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Early Prediction Of Mortality And Morbidities In Vlbw Preterm Neonates Using Machine Learning, Chi-Hung Shu, Rema Zebda, Camilo Espinosa, Jonathan Reiss, Anne Debuyserie, Kristina Reber, Nima Aghaeepour, Mohan Pammi May 2025

Early Prediction Of Mortality And Morbidities In Vlbw Preterm Neonates Using Machine Learning, Chi-Hung Shu, Rema Zebda, Camilo Espinosa, Jonathan Reiss, Anne Debuyserie, Kristina Reber, Nima Aghaeepour, Mohan Pammi

Faculty, Staff and Students Publications

Background: Predicting mortality and specific morbidities before they occur may allow for interventions that may improve health trajectories.

Hypothesis: Integrating key maternal and postnatal infant variables in the first 2 weeks of age into machine learning (ML) algorithms will reliably predict survival and specific morbidities in VLBW preterm infants.

Methods: ML algorithms were developed to integrate 47 features for predicting mortality, bronchopulmonary dysplasia (BPD), neonatal sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP). A retrospective cohort (n = 3341) was used to train and validate the models with a repeated 10-fold cross-validation …


Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro May 2025

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …


A Multidisciplinary Approach To Brachial Plexus Birth Injury: An Overview And Institutional Experience, Winston R Owens, Vamsi C Mohan, Diego M Quirarte, John D Bovill, Gabrielle T Nguyen, James H Northcutt Ii, Jenny Lee Nguyen, William C Pederson May 2025

A Multidisciplinary Approach To Brachial Plexus Birth Injury: An Overview And Institutional Experience, Winston R Owens, Vamsi C Mohan, Diego M Quirarte, John D Bovill, Gabrielle T Nguyen, James H Northcutt Ii, Jenny Lee Nguyen, William C Pederson

Faculty, Staff and Students Publications

Without early diagnosis and intervention, brachial plexus birth injuries (BPBIs) can result in permanent upper extremity debilitation. Previously, BPBI was treated by single-specialty surgeons; however, given the complexity of the injury, BPBIs necessitate multidisciplinary team care. Common specialists involved within brachial plexus injury clinics include radiologists, physical medicine and rehabilitation physicians, occupational therapists, nerve surgeons, and shoulder surgeons. Care plans are meticulously designed by all team members, and depending on injury severity and clinical course, patients may undergo treatment including range-of-motion exercises, splinting, botulinum toxin injections, nerve surgery, or shoulder surgery. The objective of this article is to highlight and …


Challenges And Opportunities Of Acquiring Cortical Recordings For Chronic Adaptive Deep Brain Stimulation, Jeffrey Herron, Aura Kullmann, Timothy Denison, Wayne K Goodman, Aysegul Gunduz, Wolf-Julian Neumann, Nicole R Provenza, Maryam M Shanechi, Sameer A Sheth, Philip A Starr, Alik S Widge May 2025

Challenges And Opportunities Of Acquiring Cortical Recordings For Chronic Adaptive Deep Brain Stimulation, Jeffrey Herron, Aura Kullmann, Timothy Denison, Wayne K Goodman, Aysegul Gunduz, Wolf-Julian Neumann, Nicole R Provenza, Maryam M Shanechi, Sameer A Sheth, Philip A Starr, Alik S Widge

Faculty, Staff and Students Publications

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex. Yet capturing those markers requires the placement of cortex-optimized electrodes in addition …


Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor May 2025

Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges …


Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo May 2025

Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo

Faculty, Staff and Students Publications

Purpose

Following the Global Health Symposium at the Spina Bifida World Congress in 2023, the purpose of this work is to provide a historical overview and a state-of-the-art update on the current global practice of myelomeningocele (MMC) closure and to highlight the importance of care coordination and outcomes reporting to mitigate care fragmentation through a multidisciplinary approach.

Methods

Panelists from the Spina Bifida World Congress Global Health Symposium reviewed their institutions’ history and experience with risk for fragmentation of care following prenatal repair and proposed solutions to address fragmentation of care.

