Diane McKee
Subjects: Acute pain, Nonpharmacologic, Randomized controlled trial, Integrative medicine, Miscellaneous systems and treatments, RZ409.7-999
Abstract: Background: Pain plays a significant role in emergency department (ED) visits, however safe and effective nonpharmacologic options are needed. Prior studies of acupuncture in the ED reported pain reduction with minimal side effects, but most were small and single site. Methods: We conducted ACUITY, a prospectively designed multi-center feasibility RCT. Our goal was to recruit 165 adults with acute non-emergent pain ≥4 on a 0–10-point scale at three EDs affiliated with BraveNet Practice Based Research Network. At baseline and 45–60 min later (post), participants self-assessed their pain and anxiety using a 0–10 rating scale. The primary feasibility outcome was recruitment of participants, whereas secondary outcomes were retention, and participant/provider acceptability. Results: From May 3, 2021, to September 24, 2022, 632 eligible individuals were approached and 165 enrolled (165/632: 26.1 %), meeting our recruitment goal. Notably, 42.4 % of enrollees were Black/African American, 42.4 % were White/Caucasian, and 13.9 % were Hispanic/Latino. Participants were randomized to Acupuncture (n = 83) or Usual care (n = 82), of which 151 (91.5 %) and 128 (77.6 %) provided pain and anxiety scores at post-treatment and 1-week respectively. Acupuncture was rated acceptable to participants and providers. Mean pain ratings (pre-to-post) were 7.4 (2.2) to 4.8 (2.8) for acupuncture and 7.1 (2.3) to 6.4 (2.5) for usual care. Mean anxiety ratings (pre-to-post) were 4.5 (3.4) to 2.5 (2.6) for acupuncture and 4.1 (3.4) to 3.5 (3.2) for usual care. Conclusion: Successful completion of ACUITY indicates we have the expertise and preliminary data to conduct a future definitive, multi-center RCT. Trial registration: Clinical trials.gov: NCT04880733.
Published: 2024
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26. Male Akita diabetic mice develop underactive bladder independent of NLRP3 that can be prevented with blood glucose control

Author: Austin J. Livingston, J. Todd Purves, Michael R. Odom, Huixia Jin, and Francis M. Hughes, Jr.
Subjects: Bladder, Diabetes, Complications, Inflammation, Urodynamics, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Aim:: Diabetic bladder dysfunction (DBD) is the most common diabetic complication. Patients present with overactive symptoms, underactive symptoms, or both. While strict glucose control may be expected to reverse DBD, prior studies have not been supportive. However, we hypothesize that strict control, soon after hyperglycemia appears, can prevent DBD development. Moreover, 50% of adult diabetics are poorly-controlled and it is unknown how this effects development of DBD. Thus, we investigated the effect of early glucose control (poor and strict) on DBD in male Akita diabetic mice (type 1). NLRP3-induced inflammation is critical to development of DBD in female Akita. Therefore, we also hypothesized that targeting NLRP3 may control or prevent DBD in male Akita, especially in a poorly-controlled population. Methods:: Akita mice (±NLRP3) were stratified into uncontrolled, poorly-controlled and strictly-controlled diabetic groups using insulin treatment (0, 0.125 or 0.25 U/day). Mice were assessed at 15 weeks for blood glucose, HbA1c, Evans blue dye extravasation (a marker of capillary permeability/inflammation) and bladder function. Results:: Blood glucose was elevated in diabetics, reduced in an insulin dose-dependent manner, and not affected by NLRP3 deletion. HbA1c levels followed a similar course but were more sensitive to insulin levels. Evans blue dye extravasation was prevented with glucose control and absent in NLRP3−/−mice. Diabetics exhibited signs of underactive bladder (increased void volume, decreased frequency) that was attenuated in the uncontrolled group but absent in the well-controlled group. Deleting NLRP3 did not affect voiding function. Conclusion:: Male Akita mice develop an underactive-like bladder, independent of NLRP3, which can be prevented with glucose control.
Published: 2024
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27. Protocol for modeling acquired resistance to targeted therapeutics in adherent and suspension cancer cell lines via in situ resistance assay

Author: Nancy E. Sealover, Jacob M. Hughes, Patricia L. Theard, Deepan Chatterjee, Amanda J. Linke, Bridget A. Finniff, Brianna R. Daley, Robert E. Lewis, and Robert L. Kortum
Subjects: Cell Biology, Cell culture, Cell-based Assays, Cancer, High-Throughput Screening, Science (General), Q1-390
Abstract: Summary: Acquired resistance to oncogene-targeted therapies is the major driver of mortality for patients with cancer. Here, we present a 6-to-16-week assay to model the development of acquired resistance in adherent and suspension cancer cell lines. We describe steps for determining therapeutic dose, assaying acquired resistance, and testing combination therapies. This protocol is a high-throughput, cost-effective, and scalable method to model acquired drug resistance to established and newly developed therapies.For complete details on the use and execution of this protocol, please refer to Sealover et al.1 and Theard et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Published: 2024
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28. Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer – Multi-centre study

