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Mutational Scanning And Binding Free Energy Computations Of The Sars-Cov-2 Spike Complexes With Distinct Groups Of Neutralizing Antibodies: Energetic Drivers Of Convergent Evolution Of Binding Affinity And Immune Escape Hotspots, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker Feb 2025

Mutational Scanning And Binding Free Energy Computations Of The Sars-Cov-2 Spike Complexes With Distinct Groups Of Neutralizing Antibodies: Energetic Drivers Of Convergent Evolution Of Binding Affinity And Immune Escape Hotspots, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The rapid evolution of SARS-CoV-2 has led to the emergence of variants with increased immune evasion capabilities, posing significant challenges to antibody-based therapeutics and vaccines. In this study, we conducted a comprehensive structural and energetic analysis of SARS-CoV-2 spike receptor-binding domain (RBD) complexes with neutralizing antibodies from four distinct groups (A–D), including group A LY-CoV016, group B AZD8895 and REGN10933, group C LY-CoV555, and group D antibodies AZD1061, REGN10987, and LY-CoV1404. Using coarse-grained simplified simulation models, rapid energy-based mutational scanning, and rigorous MM-GBSA binding free energy calculations, we elucidated the molecular mechanisms of antibody binding and escape mechanisms, identified key …


Author Correction: Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao Feb 2025

Author Correction: Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Correction to: Nature Communications 10.1038/s41467-024-55134-9, published online 30 December 2024

In the version of the article initially published, there were errors in Fig. 3d, where in the x-axis labels now reading “GPP-shRNA1, GPP-shRNA2, GPP-shRNA3…,” the second and third labels were duplicates of the first. The figure is amended in the HTML and PDF versions of the article.


Violence Among Nigeria’S Female And Predictors Of Help-Seeking Behavior Using Technology, Abayomi Karunwi Feb 2025

Violence Among Nigeria’S Female And Predictors Of Help-Seeking Behavior Using Technology, Abayomi Karunwi

Walden Dissertations and Doctoral Studies

The decision-making autonomy of female intimate partner violence (IPV) survivors to make financial transactions is a stronger predictor of help-seeking behavior that is not yet fully explored. Despite the plausibility of using the mobile phone for financial transactions, it is yet to be explored as a predictor of help-seeking behavior after IPV events through digital financial inclusion. The dataset from the 2018 Nigerian Demographic Health Survey was used to explore if digital financial inclusion could predict help-seeking behavior instead of the severity of abuse among ever-partnered Nigerian female IPV survivors (aged 15 to 49 years) who use their mobile phones …


Exploring The Relationship Between Psychiatric Illness And Dermatological Disorders: A Narrative Review, Alan D. Kaye, Rahib K. Islam, Abigayle M. Castine, Grace C. Wester, William T. Barham, Catherine G. Nguyen, Elena Plakotaris, Bradley Dorius, Julian Kim, Patricia Griffin, Amber Edinoff, Sahar Shekoohi, Giustino Varrassi Feb 2025

Exploring The Relationship Between Psychiatric Illness And Dermatological Disorders: A Narrative Review, Alan D. Kaye, Rahib K. Islam, Abigayle M. Castine, Grace C. Wester, William T. Barham, Catherine G. Nguyen, Elena Plakotaris, Bradley Dorius, Julian Kim, Patricia Griffin, Amber Edinoff, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

The interplay between psychiatric conditions and dermatological disorders is complex and multifaceted, often resulting in significant challenges for both diagnosis and treatment. This narrative review examines associations between specific psychiatric conditions, trichotillomania, attention deficit hyperactivity disorder, schizophrenia, bipolar disorder, and various dermatological disorders. The present investigation delves into pathophysiological mechanisms, clinical presentations, and management strategies of these comorbid conditions. Psychiatric disorders can exacerbate dermatological conditions through mechanical trauma, medication side effects, and stress-induced exacerbations, while dermatological disorders can lead to significant psychiatric morbidity. The biopsychosocial approach, emphasizing the importance of integrated care involving dermatologists and mental health professionals, is crucial …


Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker Feb 2025

Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups …


Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya Feb 2025

Evaluating Maternal Drug Use Disparities, Risk Factors And Outcomes In Northeast Arkansas: A Pre, During, And Post-Covid-19 Pandemic Analysis., Enrique Gomez Pomar, Johnna Berryhill, Sudeepa Bhattacharyya

Pediatrics Faculty Publications

INTRODUCTION: The use of addictive substances remains a major health problem in the U.S. An increase in drug overdose and mortality was observed during the COVID-19 pandemic, especially in underserved populations. This surge also impacted pregnant women especially with the use of marijuana (THC) and opioids.

METHODS: Retrospective study analyzing mother-infant dyads with reported Meconium Drug Screen (MDS) results, from January 2018 through April 2023 at a reference hospital serving an urban and rural area of Arkansas. Due to the absence of universal screening, the prevalence of drug use was variable during the study period. An adjusted monthly positive rate …


Efficacy Of Zenocutuzumab In Nrg1 Fusion-Positive Cancer, Alison M Schram, Koichi Goto, Dong-Wan Kim, Teresa Macarulla, Antoine Hollebecque, Eileen M O'Reilly, Sai-Hong Ignatius Ou, Jordi Rodon, Sun Young Rha, Kazumi Nishino, Michaël Duruisseaux, Joon Oh Park, Cindy Neuzillet, Stephen V Liu, Benjamin A Weinberg, James M Cleary, Emiliano Calvo, Kumiko Umemoto, Misako Nagasaka, Christoph Springfeld, Tanios Bekaii-Saab, Grainne M O'Kane, Frans Opdam, Kim A Reiss, Andrew K Joe, Ernesto Wasserman, Viktoriya Stalbovskaya, Jim Ford, Shola Adeyemi, Lokesh Jain, Shekeab Jauhari, Alexander Drilon, Enrgy Investigators Feb 2025

Efficacy Of Zenocutuzumab In Nrg1 Fusion-Positive Cancer, Alison M Schram, Koichi Goto, Dong-Wan Kim, Teresa Macarulla, Antoine Hollebecque, Eileen M O'Reilly, Sai-Hong Ignatius Ou, Jordi Rodon, Sun Young Rha, Kazumi Nishino, Michaël Duruisseaux, Joon Oh Park, Cindy Neuzillet, Stephen V Liu, Benjamin A Weinberg, James M Cleary, Emiliano Calvo, Kumiko Umemoto, Misako Nagasaka, Christoph Springfeld, Tanios Bekaii-Saab, Grainne M O'Kane, Frans Opdam, Kim A Reiss, Andrew K Joe, Ernesto Wasserman, Viktoriya Stalbovskaya, Jim Ford, Shola Adeyemi, Lokesh Jain, Shekeab Jauhari, Alexander Drilon, Enrgy Investigators

Faculty, Staff and Student Publications

Background: Neuregulin 1 (NRG1) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways. The efficacy and safety of zenocutuzumab, a bispecific antibody against HER2 and HER3, in patients with NRG1 fusion-positive solid tumors are unclear.

Methods: In this registrational, phase 2 clinical study, we assigned patients with advanced NRG1 fusion-positive cancer involving any tumor type to receive zenocutuzumab at a dose of 750 mg intravenously every 2 weeks. The primary end point was overall …


