Digital Commons Network^™

Biocompatibility Of Silver And Hydroxyapatite Antimicrobial Nanocoatings On Titanium Alloy Dental Implants With Human Gingival Fibroblasts, S Morgan, R D Handy, V M Salih, R N Salaie, C J Tredwin, A Besinis

School of Engineering, Computing and Mathematics

OBJECTIVES: Peri-implantitis compromises soft and hard tissues around dental implants, often leading to implant failure. Antibacterial nanocoatings offer a promising infection control strategy, but maintaining biocompatibility is essential. This study investigated, through a range of assays and analytical techniques, the biocompatibility of antimicrobial silver and hydroxyapatite (HA) nanocoatings applied to titanium implants with human gingival fibroblasts (HGFs).

METHODS: Silver and hydroxyapatite nanocoatings were applied to the surface of titanium alloy specimens using electroplating, deposition and sintering techniques. The biocompatibility of the nanocoatings with HGFs was assessed by measuring cell metabolic activity (alamarBlue), lactate dehydrogenase (LDH) release, collagen production (Sircol assay), …

Heat Transfer From A Partially Buried Circular Cylinder In Oscillatory Flow, H. Thomas, R. Stuhlmeier, A. G.L. Borthwick, S. Michele

School of Engineering, Computing and Mathematics

With the growing abundance of man-made cylindrical structures located on or close to the seabed, it is important to be able to assess their potential environmental impact. Herein, a model is presented of the viscous-thermal boundary layer in the vicinity of a circular cylinder resting on, or partially buried in, an otherwise flat seabed. To model the influence of wave-induced motions near such a cylinder, we assume oscillatory flow in which the water particle displacements are small with respect to the cylinder radius. A perturbation expansion is utilised to derive solutions of the boundary layer equations, leading to analytical solutions …

Microplastics, Nanoplastics And Liver Disease: An Emerging Health Concern?, Shilpa Chokshi, Ashwin Dhanda, Matthew E. Cramp, Richard Thompson

Peninsula Medical School

Human liver tissue has been found to contain microplastics and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has markedly increased over the past 10 years, prompting critical questions regarding their potential causal role in liver disease. In cell-based and murine models, MNP exposure can trigger oxidative stress, fibrogenesis and inflammation, pathological features that resemble those of advanced liver disease, suggesting shared mechanistic pathways. Furthermore, the capacity for MNPs to act as vectors for microbial pathogens, antimicrobial resistance, endocrine-disrupting chemicals and carcinogenic additives might have important implications for liver pathology. This Perspective examines emerging evidence on the consequences of MNPs …

The Utility Of Fret/Flim-Based Bioassays For Monitoring Nrf2 Activation In Single Live Cells, Dina Dikovskaya, Albena T Dinkova-Kostova

Peninsula Medical School

The Kelch-like ECH-associated protein 1 - Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) partnership is vital for protection against oxidative stress, and its dysregulation has been linked to the pathogenesis of numerous chronic diseases. Under homeostatic conditions, Keap1 targets Nrf2 for ubiquitination and proteasomal degradation. When Keap1 is inactivated by electrophiles or Keap1-Nrf2 protein-protein interaction (PPI) inhibitors (termed inducers), Nrf2 accumulates and, in association with a small musculoaponeurotic fibrosarcoma (sMaf) protein, induces the transcription of networks of genes encoding cytoprotective proteins. To understand the PPIs between Nrf2 and Keap1 and the effect of inducers in the cellular context, we expressed …

Diagnosing Long-Term Divergence In Build Back Better Outcomes In Low- And Lower-Middle-Income Communities, E. A. Opabola, M. Baiguera, A. Raby, T. Rossetto, A. Pomonis, E. Meilianda, Y. Idris, S. Nurdin, K. Adams, D. J. Mcgovern, N. Acikgoz, H. Mistry, F. Marafini

School of Engineering, Computing and Mathematics

Low-income communities in disaster-prone regions face persistent challenges in translating post-disaster recovery investments into sustained resilience, as they navigate trade-offs among engineering objectives, policy constraints, and evolving socio-economic needs. Despite the widespread adoption of Build Back Better (BBB) principles, evidence on the long-term sustainability of outcomes remains limited, particularly in low- and lower-middle-income contexts. This study examines the sustainability of BBB outcomes in two Indonesian case studies: Banda Aceh (approximately 18 years after the 2004 Indian Ocean tsunami) and Central Sulawesi (approximately 4 years after the 2018 earthquake, liquefaction, and tsunami). Drawing on structured housing assessments, household surveys, semi-structured interviews, …

