Medical Specialties Commons^™

Intraoperative Status Asthmaticus In A Morbidly Obese Preteen Undergoing Concomitant Vertical Sleeve Gastrectomy And Orthotopic Liver Transplant, Abigail Pint, Neal Campbell, Preethi Tumati

Posters

10-year-old morbidly obese male with cirrhotic ESLD secondary to vertically transmitted Hepatitis C presented for liver transplantation and concomitant vertical sleeve gastrectomy. Other history included moderate persistent asthma, OSA, and presumed HPS with baseline SpO2 of 94%. Induction was smooth; intubation with an armored ETT was easy. During invasive monitor placement, bronchospasm worsened SpO2. Continuous albuterol nebulization provided reasonable reversal, and all stakeholders agreed to proceed. Postoperative course was complicated by status asthmaticus and dramatic extubation on POD3 when patient bit and kinked armored ETT. To date, patient has good graft function and a 16% reduction from his peak BMI.

Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial …

Does Glial Lipid Dysregulation Alter Sleep In Alzheimer’S And Parkinson’S Disease?, Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep. In disease models, this process is disrupted, arguing a connection to sleep dysregulation. Relevant to PD, the degradation of neuronally synthesized glucosylceramides by glia requires glucocerebrosidase (GBA, a PD-associated risk factor) …

Cerebellar Deep Brain Stimulation As A Dual-Function Therapeutic For Restoring Movement And Sleep In Dystonic Mice, Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect …

Unusual Metastatic Pathways: A Case Of Colorectal Adenocarcinoma Presenting As A Cervical Neck Mass, Taha Al Hassan, Jessica Flores, Adam Bender-Heine, Rachel A. Giese

School of Medicine Publications

Head and neck metastasis of colorectal adenocarcinoma is exceedingly rare with most cases presenting in the liver, lungs, or peritoneum. This report describes the case of a 53-year-old female patient with a past medical history significant for mucinous adenocarcinoma of the colon treated with a right hemicolectomy. She was thought to be in remission but presented a few years later with a new, isolated left cervical neck mass and symptoms of left eye ptosis and dryness. Diagnostic imaging and biopsy confirmed the neck mass to be a metastatic lesion from her prior mucinous adenocarcinoma, with immunohistochemical findings specific for colorectal …

Supporting African Communities To Increase Resilience And Mental Health Of Kids With Developmental Disabilities And Their Caregivers Using The World Health Organization’S Caregiver Skills Training Programme (Spark Trial): Study Protocol For A Cluster Randomised Clinical Controlled Trial, Melissa Nortey, Vibian Angweny, Beatrice Mkubwa, Rosa Hoekstra, Andrew Healey, Rahel Birhane, Nadine Seward, Temesgen Azmeraw, Fikite Girma

Institute for Human Development, East Africa

Background: Most children with developmental disabilities (DD) live in low- and middle-income countries, but access to services is limited, impacting their ability to thrive. Pilot study findings of the World Health Organization’s Caregiver Skills Training (WHO CST) intervention, which equips caregivers with strategies to facilitate learning and adaptive behaviours in children with DD, are promising but evidence from an appropriately powered trial delivered by non-specialist facilitators is lacking. This study will investigate the effectiveness and the resource impacts and costs and consequences of the WHO CST intervention in four sites in rural and urban Kenya and Ethiopia.

Methods: …

The Grenada Learning And Memory Scale: Psychometric Features And Normative Data In Caribbean Preschool Children, Karen Blackmon, Roberta Evans, Lauren Mohammed, Kemi Burgen, Erin Ingraham, Bianca Punch, Rashida Isaac, Toni Murray, Jesma Noel, Cora Belmar-Roberts

Brain and Mind Institute

Objective: Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially pertinent in low- and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. The Grenada Learning and Memory Scale (GLAMS) was created for use in limited resource settings and includes a shopping list and face-name association test. Here, we present psychometric and normative data for the GLAMS in a Grenadian preschool sample.

