Medicine and Health Sciences Commons^™

Childhood Neglect Is Associated With Alterations In Neural Prediction Error Signaling And The Response To Novelty, Joseph Aloi, Kathleen I Crum, Karina S Blair, Ru Zhang, Johannah Bashford-Largo, Sahil Bajaj, Soonjo Hwang, Bruno B Averbeck, Nim Tottenham, Matthew Dobbertin, R James R Blair

Faculty, Staff and Student Publications

Background: One in eight children experience early life stress (ELS), which increases risk for psychopathology. ELS, particularly neglect, has been associated with reduced responsivity to reward. However, little work has investigated the computational specifics of this disrupted reward response - particularly with respect to the neural response to Reward Prediction Errors (RPE) - a critical signal for successful instrumental learning - and the extent to which they are augmented to novel stimuli. The goal of the current study was to investigate the associations of abuse and neglect, and neural representation of RPE to novel and non-novel stimuli.

Methods: One hundred …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Phenormgpt: A Framework For Extraction And Normalization Of Key Medical Findings, Ekin Soysal, Kirk Roberts

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This manuscript presents PheNormGPT, a framework for extraction and normalization of key findings in clinical text. PheNormGPT relies on an innovative approach, leveraging large language models to extract key findings and phenotypic data in unstructured clinical text and map them to Human Phenotype Ontology concepts. It utilizes OpenAI's GPT-3.5 Turbo and GPT-4 models with fine-tuning and few-shot learning strategies, including a novel few-shot learning strategy for custom-tailored few-shot example selection per request. PheNormGPT was evaluated in the BioCreative VIII Track 3: Genetic Phenotype Extraction from Dysmorphology Physical Examination Entries shared task. PheNormGPT achieved an F1 score of 0.82 for standard …

Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis And Regulates A Schizophrenia Susceptibility Gene Network Within The Mouse Dentate Gyrus, Prithviraj Rajebhosale, Alice Jone, Kory R Johnson, Rohan Hofland, Camille Palarpalar, Samara Khan, Lorna W Role, David A Talmage

Faculty, Staff and Student Publications

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by γ-secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V

Feasibility Of The Mind+Soul Culturally Tailored Brain Healthy Diet: A Pilot Study, Ashley R Shaw, Robyn Honea, Dinesh Pal Mudaranthakam, Kate Young, Eric D Vidoni, Jill K Morris, Sandra Billinger, Mickeal N Key, Jannette Berkley-Patton, Jeffrey M Burns

Faculty, Staff and Student Publications

Alzheimer’s disease (AD) disproportionately impacts Black Americans, who are three times more likely to develop AD. While heart-healthy diets have shown potential in reducing AD risk, research on adapted dietary interventions for Black American communities remains limited. This pilot study assessed the feasibility and acceptability of an adapted brain healthy diet intervention (MIND + SOUL) and explored changes in cardiometabolic risk and cognition. Twenty-nine participants completed the 12-week intervention, which included culturally tailored health education, cooking classes, health coaching, and groceries. Feasibility was assessed by attendance and retention rates, while acceptability was measured by two questionnaires. Participants had a mean …

Therapeutic Approaches To Modulate The Immune Microenvironment In Gliomas, Andreas Sarantopoulos, Chibawanye Ene, Elisa Aquilanti

Faculty, Staff and Student Publications

Immunomodulatory therapies, including immune checkpoint inhibitors, have drastically changed outcomes for certain cancer types over the last decade. Gliomas are among the cancers that have seem limited benefit from these agents, with most trials yielding negative results. The unique composition of the glioma immune microenvironment is among the culprits for this lack of efficacy. In recent years, several efforts have been made to improve understanding of the glioma immune microenvironment, aiming to pave the way for novel therapeutic interventions. In this review, we discuss some of the main components of the glioma immune microenvironment, including macrophages, myeloid-derived suppressor cells, neutrophils …