Post-Release Mortality Of European Bass (Dicentrarchus Labrax) Discarded From Small-Scale Estuarine Fishing, J. E. Stewart, T. Stamp, P. Davies, A. Hall, T. Robbins, L. Stewart, E. V. Sheehan

School of Biological and Marine Sciences

Estuaries provide essential habitats for many fish species, but their confined and accessible nature may increase fish vulnerability to capture, and few empirical studies have quantified the value of restricting net fisheries in such areas. Furthermore, management measures for some fisheries promote discarding (e.g., of European sea bass; Dicentrarchus labrax), yet the mortality of fish discarded from small-scale inshore fisheries is poorly understood. We used condition assessments, Reflex Action Mortality Predictor scores and acoustic tracking to evaluate post-release mortality of bass captured in small-scale estuarine netting and angling. Gillnet-caught bass exhibited a range of stress responses and 20%–24% mortality shortly …

On The Edge Of Science?: Commentary On Birch On Edge Of Sentience, Mark Briffa, Lynne U. Sneddon

School of Biological and Marine Sciences

In The Edge of Sentience, Jonathan Birch (2024) provides a thought-provokingsynthesis of current perspectives on animal (and artificial) sentience. He addresses the question from conceptual, ethical, regulatory and empirical viewpoints. Here we focus on some of the scientific issues raised, including defining and operationalising the concept of sentience and the implications for policy and regulation. Despite unresolved conceptual challenges, the book makes a compelling case for the continued scientific investigation of animal sentience.

Investigating Spatial And Seasonal Differences In Microgastropod Assemblages Within The Little-Studied Camamu Bay, Brazil: A Potential Bioindicator For Remote Tropical Areas?, Francisco Kelmo, Sol De Maria Cesar Ferreira, Eduardo Henrique Galvão, Martin J. Attrill

School of Biological and Marine Sciences

This study investigates spatial and seasonal variation in the assemblages of benthic microgastropods (snails < 5–10 mm in length) within a poorly studied tropical bay. As these organisms are abundant, diverse and relatively easy to sample, with well-established taxonomy, they may prove a highly suitable group for ecological studies in such areas. Sediment samples were collected from three river basins in Camamu Bay, Brazil, during the wet and dry seasons. A total of 132 microgastropod species was recorded, demonstrating high diversity. The most abundant species were Eulithidium affine, Bittiolum varium, Cerithium atratum, Vitta virginea and Schwartziella bryerea. The least abundant species were Tenaturris gemma, Turbinella laevigata, Petaloconchus erectus, Parviturboides interruptus and Vitrinella cupidinensis. Statistical analysis revealed significant seasonal and spatial differences in diversity and assemblage composition, which correlated with environmental gradients. The results suggest that microgastropods are a suitable component of the biota for ecological and applied studies in marine sediments, particularly in remote tropical locations where full macrofaunal analysis may be challenging. Whilst further testing across impact gradients is needed, this approach offers a practical solution for ecological investigations in remote regions with limited taxonomic expertise and highlights microgastropods as a useful indicator taxon for impact biomonitoring in tropical marine sediments.

Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs

Faculty, Staff and Student Publications

Radioactive iodine (RAI) therapy with 131-iodine (131I) remains a cornerstone in the postoperative management of differentiated thyroid carcinoma (DTC). The standard route of administration is oral, typically in capsule form and less commonly as a liquid. However, in patients with severe dysphagia and compromised airway, traditional oral 131I delivery may be contraindicated due to the risk of aspiration and radioactivity contamination. These scenarios present unique clinical challenges that necessitate deviation from conventional protocols. While liquid 131I may be administered through the mouth or via nasogastric or percutaneous gastrostomy tubes, there is currently no standardized approach, and potential risks, such as …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …

Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan

Faculty, Staff and Student Publications

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing …

A Combinatorial Approach To Synthetic Data Generation For Machine Learning, Krishna Khadka, Jaganmohan Chandrasekaran, Yu Lei, Raghu Kacker, D Richard Kuhn

Faculty, Staff and Student Publications

Datasets used in machine learning often contain sensitive information, including personally identifiable health and financial details. A common challenge faced by organizations and researchers is the risk of privacy breaches when using real-world data. Synthetic data can be used as an alternative to the real-world data. In existing synthetic data generation techniques, an encoder processes the real-world data to map it into a lower-dimensional latent space. Random sampling is then performed in this latent space. Subsequently, a decoder network is utilized to generate synthetic data from these sampled points in the latent space. Such approaches typically require generating a large …