Methods: Typically developing children between 36 and 72 months of age, primarily English speaking, were recruited from public preschools in …

A Nurse-Driven Screening Process To Increase Icu Palliative Care Utilization, Sara L. Stock

Doctor of Nursing Practice Final Project Abstract

Purpose

A scholarly project aimed to increase palliative care by 25% for intensive care unit patients in eight weeks by integrating nurse-driven screening process into multidisciplinary rounds.

Background

Palliative care provides valuable mental, emotional, and spiritual support for patients and families. These benefits are available to any patient with a disease process causing symptoms affecting quality of life. Palliative care is falsely equated with hospice care, leading to further delay. The original referral model relied only on intensivist identification of eligibility The project was implemented in a 20-bed medical and surgical ICU in a community hospital in the Houston area. …

Improving Adherence Amongst Post-Stroke Patients In The Outpatient Setting, Olivea Adetu

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This quality improvement (QI) project aimed to enhance medication adherence and follow-up rates through structured, personalized phone calls to recently discharged post-stroke patients. The project was implemented at an outpatient neuroscience clinic in Greater Houston.

BACKGROUND

Low medication adherence and poor attendance at the first neurology follow-up appointment among post-stroke patients contribute to increased morbidity and higher risk of recurrent stroke. Despite receiving discharge instructions, many patients do not consistently take their prescribed medications or attend their initial neurology visit.

METHODOLOGY

Guided by the Plan-Do-Study-Act (PDSA) cycle, this project engaged a medical assistant to call recently discharged stroke patients …

Considerations For Widespread Implementation Of Blood-Based Biomarkers Of Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali

Brain and Mind Institute

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges …

Recommendations For Clinical Implementation Of Blood-Based Biomarkers For Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali, Chinedu Momoh

Brain and Mind Institute

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational …

Elevated Tryptase Level Identifies A Case Of Hereditary Alpha Tryptasemia, Ali H. Alnajim, Salman Aljubran

Posters

Introduction Hereditary alpha tryptasemia (HaT) is a rare genetic disorder characterized by elevated serum tryptase levels due to duplication or triplication of the TPSAB1 gene. Affecting 6 to 8 percent of the population, HaT presents with diverse symptoms, including idiopathic anaphylaxis, skin rashes, and gastrointestinal issues. This report highlights a case that underscores the complexities and diagnostic challenges of HaT. Case Description A 4-year-old male presented with recurrent skin rashes and gastrointestinal symptoms following ingestion of certain foods, despite negative allergy tests. Persistent symptoms led to further investigations, revealing elevated tryptase levels of 10.3 ng/ml, 12.1 ng/ml, and 8.3 ng/ml …

Radiographic Outcomes And Subsidence Rate In Hyperlordotic Versus Standard Lordotic Interbody Spacers In Patients Undergoing Anterior Cervical Discectomy And Fusion, Rajkishen Narayanan, Nicholas Pohl, Jonathan Dalton, Yunsoo Lee, Anthony Labarbiera, Meryem Guler, Emilie Sawicki, Sebastian Fras, Mark Kurd, John Mangan, I David Kaye, Jose Canseco, Alan Hilibrand, Alex Vaccaro, Christopher Kepler, Gregory Schroeder, Joseph Lee

Rothman Institute Papers

Background: Anterior cervical discectomy and fusion (ACDF) is a common surgery for patients with degenerative cervical disease and current interbody spacers utilized vary based on material composition, structure, and angle of lordosis. Currently, there is a lack of literature comparing subsidence rates or long-term radiographic outcomes with hyperlordotic and standard lordotic spacers. This study compares long-term radiographic outcomes, subsidence rate, and rate of fusion in patients who underwent ACDF with hyperlordotic or standard interbody placement. Materials and Methods: Patients who underwent 1-3-level ACDF with either a standard lordosis or hyperlordotic interbody were included. Standard radiographs were evaluated for C2-7 lordosis …

