3,019 results on '"Hoskin, P."'
Search Results
2. Immune effects of α and β radionuclides in metastatic prostate cancer
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Lunj, Sapna, Smith, Tim Andrew Davies, Reeves, Kimberley Jayne, Currell, Fred, Honeychurch, Jamie, Hoskin, Peter, and Choudhury, Ananya
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- 2024
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3. Clipped Axillary Node as a Potential Surrogate for Overall Axillary Nodal Status in Inflammatory Breast Cancer Patients after Neoadjuvant Chemotherapy
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Lohani, Kush R., Hoskin, Tanya L., Yasir, Saba, Olson, Carrie A., Boughey, Judy C., Hieken, Tina J., and Degnim, Amy C.
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- 2024
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4. Discontinuous Galerkin Methods for Hypersonic Flows
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Hoskin, Dominique S., Van Heyningen, R. Loek, Nguyen, Ngoc Cuong, Vila-Pérez, Jordi, Harris, Wesley L., and Peraire, Jaime
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Physics - Fluid Dynamics ,76M10, 76F65, 76K05 - Abstract
In recent years, high-order discontinuous Galerkin (DG) methods have emerged as an attractive approach for numerical simulations of compressible flows. This paper presents an overview of the recent development of DG methods for compressible flows with particular focus on hypersononic flows. First, we survey state-of-the-art DG methods for computational fluid dynamics. Next, we discuss both matrix-based and matrix-free iterative methods for the solution of discrete systems stemming from the spatial DG discretizations of the compressible Navier-Stokes equations. We then describe various shock capturing methods to deal with strong shock waves in hypersonic flows. We discuss adaptivity techniques to refine high-order meshes, and synthetic boundary conditions to simulate free-stream disturbances in hypersonic boundary layers. We present a few examples to demonstrate the ability of high-order DG methods to provide accurate solutions of hypersonic laminar flows. Furthermore, we present direct numerical simulations of hypersonic transitional flow past a flared cone at Reynolds number $10.8 \times 10^6$, and hypersonic transitional shock wave boundary layer interaction flow over a flat plate at Reynolds number $3.97 \times 10^6$. These simulations run entirely on hundreds of graphics processing units (GPUs) and demonstrate the ability of DG methods to directly resolve hypersonic transitional flows, even at high Reynolds numbers, without relying on transition or turbulence models. We end the paper by offering our perspectives on error estimation, turbulence modeling, and real gas effects in hypersonic flows., Comment: 34 pages, 25 figures, and 1 table
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- 2023
5. Correlation of PET-CT Nodal Imaging and Pathologic Response to Neoadjuvant Immunotherapy for Node-Positive Breast Cancer
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Carroll, Jennifer F., Hoskin, Tanya L., and Hieken, Tina J.
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- 2024
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6. Optimizing processing parameters to produce a novel spray dried hydrolyzed rice-derived ingredient using response surface methodology
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Garcia, Diego, de Medeiros, Fábio Gonçalves Macȇdo, Hoskin, Roberta Targino, and Moncada, Marvin
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- 2024
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7. In-Breast Tumor Progression During Neoadjuvant Chemotherapy: Impact on and Factors Influencing Distant Recurrence-Free Survival
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Eckert, Kathryn M., Hoskin, Tanya L., Olson, Carrie A., Goetz, Matthew P., and Boughey, Judy C.
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- 2024
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8. Microcalcifications in benign breast biopsies: association with lesion type and risk
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Schrup, Sarah, Hardway, Heather, Vierkant, Robert A., Winham, Stacey J., Jensen, Matthew R., McCauley, Bryan, Hoskin, Tanya, Seymour, Lisa, Gehling, Denice, Fischer, Jessica, Vachon, Celine M., Maimone, Santo, Pacheco-Spann, Laura, Radisky, Derek C., Carter, Jodi M., Degnim, Amy C., and Sherman, Mark E.
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- 2024
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9. Impact of Presenting Stage on Overall Survival in Patients Treated with Neoadjuvant Chemotherapy for Triple Negative Breast Cancer
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Carroll, Jennifer F., Hoskin, Tanya L., Leon-Ferre, Roberto A., and Boughey, Judy C.
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- 2024
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10. Sonoprocessing coupled to spray drying as a novel strategy to encapsulate bioactive compounds from acerola pomace extract into Saccharomyces cerevisiae cells
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de Andrade, Eduardo Wagner Vasconcelos, Hoskin, Roberta Targino, Dupont, Sébastien, Beney, Laurent, Caon, Thiago, and da Silva Pedrini, Márcia Regina
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- 2024
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11. Main sequence companions to white dwarfs II: the age-activity-rotation relation from a sample of Gaia common proper motion pairs
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Rebassa-Mansergas, A., Maldonado, J., Raddi, R., Torres, S., Hoskin, M., Cunningham, T., Hollands, M. A., Ren, J., Gaensicke, B. T., Tremblay, P. -E., and Camisassa, M.
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
Magnetic activity and rotation are related to the age of low-mass main sequence stars. To further constrain these relations, we study a sample of 574 main sequence stars members of common proper motion pairs with white dwarfs, identified thanks to Gaia astrometry. We use the white dwarfs as age indicators, while the activity indexes and rotational velocities are obtained from the main sequence companions using standard procedures. We find that stars older than 5 Gyr do not display Halpha nor Caii H&K emission unless they are fast rotators due to tidal locking from the presence of unseen companions and that the rotational velocities tend to decrease over time, thus supporting the so-called gyrochronology. However, we also find moderately old stars (~2-6 Gyr) that are active presumably because they rotate faster than they should for their given ages. This indicates that they may be suffering from weakened magnetic braking or that they possibly evolved through wind accretion processes in the past. The activity fractions that we measure for all stars younger than 5 Gyr range between ~10-40 per cent. This is line with the expectations, since our sample is composed of F, G, K and early M stars, which are thought to have short (<2 Gyr) activity lifetimes. Finally, we observe that the Halpha fractional luminosities and the R'HK indexes for our sample of (slowly rotating) stars show a spread (-4>log(LHalpha/Lbol); log(R'HK)> -5) typically found in inactive M stars or weakly active/inactive F, G, K stars., Comment: Acceted for publication by MNRAS
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- 2023
12. An HST COS ultra-violet spectroscopic survey of 311 DA white dwarfs.I. Fundamental parameters and comparative studies
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Sahu, Snehalata, Gaensicke, Boris T., Tremblay, Pier-Emmanuel, Koester, Detlev, Hermes, J. J., Wilson, David J., Toloza, Odette, Hoskin, Matthew J., Farihi, Jay, Manser, Christopher J., and Redfield, Seth
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Astrophysics - Solar and Stellar Astrophysics - Abstract
White dwarf studies carry significant implications across multiple fields of astrophysics, including exoplanets, supernova explosions, and cosmological investigations. Thus, accurate determinations of their fundamental parameters (Teff and log g) are of utmost importance. While optical surveys have provided measurements for many white dwarfs, there is a lack of studies utilising ultraviolet (UV) data, particularly focusing on the warmer ones that predominantly emit in the UV range. Here, we present the medium-resolution far-UV spectroscopic survey of 311 DA white dwarfs obtained with Cosmic Origins Spectrograph (COS) onboard Hubble Space Telescope confirming 49 photometric Gaia candidates. We used 3D extinction maps, parallaxes, and hydrogen atmosphere models to fit the spectra of the stars that lie in the range 12 000 < Teff < 33 000 K, and 7 <= log g < 9.2. To assess the impact of input physics, we employed two mass-radius relations in the fitting and compared the results with previous studies. The comparisons suggest the COS Teff are systematically lower by 3 per cent on average than Balmer line fits while they differ by only 1.5 per cent from optical photometric studies. The mass distributions indicate that the COS masses are smaller by approximately 0.05 Msol and 0.02 Msol than Balmer lines and photometric masses, respectively. Performing several tests, we find that the discrepancies are either arising due to issues with the COS calibration, broadening theories for hydrogen lines, or interstellar reddening which needs further examination. Based on comparative analysis, we identify 30 binary candidates drawing attention for follow-up studies to confirm their nature., Comment: Accepted for publication in MNRAS. 17 pages, 17 figures, 4 Tables
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- 2023
13. Study protocol for Early Tracking of Childhood Health determinants (ETCHED): A longitudinal observational life course study
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Elsa Vazquez Arreola, Dean V. Coonrod, Sourav Roy Choudhury, William C. Knowler, Mary Hoskin, Dorota Wasak, Rachel Williams, Robert L. Hanson, Elena Pack, Rachel Caballero, Amanda Gonzalez, and Madhumita Sinha
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Childhood obesity ,Minority health ,Gestational diabetes ,Youth onset diabetes ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background The prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk. Methods ETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child’s 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years. Discussion This is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention. Trial registration number ClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1 .