Genomic And Phenotypic Correlates Of Mosaic Loss Of Chromosome Y In Blood, Yasminka A Jakubek, Xiaolong Ma, Adrienne M Stilp, Fulong Yu, Jason Bacon, Justin W Wong, Francois Aguet, Kristin Ardlie, Donna K Arnett, Kathleen Barnes, Joshua C Bis, Tom Blackwell, Lewis C Becker, Eric Boerwinkle, Russell P Bowler, Matthew J Budoff, April P Carson, Jiawen Chen, Michael H Cho, Josef Coresh, Nancy J Cox, Paul S De Vries, Dawn L Demeo, David W Fardo, Myriam Fornage, Xiuqing Guo, Michael E Hall, Nancy Heard-Costa, Bertha Hidalgo, Marguerite Ryan Irvin, Andrew D Johnson, Eric Jorgenson, Eimear E Kenny, Michael D Kessler, Daniel Levy, Yun Li, Joao A C Lima, Yongmei Liu, Adam E Locke, Ruth J F Loos, Mitchell J Machiela, Rasika A Mathias, Braxton D Mitchell, Joanne M Murabito, Josyf C Mychaleckyj, Kari E North, Peter Orchard, Stephen C J Parker, Yash Pershad, Patricia A Peyser, Katherine A Pratte, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Sanjiv J Shah, Jennifer A Smith, Aaron P Smith, Albert Smith, Margaret A Taub, Hemant K Tiwari, Russell Tracy, Bjoernar Tuftin, Alexander G Bick, Vijay G Sankaran, Alexander P Reiner, Paul Scheet, Paul L Auer Feb 2025

Genomic And Phenotypic Correlates Of Mosaic Loss Of Chromosome Y In Blood, Yasminka A Jakubek, Xiaolong Ma, Adrienne M Stilp, Fulong Yu, Jason Bacon, Justin W Wong, Francois Aguet, Kristin Ardlie, Donna K Arnett, Kathleen Barnes, Joshua C Bis, Tom Blackwell, Lewis C Becker, Eric Boerwinkle, Russell P Bowler, Matthew J Budoff, April P Carson, Jiawen Chen, Michael H Cho, Josef Coresh, Nancy J Cox, Paul S De Vries, Dawn L Demeo, David W Fardo, Myriam Fornage, Xiuqing Guo, Michael E Hall, Nancy Heard-Costa, Bertha Hidalgo, Marguerite Ryan Irvin, Andrew D Johnson, Eric Jorgenson, Eimear E Kenny, Michael D Kessler, Daniel Levy, Yun Li, Joao A C Lima, Yongmei Liu, Adam E Locke, Ruth J F Loos, Mitchell J Machiela, Rasika A Mathias, Braxton D Mitchell, Joanne M Murabito, Josyf C Mychaleckyj, Kari E North, Peter Orchard, Stephen C J Parker, Yash Pershad, Patricia A Peyser, Katherine A Pratte, Bruce M Psaty, Laura M Raffield, Susan Redline, Stephen S Rich, Jerome I Rotter, Sanjiv J Shah, Jennifer A Smith, Aaron P Smith, Albert Smith, Margaret A Taub, Hemant K Tiwari, Russell Tracy, Bjoernar Tuftin, Alexander G Bick, Vijay G Sankaran, Alexander P Reiner, Paul Scheet, Paul L Auer

Faculty, Staff and Student Publications

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences …


One Center's Experience Of Pulmonary Embolism After Covid-19: Impact Of Vaccination Status, Cara Gose, Kaylee Dixon, Andrea M. Bodine Md Feb 2025

One Center's Experience Of Pulmonary Embolism After Covid-19: Impact Of Vaccination Status, Cara Gose, Kaylee Dixon, Andrea M. Bodine Md

Advances in Clinical Medical Research and Healthcare Delivery

Background: The incidence of pulmonary embolism (PE) has increased since the outbreak of the COVID-19 pandemic and may be due to the observed hypercoagulable state. There is conflicting evidence that thromboembolism risk increases after vaccination and that vaccines decrease the probability of having a thromboembolic event. This study aimed to explore how vaccination status impacts occurrence of PE after a positive COVID-19 test. The hypothesis was that vaccinated, immunocompetent patients have a lower incidence of PE after COVID-19 compared to unvaccinated patients.