Trajectories Of Diabetes-Related Sequelae For Identifying Transition Probabilities, And Optimal Timepoints For Prevention Of Ulceration, Infection, And Amputation, Daniel C. Jupiter, Yuanyi Zhang, Naohiro Shibuya

School of Podiatric Medicine Publications

To reduce diabetes-related complications and to avoid futile procedures, foot and ankle surgeons need to understand the relative timings of catastrophic events, their incidence, and probabilities of transitions between disease states in diabetes in different patient populations. For this study, we tracked medical events (including an initial diagnosis of diabetes, ulcer, wound care, osteomyelitis, amputation, and reamputation, in order of severity) and the time between each such event in patients with diabetes, stratifying by sex, race, and ethnicity. We found that the longest average duration between the different lower extremity states was a diagnosis of diabetes to the occurrence of …

Transcription And Post-Translational Mechanisms: Dual Regulation Of Adiponectin-Mediated Occludin Expression In Diabetes, Yanru Duan, Demin Liu, Huahui Yu, Shihan Zhang, Yihua Xia, Zhiyong Du, Yanwen Qin, Yajing Wang, Xin-Liang Ma, Huirong Liu, Yunhui Du

Department of Emergency Medicine Faculty Papers

BACKGROUND: Occludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear.

METHODS AND RESULTS: Endothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN's protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN's regulatory role in Occludin expression through a …

Does The Use Of Dacc-Coated Dressings Improve Clinical Outcomes For Hard To Heal Wounds: A Systematic Review, Saskia Schwarzer, Jose Luis Lazaro-Martinez, Amanda L. Killeen, Paulo Alves, Andrea Gledhill, Erik Nygren, Lawrence A. Lavery, Matthew Malone

School of Podiatric Medicine Publications

Reports of overuse and antimicrobial resistance have fuelled some clinicians to adopt alternative wound dressings termed to be non-medicated or non-antimicrobials, which still claim antimicrobial or antibacterial activity. In this PROSPERO-registered systematic review, we evaluated the in vivo clinical evidence for the effectiveness of DACC-coated dressings in chronic, hard to heal wound-related outcomes. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Framework was adopted as the template in constructing this systematic review. The PICO format (Population [or patients], Intervention, Comparison [control], Outcome/s) was used to identify key clinical questions in determining patient outcomes under two domains (infection control and …

Navigating The Uncommon: Providencia Rettgeri In Diabetic Foot Ulcers, Nikita Gambhir, Heather V. Tran, Stephanie N. Campbell, Mihir Panchal

School of Podiatric Medicine Publications

A case study presents with a rare microorganism, Providencia rettgeri, as a pathogen identified in a non-healing diabetic foot ulcer with osteomyelitis. P. rettgeri remains an emerging pathogen with documented drug-resistant hospital associated infections. Given the rarity of this organism in such wounds and its intrinsic resistance to multiple antibiotics, this study aims to understand the pathogen’s role in diabetic foot infections and improve clinical management practices.

Providencia has been classified as Critical Priority 1 on World Health Organization’s global priority pathogen list for the need of new antibiotics, highlighting its international significance. P. rettgeri tends to grow in nosocomial …

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …

Clinical Outcome-Guided Deep Temporal Clustering For Disease Progression Subtyping, Dulin Wang, Xiaotian Ma, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Objective: Complex diseases exhibit heterogeneous progression patterns, necessitating effective capture and clustering of longitudinal changes to identify disease subtypes for personalized treatments. However, existing studies often fail to design clustering-specific representations or neglect clinical outcomes, thereby limiting the interpretability and clinical utility.

Method: We design a unified framework for subtyping longitudinal progressive diseases. We focus on effectively integrating all data from disease progressions and improving patient representation for downstream clustering. Specifically, we propose a clinical Outcome-Guided Deep Temporal Clustering (OG-DTC) that generates representations informed by clustering and clinical outcomes. A GRU-based seq2seq architecture captures the temporal dynamics, and the model …

Une Com Research And Scholarship Fall Forum November 2024, Une Com Research & Scholarship

Osteopathic Student Research Symposia

Program including abstracts from the University of New England College of Osteopathic Medicine’s 2024 Research and Scholarship Fall Forum.