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- 2024
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14. Presenting Concerns and Psychotherapy Utilization in University Counseling Centers: What Do We Know about Asian American and International Asian Students?
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Yoko Caldwell, Heidi A. Vogeler, David M. Erekson, Derek Griner, Mark E. Beecher, Klinton Hobbs, Dominic Schmuck, Vaughn Worthen, Jason M. Hoskin, Brett M. Merrill, and Jared Hales
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Individuals from Asian American (AA) and international Asian (IA) backgrounds are often lumped together in mental health research, which may obscure important differences in mental health presentation and need. While previous research has examined differences amongst AA and IA students seeking therapy at a single university counseling center, our study sought to better generalize these findings by utilizing a national data set to examine differences in treatment utilization, presenting concerns, overall distress, and improvement in treatment. Our results showed that IA students utilize therapy at lower rates than AA students. However, both groups attended appointments at roughly the same rate. Distress at intake was significantly higher for IA students across most domains measured. Finally, both groups improved in treatment at similar rates, with some differences observed between IA undergraduate and graduate students. We discuss implications for college counseling professionals and urge further research in this domain.
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- 2024
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15. Comparing Psychotherapeutic Treatment Rates in University Counseling Centers between American Latinx and International Latinx University Students
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Jason M. Hoskin, Heidi Vogeler, Jessica Kirchhoefer, Brett M. Merrill, David Erekson, Mark E. Beecher, and Derek Griner
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As the press for services at university counseling centers increases, so does the need to provide optimal therapeutic services. Ethnic glossing in previous research has combined rather disaggregated the mental health treatment experiences of American Latinx (AL) students and International Latinx (IL) students. The purpose of this paper was to examine potential differences in (1) the number of attended sessions, (2) symptom severity, and (3) treatment improvement rates. We used a nationwide dataset including 13,156 AL students and 911 IL students. Results indicated that (1) there was no significant difference in attendance rates, (2) AL students had significantly worse initial symptom severity (d = 0.24), and (3) there were no significant differences in improvement rates. We discuss the importance of understanding the different clinical presentations of AL and IL students, as well as the importance of addressing ethnic glossing in future research and clinical work.
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- 2024
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16. Stakeholder Views on Cognitive Communication Assessment and Intervention for a Person Living Independently in the Community with Severe Traumatic Brain Injury
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Susan Howell, Joanna Hoskin, Debbie Eaton, Mark Holloway, and Rosemary Varley
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Background: Cognitive communication disorder (CCD) following traumatic brain injury (TBI) is well documented and these communication problems impede successful re-integration into community living. While there is growing evidence for intervention to both detect and treat the impact of these deficits across the rehabilitation continuum, there are barriers to accessing services. Cognitive communication impairments may be missed because the person can talk, and this may mask the subtle but debilitating impact of a CCD. Referral to a speech and language therapist (SLT) may be overlooked or not timely, which prevents the individual accessing evidence-based interventions. Inadequate treatment provision and an under- or overestimation of communication capability can potentially undermine the effectiveness of wider team assessment and intervention. Aims: To report stakeholder views on specialist SLT input for CCD within a multidisciplinary team intervention for a community-dwelling individual with severe TBI. The investigation explored perspectives on understanding of CCD, on practice and on outcomes, in order to inform professional groups on perceived impacts of the evidence-to-practice gap. Methods and Procedures: A semi-structured interview methodology was employed with 11 stakeholder participants involved in a single case. Data were evaluated using a thematic framework method. Themes were inductively derived from the stakeholder narratives. Outcomes: Stakeholders reported the following outcomes from specialist SLT input for CCD within a collaborative team approach: improved engagement with rehabilitation and support teams, improved health-related quality of life and well-being, and increased client participation in community activities of personal relevance. Stakeholders also reported inequities in wider service provision where limitations in professional understanding of CCD and knowledge of best practice recommendations preclude access to specialist SLT services. Conclusions: CCDs are under-recognised and this can have a devastating effect on people with CCD and on those around them. Stakeholder reports provide evidence for the effectiveness of SLT practice recommendations for the treatment of CCD following TBI. They also provide additional evidence of persisting barriers to accessing treatment. Future research to explore ways to close this evidence-to-practice gap is required.
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- 2024
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17. ASO Visual Abstract: Clipped Axillary Node as a Potential Surrogate for Overall Axillary Nodal Status in Patients with Inflammatory Breast Cancer After Neoadjuvant Chemotherapy
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Lohani, Kush R., Hoskin, Tanya L., Yasir, Saba, Olson, Carrie A., Boughey, Judy C., Hieken, Tina J., and Degnim, Amy C.
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- 2024
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18. ASO Author Reflections: Time to Explore Minimally Invasive Axillary Nodal Staging After Neo-Adjuvant Chemotherapy in Inflammatory Breast Cancer
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Lohani, Kush R., Hoskin, Tanya L., Yasir, Saba, Olson, Carrie A., Boughey, Judy C., Hieken, Tina J., and Degnim, Amy C.