Methods: This was a retrospective chart review at a teaching hospital in New England from 1/01/2021 to 3/31/2023 …


Celebrating World Cancer Day: Innovative Biological Approaches To Cancer And Their Alignment With Sustainable Development Goals (Sdgs), Hamed Kioumarsi, Bolin Liu Feb 2025

Celebrating World Cancer Day: Innovative Biological Approaches To Cancer And Their Alignment With Sustainable Development Goals (Sdgs), Hamed Kioumarsi, Bolin Liu

School of Medicine Faculty Publications

No abstract provided.


Infection-Related Hospitalization And Incident Heart Failure: The Atherosclerosis Risk In Communities Study, Rebecca L Molinsky, Amil Shah, Melana Yuzefpolskaya, Bing Yu, Jeffrey R Misialek, Bruno Bohn, David Vock, Richard Maclehose, Barry A Borlaug, Paolo C Colombo, Chiadi E Ndumele, Junichi Ishigami, Kunihiro Matsushita, Pamela L Lutsey, Ryan T Demmer Feb 2025

Infection-Related Hospitalization And Incident Heart Failure: The Atherosclerosis Risk In Communities Study, Rebecca L Molinsky, Amil Shah, Melana Yuzefpolskaya, Bing Yu, Jeffrey R Misialek, Bruno Bohn, David Vock, Richard Maclehose, Barry A Borlaug, Paolo C Colombo, Chiadi E Ndumele, Junichi Ishigami, Kunihiro Matsushita, Pamela L Lutsey, Ryan T Demmer

Faculty, Staff and Student Publications

Background: The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection-related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction.

Methods and results: We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987-1989). IRH was identified using select International Classification of Diseases (ICD) codes in hospital discharge records and was treated as a time-varying exposure. HF incidence was defined as the first occurrence …


Immunogenicity And Reactogenicity Of High- Or Standard-Dose Influenza Vaccine In A Second Consecutive Influenza Season., Hannah Bahakel, Andrew J. Spieker, Haya Hayek, Jennifer E. Schuster, Lubna Hamdan, Daniel E. Dulek, Carrie L. Kitko, Tess Stopczynski, Einas Batarseh, Zaid Haddadin, Laura S. Stewart, Anna Stahl, Molly Potter, Herdi Rahman, Justin Amarin, Spyros A. Kalams, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Christopher J. Harrison, Jason Freedman, Paul A. Carpenter, Janet A. Englund, Flor M. Munoz, Lara Danziger-Isakov, Natasha Halasa, Pediatric Hct Flu Study Feb 2025

Immunogenicity And Reactogenicity Of High- Or Standard-Dose Influenza Vaccine In A Second Consecutive Influenza Season., Hannah Bahakel, Andrew J. Spieker, Haya Hayek, Jennifer E. Schuster, Lubna Hamdan, Daniel E. Dulek, Carrie L. Kitko, Tess Stopczynski, Einas Batarseh, Zaid Haddadin, Laura S. Stewart, Anna Stahl, Molly Potter, Herdi Rahman, Justin Amarin, Spyros A. Kalams, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Christopher J. Harrison, Jason Freedman, Paul A. Carpenter, Janet A. Englund, Flor M. Munoz, Lara Danziger-Isakov, Natasha Halasa, Pediatric Hct Flu Study

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatric hematopoietic cell transplant (HCT) recipients are at high risk for morbidity from influenza virus infection. We demonstrated in a primary phase 2 randomized controlled trial that 2 post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given 4 weeks apart were more immunogenic than 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present the immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen.

METHODS: A subcohort of study participants reenrolled and had hemagglutinin inhibition titers measured at baseline and 4 weeks after each vaccine dose in year 2. We estimated …


A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss Feb 2025

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss

Faculty, Staff and Student Publications

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …


Multimorbidity And Peak Oxygen Uptake In Patients Undergoing Cardiac Rehabilitation, Pauline F. Gomes, Audry Chacin-Suarez, Sophie A. Miller, Karen M. Fischer, Thomas P. Olson Feb 2025

Multimorbidity And Peak Oxygen Uptake In Patients Undergoing Cardiac Rehabilitation, Pauline F. Gomes, Audry Chacin-Suarez, Sophie A. Miller, Karen M. Fischer, Thomas P. Olson

Einstein Health Papers

No abstract provided.