Results

New and rapidly evolving in-utero approaches to MMC …


Functional Vision Assessment Over 4 Years In Ush2a Using The Veteran Affairs Low-Vision Visual Functioning Questionnaire, Bela Parekh, Nicholas Peck-Dimit, Jacque L Duncan, Lassana Samarakoon, Maria Fernanda Abalem, Chris A Andrews, Isabelle Audo, Allison R Ayala, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Rachel M Huckfeldt, Gabrielle D Lacy, Brett Malbin, Michel Michaelides, David C Musch, Katarina Stingl, Christina Y Weng, Alex Z Zmejkoski, Michele Melia, K Thiran Jayasundera, Foundation Fighting Blindness Clinical Consortium Investigator Group May 2025

Functional Vision Assessment Over 4 Years In Ush2a Using The Veteran Affairs Low-Vision Visual Functioning Questionnaire, Bela Parekh, Nicholas Peck-Dimit, Jacque L Duncan, Lassana Samarakoon, Maria Fernanda Abalem, Chris A Andrews, Isabelle Audo, Allison R Ayala, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Rachel M Huckfeldt, Gabrielle D Lacy, Brett Malbin, Michel Michaelides, David C Musch, Katarina Stingl, Christina Y Weng, Alex Z Zmejkoski, Michele Melia, K Thiran Jayasundera, Foundation Fighting Blindness Clinical Consortium Investigator Group

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to evaluate the validity of the Veterans Affairs Low Vision Visual Functioning Questionnaire (VALVVFQ-48) functional vision scores (FVS) in patients with USH2A-associated retinal degeneration. In addition, to correlate the change in the VALVVFQ-48 FVS with the change in visual function (VF) measurements.

Methods: The VALVVFQ-48 was administered verbally to participants ≥18 years of age at baseline, and after 2 and 4 years. Associations among changes in FVS and changes in VF measures were assessed using the Spearman correlation coefficients. Mixed effects regression models with a random intercept were used to estimate annual rates …


Precision Proteogenomics Reveals Pan-Cancer Impact Of Germline Variants, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Kathleen J Imbach, Karl R Clauser, Myvizhi Esai Selvan, Isabel Mendizabal, Yifat Geffen, Yo Akiyama, Myranda Maynard, Tomer M Yaron, Yize Li, Song Cao, Erik P Storrs, Olivia S Gonda, Adrian Gaite-Reguero, Akshay Govindan, Emily A Kawaler, Matthew A Wyczalkowski, Robert J Klein, Berk Turhan, Karsten Krug, D R Mani, Felipe Da Veiga Leprevost, Alexey I Nesvizhskii, Steven A Carr, David Fenyö, Michael A Gillette, Antonio Colaprico, Antonio Iavarone, Ana I Robles, Kuan-Lin Huang, Chandan Kumar-Sinha, François Aguet, Alexander J Lazar, Lewis C Cantley, Urko M Marigorta, Zeynep H Gümüş, Matthew H Bailey, Gad Getz, Eduard Porta-Pardo, Li Ding May 2025

Precision Proteogenomics Reveals Pan-Cancer Impact Of Germline Variants, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Kathleen J Imbach, Karl R Clauser, Myvizhi Esai Selvan, Isabel Mendizabal, Yifat Geffen, Yo Akiyama, Myranda Maynard, Tomer M Yaron, Yize Li, Song Cao, Erik P Storrs, Olivia S Gonda, Adrian Gaite-Reguero, Akshay Govindan, Emily A Kawaler, Matthew A Wyczalkowski, Robert J Klein, Berk Turhan, Karsten Krug, D R Mani, Felipe Da Veiga Leprevost, Alexey I Nesvizhskii, Steven A Carr, David Fenyö, Michael A Gillette, Antonio Colaprico, Antonio Iavarone, Ana I Robles, Kuan-Lin Huang, Chandan Kumar-Sinha, François Aguet, Alexander J Lazar, Lewis C Cantley, Urko M Marigorta, Zeynep H Gümüş, Matthew H Bailey, Gad Getz, Eduard Porta-Pardo, Li Ding

Faculty, Staff and Student Publications

We investigate the impact of germline variants on cancer patients' proteomes, encompassing 1,064 individuals across 10 cancer types. We introduced an approach, "precision peptidomics," mapping 337,469 coding germline variants onto peptides from patients' mass spectrometry data, revealing their potential impact on post-translational modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases. We identified rare pathogenic and common germline variants in cancer genes potentially affecting proteomic features, including variants altering protein abundance and structure and variants in kinases (ERBB2 and MAP2K2) impacting phosphorylation. Precision peptidome analysis predicted destabilizing events in signal-regulatory protein alpha (SIRPA) and glial …


Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora May 2025

Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora

Staff and Researcher Publications

PURPOSE/BACKGROUND: This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).