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- 2024
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19. Study protocol for Early Tracking of Childhood Health determinants (ETCHED): A longitudinal observational life course study
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Arreola, Elsa Vazquez, Coonrod, Dean V., Roy Choudhury, Sourav, Knowler, William C., Hoskin, Mary, Wasak, Dorota, Williams, Rachel, Hanson, Robert L., Pack, Elena, Caballero, Rachel, Gonzalez, Amanda, and Sinha, Madhumita
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- 2024
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20. Digital spatial profiling of the microenvironment of muscle invasive bladder cancer
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Eyers, Michael, Irlam, Joely, Marshall, Gayle, Smith, Vicky, Baker, Alexander, Frost, Lucy, Hoskin, Peter, Choudhury, Ananya, and West, Catharine
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- 2024
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21. Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer
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Leon-Ferre, Roberto A., Whitaker, Kaitlyn R., Suman, Vera J., Hoskin, Tanya, Giridhar, Karthik V., Moore, Raymond M., Al-Jarrad, Ahmad, McLaughlin, Sarah A., Northfelt, Donald W., Hunt, Katie N., Conners, Amy Lynn, Moyer, Ann, Carter, Jodi M., Kalari, Krishna, Weinshilboum, Richard, Wang, Liewei, Ingle, James N., Knutson, Keith L., Ansell, Stephen M., Boughey, Judy C., Goetz, Matthew P., and Villasboas, Jose C.
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- 2024
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22. Dose escalation of tolinapant (ASTX660) in combination with standard radical chemoradiotherapy in cervical cancer : a study protocol for a phase 1b TiTE-CRM clinical trial (CRAIN) in UK secondary care centres
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Hoskin, Peter, Lee, Marina, Dunkley, Denise, Danh, Mary, Wickens, Robin, Saunders, Geoff, Northey, Josh, Crabb, Simon, McFarlane, Vicky, Sadozye, Azmat, Cooper, Rachel, Mathew, Tony, Haslett, Kate, Reeves, Kim, Reed, Rachel, Bigos, Kamilla, Williams, Kaye J., Rowling, Emily, Choudhury, Ananya, Dancer, Sonia, Smith, Deb, and Griffiths, Gareth
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- 2024
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23. Patient-reported outcomes and healthcare resource utilization in systemic lupus erythematosus: impact of disease activity
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Touma, Zahi, Costenbader, Karen H., Hoskin, Ben, Atkinson, Christian, Bell, David, Pike, James, Berry, Pamela, and Karyekar, Chetan S.
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- 2024
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24. Beyond surgery: bladder preservation and the role of systemic treatment in localised muscle-invasive bladder cancer
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Swinton, Martin, Devi, Aarani, Song, Yee Pei, Hoskin, Peter, and Choudhury, Ananya
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- 2024
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25. Radiotherapy in metastatic bladder cancer
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Ashley, Sophie, Choudhury, Ananya, Hoskin, Peter, Song, YeePei, and Maitre, Priyamvada
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- 2024
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26. Coconut-sourced MCT oil: its potential health benefits beyond traditional coconut oil
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Duranova, Hana, Kuzelova, Lenka, Fialkova, Veronika, Simora, Veronika, Kovacikova, Eva, Joanidis, Patricia, Borotova, Petra, Straka, Dusan, Hoskin, Roberta Targino, Moncada, Marvin, de Medeiros, Fábio Gonçalves Macêdo, and Gabriny, Lucia
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- 2024
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27. Sonoprocessing enhances the stabilization of fisetin by encapsulation in Saccharomyces cerevisiae cells
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de Andrade, Eduardo Wagner Vasconcelos, Dupont, Sebastien, Beney, Laurent, Hoskin, Roberta Targino, and da Silva Pedrini, Márcia Regina
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- 2024
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28. Digital spatial profiling of the microenvironment of muscle invasive bladder cancer
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Michael Eyers, Joely Irlam, Gayle Marshall, Vicky Smith, Alexander Baker, Lucy Frost, Peter Hoskin, Ananya Choudhury, and Catharine West
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Biology (General) ,QH301-705.5 - Abstract
Abstract Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving a transcriptomic snapshot of a section of the tumour. However, tumour tissues are not homogeneous, but are composed of distinct compartments such as the tumour and stroma. To investigate the molecular profiles of bladder cancer, whilst also maintaining the spatial complexity of the tumours, we employed whole transcriptome Digital Spatial Profiling (DSP). With this method we generated a dataset of transcriptomic profiles of tumour epithelium, stroma, and immune infiltrate. With these data we investigate the spatial relationship of molecular subtype signatures and ligand signalling events. We find that Basal/Squamous and Classical subtypes are mostly restricted to tumour regions, while the stroma-rich subtype signatures are abundant within the stroma itself. Additionally, we identify ligand signalling events occurring between tumour, stroma, and immune infiltrate regions, such as immune infiltrate derived GPNMB, which was highly correlated with VEGFA expression within the tumour. These findings give us new insights into the diversity of MIBC at a molecular level and provide a dataset with detailed spatial information that was not available before in bladder cancer research.
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- 2024
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29. Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer
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Roberto A. Leon-Ferre, Kaitlyn R. Whitaker, Vera J. Suman, Tanya Hoskin, Karthik V. Giridhar, Raymond M. Moore, Ahmad Al-Jarrad, Sarah A. McLaughlin, Donald W. Northfelt, Katie N. Hunt, Amy Lynn Conners, Ann Moyer, Jodi M. Carter, Krishna Kalari, Richard Weinshilboum, Liewei Wang, James N. Ingle, Keith L. Knutson, Stephen M. Ansell, Judy C. Boughey, Matthew P. Goetz, and Jose C. Villasboas
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Breast cancer ,Immunology ,Biomarkers ,Chemotherapy ,Translational research ,Single cell technologies ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied. Methods Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal–Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC. Results There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response. Conclusions Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer. Trial registration NCT02022202 . Registered 20 December 2013.