Author: Ngu Wah Than, D. Mark Pritchard, David M. Hughes, Kai Shing Yu, Helen S. Minnaar, Amandeep Dhadda, Jamie Mills, Joakim Folkesson, Calin Radu, C.A. Duckworth, Helen Wong, Muneeb Ul Haq, Rajaram Sripadam, Mark D. Halling-Brown, Alexandra J. Stewart, and Arthur Sun Myint
Subjects: Rectal cancer, Contact X-ray Brachytherapy, Papillon, Organ preservation, Sole treatment, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background and purpose: Radical surgery is the standard of care for early rectal cancer. However, alternative organ-preserving approaches are attractive, especially in frail or elderly patients as these avoid surgical complications. We have assessed the efficacy of sole Contact X-ray Brachytherapy (CXB) treatment in stage-1 rectal cancer patients who were unsuitable for or declined surgery. Materials and methods: This retrospective multi-centre study (2009–2021) evaluated 76 patients with T1/2-N0-M0 rectal adenocarcinomas who were treated with CXB alone. Outcomes were assessed for the entire cohort and sub-groups based on the T-stage and the criteria for receiving CXB alone; Group A: patients who were fit enough for surgery but declined, Group B: patients who were high-risk for surgery and Group C: patients who had received prior pelvic radiation for a different cancer. Results: With a median follow-up of 26(IQR:12–49) months, initial clinical Complete Response (cCR) was 82(70–93)% with rates of local regrowth 18(8–29)%, 3-year actuarial local control (LC) 84(75–95)%, distant relapse 3 %, and no nodal relapse. 5-year disease-free survival (DFS) and overall survival (OS) were 66(48–78)% and 58(44–75)%. Lower OS was observed in Groups B [HR:2.54(95 %CI:1.17, 5.59), p = 0.02] and C [HR:2.75(95 %CI:1.15, 6.58), p = 0.03]. Previous pelvic radiation predicted lower cCR and OS. The main toxicity was G1-2 rectal bleeding (26 %) and symptoms of impaired anal sphincter function were not reported in any patients. Conclusion: CXB treatment alone achieved a high cCR rate with satisfactory LC and DFS. Inferior oncological outcomes were observed in patients who had received prior pelvic radiotherapy. CXB alone, with its favourable toxicity profile and avoidance of general anaesthesia and surgery risks, therefore, can be considered for patients who are unsuitable for or refuse surgery.
Published: 2024
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29. Association of circulating ketone bodies with cognitive performance and dementia in the Multi‐Ethnic Study of Atherosclerosis (MESA)

Author: Parag Anilkumar Chevli, Christopher L. Schaich, Alexis C. Wood, Luqman A. TK, Anurag Mehta, Vardhmaan Jain, Margery Connelly, Suzanne Craft, Elad Shemesh, José A. Luchsinger, Kathleen M. Hayden, Bonnie Colleen Sachs, Timothy M. Hughes, and Michael D. Shapiro
Subjects: cognitive testing, dementia, β‐hydroxybutyrate, ketone bodies, multi‐ethnic, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract Introduction Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases. Methods Associations of plasma KB with incident dementia and cognitive performances were examined among Multi‐Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000–02) and detailed cognitive testing at Exam 5 (2010–2012, N = 4392), Exam 6 (2016–2018, N = 1838), and in MESA‐MIND (2019–2021, N = 2060). Results Over 16.7 years, a doubling of total KB was associated with a greater risk of incident dementia (hazard ratio [HR]: 1.14 [1.04–1.29]). Higher total KB was associated with worse cognitive performance in the Digit Span test at exam 5 [β: −0.30 (−0.47, −0.14)]. We also found that a higher KB was associated with greater functional impairment and a higher Quick Dementia Rating Scale (QDRS) score. Discussion In a diverse, cardiovascular disease‐free population, elevated KB levels were associated with incident dementia and impaired cognitive performance in specific domains. Highlights A study of ketone bodies (KB) and cognitive performance and incident dementia. Nuclear magnetic resonance (NMR) spectroscopy was used to measure plasma KB at baseline. Doubling of baseline total KB was associated with higher incident dementia. Higher KB was also associated with worse performance on a test of working memory.
Published: 2024
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30. Social genomics, cognition, and well‐being during the COVID‐19 pandemic

Author: James R. Bateman, Sudarshan Krishnamurthy, Ellen E. Quillen, Christian E. Waugh, Kiarri N. Kershaw, Samuel N. Lockhart, Timothy M. Hughes, Teresa E. Seeman, Steve W. Cole, and Suzanne Craft
Subjects: COVID, loneliness, mild cognitive impairment, social genomics, stress, well‐being, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract INTRODUCTION Adverse psychosocial exposure is associated with increased pro‐inflammatory gene expression and reduced type‐1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well‐studied in cognitive impairment but may contribute to late‐life cognitive decline. METHODS We examined perceived stress, loneliness, well‐being, and the impact of coronavirus disease 2019 (COVID‐19) and the relationship to the expression of genes associated with the CTRA. Mixed‐effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression. RESULTS Eudaimonic well‐being (EWB) was inversely associated with CTRA gene expression in participants with both normal cognition (NC) and mild cognitive impairment (MCI). Self‐reported coping strategies differed by cognitive status and variably impacted CTRA gene expression. DISCUSSION EWB is an important correlate of stress, even in people with MCI. The prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression. Highlights Conserved transcriptional response to adversity (CTRA) gene expression is higher with lower eudaimonic well‐being. Eudaimonic well‐being was important in both participants with normal cognition and those with mild cognitive impairment. Coping strategies and impact on CTRA gene expression differed by cognitive status. Loneliness in a population with relatively low loneliness scores did not impact CTRA gene expression.
Published: 2024
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31. Impact of neighborhood disadvantage on cardiometabolic health and cognition in a community‐dwelling cohort