Functional, Pharmacogenomic, And Immune Landscapes Of Long Non-Coding Rnas In Cancer, Runhao Wang, Mei Luo, Yuan Liu, Jingwen Yang, Yamei Chen, Chengxuan Chen, Lifei Ma, Stephanie Ding, James Wengler, Yong Zang, Bora Lim, Wenbo Li, Liuqing Yang, Chunru Lin, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are emerging as key regulators in cancer, with significant potential as diagnostic, prognostic, and therapeutic targets. Here, this work systematically analyzes lncRNA associations with targeted therapies and immunotherapies across 33 cancer types using The Cancer Genome Atlas (TCGA) and real-world datasets. This work identifies 53,173 lncRNA-pathway associations, millions of lncRNA-drug response associations (via CancerRxTissue and VAEN), and extensive correlations with immune checkpoints and infiltration. This work further identifies 69 lncRNAs associated with immunotherapy response and 2,611 differentially expressed lncRNAs between low and high objective response rate (ORR) groups. Additionally, two lncRNAs are correlated with immune-related adverse …

Bop2-Comb: Bayesian Optimal Phase Ii Design For Optimizing Doses And Assessing Contribution Of Components In Drug Combinations, Xiaohan Chi, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Background: Personalized cancer treatment using combination therapies offers substantial therapeutic benefits over single-agent treatments in most cancers. However, unmet clinical needs and increasing market competition pressure drug developers to quickly optimize combination doses and clearly demonstrate the contribution of each component when developing and evaluating new combination treatments.

Methods: We propose a Bayesian optimal phase II drug-combination (BOP2-Comb) design that optimizes the combination dose and evaluates the proof-of-concept as well as the contribution of each component in two seamless stages. Our optimal calibration scheme minimizes the total trial sample size while controlling incorrect decision rates at nominal levels. This calibration …

Peripheral Cd200r Signaling: A Critical Regulator Of Post-Stroke Inflammation In Aged Mice, Conelius Ngwa, Afzal Misrani, Yan Xu, Jingjing Wang, Rodney Ritzel, Fudong Liu

Faculty, Staff and Student Publications

The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16-19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then …

The Legacy Of A Gentleman Scientist: Pierre Hainaut, Christophe Arnoult, Laura D Attardi, Kerem Batsheva, Giovanni Blandino, Kathleen H Burns, Giannino Del Sal, David G Kirsch, David P Lane, Arnold J Levine, Guillermina Lozano, David Malkin, Gerry Melino, Moshe Oren, Carol Prives, Daniel Schramek

Faculty, Staff and Student Publications

No abstract provided.

Contemporary Opportunities And Potential Of Auger Electron-Emitting Theranostics, Seok-Yong Lee, H Charles Manning

Faculty, Staff and Student Publications

Recent breakthroughs in radiopharmaceutical (RP) therapy have emerged interest in employing Auger electron (AE)-emitting radionuclides as potential agents for precise theranostics. AE provides energy with exceptional localization due to their short tissue penetration range (TPR, < 10 nm), rendering them particularly effective for targeting nuclear DNA in tumor cells. In this context, AE-emitting radionuclide therapy (AE-emitting RLT) enables the targeted destruction of tumor cells while reducing harm to adjacent healthy tissue, a significant challenge in this field. Preclinical and early clinical investigations reveal the efficacy of AE-emitting RLTs in the theranostics of diverse malignancies, such as glioblastoma, prostate cancer, and neuroendocrine tumors. Notwithstanding these developments, challenges and limitations persist regarding dosimetry, delivery efficiency, and the treatment of radiotoxicity. A new paradigm is being developed to tackle the obstacles encountered by integrating molecular target markers (e.g., PARP) that function near the nucleus to improve the intranuclear delivery efficiency of AE-emitting radionuclides. Novel radiochemical methods such as these have facilitated the more stable and efficient labeling of biomolecules with AE-emitting radionuclides. Also, recent advances in DNA-molecular targeting, nanoparticles, nucleic acid/protein engineering, click- or bioorthogonal conjugation chemistry, and artificial intelligence (AI)-based structure modeling present concrete opportunities to overcome these limitations. Moreover, the integration of diagnostic imaging companion platforms employing theranostic radioisotope pairings facilitates real-time assessment of therapeutic efficacy and biodistribution, resulting in the formulation of enhanced treatment regimens. This review summarizes the prior development, recent advancements, barriers in clinical implementation, and future perspective of AE-emitting RLTs.

Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3–5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable. Here we characterize a series of clinical-grade small-molecule catalytic NSD2 inhibitors (NSD2i) and show that the pharmacological targeting of NSD2 constitutes an epigenetic dependency with broad therapeutic efficacy in KRAS-driven preclinical cancer models. NSD2i inhibits NSD2 with single-digit nanomolar half-maximal inhibitory concentration potency and high selectivity over related methyltransferases. Structural analyses reveal that the specificity of NSD2i for NSD2 …

Respiratory Motion Effects And Plan Robustness For Lattice Radiation Therapy, Rachael M Martin-Paulpeter, Peter A Balter, Luis A Perles, Ethan B Ludmir, Joshua S Niedzielski

Faculty, Staff and Student Publications

Introduction: Lattice radiation therapy (LRT), a form of spatially fractionated radiation therapy (SFRT), has shown promise in treating bulky tumors. It consists of hot and cold spots within the tumor, and the ratio between these doses is thought to be important in clinical outcomes. Respiratory motion is expected to degrade these peak-to-valley dose ratios (PVDRs) but has largely been ignored in LRT literature and clinical practice. This work aims to quantify the response of LRT dose distributions to motion to better inform motion management decisions and improve clinical outcomes.

Methods: Respiratory motion of peak-to-peak amplitudes from 0.3 to 2 cm …

Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.

Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …

Single-Cell Lineage Trajectory Defines Cyclin-Dependent Kinase Inhibitor-Sensitive Cells-Of-Origin In Esophageal Squamous Cell Carcinoma, Kyung-Pil Ko, Jie Zhang, Sohee Jun, Jae-Il Park

Faculty, Staff and Student Publications

Background and aims: Understanding the cells of origin is essential for overcoming therapy resistance and improving early intervention strategies in esophageal squamous cell carcinoma (ESCC). Despite recent advances in genomic profiling, the precise cellular hierarchies and molecular programs driving ESCC initiation remain poorly defined.

Methods: We utilized machine learning-based single-cell trajectory analysis on 4-nitroquinoline 1-oxide-induced murine models and genetically engineered organoids to identify cellular lineages during tumorigenesis. Combined with gene regulatory network analysis, we identified transcriptional drivers of tumor initiation and employed transcriptome-based drug repurposing to predict compounds targeting these initiating populations.

Results: Our analyses revealed multiple distinct epithelial clusters …

Key Regulatory Roles Of Prdm1 In Human Nk-Cell Differentiation And Activation, Xuxiang Liu, Yunfei Shi, Jibin Zhang, Kunal Shetty, Krystie Chew, Can Küçük, Qiang Gong, Esra Esmeray, Haiqing Li, Ru Chen, Sheng Pan, Katarzyna Dąbrowska, Roger E Moore, Krystine Garcia-Mansfield, Patrick Pirrotte, Jinhui Wang, Yuping Li, Gehong Dong, Logan Lee, Timothy W Mckeithan, Javeed Iqbal, Wing C Chan

Faculty, Staff and Student Publications

PRDM1, encoding a transcription factor (TF), regulates plasma cell and CD8+ T-cell terminal differentiation and Th2 lineage specification, while its role in human NK-cell differentiation and homeostasis is largely unknown. Here, we employed a multi-omics approach to dissect the transcriptional control of PRDM1 on human NK-cells. PRDM1 is important in NK-cell terminal differentiation based on gene expression profiling and its targeting of key regulators in the process. PRDM1-deleted NK-cells displayed a less mature phenotype simulating the CD56bright NK-cell population accompanied by upregulation of stem-like gene signatures. PRDM1-bound genes were enriched in T/NK-cell receptor signaling, activation, and NK-cell effector …

Grading Melanocytic Dysplasia: Updated Histopathologic Criteria, Christopher R Shea, Victor G Prieto, Catherine M Shachaf, Scott R Florell