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- 2024
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30. Dose escalation of tolinapant (ASTX660) in combination with standard radical chemoradiotherapy in cervical cancer : a study protocol for a phase 1b TiTE-CRM clinical trial (CRAIN) in UK secondary care centres
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Peter Hoskin, Marina Lee, Denise Dunkley, Mary Danh, Robin Wickens, Geoff Saunders, Josh Northey, Simon Crabb, Vicky McFarlane, Azmat Sadozye, Rachel Cooper, Tony Mathew, Kate Haslett, Kim Reeves, Rachel Reed, Kamilla Bigos, Kaye J. Williams, Emily Rowling, Ananya Choudhury, Sonia Dancer, Deb Smith, and Gareth Griffiths
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Cervical cancer ,Tolinapant ,Chemoradiotherapy ,Cisplatin ,Phase I ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, is an IAP antagonist with an additional mechanism of action via down-regulation of NF-kB, an important regulator in cervical cancer. Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival. There is therefore a strong rationale to combine tolinapant with chemoradiotherapy (CRT). Methods CRAIN is a phase Ib open-label, dose escalation study to characterise the safety, tolerability and initial evidence for clinical activity of tolinapant when administered in combination with cisplatin based CRT. Up to 42 patients with newly diagnosed cervix cancer will be recruited from six UK secondary care sites. The number of participants and the duration of the trial will depend on toxicities observed and dose escalation decisions, utilising a TiTE-CRM statistical design. Treatment will constist of standard of care CRT with 45 Gy external beam radiotherapy given in 25 daily fractions over 5 weeks with weekly cisplatin 40mg/m2. This is followed by brachytherapy for which common schedules will be 28 Gy in 4 fractions high-dose-rate or 34 Gy in 2 fractions pulsed-dose-rate. Tolinapant will be administered in fixed dose capsules taken orally daily for seven consecutive days as an outpatient on alternate weeks (weeks 1, 3, 5) during chemoradiation. Dose levels for tolinapant which will be assessed are: 60 mg; 90 mg (starting level); 120 mg; 150 mg; 180 mg. Escalation will be guided by emerging safety data and decisions by the Safety Review Committee. Discussion If this trial determines a recommended phase II dose and shows tolinapant to be safe and effective in combination with CRT, it would warrant future phase trials. Ultimately, we hope to provide a synergistic treatment option for these patients to improve outcome. Trial registrations EudraCT Number: 2021-006555-34 (issued 30th November 2021); ISRCTN18574865 (registered 30th August 2022).
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- 2024
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31. Patient-reported outcomes and healthcare resource utilization in systemic lupus erythematosus: impact of disease activity
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Zahi Touma, Karen H. Costenbader, Ben Hoskin, Christian Atkinson, David Bell, James Pike, Pamela Berry, and Chetan S. Karyekar
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Disease activity ,Healthcare resource utilization ,Patient-reported outcomes ,Real world systemic lupus erythematosus ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Limited real-world data exists on clinical outcomes in systemic lupus erythematosus (SLE) patients by SLE Disease Activity Index 2000 (SLEDAI-2 K), hereafter, SLEDAI. We aimed to examine the association between SLEDAI score and clinical, patient-reported and economic outcomes in patients with SLE. Methods Rheumatologists from the United States of America and Europe provided real-world demographic, clinical, and healthcare resource utilization (HCRU) data for SLE patients. Patients provided self-reported outcome data, capturing their general health status using the EuroQol 5-dimension 3-level questionnaire (EQ-5D-3 L), health-related quality of life using the Functional Assessment of Chronic Illness Therapy (FACIT) and work productivity using the Work Productivity and Activity Impairment questionnaire (WPAI). Low disease activity was defined as SLEDAI score ≤ 4 and ≤ 7.5 mg/day glucocorticoids; patients not meeting these criteria were considered to have “higher” active disease. Data were compared between patients with low and higher disease activity. Logistic regression estimated a propensity score for SLE based on demographic and clinical characteristics. Propensity score matched analyses compared HCRU, patient-reported outcomes, income loss and treatment satisfaction in patients with low disease activity versus higher active disease. Results Data from 296 physicians reporting on 730 patients (46 low disease activity, 684 higher active disease), and from 377 patients’ self-reported questionnaires (24 low disease activity, 353 higher active disease) were analyzed. Flaring in the previous 12 months was 2.6-fold more common among patients with higher versus low active disease. Equation 5D-3 L utility index was 0.79 and 0.88 and FACIT-Fatigue scores were 34.78 and 39.79 in low versus higher active disease patients, respectively, indicating better health and less fatigue, among patients with low versus higher active disease. Absenteeism, presenteeism, overall work impairment, and total activity impairment were 47.0-, 2.0-, 2.6- and 1.5-fold greater in patients with higher versus low disease activity. In the previous 12 months there were 28% more healthcare consultations and 3.4-fold more patients hospitalized in patients with higher versus low disease activity. Conclusion Compared to SLE patients with higher active disease, patients with low disease activity experienced better health status, lower HCRU, less fatigue, and lower work productivity impairment, with work absenteeism being substantially lower in these patients.
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- 2024
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32. The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation
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Jin, Shoko, Trager, Scott C., Dalton, Gavin B., Aguerri, J. Alfonso L., Drew, J. E., Falcón-Barroso, Jesús, Gänsicke, Boris T., Hill, Vanessa, Iovino, Angela, Pieri, Matthew M., Poggianti, Bianca M., Smith, D. J. B., Vallenari, Antonella, Abrams, Don Carlos, Aguado, David S., Antoja, Teresa, Aragón-Salamanca, Alfonso, Ascasibar, Yago, Babusiaux, Carine, Balcells, Marc, Barrena, R., Battaglia, Giuseppina, Belokurov, Vasily, Bensby, Thomas, Bonifacio, Piercarlo, Bragaglia, Angela, Carrasco, Esperanza, Carrera, Ricardo, Cornwell, Daniel J., Domínguez-Palmero, Lilian, Duncan, Kenneth J., Famaey, Benoit, Fariña, Cecilia, Gonzalez, Oscar A., Guest, Steve, Hatch, Nina A., Hess, Kelley M., Hoskin, Matthew J., Irwin, Mike, Knapen, Johan H., Koposov, Sergey E., Kuchner, Ulrike, Laigle, Clotilde, Lewis, Jim, Longhetti, Marcella, Lucatello, Sara, Méndez-Abreu, Jairo, Mercurio, Amata, Molaeinezhad, Alireza, Monguió, Maria, Morrison, Sean, Murphy, David N. A., de Arriba, Luis Peralta, Pérez, Isabel, Pérez-Ràfols, Ignasi, Picó, Sergio, Raddi, Roberto, Romero-Gómez, Mercè, Royer, Frédéric, Siebert, Arnaud, Seabroke, George M., Som, Debopam, Terrett, David, Thomas, Guillaume, Wesson, Roger, Worley, C. Clare, Alfaro, Emilio J., Prieto, Carlos Allende, Alonso-Santiago, Javier, Amos, Nicholas J., Ashley, Richard P., Balaguer-Núñez, Lola, Balbinot, Eduardo, Bellazzini, Michele, Benn, Chris R., Berlanas, Sara R., Bernard, Edouard