Author: Sudarshan Krishnamurthy, Lingyi Lu, Christian J. Johnson, Laura D. Baker, Xiaoyan Leng, Sarah A. Gaussoin, Timothy M. Hughes, Da Ma, Allison Caban‐Holt, Goldie S. Byrd, Suzanne Craft, Samuel N. Lockhart, and James R. Bateman
Subjects: Alzheimer's disease and related dementias, health equity, neighborhood disadvantage, place‐based determinants of health, social determinants of health, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract INTRODUCTION Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI). METHODS The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI. RESULTS ADI was positively associated with blood pressure and cardiometabolic index (CMI), and negatively associated with global and Preclinical Alzheimer's Cognitive Composite (PACC5) scores, in cognitively unimpaired (CU) individuals. ADI was only positively associated with hemoglobin A1c (HbA1c) in MCI. DISCUSSION Neighborhood disadvantage is associated more strongly with measures of cardiometabolic health and cognition among CU individuals rather than MCI. These findings demonstrate a need for structural solutions to address social determinants of health in an attempt to reduce cardiometabolic and cognitive risks.
Published: 2024
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32. Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Author: Colin Birkenbihl, Madison Cuppels, Rory T. Boyle, Hannah M. Klinger, Oliver Langford, Gillian T. Coughlan, Michael J. Properzi, Jasmeer Chhatwal, Julie C. Price, Aaron P. Schultz, Dorene M. Rentz, Rebecca E. Amariglio, Keith A. Johnson, Rebecca F. Gottesman, Shubhabrata Mukherjee, Paul Maruff, Yen Ying Lim, Colin L. Masters, Alexa Beiser, Susan M. Resnick, Timothy M. Hughes, Samantha Burnham, Ilke Tunali, Susan Landau, Ann D. Cohen, Sterling C. Johnson, Tobey J. Betthauser, Sudha Seshadri, Samuel N. Lockhart, Sid E. O'Bryant, Prashanthi Vemuri, Reisa A. Sperling, Timothy J. Hohman, Michael C. Donohue, and Rachel F. Buckley
Published: 2025
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33. An exploration of Northern Ireland general practice pharmacists’ views on their role in general practice: a cross-sectional survey

Author: Abrar H. F. Hassan, Heather E. Barry, and Carmel M. Hughes
Subjects: Primary care, General practice, General practice pharmacists, Cross-sectional, Northern Ireland, Medicine (General), R5-920
Abstract: Abstract Background There is limited research examining the views of general practice pharmacists (GPPs) on their role and their impact in general practice. The aim of this study was to explore GPPs’ views regarding this role and its potential impact within general practice in Northern Ireland (NI). Methods A paper-based self-administered questionnaire was mailed to 319 general practices in NI in 2022, directed to the GPP who spent most time at the practice. A variety of closed and open questions were included in six sections. Responses to closed questions were analysed descriptively whilst open question responses were analysed using content analysis. To ascertain associations between variables (e.g. GPP prescribing status, working arrangements and aspects of collaboration with GPPs), Fisher’s exact test was employed with an a priori significance level of p 80%) showed positive attitudes towards collaboration with GPs and those who worked in multiple practices were more likely to agree with the Attitudes Towards Collaboration Instrument for pharmacists (ATCI-P) statements compared to those who worked in a single practice (p
Published: 2024
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34. Specialized pro-resolution mediators in the bladder: effects of resolvin E1 on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model

Author: Anissa Cervantes, Francis M. Hughes, Huixia Jin, and J. Todd Purves
Subjects: Diabetes, Diabetic bladder, Pro-resolution, Resolvin, Inflammation, Cystitis, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction. Methods Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice. Results Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan’s blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks. Conclusions Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.
Published: 2024
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35. A human pluripotent stem cell-derived in vitro model of the blood–brain barrier in cerebral malaria

Author: Adnan Gopinadhan, Jason M. Hughes, Andrea L. Conroy, Chandy C. John, Scott G. Canfield, and Dibyadyuti Datta
Subjects: Blood–brain barrier, Cerebral malaria, Plasmodium falciparum-infected red blood cells, Human induced pluripotent stem cell-derived brain microvascular endothelial cells, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Blood–brain barrier (BBB) disruption is a central feature of cerebral malaria (CM), a severe complication of Plasmodium falciparum (Pf) infections. In CM, sequestration of Pf-infected red blood cells (Pf-iRBCs) to brain endothelial cells combined with inflammation, hemolysis, microvasculature obstruction and endothelial dysfunction mediates BBB disruption, resulting in severe neurologic symptoms including coma and seizures, potentially leading to death or long-term sequelae. In vitro models have advanced our knowledge of CM-mediated BBB disruption, but their physiological relevance remains uncertain. Using human induced pluripotent stem cell-derived brain microvascular endothelial cells (hiPSC-BMECs), we aimed to develop a novel in vitro model of the BBB in CM, exhibiting enhanced barrier properties. Methods hiPSC-BMECs were co-cultured with HB3var03 strain Pf-iRBCs up to 9 h. Barrier integrity was measured using transendothelial electrical resistance (TEER) and sodium fluorescein permeability assays. Localization and expression of tight junction (TJ) proteins (occludin, zonula occludens-1, claudin-5), cellular adhesion molecules (ICAM-1, VCAM-1), and endothelial surface markers (EPCR) were determined using immunofluorescence imaging (IF) and western blotting (WB). Expression of angiogenic and cell stress markers were measured using multiplex proteome profiler arrays. Results After 6-h of co-culture with Pf-iRBCs, hiPSC-BMECs showed reduced TEER and increased sodium fluorescein permeability compared to co-culture with uninfected RBCs, indicative of a leaky barrier. We observed disruptions in localization of occludin, zonula occludens-1, and claudin-5 by IF, but no change in protein expression by WB in Pf-iRBC co-cultures. Expression of ICAM-1 and VCAM-1 but not EPCR was elevated in hiPSC-BMECs with Pf-iRBC co-culture compared to uninfected RBC co-culture. In addition, there was an increase in expression of angiogenin, platelet factor-4, and phospho-heat shock protein-27 in the Pf-iRBCs co-culture compared to uninfected RBC co-culture. Conclusion These findings demonstrate the validity of our hiPSC-BMECs based model of the BBB, that displays enhanced barrier integrity and appropriate TJ protein localization. In the hiPSC-BMEC co-culture with Pf-iRBCs, reduced TEER, increased paracellular permeability, changes in TJ protein localization, increase in expression of adhesion molecules, and markers of angiogenesis and cellular stress all point towards a novel model with enhanced barrier properties, suitable for investigating pathogenic mechanisms underlying BBB disruption in CM.
Published: 2024
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36. Murine bone-derived mesenchymal stem cells undergo molecular changes after a single passage in culture