METHODS/PROCEDURES: Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.

FINDINGS/RESULTS: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs …


Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia May 2025

Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Center on Aging Staff Publications

Haematopoietic stem cells maintain blood production throughout life1. Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which …


The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery May 2025

The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery

Center on Aging Staff Publications

To identify the incidence of blood stream infections (BSIs) and endocarditis in patients with diabetic foot infections (DFIs), risk factors and clinical outcomes. A post hoc analysis of 280 patients using pooled patient level data from three RTCs. Blood cultures were drawn at time of admission for DFI. Deep intraoperative cultures were obtained from infected foot wounds. Data from the 12-month follow-up were used to determine clinical outcomes. 77.1% (N = 216) had blood cultures of which 15.7% (n = 34) had BSI. One patient (3.3%) had endocarditis. Risk factors for BSI included Charcot Neuroarthropathy history (20.6% vs. 7.1%, p …


Author Correction: Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman May 2025

Author Correction: Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

No abstract provided.


Artificial Intelligence (Ai)-Assisted Cardiotoxicity Management In Lung Cancer Radiotherapy, Xinru Chen May 2025

Artificial Intelligence (Ai)-Assisted Cardiotoxicity Management In Lung Cancer Radiotherapy, Xinru Chen

Dissertations and Theses (Open Access)

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with radiation therapy being a cornerstone of treatment. However, radiation-induced cardiotoxicity has emerged as a significant long-term complication, impacting patient survival and quality of life. There is increasing evidence that post-radiotherapy cardiotoxicity is better indicated by cardiac substructure dose, compared with whole heart dose. Despite this, cardiac substructures are not routinely incorporated into clinical workflows due to the significant time and resource demands associated with manual segmentation. Moreover, the relationship between dose distribution in radiotherapy plans and radiation-induced cardiotoxicity remains incompletely understood. Therefore, the development of an automated …


Cord Blood Treatment For Children With Cerebral Palsy: Individual Participant Data Meta-Analysis, Megan Finch-Edmondson, Madison C B Paton, Annabel Webb, Mahmoud Reza Ashrafi, Remy K Blatch-Williams, Charles S Cox, Kylie Crompton, Alexandra R Griffin, Minyoung Kim, Steven Kosmach, Joanne Kurtzberg, Masoumeh Nouri, Mi Ri Suh, Jessica Sun, Morteza Zarrabi, Iona Novak May 2025

Cord Blood Treatment For Children With Cerebral Palsy: Individual Participant Data Meta-Analysis, Megan Finch-Edmondson, Madison C B Paton, Annabel Webb, Mahmoud Reza Ashrafi, Remy K Blatch-Williams, Charles S Cox, Kylie Crompton, Alexandra R Griffin, Minyoung Kim, Steven Kosmach, Joanne Kurtzberg, Masoumeh Nouri, Mi Ri Suh, Jessica Sun, Morteza Zarrabi, Iona Novak

The Brown Foundation: Institute of Molecular Medicine

Context: Umbilical cord blood (UCB) is a novel treatment for cerebral palsy (CP), with trials indicating UCB can improve gross motor function. However, heterogeneity has limited the ability to interpret findings.

Objective: Assess the safety and efficacy of UCB for improving gross motor function in children with CP, including exploring cell dose effect and responder subgroups.

Data sources: Individual participant data from published reports and registered trials identified via systematic searches.

Study selection: Studies administering UCB to individuals with CP collecting Gross Motor Function Measure (GMFM) scores.