J., Best, Philip, Bettoni, Daniela, Bianco, Andrea, Bishop, Georgia, Blomqvist, Michael, Boeche, Corrado, Bolzonella, Micol, Bonoli, Silvia, Bosma, Albert, Britavskiy, Nikolay, Busarello, Gianni, Caffau, Elisabetta, Cantat-Gaudin, Tristan, Castro-Ginard, Alfred, Couto, Guilherme, Carbajo-Hijarrubia, Juan, Carter, David, Casamiquela, Laia, Conrado, Ana M., Corcho-Caballero, Pablo, Costantin, Luca, Deason, Alis, de Burgos, Abel, De Grandi, Sabrina, Di Matteo, Paola, Domínguez-Gómez, Jesús, Dorda, Ricardo, Drake, Alyssa, Dutta, Rajeshwari, Erkal, Denis, Feltzing, Sofia, Ferré-Mateu, Anna, Feuillet, Diane, Figueras, Francesca, Fossat, Matteo, Franciosin, Elena, Frasca, Antonio, Fumagalli, Michele, Gallazzi, Anna, García-Benito, Rubén, Fusillo, Nicola Gentile, Gebran, Marwan, Gilbert, James, Gledhill, T. M., Delgado, Rosa M. González, Greimel, Robert, Guarcello, Mario Giuseppe, Guerra, Jose, Gullieuszik, Marco, Haines, Christopher P., Hardcastle, Martin J., Harris, Amy, Haywood, Misha, Helmi, Amina, Hernandez, Nauzet, Herrero, Artemio, Hughes, Sarah, Irsic, Vid, Jablonka, Pascale, Jarvis, Matt J., Jordi, Carme, Kondapally, Rohit, Kordopatis, Georges, Krogager, Jens-Kristian, La Barbera, Francesco, Lam, Man I, Larsen, Søren S., Lemasle, Bertrand, Lewis, Ian J., Lhomé, Emilie, Lind, Karin, Lodi, Marcello, Longobardi, Alessia, Lonoce, Ilaria, Magrin, Laura, Apellániz, Jesús Maíz, Marchal, Olivier, Marco, Amparo, Martin, Nicolas F., Matsuno, Tadafumi, Maurogordato, Sophie, Merluzzi, Paola, Miralda-Escudé, Jordi, Molinari, Emilio, Monari, Giacomo, Morelli, Lorenzo, Mottram, Christopher J., Naylor, Tim, Negueruela, Ignacio, Oñorbe, Jose, Pancino, Elena, Peirani, Sébastien, Peletier, Reynier F., Pozzetti, Lucia, Rainer, Monica, Ramos, Pau, Read, Shaun C., Rossi, Elena Maria, Röttgering, Huub J. A., Rubiño-Martín, Jose Alberto, Montes, Jose Sabater, Juan, José San, Sanna, Nicoletta, Schallig, Ellen, Schiavon, Ricardo P., Schultheis, Mathias, Serra, Paolo, Shimwell, Timothy W., Simón-Díaz, Sergio, Smith, Russell J., Sordo, Rosanna, Sorini, Daniele, Soubiran, Caroline, Starkenburg, Else, Steele, Iain A., Stott, John, Stuik, Remko, Tolstoy, Eline, Tortora, Crescenzo, Tsantaki, Maria, Van der Swaelmen, Mathieu, van Weeren, Reinout J., Vergani, Daniela, Verheijen, Marc A. W., Verro, Kristiina, Vink, Jorick S., Vioque, Miguel, Walcher, C. Jakob, Walton, Nicholas A., Wegg, Christopher, Weijmans, Anne-Marie, Williams, Wendy L., Wilson, Andrew J., Wright, Nicholas J., Xylakis-Dornbusch, Theodora, Youakim, Kris, Zibetti, Stefano, and Zurita, Cristina
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - Solar and Stellar Astrophysics - Abstract
WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366$-$959\,nm at $R\sim5000$, or two shorter ranges at $R\sim20\,000$. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for $\sim$3 million stars and detailed abundances for $\sim1.5$ million brighter field and open-cluster stars; (ii) survey $\sim0.4$ million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey $\sim400$ neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in $z<0.5$ cluster galaxies; (vi) survey stellar populations and kinematics in $\sim25\,000$ field galaxies at $0.3\lesssim z \lesssim 0.7$; (vii) study the cosmic evolution of accretion and star formation using $>1$ million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at $z>2$. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator., Comment: 41 pages, 27 figures, accepted for publication by MNRAS; updated version including information on individual grants in a revised Acknowledgements section, corrections to the affiliation list, and an updated references list
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- 2022
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33. Half body irradiation (HBI) for bone metastases in the modern radiotherapy technique era – A systematic review
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Mateusz Bilski, Katarzyna Konat-Bąska, Federico Mastroleo, Peter Hoskin, Barbara Alicja Jereczek-Fossa, Giulia Marvaso, Mateusz Korga, Jakub Klas, Katarzyna Zych, Piotr Bijak, Andrzej Kukiełka, Jacek Fijuth, and Łukasz Kuncman
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Half-body irradiation ,HBI ,Hemi-body irradiation ,Bone metastases ,Palliative radiotherapy ,IMRT ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Bone metastases (BMs) are the most common cause of cancer-related pain and radiation therapy plays a key role in treating pain caused by it. The half-body irradiation (HBI) is a modality that can be used to treat patients with multiple painful BMs. In the modern era, concerns about toxicity and the availability of new agents requiring robust bone marrow function have limited the use of HBI in advanced cancer. Concerns about HBI toxicity stem from outdated techniques; modern methods like volumetric modulated arc therapy (VMAT) and helical tomotherapy now allow safer irradiation of complex target volumes. We conducted a systematic review to present updated information about HBI efficacy and potential toxicity. Pain relief usually occurs very quickly 2–3 weeks after HBI. The overall pain response rate was high in all the series, accounting for a median of 84 % (75.6–89 %), with a median of 36 % complete pain response. The toxicity is usually limited to G1/G2, with very rare G3 cases. More than 50 % of patients can reduce analgesic intake after HBI. Additionally, with modern radiotherapy techniques, quality of life is improved in most patients. HBI is a safe and effective method and should once again be reconsidered for more frequent use.
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- 2024
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34. A review of whole gland prostate brachytherapy with focal dose escalation to intra-prostatic lesions: Clinical efficacy and technical aspects
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Joel Poder, Peter Hoskin, Hayley Reynolds, Tsz Him Chan, and Annette Haworth
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Brachytherapy ,Intra-prostatic lesion ,Prostate ,Dose escalation ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Focal boost to intra-prostatic lesions (IPLs) in radiotherapy could enhance treatment efficacy. Brachytherapy (BT), delivering highly conformal dose with sharp dose gradients emerges as a potentially optimal approach for precise dose escalation to IPLs. This study aims to consolidate clinical and planning studies that implemented whole gland prostate BT and focal dose escalation to IPLs, with the view to synthesize evidence on the strategy’s effectiveness and variability. In this review, we identified nine clinical studies and ten planning/simulation studies focusing on whole gland prostate BT with IPL dose escalation. From the clinical studies, the use of whole gland prostate BT with focal dose escalation in combination with external beam radiotherapy (EBRT) appears to be a safe and effective 21 form of treatment for men with T1b – T2c prostate cancer with average five-year biochemical failure22 free survival (BFFS) of 94 % (range 81.1 %−100 %) and minimal grade three toxicities reported. Both clinical and planning studies exemplified the high level of focal dose escalation achievable using BT with a mean IPL D90 % of 132 % and 146 %, respectively (expressed as a % of the whole gland prescription dose). There was considerable variation in the reporting of clinical and technical data in the identified studies. To facilitate a more widespread and uniform adoption of the technique, recommendations on essential and desirable items to be included in future studies incorporating whole gland prostate BT with focal boost to IPLs are provided.