Impact Of Select Actionable Genomic Alterations On Efficacy Of Neoadjuvant Immunotherapy In Resectable Non-Small Cell Lung Cancer, Nicolas Zhou, Cheuk H Leung, William N William, Annikka Weissferdt, Apar Pataer, Myrna C B Godoy, Brett W Carter, Frank V Fossella, Anne S Tsao, George R Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M Kurie, Mehmet Altan, Charles Lu, Bonnie S Glisson, Lauren A Byers, Yasir Y Elamin, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Jack A Roth, Hai T Tran, Jia Wu, Luisa M Solis Soto, Humam Kadara, Stephen G Swisher, Ara A Vaporciyan, Don L Gibbons, Heather Y Lin, J Jack Lee, John V Heymach, Marcelo V Negrao, Boris Sepesi, Tina Cascone

Faculty, Staff and Student Publications

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Methods: Tumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF …

The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia, Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A Calin, Michael J Keating, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2-/-γc-/- MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the …

Optical Genome Mapping For Detection Of Bcr::Abl1-Another Tool In Our Toolbox, Zhenya Tang, Wei Wang, Gokce A Toruner, Shimin Hu, Hong Fang, Jie Xu, M James You, L Jeffrey Medeiros, Joseph D Khoury, Guilin Tang

Faculty, Staff and Student Publications

Background:BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and optical genome mapping (OGM). Understanding the strengths and limitations of each method is essential for the selection of appropriate method(s) of disease diagnosis and/or during the follow-up.

Methods: We compared the results of OGM, chromosomal analysis, FISH, and/or RT-PCR in 12 cases with BCR::ABL1.

Results:BCR:ABL1 was detected by FISH and RT-PCR …

Unmasking Neuroendocrine Prostate Cancer With A Machine Learning-Driven Seven-Gene Stemness Signature That Predicts Progression, Agustina Sabater, Pablo Sanchis, Rocio Seniuk, Gaston Pascual, Nicolas Anselmino, Daniel F Alonso, Federico Cayol, Elba Vazquez, Marcelo Marti, Javier Cotignola, Ayelen Toro, Estefania Labanca, Juan Bizzotto, Geraldine Gueron

Faculty, Staff and Student Publications

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-scale transcriptomic datasets. The resulting seven-gene signature (KMT5C, DPP4, TYMS, CDC25B, IRF5, MEN1, and DNMT3B) was validated across independent cohorts and patient-derived xenograft (PDX) models. This signature demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, and overall survival. Importantly, the signature not only identified specific NEPC subtypes, …

Nutritional Intervention As Adjuvant Therapy For T-Cell Acute Lymphoblastic Leukemia, Miriam B Garcia, Palaniraja Thandapani

Faculty, Staff and Student Publications

No abstract provided.

Impact Of Pik3ca Gain And Pten Loss On Mantle Cell Lymphoma Biology And Sensitivity To Targeted Therapies, Nardjas Bettazova, Jana Senavova, Kristyna Kupcova, Dana Sovilj, Anezka Rajmonova, Ladislav Andera, Karla Svobodova, Adela Berkova, Zuzana Zemanova, Lenka Daumova, Vaclav Herman, Alexandra Dolníkova, R Eric Davis, Marek Trneny, Pavel Klener, Ondrej Havranek

Faculty, Staff and Student Publications

Besides many other mutations in known cancer driver genes, mantle cell lymphoma (MCL) is characterized by recurrent genetic alterations of important regulators of the phosphoinositol-3-kinase (PI3K) cascade including PIK3CA gains and PTEN losses. To evaluate the biological and functional consequences of these aberrations in MCL, we have introduced transgenic expression of PIK3CA (PIK3CA UP) and performed knockout/knockdown of PTEN gene (PTEN KO/KD) in 5 MCL cell lines. The modified cell lines were tested for associated phenotypes including dependence on upstream B-cell receptor (BCR) signaling (by an additional BCR knockout). PIK3CA overexpression decreased the dependence of the tested MCL on prosurvival …