Supplemental content: List of award winners.

Evaluating The Impact Of Spot Position Errors On Dose Distribution: A Comparison Between Spot-Scanning Arc Therapy (Sparc) And Intensity-Modulated Proton Therapy (Impt), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To quantitatively investigate the impact of spot position error (PE) on the dose distribution in (Spot-scanning arc therapy) SPArc plans versus Intensity-Modulated Proton Therapy (IMPT).

Methods:

Four representative disease sites, including brain, lung, liver, and prostate cancers, were retrospectively selected. Spot position errors were simulated during dynamic SPArc treatment delivery. Two types of errors were generated, including randomized error and systematic error. For each random error scenario, they were further examined across four sub-scenarios (25%, 50%, 75%, and 100% of spots affected) at 1 mm and 2 mm deviations.The randomized errors used two categories with and without Gaussian distribution …

Source Model Parameters For Beam Commissioning Of Scanning Proton Therapy Treatment Planning System: Multi-Institutional Survey And Analysis, Chih-Wei Chang, Liyong Lin, Lei Dong, Heng Li, Jan Po Schuemann, Jiajian Shen, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To create a beamline-specific repository of source model parameters and beam commissioning data for scanning proton therapy (PT) treatment planning system (TPS).

Methods: We surveyed 28 PT centers, collecting beam commissioning source model parameters of diverse beamlines from different vendors: Hitachi, IBA, Varian, Mevion. Parameters included (i) beam meterset calibration in protons per MU, (ii) in-air spot size at isocenter in terms of standard deviation in x- (crossline, σ_x) and y- (inline, σ_y) directions, (iii) in-air angular spread at isocenter in x-direction (θ_x) and y-direction (θ_y). We plotted each parameter as …

Mr-Linac-Guided Stereotactic Radiotherapy For Ct-Indiscernible Intravascular Renal Cell Carcinoma Tumours, Mihir D Shanker, Zhiqian Henry Yu, Jinzhong Yang, Surena Matin, Matthew T Campbell, Pavlos Msaouel, Nizar Tannir, Surendra Prajapati, Yao Ding, Belinda Lee, Angela Sobremonte, Chad Tang

Faculty, Staff and Student Publications

Inferior vena cava tumour thrombus (IVC‐TT) is a life‐threatening complication of advanced renal cell carcinoma (RCC) occurring in 10%–25% of patients with RCC with one third of patients having concurrent distant metastatic disease. ¹ , ² Surgical resection in the form of radical nephrectomy and caval thrombectomy is the established option for obtaining local control of the disease and is associated with long‐term oncologic control; however, only 50% of patients are operative candidates at time of diagnosis. ³ , ⁴ Untreated RCC IVC‐TT has a poor natural history, with a median survival of 5 months with a 1‐year disease‐specific survival …

Physical Exercise-Related Manifestations Of Long Covid: A Systematic Review And Meta-Analysis, Chen Zheng, Jun-Jie Chen, Zi-Han Dai, Ke-Wen Wan, Feng-Hua Sun, Jun-Hao Huang, Xiang-Ke Chen

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors.

METHODS: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis.

RESULTS: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO …

Medical Students’ Self-Perceived Knowledge And Clinical Comfort With Genetics In Pakistan, Maheen Arshad, Angela Trepanier, S Shahrukh Hashmi, Rizwan Naeem, Saqib Mehmood, Myla Ashfaq

Faculty, Staff and Student Publications

Pakistan has a high rate of genetic disorders and neonatal mortality concurrent with noted lack of genetic counselors and geneticists. To meet the needs of the patient population, the responsibility of providing clinical genetic services falls on general and specialty physicians. However, their education regarding these essential services is not standardized in medical school curricula nor has it ever been evaluated. The purpose of this work is to describe the self-perceived knowledge, clinical comfort, and perspectives of Pakistani medical students toward their medical genetics' education. A web-based survey was distributed electronically to medical schools around the country. The survey comprised …

Pre-Diagnosis Tea And Coffee Consumption And Survival After A Diagnosis Of Ovarian Cancer: Results From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Elisa V Bandera, Daniel Cramer, Jennifer A Doherty, Graham G Giles, Marc T Goodman, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice W Lee, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm Pike, Celeste Leigh Pearce, Penelope M Webb

Faculty, Staff and Student Publications

BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain.

METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).

RESULTS: Compared with women who did not drink …

Molecular Architecture And Functional Dynamics Of The Pre-Incision Complex In Nucleotide Excision Repair, Jina Yu, Chunli Yan, Tanmoy Paul, Lucas Brewer, Susan E Tsutakawa, Chi-Lin Tsai, Samir M Hamdan, John A Tainer, Ivaylo Ivanov

Faculty, Staff and Student Publications

Nucleotide excision repair (NER) is vital for genome integrity. Yet, our understanding of the complex NER protein machinery remains incomplete. Combining cryo-EM and XL-MS data with AlphaFold2 predictions, we build an integrative model of the NER pre-incision complex(PInC). Here TFIIH serves as a molecular ruler, defining the DNA bubble size and precisely positioning the XPG and XPF nucleases for incision. Using simulations and graph theoretical analyses, we unveil PInC's assembly, global motions, and partitioning into dynamic communities. Remarkably, XPG caps XPD's DNA-binding groove and bridges both junctions of the DNA bubble, suggesting a novel coordination mechanism of PInC's dual incision. …

Superior Antitumor Immune Response Achieved With Proton Over Photon Immunoradiotherapy Is Amplified By The Nanoradioenhancer Nbtxr3, Yun Hu, Sébastien Paris, Narayan Sahoo, Qi Wang, Qianxia Wang, Hampartsoum B Barsoumian, Ailing Huang, Jordan Da Silva, Célia Bienassis, Claudia S Kettlun Leyton, Tiffany A Voss, Fatemeh Masrorpour, Thomas Riad, Carola Leuschner, Nahum Puebla-Osorio, Saumil Gandhi, Quynh-Nhu Nguyen, Jing Wang, Maria Angelica Cortez, James W Welsh

Faculty, Staff and Student Publications

Recent findings suggest that immunoradiotherapy (IRT), combining photon radiotherapy (XRT) or proton radiotherapy (PRT) with immune checkpoint blockade, can enhance systemic tumor control. However, the comparative efficacy of XRT and PRT in IRT remains understudied. To address this, we compared outcomes between XRT + αPD1 and PRT + αPD1 in murine αPD1-resistant lung cancer (344SQR). We also assessed the impact of the nanoparticle radioenhancer NBTXR3 on both XRT + αPD1 and PRT + αPD1 for tumor control and examined the tumor immune microenvironment using single-cell RNA sequencing (scRNAseq). Additionally, mice cured by NBTXR3 + PRT + αPD1 were rechallenged with …

Preventive Treatment With A Cd73 Small Molecule Inhibitor Enhances Immune Surveillance In K-Ras Mutant Pancreatic Intraepithelial Neoplasia, Lincoln N Strickland, Wendao Liu, Usama Hussein, Nicolette Mardik, Xian Chen, Tingting Mills, Lana A Vornik, Michelle I Savage, Shizuko Sei, John Clifford, Holger K Eltzschig, Powel H Brown, Zhongming Zhao, Florencia Mcallister, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; …

Dcis Knowledge Of Women Choosing Between Active Surveillance And Surgery For Low-Risk Dcis, E G Engelhardt, R S J M Schmitz, M A Gerritsma, C M T Sondermeijer, E Verschuur, J H E Houtzager, R Griffioen, N Bijker, R M Mann, V Retèl, F H Van Duijnhoven, J Wesseling, E M A Bleiker

Faculty, Staff and Student Publications

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. …