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- 2024
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35. Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies.
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Azad, Taha, Rezaei, Reza, Singaravelu, Ragunath, Pelin, Adrian, Boulton, Stephen, Petryk, Julia, Onsu, Kemal Alper, Martin, Nikolas T, Hoskin, Victoria, Ghahremani, Mina, Marotel, Marie, Marius, Ricardo, He, Xiaohong, Crupi, Mathieu JF, Hoang, Huy-Dung, Nik-Akhtar, Abolfazl, Ahmadi, Mahsa, Zamani, Nika Kooshki, Golshani, Ashkan, Alain, Tommy, Greer, Peter, Ardolino, Michele, Dickinson, Bryan C, Tai, Lee-Hwa, Ilkow, Carolina S, and Bell, John C
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Vaccinia virus ,Genetic Vectors ,Oncolytic Virotherapy ,Oncolytic Viruses ,Promoter Regions ,Genetic ,Gene Therapy ,Genetics ,Biotechnology ,Good Health and Well Being - Abstract
The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additional regulatory layers for VV-encoded synthetic transgene networks. The switches are applied to enable inducible expression of fusogenic proteins, dose-controlled delivery of toxic cytokines, and chemical regulation of VV replication. This toolbox enables the precise modulation of transgene circuitry in VV-vectored oncolytic virus design.
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- 2023
36. Tumor Characteristics of Bilateral Breast Cancer Compared with Unilateral Breast Cancer
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Schulze, Amy K., Hoskin, Tanya L., Moldoveanu, Dan, Sturz, Jenna L., and Boughey, Judy C.
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- 2024
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37. Nodal pCR and overall survival following neoadjuvant chemotherapy for node positive ER+/Her2- breast cancer
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Moldoveanu, Dan, Hoskin, Tanya L., Day, Courtney N., Schulze, Amy K., Goetz, Matthew P., and Boughey, Judy C.
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- 2024
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38. Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I–III MIDLC Patients
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Lohani, Kush R., Hoskin, Tanya L., Day, Courtney N., Yasir, Saba, Boughey, Judy C., and Degnim, Amy C.
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- 2024
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39. Femmephobia Is a Uniquely Powerful Predictor of Anti-Gay Behavior
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Hoskin, Rhea Ashley, Blair, Karen L., and Holmberg, Diane
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- 2024
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40. Finite Element Analysis of Mechanical Ocular Sequelae from Badminton Shuttlecock Projectile Impact
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John D. Hong, PhD, Jose A. Colmenarez, MS, Elliot H. Choi, MD, PhD, Alex Suh, BS, Andrew Suh, BS, Matthew Lam, MD, Annette Hoskin, PhD, Don S. Minckler, MD, MS, Ken Y. Lin, MD, PhD, Kourosh Shahraki, MD, Rupesh Agrawal, MD, Pengfei Dong, PhD, Linxia Gu, PhD, and Donny W. Suh, MD, MBA
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Sports-related injury ,Ocular trauma ,Glaucoma ,Lens dislocation ,Retinal injury ,Ophthalmology ,RE1-994 - Abstract
Purpose: With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact. Design: Computational simulation study. Participants: None. Methods: A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head. Main Outcome Measures: Intraocular pressure and tissue stress. Results: Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (
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- 2025
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41. Identifying targetable metabolic dependencies across colorectal cancer progression
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Danny N. Legge, Tracey J. Collard, Ewelina Stanko, Ashley J. Hoskin, Amy K. Holt, Caroline J. Bull, Madhu Kollareddy, Jake Bellamy, Sarah Groves, Eric H. Ma, Emma Hazelwood, David Qualtrough, Borko Amulic, Karim Malik, Ann C. Williams, Nicholas Jones, and Emma E. Vincent
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Colorectal cancer ,Oncometabolism ,Asparagine ,Asparagine synthetase ,Adenoma ,Adenocarcinoma ,Internal medicine ,RC31-1245 - Abstract
Colorectal cancer (CRC) is a multi-stage process initiated through the formation of a benign adenoma, progressing to an invasive carcinoma and finally metastatic spread. Tumour cells must adapt their metabolism to support the energetic and biosynthetic demands associated with disease progression. As such, targeting cancer cell metabolism is a promising therapeutic avenue in CRC. However, to identify tractable nodes of metabolic vulnerability specific to CRC stage, we must understand how metabolism changes during CRC development. Here, we use a unique model system – comprising human early adenoma to late adenocarcinoma. We show that adenoma cells transition to elevated glycolysis at the early stages of tumour progression but maintain oxidative metabolism. Progressed adenocarcinoma cells rely more on glutamine-derived carbon to fuel the TCA cycle, whereas glycolysis and TCA cycle activity remain tightly coupled in early adenoma cells. Adenocarcinoma cells are more flexible with respect to fuel source, enabling them to proliferate in nutrient-poor environments. Despite this plasticity, we identify asparagine (ASN) synthesis as a node of metabolic vulnerability in late-stage adenocarcinoma cells. We show that loss of asparagine synthetase (ASNS) blocks their proliferation, whereas early adenoma cells are largely resistant to ASN deprivation. Mechanistically, we show that late-stage adenocarcinoma cells are dependent on ASNS to support mTORC1 signalling and maximal glycolytic and oxidative capacity. Resistance to ASNS loss in early adenoma cells is likely due to a feedback loop, absent in late-stage cells, allowing them to sense and regulate ASN levels and supplement ASN by autophagy. Together, our study defines metabolic changes during CRC development and highlights ASN synthesis as a targetable metabolic vulnerability in later stage disease.