Comments On The Paper “Data-Driven Gating (Ddg)-Based Motion Match For Improved Ctac Registration Ejnmmi Physics 2024; 11(1):42”, Tinsu Pan

Faculty, Staff and Student Publications

Misregistration between CT and PET in PET/CT is mainly caused by respiratory motion or irregular respiration during the CT scan in PET/CT. Other than repeat CT, repeat PET/CT, or data-driven gated (DDG) CT, there is no practical approach to mitigate the misregistration artifacts and subsequent CT attenuation correction (CTAC) of the PET data. DDG PET derives a respiratory motion model based on the multiple phases of PET images without hardware gating and it allows for a potential correction of the misregistration artifacts based on the respiratory motion model. The purpose of this commentary was to compare the recent two publications …

The Black And African American Connections To Parkinson’S Disease (Blaac Pd) Study Protocol, Lana M Chahine, Naomi Louie, J Solle, Fulya Akçimen, Andrew Ameri, Samantha Augenbraun, Sabrina Avripas, Sarah Breaux, Christopher Causey, Shivika Chandra, Marissa Dean, Elizabeth A Disbrow, Lauren Fanty, Jessica Fernandez, Erin R Foster, Erin Furr Stimming, Deborah Hall, Vanessa Hinson, Ashani Johnson-Turbes, Cabell Jonas, Camilla Kilbane, Scott A Norris, Bao-Tran Nguyen, Mahesh Padmanaban, Kimberly Paquette, Carly Parry, Natalia Pessoa Rocha, Ashley Rawls, Ejaz A Shamim, Lisa M Shulman, Rebeka Sipma, Julia Staisch, Rami Traurig, Rainer Von Coelln, Peter Wild Crea, Tao Xie, Zih-Hua Fang, Alyssa O'Grady, Catherine M Kopil, Maggie Mcguire Kuhl, Andrew Singleton, Cornelis Blauwendraat, Sara Bandres-Ciga

Faculty, Staff and Student Publications

Determining the genetic contributions to Parkinson's disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson's Disease (BLAAC PD) study is part …

Endovascular Therapy Versus Medical Management In Isolated Posterior Cerebral Artery Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Weighted Study, Hamza Adel Salim, Benjamin Pulli, Vivek Yedavalli, Basel Musmar, Nimer Adeeb, Dhairya Lakhani, Muhammed Amir Essibayi, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Inayat Grewal, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Max Wintermark, Adrien Guenego, Adam A Dmytriw

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Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo.

Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified …

Micrornas Are Enriched At Covid-19 Genomic Risk Regions, And Their Blood Levels Correlate With The Covid-19 Prognosis Of Cancer Patients Infected By Sars-Cov-2, Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A Calin

Faculty, Staff and Student Publications

Background: Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.

Patients and methods: Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in …

Racial Variability In Immune Responses Only Partially Explains Differential Systemic Sclerosis Disease Severity, Kamini E Kuchinad, Ji Soo Kim, Adrianne Woods, Gwen Leatherman, Laura Gutierrez-Alamillo, Maureen D Mayes, Robyn Domsic, Paula S Ramos, Richard M Silver, John Varga, Lesley Ann Saketkoo, Suzanne Kafaja, Victoria K Shanmugan, Jessica Gordon, Lorinda Chung, Elana J Bernstein, Pravitt Gourh, Francesco Boin, Daniel L Kastner, Scott L Zeger, Livia Casciola-Rosen, Fredrick M Wigley, Ami A Shah

Faculty, Staff and Student Publications

Objective: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.