Author: Anastasia M. Hughes, Vincent Kuek, Joyce Oommen, Rishi S. Kotecha, and Laurence C. Cheung
Subjects: Medicine, Science
Abstract: Abstract The rarity of the mesenchymal stem cell (MSC) population poses a significant challenge for MSC research. Therefore, these cells are often expanded in vitro, prior to use. However, long-term culture has been shown to alter primary MSC properties. Additionally, early passage primary MSCs in culture are often assumed to represent the primary MSC population in situ, however, little research has been done to support this. Here, we compared the transcriptomic profiles of murine MSCs freshly isolated from the bone marrow to those that had been expanded in culture for 10 days. We identified that a single passage in culture extensively altered MSC molecular signatures associated with cell cycling, differentiation and immune response. These findings indicate the critical importance of the MSC source, highlighting the need for optimization of culture conditions to minimize the impact on MSC biology and a transition towards in vivo methodologies for the study of MSC function.
Published: 2024
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37. Gene expression plasticity facilitates acclimatization of a long-lived Caribbean coral across divergent reef environments

Author: Karl D. Castillo, Colleen B. Bove, Annabel M. Hughes, Maya E. Powell, Justin B. Ries, and Sarah W. Davies
Subjects: Acclimatization, Caribbean coral, Reciprocal transplant, Transcriptome plasticity, Environmental variability, Environmental specialization, Medicine, Science
Abstract: Abstract Local adaptation can increase fitness under stable environmental conditions. However, in rapidly changing environments, compensatory mechanisms enabled through plasticity may better promote fitness. Climate change is causing devastating impacts on coral reefs globally and understanding the potential for adaptive and plastic responses is critical for reef management. We conducted a four-year, three-way reciprocal transplant of the Caribbean coral Siderastrea siderea across forereef, backreef, and nearshore populations in Belize to investigate the potential for environmental specialization versus plasticity in this species. Corals maintained high survival within forereef and backreef environments, but transplantation to nearshore environments resulted in high mortality, suggesting that nearshore environments present strong environmental selection. Only forereef-sourced corals demonstrated evidence of environmental specialization, exhibiting the highest growth in the forereef. Gene expression profiling 3.5 years post-transplantation revealed that transplanted coral hosts exhibited profiles more similar to other corals in the same reef environment, regardless of their source location, suggesting that transcriptome plasticity facilitates acclimatization to environmental change in S. siderea. In contrast, algal symbiont (Cladocopium goreaui) gene expression showcased functional variation between source locations that was maintained post-transplantation. Our findings suggest limited acclimatory capacity of some S. siderea populations under strong environmental selection and highlight the potential limits of coral physiological plasticity in reef restoration.
Published: 2024
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38. Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease

Author: Fernando Gonzalez-Ortiz, Bjørn-Eivind Kirsebom, José Contador, Jordan E. Tanley, Per Selnes, Berglind Gísladóttir, Lene Pålhaugen, Mathilde Suhr Hemminghyth, Jonas Jarholm, Ragnhild Skogseth, Geir Bråthen, Gøril Grøndtvedt, Atle Bjørnerud, Sandra Tecelao, Knut Waterloo, Dag Aarsland, Aida Fernández-Lebrero, Greta García-Escobar, Irene Navalpotro-Gómez, Michael Turton, Agnes Hesthamar, Przemyslaw R. Kac, Johanna Nilsson, Jose Luchsinger, Kathleen M. Hayden, Peter Harrison, Albert Puig-Pijoan, Henrik Zetterberg, Timothy M. Hughes, Marc Suárez-Calvet, Thomas K. Karikari, Tormod Fladby, and Kaj Blennow
Subjects: Science
Abstract: Abstract Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer’s disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ (“A”) and neurodegeneration (“N”) abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.
Published: 2024
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39. Potentially inappropriate prescribing for people with dementia in ambulatory care: a cross-sectional observational study