Data extraction: A 1-stage individual participant data meta-analysis was conducted in R to …


Clinical Implications Of Mismatch Repair Deficiency In Pancreatic Ductal Adenocarcinoma, Zachary Kaplan, Elizabeth Prezioso, Aditi Jain, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler May 2025

Clinical Implications Of Mismatch Repair Deficiency In Pancreatic Ductal Adenocarcinoma, Zachary Kaplan, Elizabeth Prezioso, Aditi Jain, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler

Kimmel Cancer Center Faculty Papers

BACKGROUND: Pancreatic cancer is a highly aggressive and lethal disease, characterized by a limited response to chemotherapy and overall poor prognosis. Pancreatic cancers with a distinct mismatch repair deficiency, although relatively rare, have been shown to be associated with markedly better outcomes in comparison. Furthermore, whereas pancreatic cancers are generally unresponsive to current immunotherapy, this specific group of tumors has been shown to have a notable susceptibility to immune checkpoint inhibitors.

AIMS: In this review, we aim to summarize the relevant literature regarding mismatch-repair associated pancreatic cancers, the impacted biological mechanisms, and the resulting vulnerabilities for potential opportunistic immunotherapeutic treatment …


An Exposition On Prostate Cancer Dynamics: A History And Exploration Of Cancer Growth Models, Walter Navarro May 2025

An Exposition On Prostate Cancer Dynamics: A History And Exploration Of Cancer Growth Models, Walter Navarro

Electronic Theses, Projects, and Dissertations

The detection, diagnosis, and treatment of cancer are the primary objectives of the field of mathematical oncology. Our goal is to examine the history of mathematical oncology by introducing the models that have influenced it. From this vantage point, we examine five primary models that focus on the progression of prostate cancer and the development of treatment protocols at different stages. The Ideta model will be further elaborated upon by examining the effects of androgen deprivation therapy and the addition of chemotherapy on growth dynamics. Finally, clinical data will be utilized to verify the Vollmer and Humphrey model’s findings. We …


Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal May 2025

Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer related deaths with nearly a quarter of patients presenting with metastatic disease at the time of their diagnosis. Therapeutic management of metastatic CRC continues to be a major challenge due to therapy resistance and disease heterogeneity. Due to its central role in tumorigenesis, CRC is commonly treated with MAPK pathway inhibitors (MAPKi). However, clinical trials repeatedly demonstrates that durability of benefit is short-lived in many patients. While genomic mechanisms of acquired resistance have been described, they explain a minority of patients, and further research is needed to determine the underlying …


Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch May 2025

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …


Optimal Delay Time To Initiate Anticoagulation After Ischemic Stroke In Atrial Fibrillation: A Pragmatic, Response-Adaptive Randomized Clinical Trial, Steven J Warach, Lisa A Davis, Patrick Lawrence, Byron Gajewski, Jo Wick, Fred Shi, Ty T Shang, Daiwai M Olson, Sidarrth Prasad, Lee Birnbaum, Jody M Richardson, Sean I Savitz, Mark P Goldberg, Salvador Cruz-Flores, Israel Alba, Jane Anderson, Barbara Kimmel, Chethan P Venkatasubba Rao, Ben King, Adrienne N Dula, Truman J Milling May 2025

Optimal Delay Time To Initiate Anticoagulation After Ischemic Stroke In Atrial Fibrillation: A Pragmatic, Response-Adaptive Randomized Clinical Trial, Steven J Warach, Lisa A Davis, Patrick Lawrence, Byron Gajewski, Jo Wick, Fred Shi, Ty T Shang, Daiwai M Olson, Sidarrth Prasad, Lee Birnbaum, Jody M Richardson, Sean I Savitz, Mark P Goldberg, Salvador Cruz-Flores, Israel Alba, Jane Anderson, Barbara Kimmel, Chethan P Venkatasubba Rao, Ben King, Adrienne N Dula, Truman J Milling

Faculty, Staff and Students Publications

Importance: Clinical practice guidelines recommend initiation of anticoagulation within 2 weeks after stroke with atrial fibrillation. It is unknown whether there is an optimal starting day within the 14-day period that balances the risks of recurrent embolic events against serious hemorrhagic events.

