Digital Commons Network^™

Prevalence And Determinants Of Diabetes-Related Psychological Distress In A Tertiary Care Setting In Tamil Nadu: India: Cross-Sectional Study, Rohit Shankar, Samuel Tromans

Peninsula Medical School

BackgroundDiabetes distress, whereby people with diabetes experience distressing psychological symptoms associated with living with their condition, is an emerging problem in India. Diabetes distress leads to self-care deficits, suboptimal glycaemic control (which can lead to increasing risks of complications) and impaired quality of life.AimsTo determine the burden of diabetes distress and its associated factors in an Indian tertiary care centre in Trichy, Tamil Nadu, India, covering a population of 1.25 million.MethodThis prospective observational study involved a structured questionnaire covering demographic and clinical details, which was given to patients. The Diabetes Distress Scale 17 (DDS-17) was used to assess diabetes distress …

Global Manta And Devil Ray Population Declines: Closing Policy And Management Gaps To Reduce Fisheries Mortality, Betty J.L. Laglbauer, Nidhi G. D'Costa, Joshua D. Stewart, Marta D. Palacios, Melissa Cronin, Daniel Fernando, Nerea Lezama-Ochoa, Asia O. Armstrong, Rima W. Jabado, Sarah Fowler, Julia M. Lawson, Olga Koubrak, Jefferson Murua, Thanda Ko Gyi, Divya Karnad, Mayuri Chopra, Giuseppe Notarbartolo-Di-Sciara, Joshua Rambahiniarison, Don Croll, Stefany Rojas, Abdulaziz Fahmi, Joanna L. Harris, Alifa Binthe Haque, Hilario Murua, Juan Carlos Pérez-Jiménez, Emily Humble, Ellen Barrowclift, Muhammad G. Salim, Godefroy De Bruyne, Issah Seidu

School of Biological and Marine Sciences

Significant progress has been made in advancing priority actions to conserve manta and devil rays, yet implementation and enforcement of protective measures often fall short, leaving most mobulid populations at risk of overfishing. Drawing on a literature review, fisheries databases, agency reports, and expert interviews, we assess global trends in mobulid catch and mortality. We examine both targeted and incidental catch, in small (<15 m, ‘SV’) and large (>15 m, ‘LV’) vessel fisheries to identify hotspots with the highest risk of fisheries-related mortality and population decline. We estimate global fisheries catch at 264,520 (184,407–344,987) mobulids per year, with SV fisheries accounting for 87 % …

Involving Parents In Prevention: A Case Example Of Research And Intervention Development To Improve Financial Well-Being Support, Nick Axford, Gisella Hanley, Rebecca Summers, Kristin Liabo, Amy Bond, Eleanor Bryant, Georgia Smith, Rachel Silcock, Vashti Berry

Peninsula Medical School

The adverse effects on parent and child outcomes of poverty and stressors associated with low income are well established. With notable exceptions, however, the potential role of frontline services in improving family financial well-being is underexplored. This article outlines how patient and public involvement (PPI) was initiated early on in research on financial well-being support (FWbS). It illustrates how research can build on and integrate what parents say about services and how to research them. The involvement work was undertaken in one city in part to inform the adaptation of an income maximisation service to be delivered in local children’s …

Investigating The Potential For First Year Residential Field Courses To Facilitate The Establishment Of Teacher-Student Relationships In Biological Sciences Undergraduate Degrees, Anne Plessis, Alison Stokes

School of Biological and Marine Sciences

Teacher-student relationships (TSRs) in higher education impact many aspects of the student experience, including engagement and performance. However, relatively little is known about the mechanisms of establishment of TSRs, and in particular how these are influenced by specific learning environments and contexts. Here, we undertake an exploratory investigation using first year biological sciences undergraduate residential field courses to examine how this teaching context affected the frequency and nature of teacher student interactions, and consequently the development of TSRs. Data were collected from teacher and student participants using questionnaires and focus groups. We found that interactions during fieldwork took place frequently …

Next-Generation Virtual Environment Training For Cybersecurity In The Maritime Logistics Industry: A Position Paper, Tyler Cheng, Rory Hopcraft, Kimberly Tam, Ji-Jian Chin

School of Engineering, Computing and Mathematics

The maritime logistics industry is the most dependent on it in the modern world, yet it is not well protected against cyber risks. Recently, the maritime industry has been transitioning into industry-specific tech, and threats of cyberattacks are increasing as the adoption of technology and automation continues. One of the most effective methods to protect industries and ships from such security incidents, is to train seafarers to mitigate and handle such incidents. However, to the best of our knowledge, we did not find anything that addresses this gap. This article will present the idea and benefits of using virtual environments …