Faculty, Staff and Student Publications

Dr. Martin C. Mihm, Jr.'s innovative work on the dysplastic nevus achieved a milestone in his chapter in the World Health Organisation Classification of Skin Tumours (WHO-C). WHO-C presents a dichotomous classification (high-grade versus low-grade dysplastic nevi) and a quantitative metric to assess melanocytic nuclear enlargement. The Duke classification is a related approach that provides mostly quantitative histopathologic criteria for dysplastic nevi and gives due weight to architectural features as well as cytology. This paper proposes and illustrates updated criteria for scoring and grading melanocytic dysplasia, incorporating some of the definitions and categories of WHO-C, while refining the quantitative and …

Evaluation Of Organ-Specific Relative Biological Effectiveness Of Proton Therapy Using Radiation-Induced Pneumonitis As An Endpoint, Li Liao, Ting Xu, Mei Chen, Tingshi Su, Narayan Sahoo, Xiaorong Zhu, Steven J Frank, Quynh-Nhu Nguyen, Zhongxing Liao, Xiaodong Zhang

Faculty, Staff and Student Publications

Background and purpose: Proton therapy has become widely used for non-small cell lung cancer (NSCLC) due to its ability to spare normal tissue. However, the commonly assumed relative biological effectiveness (RBE) of 1.1 may underestimate the therapy's true biological effects on lung, potentially leading to a higher than expected incidence of radiation-induced pneumonitis (RP). In this retrospective study, we evaluated the variability of organ-specific RBE of proton therapy using RP grade 2 or higher (RP2+) as an endpoint.

Materials and methods: Data from 270 NSCLC patients across two clinical trials were analyzed, with 134 given photon therapy and 136 given …

Trial Interviews To Explore Glycogen Storage Disease Type Ia Patient Experiences Following Gene Therapy, Diane M Turner-Bowker, Jessica Butler, Shayna Egan, David A Weinstein, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, Rebecca Riba-Wolman, John J Mitchell, Christina Theodore-Oklota

Faculty, Staff and Student Publications

Background: Glycogen storage disease type Ia (GSDIa) is a rare, inherited, autosomal recessive deficiency of glucose-6-phosphatase (G6Pase), an enzyme necessary in glycogenolysis and gluconeogenesis. To maintain normal blood glucose levels and ensure survival, individuals living with GSDIa must frequently consume complex carbohydrates (eg, uncooked cornstarch). Dietary management can result in chronic complications and significant patient burden. DTX401 (pariglasgene brecaparvovec) is an investigational adeno-associated virus serotype 8 vector (AAV8)-based gene therapy designed to restore endogenous glucose production.

Objectives: Patient experience interviews were conducted as part of an open-label, phase 1/2 dose-escalation trial (NCT03517085) evaluating the safety and efficacy of …

Dietetic Guidance For Nutritional Management Of People With Phenylketonuria Receiving Sepiapterin, Anita Macdonald, Kirsten Ahring, Alexa Bledsoe, Hiroki Fujimoto, Sara Giorda, Christian Kogelmann, Jessica Kopesky, Laura Nagy, Sara O'Neill, Alex Pinto, Soraia Poloni, Paige Roberts, Annemiek M J Van Wegberg, Suzanne Hollander

Faculty, Staff and Student Publications

Background/objectives: Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. If untreated, elevated blood phenylalanine (Phe) levels lead to neurological and behavioral impairments. Phe levels can be managed through a lifelong Phe-restricted diet; however, this can be challenging to maintain. Sepiapterin is an adjunct therapy for PKU that has shown efficacy in reducing blood Phe levels in both tetrahydrobiopterin (BH4)-responsive and BH4-non-responsive people with PKU in clinical trials. Practical guidance is needed for dietitians and other healthcare professionals supporting the dietary management of people with PKU who are initiating or receiving sepiapterin.

Methods: A group of international dietitians participated …

Digital Marine Citizenship Training Module: Toolkit For Digital Placemaking, Katharine Willis

School of Art, Design and Architecture

As a coastal nation, the UK has long drawn inspiration from the sea - shaping our history through travel, industry, the arts, leisure and more. The coastline remains a place of identity and possibility. It also offers signifi cant benefi ts for health, wellbeing and connection, yet many local people are disconnected from nearby shores.This Training Module is an easy to use resource to reimagine community relationships with the sea and make coastal spaces more inclusive, welcoming and vibrant for all.Connected SeascapesOrigins of the Training Module The Connected Seascapes Toolkit stems from a collaborative project between Plymouth City Council, the …

Review Of 'The Royal Musical Association: Creating Scholars, Advancing Research' By Leanne Langley, Nuria Bonet

School of Art, Design and Architecture

No abstract provided.