Post-Term Births As A Risk Factor For Small For Gestational Age Births And Infant Mortality In Brazil, Mexico, And Palestinian Refugees: An Analysis Of Electronic Birth Records, Zeina Jamaluddine, Lorena Suarez Idueta, Enny S. Paixao, Julia M. Pescarini, Hala Ghattas Ph.D., Miho Sato, Akihiro Seita, Luis A. Martinez-Juarez, Mauricio L. Barreto, Eric O. Ohuma, Louise T. Day, Oona M.R. Campbell, Hannah Blencowe Feb 2025

Post-Term Births As A Risk Factor For Small For Gestational Age Births And Infant Mortality In Brazil, Mexico, And Palestinian Refugees: An Analysis Of Electronic Birth Records, Zeina Jamaluddine, Lorena Suarez Idueta, Enny S. Paixao, Julia M. Pescarini, Hala Ghattas Ph.D., Miho Sato, Akihiro Seita, Luis A. Martinez-Juarez, Mauricio L. Barreto, Eric O. Ohuma, Louise T. Day, Oona M.R. Campbell, Hannah Blencowe

Faculty Publications

Background:

Post-term pregnancy, defined as reaching or exceeding 42 + 0 weeks of gestation, is known to be associated with unfavourable birth outcomes. High-income countries have responded to this risk by widely adopting labour induction protocols in late-term, but many low- and middle-income countries have not. However, understanding underlying mechanisms linking post-term births to adverse newborn and infant outcomes remains limited.

Objective:

To investigate the (a) prevalence of post-term, (b) the risk factors associated with post-term (c) the association between post-term births and the risk of small-for-gestational-age (SGA) neonates and of infant mortality in middle-income settings.

Methods:

We used existing …


Evaluating Donor-Recipient Sex Mismatch In Anterior Cruciate Ligament Reconstruction With Allograft: Outcomes At 2 Years Postoperatively, Connor Crutchfield, Natalie Lowenstein, Chilan Leite, Christian Lattermann, Elizabeth Matzkin Feb 2025

Evaluating Donor-Recipient Sex Mismatch In Anterior Cruciate Ligament Reconstruction With Allograft: Outcomes At 2 Years Postoperatively, Connor Crutchfield, Natalie Lowenstein, Chilan Leite, Christian Lattermann, Elizabeth Matzkin

SKMC Student Presentations and Publications

BACKGROUND: Female patients tend to suffer a greater risk of reinjury and worse patient-reported outcome measures (PROMs) after anterior cruciate ligament reconstruction (ACLR) than male patients, regardless of the graft type used.

PURPOSE/HYPOTHESIS: This study explored the role of donor-recipient sex mismatching to help explain these sex-based dispar- ities in outcomes after ACLR with an allograft. The hypothesis was that allograft donor-recipient sex mismatch would adversely affect surgical outcomes at a 2-year follow-up, with male-to-female graft donations yielding the lowest rates of success.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Patients who underwent primary ACLR with an allograft …


The Built Environment And Place Attachment: Insights From Japanese Cities, Juiling Li, Mohammed Javad Koohsari, Andrew T. Kaczynski, Ryo Tanimoto, Reo Watanabe, Tomoki Nakaya, Yufeng Luo, Jing Zhao, Akitomo Yasunaga, Koichiro Oka, Tomoya Hanibuchi Feb 2025

The Built Environment And Place Attachment: Insights From Japanese Cities, Juiling Li, Mohammed Javad Koohsari, Andrew T. Kaczynski, Ryo Tanimoto, Reo Watanabe, Tomoki Nakaya, Yufeng Luo, Jing Zhao, Akitomo Yasunaga, Koichiro Oka, Tomoya Hanibuchi

Faculty Publications

Objective

Place attachment plays an important role in individuals' health and well-being. Understanding the associations between urban design attributes and place attachment can inform strategies to promote place attachment. This study aims to examine the associations between walkable built environment metrics and place attachment.