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- 2024
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42. Predicting radiotherapy response, Toxicities and quality-of-life related functional outcomes in soft tissue sarcoma of the extremities (PredicT) using dose–volume constraints development: a study protocol
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Rita Simões, Kevin Harrington, Shane Zaidi, Peter Hoskin, Elizabeth Miles, Beatrice Seddon, Martin Robinson, Hakim-Moulay Dehbi, Piers Gaunt, Kabir Mohammed, Aisha Miah, Ana Hughes, Sharon Forsyth, Sarah Gulliford, Thuy-Giang Nguyen, and Stephanie Elston
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Medicine - Abstract
Introduction Radiotherapy improves local tumour control in patients with soft tissue sarcoma of the extremities (STSE) but it also increases the probability of long-term toxicities such as tissue fibrosis, joint stiffness and lymphoedema. The use of radiation dose and volume thresholds, called dose constraints, may potentially reduce the development of toxicities in STSE. The aim of this study is to determine predictors of radiotherapy-related side effects for STSE.Methods and analysis Predicting radiotherapy response, Toxicities and quality-of-life related functional outcomes in soft tissue sarcoma of the extremities (PredicT) is a multicentre observational study comprising two cohorts (PredicT A and B). PredicT A, a retrospective analysis of the UK VorteX (NCT00423618) and IMRiS clinical trials (NCT02520128), is aimed at deriving a statistical model for development of dose–volume constraints. This model will use receiving operator characteristics and multivariate analysis to predict radiotherapy side effects and patient-reported outcomes. PredicT B, a prospective cohort study of 150 patients with STSE, is aimed at testing the validity of those dose–volume constraints. PredicT B is open and planned to complete recruitment by September 2024.Ethics and dissemination PredicT B has received ethical approval from North West - Liverpool Central Research Ethics Committee (20/NW/0267). Participants gave informed consent to participate in the study before taking part. We will disseminate our findings via publications, presentations, national and international conference meetings and engage with local charities.Trial registration number NCT05978024.
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- 2024
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43. Urinary biomarkers in metastatic bone pain: Results from a multicentre randomized trial of ibandronate compared to single dose radiotherapy for localized metastatic bone pain in prostate cancer (RIB)
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P.J. Hoskin, Aman Malhi, Krystyna Reczko, and Allan Hackshaw
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Ibandronate ,Radiotherapy ,Bisphosphonate ,Osteoclasts ,Metastatic bone pain ,Biomarkers ,Diseases of the musculoskeletal system ,RC925-935 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The Radiotherapy IBandronate (RIB) trial compared single dose radiotherapy and a single infusion of ibandronate in 470 bisphosphonate naïve patients with metastatic bone pain from prostate cancer randomised into a non-inferiority two arm study. Results for the primary endpoint of pain score response at 4 weeks showed that the ibandronate arm was non-inferior to single dose radiotherapy. Patients and method: In addition to pain assessments including analgesic use made at baseline, 4, 8, 12, 26 and 52 weeks, urine was collected at baseline, 4 and 12 weeks. It was subsequently analysed for urinary N-telopeptide (NTx) and cystatin C. Linear regression models were used to compare the continuous outcome measures for urinary markers within treatment arms and baseline measurements were included as covariates. Interaction terms were fitted to allow for cross-treatment group comparisons. Results: The primary endpoint of the RIB trial was worst pain response at 4 weeks and there was no treatment difference seen. Urine samples and paired pain scores at 4 weeks were available for 273 patients (radiotherapy 168; ibandronate 159)The baseline samples measured for the RIB trial had an average concentration of 193 nM BCE/mM creatinine (range of 7.3–1871) compared to the quoted normal range of 33 nM BCE/mM creatinine (3 to 63). In contrast the average value of Cystatin C was 66 ng/ml (ranges ND – 1120 ng/ml) compared to the quoted normal range of 62.9 ng/ml (ranges 12.6–188 ng/ml). A statistically significant reduction in NTx concentrations between baseline and 4 weeks was seen in the ibandronate arm but not in the radiotherapy arm. No correlation between pain response and urinary marker concentration was seen in either the ibandronate or radiotherapy cohort at any time point. Conclusion: NTx was significantly raised compared to the normal range consistent with a role as a biomarker for bone metastases from prostate cancer. A significant reduction in NTx 4 weeks after ibandronate is consistent with its action in osteoclast inhibition which was not seen after radiotherapy implying a different mode of action for radiation. There was no correlation between bone biomarker levels and pain response.
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- 2024
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44. A method to image brain tissue frozen at autopsy
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Govind Nair, Roy Sun, Hellmut Merkle, Qing Xu, Kyra Hoskin, Kendyl Bree, Stephen Dodd, and Alan P. Koretsky
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Postmortem imaging ,Frozen tissue ,MRI ,Targeted histology ,Pathology ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Magnetic Resonance Imaging (MRI) can provide the location and signal characteristics of pathological regions within a postmortem tissue block, thereby improving the efficiency of histopathological studies. However, such postmortem-MRI guided histopathological studies have so far only been performed on fixed samples as imaging tissue frozen at the time of extraction, while preserving its integrity, is significantly more challenging. Here we describe the development of cold-postmortem-MRI, which can preserve tissue integrity and help target techniques such as transcriptomics. As a first step, RNA integrity number (RIN) was used to determine the rate of tissue biomolecular degradation in mouse brains placed at various temperatures between -20 °C and +20 °C for up to 24 h. Then, human tissue frozen at the time of autopsy was immersed in 2-methylbutane, sealed in a bio-safe tissue chamber, and cooled in the MRI using a recirculating chiller to determine MRI signal characteristics. The optimal imaging temperature, which did not show significant RIN deterioration for over 12 h, at the same time giving robust MRI signal and contrast between brain tissue types was deemed to be −7 °C. Finally, MRI was performed on human tissue blocks at this optimal imaging temperatures using a magnetization-prepared rapid gradient echo (MPRAGE, isotropic resolution between 0.3–0.4 mm) revealing good gray-white matter contrast and revealing subpial, subcortical, and deep white matter lesions. RINs measured before and after imaging revealed no significant changes (n = 3, p = 0.18, paired t-test). In addition to improving efficiency of downstream processes, imaging tissue at sub-zero temperatures may also improve our understanding of compartment specificity of MRI signal.
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- 2024
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45. Spray dried insect protein-polyphenol particles deliver health-relevant value-added food ingredients
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Edilene Souza da Silva, Jia Xiong, Fábio Gonçalves Macêdo de Medeiros, Mary Grace, Marvin Moncada, Mary Ann Lila, and Roberta Targino Hoskin
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Alternative protein ,Cricket ,Food ingredients ,Revalorization ,Nutrition. Foods and food supply ,TX341-641 ,Food processing and manufacture ,TP368-456 - Abstract
A novel strategy to create value-added insect protein-derived ingredients is presented in this study. Spray dried protein-polyphenol particles were produced using aqueous polyphenol extracts of rosemary (RM) or muscadine grape pomace (MG) complexed with insect protein (IP) alone or blended with pea protein 50:50 (IPP). The spray drying process was evaluated (solids recovery SR and polyphenol retention PR) and the four experimental protein-polyphenol treatments IP–RM, IP-MG, IPP–RM and IPP–MG were characterized regarding their physicochemical, bioactivity, functional, bioaccessibility and thermal stability properties. Higher SR (53.7–53.3%) and PR (53.1–62.5%) were observed for IPP-derived particles (p < 0.05). Particles had water activity in the microbiologically stable range (0.24–0.32) and high protein content (29.5%–38.3%). All particles had low hygroscopicity (68.5 mg GAE/g) was shown for MG-derived particles. Good emulsifying activity (1.85–16.46 m2/g) and emulsifying stability (>60%), foaming capacity (4–57%) and foaming stability (2.0–37.3%) were observed for all insect protein-polyphenol particles. Differently from MG-derived particles, RM-derived treatments showed higher polyphenol bioaccessibility than non-complexed polyphenols (p < 0.05). Overall, our study demonstrates that spray drying microencapsulation is an efficient strategy to produce attractively colored, value-added functional protein-polyphenol ingredients using insect protein.