Investigating The Impact Of Carboxylated Polystyrene Nanoplastics In The Liver Using Cell Lines And Precision-Cut Liver Slices, Namrata Pandey, Paula Boeira, Nathaniel J. Clark, Eleanor T. Walker, Somaiah Aroori, Jemimah Denson, Richard C. Thompson, Matthew E. Cramp, Shilpa Chokshi, Ashwin Dhanda

Peninsula Medical School

Background and Aims: Increasing reports of plastic accumulation in human tissue have raised concerns about potential adverse health outcomes. Evidence of negative effects of nanoplastics is heterogeneous and provides limited insights into the underlying pathogenic toxicity mechanisms in humans. Methods: In the present study, carboxylate-modified fluorescently labelled polystyrene nanoparticles (PS NPs) were used to investigate uptake and cytotoxicity in three different hepatic models of varying complexity, including HepG2 cells, IHH cells, and human precision-cut liver slices (hPCLS). Results: The results show model- and dose-dependent effects on hepatocytes. 74.2% ± 13.4% of the IHH cells showed PS NPs uptake at 0.1 …

Healthcare Providers’ Prescribing Practices And Emergency Management Planning For Pre-Hospital Seizure Emergencies: A Comparison Of Hungary To Norway And The United Kingdom, Rohit Shankar

Peninsula Medical School

Background: Seizure emergencies, include prolonged seizures and status epilepticus (SE). Benzodiazepines are recommended as first-line rescue therapy. We investigate prescribing practices, emergency planning, and clinician experiences regarding rescue medication in Hungary and compare findings with those from the United Kingdom and Norway. Methods: A cross-sectional online survey (CHERRIES-compliant) was conducted between March and October 2025 among neurologists and pediatric neurologists in Hungary. The questionnaire explored demographics, prescribing behaviours, emergency management planning, and training practices. Descriptive statistics were used for Hungarian data, and comparative analyses with the combined UK and Norwegian cohorts were performed using chi-squared, Fisher's exact, and Mann–Whitney U …

Scope 3 Carbon Emissions Assessment For Manufacturing Smes, Kourosh Halat, Stephen Childe, Nick Golding, John Summerscales

School of Engineering, Computing and Mathematics

This paper addresses the challenges facing managers of Small-andMedium-Size Enterprises (SMEs) when conducting environmental sustainability assessment at the value chain level, particularly Scope 3 Greenhouse Gases GHG) emissions. The paper investigates issues related to data availability and data quality for Scope 3 assessment and identifies dimensions of Scope 3 reliability.Utilising a series of in-depth case study analyses with SMEs in the south-west of England, UK, the paper fills a gap in supply chain sustainability research by identifying practical challenges. The findings show that SMEs encounter persistent difficulties in assessing emissions associated with purchased goods and services and downstream activities linked …

Usable Authentication: Are We There Yet?, Nathan Clarke, Steven Furnell

School of Engineering, Computing and Mathematics

With technology increasingly embedded in everyday life, the demand for secure and usable authentication methods has never been greater. Traditional password-based systems continue to dominate, despite well-known usability and security challenges. This paper explores the evolution of user authentication technologies, from secret knowledge and tokens to biometrics and emerging approaches such as Passkeys. It critically evaluates the extent to which usability has been achieved, identifying both successes—such as biometrics integrated into smartphones—and persistent issues, including inconsistent guidance, ecosystem dependence, and accessibility barriers. Drawing on academic and commercial developments, the discussion highlights the growing burden on users who must authenticate across …

From Predictions To Explanations: Explainable Ai For Autism Diagnosis And Identification Of Critical Brain Regions: 18th International Joint Conference, Biostec 2025, Kush Gupta, Amir Aly, Emmanuel Ifeachor, Rohit Shankar

School of Engineering, Computing and Mathematics

Autism spectrum disorder (ASD) is a neurodevelopmentalcondition characterized by atypical brain maturation. However, the adaptationof transfer learning paradigms in machine learning for ASD researchremains notably limited. In this study, we propose a computeraideddiagnostic framework with two modules. This chapter presents atwo-module framework combining deep learning and explainable AI forASD diagnosis. The first module leverages a deep learning model finetunedthrough cross-domain transfer learning for ASD classification. Thesecond module focuses on interpreting the model’s decisions and identifyingcritical brain regions. To achieve this, we employed three explainableAI (XAI) techniques: saliency mapping, Gradient-weighted Class ActivationMapping, and SHapley Additive exPlanations (SHAP) analysis.This framework demonstrates that …

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 …