Methods

This study used data collected from October to November 2020, involving 25,340 adults across 21 major cities in Japan. Geographic address information was used to measure objective walkability, while perceived walkability and place attachment were assessed using adapted scales. Ordinary least squares regression models were employed to analyse associations.

Results

For individual metrics, three …


Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree Mcafee, Pamela Hull, Amy Leader, Christopher Mcnair Feb 2025

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree Mcafee, Pamela Hull, Amy Leader, Christopher Mcnair

Kimmel Cancer Center Faculty Papers

The National Cancer Institute's (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …


Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling, Moeez Rathore, Kimberly Curry, Wei Huang, Michel'le Wright, Daniel Martin, Jiyeon Baek, Derek Taylor, Masaru Miyagi, Wen Tang, Hao Feng, Yamu Li, Zhenghe Wang, Hallie Graor, Joseph Willis, Elizabeth Bryson, Christina S Boutros, Omkar Desai, Bianca N Islam, Lee M Ellis, Stephen E Moss, Jordan M Winter, John Greenwood, Rui Wang Feb 2025

Leucine-Rich Alpha-2-Glycoprotein 1 Promotes Metastatic Colorectal Cancer Growth Through Human Epidermal Growth Factor Receptor 3 Signaling, Moeez Rathore, Kimberly Curry, Wei Huang, Michel'le Wright, Daniel Martin, Jiyeon Baek, Derek Taylor, Masaru Miyagi, Wen Tang, Hao Feng, Yamu Li, Zhenghe Wang, Hallie Graor, Joseph Willis, Elizabeth Bryson, Christina S Boutros, Omkar Desai, Bianca N Islam, Lee M Ellis, Stephen E Moss, Jordan M Winter, John Greenwood, Rui Wang

Faculty, Staff and Student Publications

Background & aims: Therapy failure in patients with metastatic colorectal cancer (mCRC, ∼80% occur in the liver) remains an overarching challenge. Preclinical studies demonstrated that human epidermal growth factor receptor 3 (HER3) promotes colorectal cancer (CRC) cell survival, but therapies blocking the neuregulin-induced canonical HER3 signaling have made little impact in the clinic. Recent studies suggest that the liver microenvironment promotes CRC growth by activating HER3 in a neuregulin-independent fashion, thus elucidation of these mechanisms may reveal new strategies for treating patients with mCRC.

Methods: Patient-derived primary liver endothelial cells (ECs) were used to interrogate EC-CRC crosstalk. We conducted proteomic …


Vaxbot-Hpv: A Gpt-Based Chatbot For Answering Hpv Vaccine-Related Questions, Yiming Li, Jianfu Li, Manqi Li, Evan Yu, Danniel Rhee, Muhammad Amith, Lu Tang, Lara S Savas, Licong Cui, Cui Tao Feb 2025

Vaxbot-Hpv: A Gpt-Based Chatbot For Answering Hpv Vaccine-Related Questions, Yiming Li, Jianfu Li, Manqi Li, Evan Yu, Danniel Rhee, Muhammad Amith, Lu Tang, Lara S Savas, Licong Cui, Cui Tao

Faculty, Staff and Student Publications

OBJECTIVE: Human Papillomavirus (HPV) vaccine is an effective measure to prevent and control the diseases caused by HPV. However, widespread misinformation and vaccine hesitancy remain significant barriers to its uptake. This study focuses on the development of VaxBot-HPV, a chatbot aimed at improving health literacy and promoting vaccination uptake by providing information and answering questions about the HPV vaccine.