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- 2024
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46. Workshop report: Workshop on psychiatric prescribing and psychology testing and intervention in children and adults with Duchenne muscular dystrophy
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Linda Bouquillon, Dot Bindman, Jos Hendriksen, Phillipe Collin, Janet Hoskin, Rory Conn, Chloe Geagan, and Ros Quinlivan
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Duchenne muscular dystrophy ,psychosocial ,psychia ,Science - Abstract
This workshop aimed at summarising knowledge and key issues in psychiatric prescribing and psychological testing in children and adults with Duchenne muscular dystrophy (DMD). It comprised clinicians and patient representatives from the UK and the Netherlands. The following topics were discussed: a model for capturing the range of non-motor problems in the domains of cognition, learning, emotion and behaviour; psychosocial screening tools for use with children and adults; assessing neurocognitive functioning in children and adults; parent and teacher perspectives on psychosocial needs; and psychopharmacological treatment for affective disorders, anxiety disorders, obsessive compulsive disorder, attention deficit hyperactivity disorder (ADHD) and insomnia. Some key considerations included: the need for tools used to assess behavioural and psychosocial functioning to consider motor aspects in DMD; to understand more about working memory performance; the need for early interventions for automatisation problems, which affect reading and arithmetic; appropriate selection of tests for neuropsychology assessments; in schools, acknowledging the range of psychosocial risks and gathering evidence of psychosocial needs; the suitability of selective serotonin reuptake inhibitors for mood and anxiety disorders; the use of stimulant medications for ADHD; melatonin use for insomnia; the cautious use of benzodiazepines; and the need for improving pathways for psychosocial care.
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- 2024
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47. Ongoing declines for the world’s amphibians in the face of emerging threats
- Author
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Luedtke, Jennifer A., Chanson, Janice, Neam, Kelsey, Hobin, Louise, Maciel, Adriano O., Catenazzi, Alessandro, Borzée, Amaël, Hamidy, Amir, Aowphol, Anchalee, Jean, Anderson, Sosa-Bartuano, Ángel, Fong G., Ansel, de Silva, Anslem, Fouquet, Antoine, Angulo, Ariadne, Kidov, Artem A., Muñoz Saravia, Arturo, Diesmos, Arvin C., Tominaga, Atsushi, Shrestha, Biraj, Gratwicke, Brian, Tjaturadi, Burhan, Martínez Rivera, Carlos C., Vásquez Almazán, Carlos R., Señaris, Celsa, Chandramouli, S. R., Strüssmann, Christine, Cortez Fernández, Claudia Fabiola, Azat, Claudio, Hoskin, Conrad J., Hilton-Taylor, Craig, Whyte, Damion L., Gower, David J., Olson, Deanna H., Cisneros-Heredia, Diego F., Santana, Diego José, Nagombi, Elizah, Najafi-Majd, Elnaz, Quah, Evan S. H., Bolaños, Federico, Xie, Feng, Brusquetti, Francisco, Álvarez, Francisco S., Andreone, Franco, Glaw, Frank, Castañeda, Franklin Enrique, Kraus, Fred, Parra-Olea, Gabriela, Chaves, Gerardo, Medina-Rangel, Guido F., González-Durán, Gustavo, Ortega-Andrade, H. Mauricio, Machado, Iberê F., Das, Indraneil, Dias, Iuri Ribeiro, Urbina-Cardona, J. Nicolas, Crnobrnja-Isailović, Jelka, Yang, Jian-Huan, Jianping, Jiang, Wangyal, Jigme Tshelthrim, Rowley, Jodi J. L., Measey, John, Vasudevan, Karthikeyan, Chan, Kin Onn, Gururaja, Kotambylu Vasudeva, Ovaska, Kristiina, Warr, Lauren C., Canseco-Márquez, Luis, Toledo, Luís Felipe, Díaz, Luis M., Khan, M. Monirul H., Meegaskumbura, Madhava, Acevedo, Manuel E., Napoli, Marcelo Felgueiras, Ponce, Marcos A., Vaira, Marcos, Lampo, Margarita, Yánez-Muñoz, Mario H., Scherz, Mark D., Rödel, Mark-Oliver, Matsui, Masafumi, Fildor, Maxon, Kusrini, Mirza D., Ahmed, Mohammad Firoz, Rais, Muhammad, Kouamé, N’Goran G., García, Nieves, Gonwouo, Nono Legrand, Burrowes, Patricia A., Imbun, Paul Y., Wagner, Philipp, Kok, Philippe J. R., Joglar, Rafael L., Auguste, Renoir J., Brandão, Reuber Albuquerque, Ibáñez, Roberto, von May, Rudolf, Hedges, S. Blair, Biju, S. D., Ganesh, S. R., Wren, Sally, Das, Sandeep, Flechas, Sandra V., Ashpole, Sara L., Robleto-Hernández, Silvia J., Loader, Simon P., Incháustegui, Sixto J., Garg, Sonali, Phimmachak, Somphouthone, Richards, Stephen J., Slimani, Tahar, Osborne-Naikatini, Tamara, Abreu-Jardim, Tatianne P. F., Condez, Thais H., De Carvalho, Thiago R., Cutajar, Timothy P., Pierson, Todd W., Nguyen, Truong Q., Kaya, Uğur, Yuan, Zhiyong, Long, Barney, Langhammer, Penny, and Stuart, Simon N.
- Published
- 2023
- Full Text
- View/download PDF
48. An invasive pathogen drives directional niche contractions in amphibians
- Author
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Scheele, Ben C., Heard, Geoffrey W., Cardillo, Marcel, Duncan, Richard P., Gillespie, Graeme R., Hoskin, Conrad J., Mahony, Michael, Newell, David, Rowley, Jodi J. L., and Sopniewski, Jarrod
- Published
- 2023
- Full Text
- View/download PDF
49. The first linkage map for Australo-Papuan Treefrogs (family: Pelodryadidae) reveals the sex-determination system of the Green-eyed Treefrog (Litoria serrata)
- Author
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Bertola, Lorenzo V., Hoskin, Conrad J., Jones, David B., Zenger, Kyall R., McKnight, Donald T., and Higgie, Megan
- Published
- 2023
- Full Text
- View/download PDF
50. Clinical Behavior, Management, and Treatment Response of Estrogen Receptor Low (1–10%) Breast Cancer
- Author
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Moldoveanu, Dan, Hoskin, Tanya L., Day, Courtney N., Schulze, Amy K., Goetz, Matthew P., and Boughey, Judy C.
- Published
- 2023
- Full Text
- View/download PDF
Catalog
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