Objective: To determine if there is an optimal delay time to initiate treatment with a direct oral anticoagulant after atrial fibrillation-related stroke that minimizes the risk of a composite outcome of ischemic or hemorrhagic events.

Design, setting, and participants: This phase 2, pragmatic, response-adaptive randomized clinical trial was conducted between June 2017 and June 2023 at acute care …


Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham May 2025

Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham

Faculty, Staff and Students Publications

Introduction: A growing number of studies implicate functional brain networks in intelligence, but it is unclear if network nodal structure relates to intelligence.

Methods: Using MRI, we studied the relationship of the general intelligence factor (g) with cortical thickness (CT), local gyrification index (LGI), and voxel-based morphometry in the nodes of the default mode network (DMN) and task-positive network (TPN) in a cohort of 44 young, healthy adults. Employing a novel strategy, we performed repeated analyses with multiple sets of g estimates to remove false positives.

Results: CT and LGI in medial and temporal nodes of the DMN were reliably …


Immune Landscape Of Early Liver Metastatic Lesions In A Novel Immunocompetent Murine Colorectal Cancer Metastasis Model, Alaa Mohamed May 2025

Immune Landscape Of Early Liver Metastatic Lesions In A Novel Immunocompetent Murine Colorectal Cancer Metastasis Model, Alaa Mohamed

Dissertations and Theses (Open Access)

Colorectal cancer minimal residual disease (MRD) represents a major clinical problem for colorectal cancer patients, with failure rates of surgery and adjuvant chemotherapy between 5% to 40% depending on stage of disease. In our study, we simulated MRD using genetically engineered organoids with precise somatic editing of APC and TP53, creating a murine model that mimics human liver metastatic colorectal cancer. By implementing a meticulously timed experimental metastatic model, we could detect microscopic tumor lesions. Through genomic and transcriptomic analyses, we pinpointed the importance of macrophages, particularly those expressing high levels of CSF1R, in these microscopic metastatic focal lesions. We …


Development Of Lineal Energy Spectrum-Based Biological Effects Models For Protons, Joseph M. Decunha, Fada Guan, David Grosshans, Zhongxing Liao, Dragan Mirkovic, Oleg Vassiliev, Radhe Mohan May 2025

Development Of Lineal Energy Spectrum-Based Biological Effects Models For Protons, Joseph M. Decunha, Fada Guan, David Grosshans, Zhongxing Liao, Dragan Mirkovic, Oleg Vassiliev, Radhe Mohan

Dissertations and Theses (Open Access)

In this dissertation, methods are developed and described to allow for the rapid calculation of microdosimetric spectra (specifically, lineal energy) for protons. SuperTrack, a GPU-accelerated tool for calculation of microdosimetric spectra was developed and is capable of computing lineal energy spectra up to 5000x faster than using Geant4 directly. Proton lineal energy spectra generated by SuperTrack are indistinguishable from those generated by Geant4. With SuperTrack, large libraries of lineal energy spectra for monoenergetic protons spanning 0-300 MeV have been developed. The proton lineal energy spectra calculated by SuperTrack have been compared to experimental measurements made by a tissue equivalent proportional …


Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave May 2025

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …


Automated To Ols For Contour Review In Radiotherapy, Barbara Marquez May 2025

Automated To Ols For Contour Review In Radiotherapy, Barbara Marquez

Dissertations and Theses (Open Access)

Peer review of organ-at-risk and target volume delineation is essential for patient safety and optimization of treatment outcomes. Peer review makes a substantial impact on patient outcomes, reporting notable rates of plan changes when reviewed and worse survival when patient cases are not reviewed. In around half of revised cases, target volume change is the required cause for modification (related to tumor control); in one in ten cases, it is normal tissue sparing (related to treatment toxicity). Essentially all North American institutions with accredited residency training programs hold peer review to some capacity. However, accessibility to practicing routine peer review …


Denial Of Inpatient Genetic Testing: A Study On Outpatient Yield And Outcomes, Cindy Y. Canales May 2025

Denial Of Inpatient Genetic Testing: A Study On Outpatient Yield And Outcomes, Cindy Y. Canales

