Digital Commons Network^™

Lung Inflammation From Daily Exposure To Airborne Particulate Matter In A Trade School, Kynda Tinawi, Céline Plante, Alan Da Silveira Fleck, Édith Giasson, Isabelle Valois, Caroline Couture, Eva Suarthana, Maximilien Debia, Audrey Smargiassi

Études primaires

Background Workers are exposed daily to various airborne chemical agents, however, associations between daily exposures to particulate matter and lung inflammation in occupational settings have been little explored. Objective To estimate the association between daily occupational exposure to respirable (PM4 and PM2.5), ultrafine particles, their oxidative potential, and fractional exhaled nitric oxide within apprentices in a school of construction trades. Methods We used a repeated measures design over 5 consecutive days in 56 apprentices from 3 construction trade sectors (bricklaying, welding, and carpentry). Fractional exhaled nitric oxide was measured each day post-work. Personal and work area daily PM4 were collected …

Early Drowsiness Detection Via Second-Order Derivative Analysis Of Heart Rate Variability: A Non-Contact Ecg Approach With Machine Learning, Fabrice Vaussenat, Abhiroop Bhattacharya, Julie Payette, Alireza Saidi, Victor Bellemin, Geordi-Gabriel Renaud-Dumoulin, Sylvain G. Cloutier, Ghislain Gagnon

Études primaires

Drowsy driving contributes to roughly 20% of traffic fatalities, yet most detection systems rely on behavioral cues that appear only after impairment has set in. Here we ask whether first and second derivatives of heart rate variability (HRV) can detect pre-crash states earlier than conventional approaches. Twenty-five participants completed 49 driving simulator sessions while we recorded cardiac activity through capacitive ECG electrodes embedded in the seat backrest—a non-contact method that avoids the privacy concerns of camera-based monitoring. To prevent circular evaluation, ground truth labels were based solely on crash proximity rather than HRV-derived scores. The combined HRV feature set (conventional …

If Only Pickups And Vans Could Fly: Vehicle Maintenance And The Challenge Of Safely Lifting Large Vehicles On A Two-Post Lift, Damien Burlet-Vienney, Sylvie Beaugrand, Maud Gonella, Bertrand Galy, Élise Ledoux

Études primaires

The use of automotive lifts requires mechanics to work under or near a multi-ton load. Based on consultation with stakeholders, pickups and vans appear to pose problems when raised using two-post above-ground lifts (2PAG lifts), the most common type of automotive lift in garages. The aim of this study is therefore to highlight the work activity performed by mechanics when raising pickups and vans on 2PAG lifts and to describe the factors they take into account to ensure vehicle stability. Data collection took place under actual conditions in five garages. A total of 108 lifting situations were filmed and analyzed, …

Managing Complexity: Manager-Stakeholder Communication, Relational Dynamics, And The Dual Nature Of Rtw Communication, H. Bertolini, Marc Corbière, Alessia Negrini, Nadine Larivière, Patrizia Villotti, Dominic Prévost, Meryl Caiada, Jason Amorim, Fergal O'Hagan

Études primaires

Purpose

The return to work (RTW) process of worker absent due to common mental disorders (CMD) or musculoskeletal disorders (MSD) represents a complex challenge that involves multiple stakeholders. The aim of this study was to examine how managers perceive the factors that facilitate or hinder communication with other stakeholders during the RTW process.

This qualitative study was based on four focus groups conducted in Canada (Quebec and Ontario) with 18 managers.

Thematic analysis identified five themes related to facilitators and seven themes related to communication obstacles. Among the main facilitators, trust, clarity, and collaboration emerged as key elements …

Le Parcours Des Travailleurs Immigrants Blessés Et Son Incidence Sur L’Alliance Thérapeutique : Une Étude De Cas Longitudinale En Contexte De Réadaptation Au Travail Au Québec, Maude Arsenault, Jessica Dubé, Daniel Côté

Études primaires

Cette étude explore l’incidence du parcours prélésionnel des travailleuses et travailleurs immigrants (TI) blessés sur l’alliance thérapeutique (AT) en réadaptation au travail. À partir d’une ethnographie longitudinale menée dans une clinique québécoise, sept trajectoires ont été analysées selon leurs dimensions migratoires, socioprofessionnelles et linguistiques. Les résultats montrent que le déclassement professionnel, la précarité de l’emploi, les barrières linguistiques et les expériences de racisme fragilisent la construction du lien de confiance et la définition partagée des objectifs de retour au travail. Lorsque l’emploi prélésionnel est perçu comme transitoire ou inadéquat, l’obligation institutionnelle d’y retourner crée une rupture symbolique qui entre en …

Occupational Exposure To Pesticides Increases The Risk Of Amyotrophyc Lateral Sclerosis: A Systematic Review And Meta-Analysis, France Labrèche, Pamela Prudhomme, Maryse Gagnon, Nicolas Dupré, Sabrina Gravel

Études primaires

Objective To systematically review the evidence on the association between occupational exposure to pesticides and the risk of amyotrophic lateral sclerosis (ALS).