Author: Nahla A. Alageel, Carmel M. Hughes, Monira Alwhaibi, Walid Alkeridy, and Heather E. Barry
Subjects: Ambulatory care, Dementia, Electronic health records, Inappropriate prescribing, Pharmacoepidemiology, Polypharmacy, Geriatrics, RC952-954.6
Abstract: Abstract Background Studies have shown that potentially inappropriate prescribing (PIP) is highly prevalent among people with dementia (PwD) and linked to negative outcomes, such as hospitalisation and mortality. However, there are limited data on prescribing appropriateness for PwD in Saudi Arabia. Therefore, we aimed to estimate the prevalence of PIP and investigate associations between PIP and other patient characteristics among PwD in an ambulatory care setting. Methods A cross-sectional, retrospective analysis was conducted at a tertiary hospital in Saudi Arabia. Patients who were ≥ 65 years old, had dementia, and visited ambulatory care clinics between 01/01/2019 and 31/12/2021 were included. Prescribing appropriateness was evaluated by applying the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria. Descriptive analyses were used to describe the study population. Prevalence of PIP and the prevalence per each STOPP criterion were calculated as a percentage of all eligible patients. Logistic regression analysis was used to investigate associations between PIP, polypharmacy, age and sex; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Analyses were conducted using SPSS v27. Results A total of 287 PwD were identified; 56.0% (n = 161) were female. The mean number of medications prescribed was 9.0 [standard deviation (SD) ± 4.2]. The prevalence of PIP was 61.0% (n = 175). Common instances of PIP were drugs prescribed beyond the recommended duration (n = 90, 31.4%), drugs prescribed without an evidence-based clinical indication (n = 78, 27.2%), proton pump inhibitors (PPIs) for > 8 weeks (n = 75, 26.0%), and acetylcholinesterase inhibitors with concurrent drugs that reduce heart rate (n = 60, 21.0%). Polypharmacy was observed in 82.6% (n = 237) of patients and was strongly associated with PIP (adjusted OR 24.1, 95% CI 9.0–64.5). Conclusions Findings have revealed a high prevalence of PIP among PwD in Saudi Arabia that is strongly associated with polypharmacy. Future research should aim to explore key stakeholders’ experiences and perspectives of medicines management to optimise medication use for this vulnerable patient population.
Published: 2024
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40. Improving medication dispensing and counselling for patients with vision impairment: a qualitative study of pharmacist-reported barriers and facilitators

Author: Basma Y. Kentab, Heather E. Barry, Sinaa A. Al-Aqeel, and Carmel M. Hughes
Subjects: Qualitative research, Theoretical domains framework, Behaviour change, Vision impairment, Pharmacists, Dispensing, Public aspects of medicine, RA1-1270
Abstract: Abstract Background People with vision impairment encounter many difficulties when it comes to medicines use. However, evidence indicates that there are major gaps in pharmaceutical care service provision worldwide and limited research on interventions to optimise medication use for this patient population. The Theoretical Domains Framework (TDF) provides a method for theoretically understanding individuals’ behaviour and informing development of interventions. The aim of this research was to (a) identify the barriers and facilitators to the provision of medication dispensing and counselling services by pharmacists to patients with vision impairment, and (b) identify key TDF domains to be targeted in a future intervention. Methods Semi-structured interviews were conducted with pharmacists from different pharmacy practice settings/areas in Saudi Arabia. The 14-domain TDF was utilised as the theoretical lens through which pharmacists’ behaviours were examined. Interviews were conducted in Arabic or English, either face-to-face or over the telephone based on the participant’s preference. Following transcription, interviews conducted in Arabic were translated into English before analysis. Data analysis involved using the framework method and content analysis to identify important barriers and facilitators to the provision of dispensing and counselling services to those with vision impairment. Key TDF domains that could be targeted in a future intervention were then identified using a consensus-based approach. Results Twenty-six pharmacists were interviewed. Pharmacists’ experience in pharmacy practice ranged from two to 28 years. A range of barriers and facilitators were highlighted as important in providing services to those with vision impairment. Eight domains were identified as ‘key domains’ including: ‘Knowledge’, ‘Skills’, ‘Beliefs about capabilities’, ‘Goals’, ‘Memory, attention, and decision processes’, ‘Environmental context and resources’, ‘Social influences’, and ‘Behavioural regulation’. Conclusions Barriers and facilitators identified by pharmacists will inform the development of an intervention to ensure its applicability to everyday practice. Future research will focus on the process of developing the proposed intervention through targeting key TDF domains to improve medication dispensing and counselling by pharmacists to patients with vision impairment.
Published: 2024
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41. Contact X-ray brachytherapy (CXB) as a salvage treatment for rectal cancer patients who developed local tumor re-growth after watch-and-wait approach

Author: Ngu Wah Than, Mark Pritchard, Carrie. A. Duckworth, David M. Hughes, Helen Wong, Rajaram Sripadam, and Arthur Sun Myint
Subjects: contact x-ray brachytherapy, papillon, watch-and-wait, neoadjuvant (chemo)radiation, salvage treatment, alternative to surgery, Medicine
Published: 2024
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42. Long-Term Outcomes of Patients with Poor Prognostic Factors Following Transanal Endoscopic Microsurgery (TEMS) for Early Rectal Cancer