Dissertations and Theses (Open Access)

This study investigates the difference in diagnostic yield between patients approved for inpatient genetic testing compared to those denied inpatient testing and the effect of an earlier diagnosis on outcomes and medical/clinical care. In the literature, research has explored the impact of a diagnostic delay for patients with genetics conditions, assessed the utility of genetic testing in the inpatient setting, and described the impact to care of an earlier diagnosis. However, gaps remain on research exploring the diagnostic yields of inpatient versus outpatient settings and the potential impact to care an inpatient genetic testing request denial may pose. This is …


Group Therapy For Autistic Adults Over Telehealth: Challenges And Guidelines For Clinicians, Antonio F Pagán, Stephen Armstrong, Amy Izuno-Garcia, Killian R Hughes, Katherine A Loveland May 2025

Group Therapy For Autistic Adults Over Telehealth: Challenges And Guidelines For Clinicians, Antonio F Pagán, Stephen Armstrong, Amy Izuno-Garcia, Killian R Hughes, Katherine A Loveland

Faculty, Staff and Student Publications

Autism spectrum disorder (ASD) is associated with challenges in areas such as social skills and behavior, with 1 in 36 children diagnosed in the U.S. Annually, over 100,000 adolescents with ASD transition to adulthood, often facing a "service cliff" where support diminishes. Group therapy can help autistic adults by enhancing social skills, executive functioning, and emotional regulation while fostering belonging and reducing isolation. Telehealth-based group therapy offers additional benefits, particularly for those with social anxiety, geographic barriers, or limited transportation. While telehealth is effective for autistic adults, practical guidelines for virtual group therapy are lacking. This article provides recommendations for …


Glim Consensus Approach To Diagnosis Of Malnutrition: A 5-Year Update., Gordon L Jensen, Tommy Cederholm, M Isabel T D Correia, M Cristina Gonzalez, Ryoji Fukushima, Veeradej Pisprasert, Renee Blaauw, Diana Cardenas Braz, Fernando Carrasco, Alfonso J Cruz Jentoft, Cristina Cuerda, David C Evans, Vanessa Fuchs-Tarlovsky, Leah Gramlich, Han Ping Shi, Jeanette M Hasse, Michael Hiesmayr, Naoki Hiki, Harriët Jager-Wittenaar, Shukri Jahit, Anayanet Jáquez, Heather Keller, Stanislaw Klek, Ainsley Malone, Kris M Mogensen, Naoharu Mori, Manpreet Mundi, Maurizio Muscaritoli, Doris Ng, Ibolya Nyulasi, Matthias Pirlich, Stephane Schneider, Marian De Van Der Schueren, Soranit Siltharm, Pierre Singer, Alison Steiber, Kelly A Tappenden, Jianchun Yu, André Van Gossum, Jaw-Yuan Wang, Marion F Winkler, Charlene Compher, Rocco Barazzoni May 2025

Glim Consensus Approach To Diagnosis Of Malnutrition: A 5-Year Update., Gordon L Jensen, Tommy Cederholm, M Isabel T D Correia, M Cristina Gonzalez, Ryoji Fukushima, Veeradej Pisprasert, Renee Blaauw, Diana Cardenas Braz, Fernando Carrasco, Alfonso J Cruz Jentoft, Cristina Cuerda, David C Evans, Vanessa Fuchs-Tarlovsky, Leah Gramlich, Han Ping Shi, Jeanette M Hasse, Michael Hiesmayr, Naoki Hiki, Harriët Jager-Wittenaar, Shukri Jahit, Anayanet Jáquez, Heather Keller, Stanislaw Klek, Ainsley Malone, Kris M Mogensen, Naoharu Mori, Manpreet Mundi, Maurizio Muscaritoli, Doris Ng, Ibolya Nyulasi, Matthias Pirlich, Stephane Schneider, Marian De Van Der Schueren, Soranit Siltharm, Pierre Singer, Alison Steiber, Kelly A Tappenden, Jianchun Yu, André Van Gossum, Jaw-Yuan Wang, Marion F Winkler, Charlene Compher, Rocco Barazzoni

Ambulatory and Primary Care Articles

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) introduced an approach for malnutrition diagnosis in 2019 that comprised screening followed by assessment of three phenotypic criteria (weight loss, low body mass index [BMI], and low muscle mass) and two etiologic criteria (reduced food intake/assimilation and inflammation/disease burden). This planned update reconsiders the GLIM framework based on published knowledge and experience over the past 5 years.