Methods A systematic search, conducted in eight bibliographic databases for publications between 1990 and 2025, identified observational studies estimating the risk of ALS after occupational pesticide exposure. Study quality was assessed using the WHO Risk of Bias (RoB) assessment instrument for systematic reviews, with the ROBINS-E (RoB in non-randomised studies of exposure) tool domains of bias. Pooled risk estimates were produced using random-effects models with restricted maximum likelihood, heterogeneity was assessed with I² statistics, and meta-regressions and publication …

On The Use Of Hearing Aid Algorithms In Industrial Noise: Balancing Speech Intelligibility And Hearing Protection, Solenn Ollivier, Fabien Bonnet, Alexis Pinsonnault-Skvarenina, Christian Giguère, Jérémie Voix, Hugues Nélisse

Études primaires

Hearing protection devices (HPDs) are widely used to mitigate the risks of noise-induced hearing loss in industrial environments. However, conventional HPDs can often hinder communication for workers with hearing loss. While those workers may rely on hearing aids in their daily lives, the potential benefits and associated risks of using such devices in noisy workplaces remain unexplored. This study evaluated the effects of different hearing aid signal processing algorithms on speech intelligibility and estimated noise exposure under industrial noise conditions to characterize the balance between communication and protection needed to develop solutions for workers with hearing loss. A digital hearing …

Tracking Vigilance While Driving: Pilot Study Of Heart Rate Variability Classification Under A Controlled Sleep-Deprivation Protocol, James Elber Duverger, Eli Moser, Philippe Boudreau, Marie Claude Ouimet, Diane B. Boivin, Alireza Saidi

Études primaires

Decreased vigilance associated with drowsiness is a major cause of motor vehicle crashes, but its physiological characterization and detection remain difficult due to behavioral and environmental confounding factors. This study presents an original experimental framework combining a highly controlled sleep-deprivation protocol, repeated driving simulations, and a machine-learning-based heart rate variability (HRV) analysis to study the physiological and behavioral changes in vigilance during a prolonged period of wakefulness while driving. Twelve healthy young adults participated in a 30-h sleep-deprivation constant routine protocol that included driving simulations every two hours, with data collection: electrocardiography (ECG), subjective ratings of drowsiness, psychomotor vigilance test, …

Computer Vision-Based Collision Prevention In Construction: Bridging Academic Advances And Industrial Requirements, Marwa Ziadia, François Gauthier, Damien Burlet-Vienney

Études primaires

Computer vision (CV) technologies have emerged as promising tools for real-time collision risk management. This paper examines CV-based collision-prevention systems from academic and industrial perspectives with a focus on identifying technical and implementation challenges affecting their deployment on construction sites. A scoping review of 158 publications was conducted, alongside an assessment of commercial CV-based collision-prevention systems currently used in construction. The analysis focused on five key functions: object detection, distance measurement and proximity estimation, tracking, worker re-identification (ReID), and deployment robustness. Academic studies demonstrate substantial progress in detection accuracy, real-time processing, trajectory tracking, and predictive risk assessment through deep learning …

Partnerships To Advance Patient Safety And Address Preventable Harm: Case Studies From International Health Care Leaders, Rachel Bonesteel, Robert Saunders, Tilithia Mcbride, Susan Sheridan, David W Bates, Mark Mcclellan, Charles H Kahn, Eyal Zimlichman

Faculty, Staff and Students Publications

There have been notable improvements in patient safety in recent years; however, significant challenges remain in reducing the incidence of preventable patient harm. Supporting patient safety efforts is increasingly important given increasing complexity of care and changing health needs, especially with aging populations. Emerging technologies and capabilities open new possibilities to address longstanding patient safety problems. For example, predictive analytics to support provider decision-making, increased patient interest in engagement in their care, and artificial intelligence provide opportunities to further reduce harm. Many of these examples support a more proactive approach to patient safety by focusing on anticipating, predicting, and preventing …

External Validation Of A Machine Learning Model To Predict Postpartum Hemorrhage In A Us Northeastern Healthcare System, Vesela P Kovacheva, Ricardo Kleinlein, Nolan Wheeler, Kartik K Venkatesh, Eric Jelovsek, David W Bates, Kathryn J Gray

Faculty, Staff and Students Publications

Introduction: Postpartum hemorrhage (PPH) is a major cause of maternal morbidity and mortality. Timely prediction may prevent adverse maternal outcomes, and efforts are needed to develop accurate predictive tools. A high-performing machine learning model to predict PPH using data from the US Consortium for Safe Labor (CSL) remains to be widely validated in contemporary clinical settings using electronic health record (EHR) data. Our goal was to evaluate the performance of the CSL PPH predictive model using EHR data across a large healthcare system in the Northeastern United States.

Methods: We conducted a retrospective cohort study across eight hospitals in the …

Contralateral Breast Cancer After Radiotherapy And Hormone Therapy In Two Cohorts Of Us Breast Cancer Survivors, Lene H S Veiga, Gretchen L Gierach, Susan A Smith, Rebecca M Howell, Matthew M Mille, Monjoy Saha, Rochelle E Curtis, Cody Ramin, Clara Bodelon, Heather Spencer Feigelson, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Jacqueline B Vo, Choonsik Lee, Amy Berrington De Gonzalez

Faculty, Staff and Student Publications

Background: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

Methods: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use.

Results: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); SEER cohort (n = 244,834) included 10,470 cases (72% ER+). Among women with ER+ …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin

Faculty, Staff and Student Publications

This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13). Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18). Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24). The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication …

Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner

Faculty, Staff and Student Publications

Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …

Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing

Faculty, Staff and Student Publications

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …

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 …