Author: Muneeb Ul Haq, Khaled Noureldin, David Mark Pritchard, Arthur Sun Myint, Carrie A. Duckworth, Ngu Wah Than, David M. Hughes, Shakil Ahmed, and Muhammad Ahsan Javed
Subjects: rectal cancer, adjuvant treatment, local excision, Biology (General), QH301-705.5
Abstract: Background: Transanal endoscopic microsurgery (TEMS) is an organ-preserving approach for treatment of early rectal cancer (ERC). However, adverse histopathological features identified post-TEMS often necessitate adjuvant therapy. This study aims to compare the long-term oncological outcomes of patients who underwent TEMS and were offered adjuvant treatments with total mesorectal excision (TME), chemoradiotherapy (CRT), radiotherapy (RT), active surveillance, or dose escalation with contact X-ray brachytherapy (CXB). Methods: This study included patients treated with TEMS for ERC between September 2012 and December 2022, with follow-up until December 2023. Patients with adverse histopathological features (extra-mural venous invasion, lympho-vascular invasion, R1 margins, tumour budding) were assigned to adjuvant treatments. Inverse probability of treatment weighting (IPTW) was applied to mitigate selection bias. Results: Of the 117 patients, 24 underwent TME, 17 received CRT, 25 received RT, 14 underwent active surveillance, and 37 patients received CXB boost along with CRT. The median follow-up was 60 months (IQR 52–73). During this time, 29 patients developed recurrence, and 15 died. The 5-year overall survival (OS) was 78.6%, and disease-free survival (DFS) was 70.9%. Compared to CXB, the mortality risk for CRT (HR = 0.81; 95% CI: 0.20–3.28; p = 0.77) and TME (HR = 3.68; 95% CI: 0.46–29.79; p = 0.22) was not significantly different. However, TME was associated with a significantly higher recurrence risk compared to CXB (HR = 7.57; 95% CI: 1.23–46.84; p = 0.029). Conclusions: An organ-preserving strategy with CRT or CRT combined with a CXB boost may offer comparable long-term outcomes and reduced recurrence risks for patients undergoing TEMS for ERC with poor prognostic features. Further research with larger cohorts is needed to validate these results.
Published: 2025
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43. Author Correction: The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

Author: Ann M. Mc Cartney, Giulio Formenti, Alice Mouton, Diego De Panis, Luísa S. Marins, Henrique G. Leitão, Genevieve Diedericks, Joseph Kirangwa, Marco Morselli, Judit Salces-Ortiz, Nuria Escudero, Alessio Iannucci, Chiara Natali, Hannes Svardal, Rosa Fernández, Tim De Pooter, Geert Joris, Mojca Strazisar, Jonathan M. D. Wood, Katie E. Herron, Ole Seehausen, Phillip C. Watts, Felix Shaw, Robert P. Davey, Alice Minotto, José M. Fernández, Astrid Böhne, Carla Alegria, Tyler Alioto, Paulo C. Alves, Isabel R. Amorim, Jean-Marc Aury, Niclas Backstrom, Petr Baldrian, Laima Baltrunaite, Endre Barta, Bertrand BedHom, Caroline Belser, Johannes Bergsten, Laurie Bertrand, Helena Bilandija, Mahesh Binzer-Panchal, Iliana Bista, Mark Blaxter, Paulo A. V. Borges, Guilherme Borges Dias, Mirte Bosse, Tom Brown, Rémy Bruggmann, Elena Buena-Atienza, Josephine Burgin, Elena Buzan, Alessia Cariani, Nicolas Casadei, Matteo Chiara, Sergio Chozas, Fedor Čiampor, Angelica Crottini, Corinne Cruaud, Fernando Cruz, Love Dalen, Alessio De Biase, Javier del Campo, Teo Delic, Alice B. Dennis, Martijn F. L. Derks, Maria Angela Diroma, Mihajla Djan, Simone Duprat, Klara Eleftheriadi, Philine G. D. Feulner, Jean-François Flot, Giobbe Forni, Bruno Fosso, Pascal Fournier, Christine Fournier-Chambrillon, Toni Gabaldon, Shilpa Garg, Carmela Gissi, Luca Giupponi, Jessica Gomez-Garrido, Josefa González, Miguel L. Grilo, Björn Grüning, Thomas Guerin, Nadege Guiglielmoni, Marta Gut, Marcel P. Haesler, Christoph Hahn, Balint Halpern, Peter W. Harrison, Julia Heintz, Maris Hindrikson, Jacob Höglund, Kerstin Howe, Graham M. Hughes, Benjamin Istace, Mark J. Cock, Franc Janžekovič, Zophonias O. Jonsson, Sagane Joye-Dind, Janne J. Koskimäki, Boris Krystufek, Justyna Kubacka, Heiner Kuhl, Szilvia Kusza, Karine Labadie, Meri Lähteenaro, Henrik Lantz, Anton Lavrinienko, Lucas Leclère, Ricardo Jorge Lopes, Ole Madsen, Ghislaine Magdelenat, Giulia Magoga, Tereza Manousaki, Tapio Mappes, Joao Pedro Marques, Gemma I. Martinez Redondo, Florian Maumus, Shane A. McCarthy, Hendrik-Jan Megens, Jose Melo-Ferreira, Sofia L. Mendes, Matteo Montagna, Joao Moreno, Mai-Britt Mosbech, Mónica Moura, Zuzana Musilova, Eugene Myers, Will J. Nash, Alexander Nater, Pamela Nicholson, Manuel Niell, Reindert Nijland, Benjamin Noel, Karin Noren, Pedro H. Oliveira, Remi-Andre Olsen, Lino Ometto, Rebekah A. Oomen, Stephan Ossowski, Vaidas Palinauskas, Snaebjorn Palsson, Jerome P. Panibe, Joana Pauperio, Martina Pavlek, Emilie Payen, Julia Pawlowska, Jaume Pellicer, Graziano Pesole, Joao Pimenta, Martin Pippel, Anna Maria Pirttilä, Nikos Poulakakis, Jeena Rajan, Rúben M.C. Rego, Roberto Resendes, Philipp Resl, Ana Riesgo, Patrik Rodin-Morch, Andre E. R. Soares, Carlos Rodriguez Fernandes, Maria M. Romeiras, Guilherme Roxo, Lukas Rüber, Maria Jose Ruiz-Lopez, Urmas Saarma, Luis P. da Silva, Manuela Sim-Sim, Lucile Soler, Vitor C. Sousa, Carla Sousa Santos, Alberto Spada, Milomir Stefanovic, Viktor Steger, Josefin Stiller, Matthias Stöck, Torsten H. Struck, Hiranya Sudasinghe, Riikka Tapanainen, Christian Tellgren-Roth, Helena Trindade, Yevhen Tukalenko, Ilenia Urso, Benoit Vacherie, Steven M. Van Belleghem, Kees Van Oers, Carlos Vargas-Chavez, Nevena Velickovic, Noel Vella, Adriana Vella, Cristiano Vernesi, Sara Vicente, Sara Villa, Olga Vinnere Pettersson, Filip A. M. Volckaert, Judit Voros, Patrick Wincker, Sylke Winkler, Claudio Ciofi, Robert M. Waterhouse, and Camila J. Mazzoni
Subjects: General. Including nature conservation, geographical distribution, QH1-199.5
Published: 2024
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44. Our Heritage, Our Stories: developing AI tools to link and support community-generated digital cultural heritage.