METHODS: We constructed the knowledge base (KB) for VaxBot-HPV, which consists of 451 documents from biomedical literature and web sources on the HPV vaccine. We extracted 202 question-answer pairs from the KB and 39 questions generated by GPT-4 for training and …


Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker Feb 2025

Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker

Faculty, Staff and Student Publications

INTRODUCTION: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS: Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS: Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR …


On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler Feb 2025

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …


Development Of The Navigation Guide Evidence-To-Decision Framework For Environmental Health: Version 1.0, Nicholas Chartres, Max T. Aung, Sustan L. Norris, Courtney Cooper, Lia A. Bero, Roger Chou, Devon C. Payne-Sturges, Wendy E. Wagner, Jessica W. Reyes, Lisa M. Askie, Daniel A. Axelrad, Deysi Flores Vigo, Jill E. Johnston, Juleen Lam, Keeve E. Nachman, Eva Rehfuess, Rachel Rothschild, Patrice Sutton, Lauren Zeise, Tracey J. Woodruff Feb 2025

Development Of The Navigation Guide Evidence-To-Decision Framework For Environmental Health: Version 1.0, Nicholas Chartres, Max T. Aung, Sustan L. Norris, Courtney Cooper, Lia A. Bero, Roger Chou, Devon C. Payne-Sturges, Wendy E. Wagner, Jessica W. Reyes, Lisa M. Askie, Daniel A. Axelrad, Deysi Flores Vigo, Jill E. Johnston, Juleen Lam, Keeve E. Nachman, Eva Rehfuess, Rachel Rothschild, Patrice Sutton, Lauren Zeise, Tracey J. Woodruff

Articles

Environmental exposures, including widespread industrial pollution, impact human health and are amplified in more highly exposed communities. Policy and regulatory frameworks for making decisions and recommendations on interventions to mitigate or prevent exposures tend to narrowly focus on exposure and some health-related data related to risks. Typically, such frameworks do not consider other factors, including essentiality, health equity, and distribution of benefits and costs. Further, decisions and recommendations lack transparency regarding how they were developed. We developed the Navigation Guide Evidence-to-Decision Framework for Environmental Health (E2DFEH) to provide a structured and transparent framework incorporating a range of scientific information and …


Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang Feb 2025

Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H2O2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 …


Cardiac Surgical Bleeding, Transfusion, And Quality Metrics: Joint Consensus Statement By The Enhanced Recovery After Surgery Cardiac Society And Society For The Advancement Of Patient Blood Management, Rawn Salenger, Rakesh C Arora, Arthur Bracey, Mario D'Oria, Daniel T Engelman, Caroline Evans, Michael C Grant, Serdar Gunaydin, Vicki Morton, Sherri Ozawa, Prakash A Patel, Jacob Raphael, Todd K Rosengart, Linda Shore-Lesserson, Pierre Tibi, Aryeh Shander Feb 2025

Cardiac Surgical Bleeding, Transfusion, And Quality Metrics: Joint Consensus Statement By The Enhanced Recovery After Surgery Cardiac Society And Society For The Advancement Of Patient Blood Management, Rawn Salenger, Rakesh C Arora, Arthur Bracey, Mario D'Oria, Daniel T Engelman, Caroline Evans, Michael C Grant, Serdar Gunaydin, Vicki Morton, Sherri Ozawa, Prakash A Patel, Jacob Raphael, Todd K Rosengart, Linda Shore-Lesserson, Pierre Tibi, Aryeh Shander

Faculty, Staff and Students Publications

Background: Excessive perioperative bleeding is associated with major complications in cardiac surgery, resulting in increased morbidity, mortality, and cost.

Methods: An international expert panel was convened to develop consensus statements on the control of bleeding and management of transfusion and to suggest key quality metrics for cardiac surgical bleeding. The panel reviewed relevant literature from the previous 10 years and used a modified RAND Delphi methodology to achieve consensus.