Methods: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding …

Perioperative Chemoimmunotherapy Induces Strong Immune Responses And Long-Term Survival In Patients With Hla Class I-Deficient Non-Small Cell Lung Cancer, Marta Molina-Alejandre, Francisco Perea, Virginia Calvo, Cristina Martinez-Toledo, Ernest Nadal, Belén Sierra-Rodero, Marta Casarrubios, Joaquín Casal-Rubio, Alex Martinez-Martí, Amelia Insa, Bartomeu Massuti, Santiago Viteri, Isidoro Barneto Aranda, Delvys Rodriguez-Abreu, Javier De Castro, Joaquín Mosquera Martínez, Manuel Cobo, Ignacio I Wistuba, Edwin R Parra, Javier Martín-López, Diego Megías, Rafael Muñoz-Viana, Federico Garrido, Natalia Aptsiauri, Francisco Ruiz-Cabello, Mariano Provencio, Alberto Cruz-Bermúdez

Faculty, Staff and Student Publications

BACKGROUND: Loss of human leukocyte antigen (HLA) class I expression and loss of heterozygosity (LOH) are common events implicated in the primary resistance of non-small cell lung cancer (NSCLC) to immunotherapy. However, there is no data on perioperative chemoimmunotherapy (ChIO) efficacy or response mechanisms in the context of HLA class I defects.

METHODS: Baseline HLA class I tumor status (HLA-deficient (HLA-DEF) or HLA-proficient (HLA-PRO)) was determined by DNA LOH combined with immunohistochemistry for protein levels in tissue of 24 patients with NSCLC treated with perioperative nivolumab plus chemotherapy from NADIM trial (NCT03081689). We integrated HLA tumor status with molecular data …

Estrogen Plus Progestin And Colorectal Cancer: Long-Term Findings From The Women's Health Initiative Randomized Clinical Trial, Rowan T Chlebowski, Aaron K Aragaki, Kathy Pan, Juhua Luo, Thomas E Rohan, Karen C Johnson, Jean Wactawski-Wende, Su Yon Jung, Qian Xiao, Sayeh Lavasani, Joann E Manson, Michael S Simon

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We report long-term colorectal cancer findings from the Women’s Health Initiative trial where 16,608 postmenopausal women with a uterus were randomized to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. When intervention ended after 5.6-years, while there were 44% fewer colorectal cancers in the intervention group (43 vs 72, P = 0.003), the cancers more commonly were lymph node positive (59.0% vs 29.4%, P = 0.003). Now after cumulative 24-year follow-up, with 431 breast cancers, CEE plus MPA no longer influenced colorectal cancer incidence (215 [0.15, annualized rate %] vs 216 [0.15], HR …

Norovirus Acute Gastroenteritis Amongst Us And European Travellers To Areas Of Moderate To High Risk Of Travellers’ Diarrhoea: A Prospective Cohort Study, Martin Alberer, Christine L Moe, Christoph Hatz, Kerstin Kling, Amy E Kirby, Lisa Lindsay, Hans D Nothdurft, Margarita Riera-Montes, Robert Steffen, Thomas Verstraeten, Henry M Wu, Herbert L Dupont

Faculty, Staff and Student Publications

BACKGROUND: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact amongst travellers is limited.

METHODS: Prospective, multi-site, observational cohort study conducted 2015-2017, amongst adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms whilst travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14 days …

Policy-Relevant Differences Between Secondhand And Thirdhand Smoke: Strengthening Protections From Involuntary Exposure To Tobacco Smoke Pollutants, Georg E Matt, Lydia Greiner, Rachael A Record, Heather Wipfli, Jamie Long, Nathan G Dodder, Eunha Hoh, Nicolas Lopez Galvez, Thomas E Novotny, Penelope J E Quintana, Hugo Destaillats, Xiaochen Tang, Antoine M Snijders, Jian-Hua Mao, Bo Hang, Suzaynn Schick, Peyton Jacob, Prue Talbot, E Melinda Mahabee-Gittens, Ashley L Merianos, Thomas F Northrup, Lara Gundel, Neal L Benowitz

Faculty, Staff and Student Publications

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand …

Characterizing The Progression From Mild Cognitive Impairment To Dementia: A Network Analysis Of Longitudinal Clinical Visits, Muskan Garg, Sara Hejazi, Sunyang Fu, Maria Vassilaki, Ronald C Petersen, Jennifer St Sauver, Sunghwan Sohn

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Background: With the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare.