Author: Ewan David Hannaford, Viktor Schlegel, Rhiannon Lewis, Stefan Ramsden, Jenny Bunn, John Moore, Marc Alexander, Hannah Barker, Riza Batista-Navarro, Lorna M. Hughes, and Goran Nenadic
Published: 2024
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45. Organizational Characteristics of Hospitals Meeting STRIDE Program Adoption Benchmarks to Support Mobility for Hospitalized Persons

Author: Leah L. Zullig PhD, MPH, Connor Drake PhD, Amy Webster BS, Matthew Tucker BA, Ashley Choate MPH, Karen M. Stechuchak MS, Cynthia J. Coffman PhD, Caitlin B. Kappler MSW, Cassie Meyer BS, Courtney H. Van Houtven PhD, Kelli D. Allen PhD, Jaime M. Hughes PhD, MPH, MSW, Nina Sperber PhD, and Susan Nicole Hastings MD, MHS
Subjects: Public aspects of medicine, RA1-1270
Abstract: There are few validated contextual measures predicting adoption of evidence-based programs. Variation in context at clinical sites can hamper dissemination. We examined organizational characteristics of Veterans Affairs hospitals implementing STRIDE, a hospital walking program, and characteristics’ influences on program adoption. Using a parallel mixed-method design, we describe context and organizational characteristics by program adoption. Organizational characteristics included: organizational resilience, implementation climate, organizational readiness to implement change, highest complexity sites versus others, material support, adjusted length of stay (LOS) above versus below national median, and improvement experience. We collected intake forms at hospital launch and qualitative interviews with staff members at 4 hospitals that met the initial adoption benchmark, defined as completing supervised walks with 5+ unique hospitalized Veterans during months 5 to 6 after launch with low touch implementation support. We identified that 31% (n = 11 of 35) of hospitals met adoption benchmarks. Seven percent of highest complexity hospitals adopted compared to 48% with lower complexity. Forty-three percent that received resources adopted compared to 29% without resources. Thirty-six percent of hospitals with above-median LOS adopted compared to 23% with below-median. Thirty-five percent with at least some implementation experience adopted compared to 0% with very little to no experience. Adopters reported higher organizational resilience than non-adopters (mean = 23.5 [SD = 2.6] vs 22.7 [SD = 2.6]). Adopting hospitals reported greater organizational readiness to change than those that did not (mean = 4.2 [SD = 0.5] vs 3.8 [SD = 0.6]). Qualitatively, all sites reported that staff were committed to implementing STRIDE. Participants reported additional barriers to adoption including challenges with staffing and delays associated with hiring staff. Adopters reported that having adequate staff facilitated implementation. Implementation climate did not have an association with meeting STRIDE program adoption benchmarks in this study. Contextual factors which may be simple to assess, such as resource availability, may influence adoption of new programs without intensive implementation support.
Published: 2024
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46. Stakeholders' perspectives about challenges, strategies and outcomes of importance associated with adherence to appropriate polypharmacy in older patients – A qualitative study

Author: Hanadi A. Al Shaker, Heather E. Barry, and Carmel M. Hughes
Subjects: Adherence, Polypharmacy, Older people, Qualitative research, Interview, Outcomes, Pharmacy and materia medica, RS1-441
Abstract: Background: Older patients experience challenges when taking polypharmacy. Studies have applied different interventions to improve adherence to polypharmacy. However, inconsistencies in outcomes have impeded the synthesis of evidence. To generate high-quality studies and selectively report outcomes, a Core Outcome Set (COS) is advocated. Objective(s): This study explored stakeholders' perspectives about the challenges older patients face when taking polypharmacy, strategies to overcome each challenge, and outcomes of importance that may contribute to COS development. Methods: Semi-structured interviews were undertaken with academics, healthcare professionals, and public participants. A series of open-ended questions investigated challenges with adherence to polypharmacy in older patients and strategies to overcome these challenges. A list of outcomes (n = 7) compiled from previous studies associated with adherence to polypharmacy was presented to participants for their views. Content analysis was conducted to identify key themes and outcomes proposed by participants. Results: Participants suggested 11 multidimensional healthcare system-related, medication-related, patient-related, and socioeconomic-related challenges and 16 educational and behavioural strategies associated with adherence to polypharmacy in older patients. Participants agreed with the importance of the seven outcomes presented and suggested a further six outcomes they deemed to be important for use in trials aimed at improving adherence to appropriate polypharmacy in older patients. Conclusions: Adherence to polypharmacy was deemed challenging, requiring supportive interventions. A list of 13 outcomes in the context of adherence to appropriate polypharmacy in older patients was identified to inform a future study that will develop a COS for clinical trials targeting interventions to improve adherence to appropriate polypharmacy in older patients.
Published: 2024
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47. Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques

Author: Benjamin N. Bimber, Justine Sunshine, G. W. McElfresh, Jason S. Reed, Reese Pathak, Katherine B. Bateman, Colette M. Hughes, Roxanne M. Gilbride, Julia C. Ford, David Morrow, Jeffrey D. Lifson, Jonah B. Sacha, Scott G. Hansen, and Louis J. Picker
Subjects: SIV, viral escape, CMV vaccine vector, viral sequence analysis, HIV/SIV, Immunologic diseases. Allergy, RC581-607
Abstract: Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations. While low level viral mutations accumulated in all animals by 28 days-post-challenge, which is after the establishment of viral control in protected animals, the dominant circulating virus in virtually all unprotected RMs was nearly identical to the challenge stock, and there was no difference in mutation patterns between this cohort and unvaccinated controls. These data definitively demonstrate that viral mutation does not explain lack of viral control in RMs not protected by RhCMV/SIV vaccination. We further demonstrate that during chronic infection RhCMV/SIV vaccinated RMs do not acquire escape mutation in epitopes targeted by RhCMV/SIV, but instead display mutation in canonical MHC-Ia epitopes similar to unvaccinated RMs. This suggests that after the initial failure of viral control, unconventional T cell responses induced by 68-1 RhCMV/SIV vaccination do not exert strong selective pressure on systemically replicating SIV.
Published: 2024
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48. The protective role of GATA6+ pericardial macrophages in pericardial inflammation

Author: David M. Hughes, Taejoon Won, Monica V. Talor, Hannah M. Kalinoski, Ivana Jurčová, Ondrej Szárszoi, Ilja Stříž, Lenka Čurnová, William Bracamonte-Baran, Vojtěch Melenovský, and Daniela Čiháková
Subjects: Natural sciences, Biological sciences, Biochemistry, Physiology, cell biology, Science
Abstract: Summary: Prior research has suggested that GATA6+ pericardial macrophages may traffic to the myocardium to prevent interstitial fibrosis after myocardial infarction (MI), while subsequent literature claims that they do not. We demonstrate that GATA6+ pericardial macrophages are critical for preventing IL-33 induced pericarditis and attenuate trafficking of inflammatory monocytes and granulocytes to the pericardial cavity after MI. However, absence of GATA6+ macrophages did not affect myocardial inflammation due to MI or coxsackievirus-B3 induced myocarditis, or late-stage cardiac fibrosis and cardiac function post MI. GATA6+ macrophages are significantly less transcriptionally active following stimulation in vitro compared to bone marrow-derived macrophages and do not induce upregulation of inflammatory markers in fibroblasts. This suggests that GATA6+ pericardial macrophages attenuate inflammation through their interactions with surrounding cells. We therefore conclude that GATA6+ pericardial macrophages are critical in modulating pericardial inflammation, but do not play a significant role in controlling myocardial inflammation or fibrosis.
Published: 2024
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49. Environmental impact assessments should include rigorous scientific peer review

Author: Robert M. Hughes, David M. Chambers, Dominick A. DellaSala, James R. Karr, Susan C. Lubetkin, Sarah O'Neal, Robert L. Vadas, Jr., and Carol Ann Woody
Subjects: Ecological evaluation, Environmental assessment, Independent scientific peer review, National environmental policy act (NEPA), Risk assessment, Environmental sciences, GE1-350, Biology (General), QH301-705.5
Abstract: Twenty USA states or jurisdictions and 125 nations have modeled national environmental policies after the National Environmental Policy Act. That act mandates that federal agencies initiate environmental impact statements (EISs) when substantive environmental or human health consequences are likely because of an agency action related to proposed development projects. The science used to inform the EIS process, however, does not require independent scientific peer review (ISPR) in the USA or most other nations. But ISPR is needed for governments to accurately inform the EIS decision-making and public reporting processes. Instead, science is routinely manipulated during EIS reviews to generate expedient project outcomes with substantially negative ecological, political, and long-term economic consequences. We provide four examples of EISs that lack ISPR, as well as four examples where reviews by independent scientists were helpful to improve agency decisions. We also recommend that independent scientists (no affiliation with the project proponents or agencies overseeing projects) be used to help assess potential environmental and socio-economic impacts, as well as offer appropriate risk assessments, study designs, and monitoring timeframes. We conclude that nations should convene formal reviews using independent scientists as a form of peer review in the EIS process.
Published: 2024
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50. Examining the Academic Distress and Career Concerns among Sexual and Gender Minority College Students Who Seek Counseling

Author: Christopher M. Hughes
Abstract: This study aims to explore the relationship of Gender and Sexual Minority (GSM) college students with academic stress through the use of counseling and how this may differ based on sexual orientation and gender identity. In addition, this study examined frequency of career concerns among GSM college students. Further this study aimed to determine if there are differences in the change in academic distress for GSM college students when considering their racial and ethnic identity. A secondary data set including 42,035 participants was obtained from the Collegiate Center for Mental Health (CCMH). One-Way ANOVA, Chi-Square, and Multiple Linear Regression were utilized to investigate the research questions. Results showed that there were differences in initial academic distress scores based on sexual orientation, gender identity and race and ethnicity were statistically significant predictors of academic change, and there were a difference between GSM college students and non-GSM college students with frequency of career concerns. Implications for counselors, counseling centers, and university student services are discussed as well as areas for future research. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]
Published: 2023

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