Results: The panel developed 30 consensus statements in 8 categories, including prioritizing control of bleeding, prechest closure checklists, and the need for additional quality indicators beyond reexploration rate, such as time …


Virus-Specific T-Cell Therapy For The Management Of Viral Infections In The Immunocompromised, Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou Feb 2025

Virus-Specific T-Cell Therapy For The Management Of Viral Infections In The Immunocompromised, Kiriakos Koukoulias, Penelope Georgia Papayanni, Ann Marie Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the …


Expert Clinical Management Of Inflammatory Immune-Related Arthritis In Patients With Cancer Receiving Immune Checkpoint Inhibitors, Sebastian Bruera, Mar Riveiro-Barciela, Alexa Meara, Maria E Suarez-Almazor Feb 2025

Expert Clinical Management Of Inflammatory Immune-Related Arthritis In Patients With Cancer Receiving Immune Checkpoint Inhibitors, Sebastian Bruera, Mar Riveiro-Barciela, Alexa Meara, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

Introduction: Treatment guidelines for immune-related inflammatory arthritis (irAE-IA) in patients with cancer receiving immune checkpoint inhibitors (ICIs) are vague with respect to the use of specific agents. Patients are usually referred to rheumatologists for treatment. We conducted a survey of expert rheumatologists to determine current practices. We also assessed experts' views on the potential deleterious effects of various agents on tumor progression.

Methods: We conducted a survey of international experts in the treatment of irAE-IA, identified as members of collaborative scientific workgroups in this area. Experts were presented with a case of a patient with moderate irAE-IA and were asked …


The Cost Of Inflammatory Bowel Disease Care: How To Make It Sustainable, Johan Burisch, Jennifer Claytor, Inmaculada Hernandez, Jason Ken Hou, Gilaad G Kaplan Feb 2025

The Cost Of Inflammatory Bowel Disease Care: How To Make It Sustainable, Johan Burisch, Jennifer Claytor, Inmaculada Hernandez, Jason Ken Hou, Gilaad G Kaplan

Faculty, Staff and Students Publications

The rising global prevalence of inflammatory bowel diseases (IBDs), such as Crohn's disease and ulcerative colitis, underscores the need to examine current and future IBD care costs. Direct health care expenses, including ambulatory visits, hospitalizations, and medications, are substantial, averaging $9,000 to $12,000 per person annually in high-income regions. However, these estimates do not fully account for factors such as disease severity, accessibility, and variability in health care infrastructure among regions. Indirect costs, predominantly stemming from loss in productivity due to absenteeism, presenteeism, and other intangible costs, further contribute to the financial burden of IBD. Despite efforts to quantify indirect …


Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou Jan 2025

Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou

School of Medicine Faculty Publications

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. …


Investigating Suicide Risk Factors Among Appalachian West Virginian Adults, Erin D. Caswell, Angela M. Dyer, Summer D. Hartley, Caroline P. Groth, Mary Christensen, Sahiti K. Tulabandu, Bryce K. Weaver, Ruchi Bhandari Jan 2025

Investigating Suicide Risk Factors Among Appalachian West Virginian Adults, Erin D. Caswell, Angela M. Dyer, Summer D. Hartley, Caroline P. Groth, Mary Christensen, Sahiti K. Tulabandu, Bryce K. Weaver, Ruchi Bhandari

Journal of Appalachian Health

Introduction: Suicide rates in the United States have increased over the past two decades, with rural areas, particularly the Appalachian Region, facing unique challenges that elevate suicide risk. These include economic hardships, social isolation, and limited access to mental health services.

Purpose: This study addresses critical gaps in understanding lifetime suicide risk in West Virginia (WV), a predominantly rural state entirely within the Appalachian Region. By identifying the factors driving urban-rural differences in suicide risk, this research seeks to inform interventions tailored to the state's distinct needs and provide insights applicable to the broader Appalachian Region

Methods: Using 2021 Mountain …