Objective: We aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, …

Health Risks Associated With Adopting New-Generation Disposable Products Among Young Adults Who Use E-Cigarettes, Shuyao Ran, James J Yang, Megan E Piper, Hsien-Chang Lin, Anne Buu

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New-generation disposable e-cigarettes have become increasingly popular among young adults in the USA since the FDA's partial flavor ban. This study aims to examine longitudinal changes in health risks among young adults who adopted these novel products, as well as the health effects of device types beyond the effects of other important e-cigarette characteristics. This study recruited e-cigarette users via voluntary response sampling from three college campuses in the USA to respond to four-wave online surveys conducted in four consecutive semesters. Among the participants who adopted disposables during the study, their health risks (dependence symptoms, respiratory symptoms, combustible tobacco use) …

The Telehealth Shared Decision-Making Coaching And Navigation In Primary Care (Telescope) Intervention: A Study Protocol For Delivering Shared Decision-Making For Lung Cancer Screening By Patient Navigators, Naomi Q P Tan, Lisa M Lowenstein, Elisa E Douglas, Jeanne Silva, Joshua M Bershad, Jinghua An, Sanjay S Shete, Michael B Steinberg, Jeanne M Ferrante, Elizabeth C Clark, Ana Natale-Pereira, Novneet N Sahu, Shirin E Hastings, Richard M Hoffman, Robert J Volk, Anita Y Kinney

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BACKGROUND: Lung cancer screening (LCS) can reduce lung cancer mortality but has potential harms for patients. A shared decision-making (SDM) conversation about LCS is required by the Centers for Medicare & Medicaid Services (CMS) for LCS reimbursement. To overcome barriers to SDM in primary care, this protocol describes a telehealth decision coaching and navigation intervention for LCS in primary care clinics delivered by patient navigators. The objective of the study is to evaluate the effectiveness of the intervention and its implementation potential, compared with an enhanced usual care (EUC) arm.

METHODS: Patients (n = 420) of primary care clinicians (n …

Nonclinical Profile Of Pf-06952229 (Mdv6058), A Novel Tgfβri/Activin Like Kinase 5 Inhibitor Supports Clinical Evaluation In Cancer, Mausumee Guha, Stephane Thibault, Son Pham, Sebastian Bernales, Rama Pai, Francisco J Herrera, Theodore R Johnson, Allison Vitsky, Tina Fernando, Martin Finkelstein

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The development of transforming growth factor βreceptor inhibitors (TGFβRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker (≥60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7-day on/7-day off/cycle; 5 cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic …

A Scoping Review Of Patient Safety Checklists In Dentistry, K Zouaidi, T W Miner, M F Walji, E Kalenderian, D B Rindal, K J Suda

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Objectives: Not much is known about safety checklists use in dentistry. We aim to examine, assess, and provide a comprehensive understanding of the current knowledge concerning the use of checklists to improve patient safety in dentistry.

Methods: We conducted a comprehensive literature search using Medline and Embase for studies that use or describe the development of dental patient safety checklists. All study designs were included for citations published through December 2023.

Results: Following abstract and full-text screening, 27 studies remained for data extraction and analysis. Oral surgery emerged as the main dental specialty where the utilization and evaluation of checklists …

Progress In Physical Activity Research, Policy, And Surveillance In Canada: The Global Observatory For Physical Activity – Gopa!, Ashley Cathro, John C Spence, Christine Cameron, Andrea Ramirez Varela, Diana Morales, Eduardo Ribes Kohn, Michael Pratt, Pedro C Hallal

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BACKGROUND: The purpose of this paper is to examine the evolution of physical activity research and the comprehensiveness of national physical activity policies and surveillance systems in Canada.

METHODS: A systematic review was conducted by the Global Observatory for Physical Activity (GoPA! ) on physical activity and health publications between 1950 and 2019. Findings from Canada were extracted and included in the present analysis. The number of articles published, female researcher involvement in authorship, author institution affiliations, and publication themes were examined. Policies were evaluated by determining if there was a standalone physical activity plan and if national guidelines existed. …