METHODS: A working group (n = 43 members) conducted a literature search spanning 2019-2024 using the keywords "Global Leadership Initiative on Malnutrition or GLIM." Prior GLIM guidance activities for using the criteria on muscle mass …


Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia May 2025

Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia

Faculty, Staff and Student Publications

Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …


Targeting Discrepancies In Linear Growth Measurements In The Neonatal Intensive Care Unit Through Nursing Interventions: A Quality Improvement Initiative, Gail Snyder, Rebekah Wilkinson, Raina Evans, Meagan Owen, Akram Yazdani, Covi Tibe, Catherine Perez, Lindsay F Holzapfel May 2025

Targeting Discrepancies In Linear Growth Measurements In The Neonatal Intensive Care Unit Through Nursing Interventions: A Quality Improvement Initiative, Gail Snyder, Rebekah Wilkinson, Raina Evans, Meagan Owen, Akram Yazdani, Covi Tibe, Catherine Perez, Lindsay F Holzapfel

Faculty, Staff and Student Publications

Objective: Accurate length measurements are essential for infants to identify growth deficiencies and adjust nutrition accordingly. The gold standard for length measurement in infants is using a length board with two people to obtain an accurate clinical assessment. We aimed to improve the number of measurements with the desired minimal difference, defined as a discrepancy ≤1 cm between nurse and audit measurements, in our center. Our secondary aim was to increase and maintain the number of length boards available.

Methods: This quality improvement (QI) study used a before-and-after intervention comparison design in a single-level IV neonatal intensive care unit between …


The Contribution Of De Novo Coding Mutations To Meningomyelocele, Yoo-Jin Jiny Ha, Ashna Nisal, Isaac Tang, Chanjae Lee, Ishani Jhamb, Cassidy Wallace, Robyn Howarth, Sarah Schroeder, Keng Ioi Vong, Naomi Meave, Fiza Jiwani, Chelsea Barrows, Sangmoon Lee, Nan Jiang, Arzoo Patel, Krisha Bagga, Niyati Banka, Liana Friedman, Francisco A Blanco, Seyoung Yu, Soeun Rhee, Hui Su Jeong, Isaac Plutzer, Michael B Major, Béatrice Benoit, Christian Poüs, Caleb Heffner, Zoha Kibar, Gyang Markus Bot, Hope Northrup, Kit Sing Au, Madison Strain, Allison E Ashley-Koch, Richard H Finnell, Joan T Le, Hal S Meltzer, Camila Araujo, Helio R Machado, Roger E Stevenson, Anna Yurrita, Sara Mumtaz, Awais Ahmed, Mulazim Hussain Khara, Osvaldo M Mutchinick, José Ramón Medina-Bereciartu, Friedhelm Hildebrandt, Gia Melikishvili, Ahmed I Marwan, Valeria Capra, Mahmoud M Noureldeen, Aida M S Salem, Mahmoud Y Issa, Maha S Zaki, Libin Xu, Ji Eun Lee, Donghyuk Shin, Anna Alkelai, Alan R Shuldiner, Stephen F Kingsmore, Stephen A Murray, Heon Yung Gee, W Todd Miller, Kimberley F Tolias, John B Wallingford, Spina Bifida Sequencing Consortium, Sangwoo Kim, Joseph G Gleeson May 2025

The Contribution Of De Novo Coding Mutations To Meningomyelocele, Yoo-Jin Jiny Ha, Ashna Nisal, Isaac Tang, Chanjae Lee, Ishani Jhamb, Cassidy Wallace, Robyn Howarth, Sarah Schroeder, Keng Ioi Vong, Naomi Meave, Fiza Jiwani, Chelsea Barrows, Sangmoon Lee, Nan Jiang, Arzoo Patel, Krisha Bagga, Niyati Banka, Liana Friedman, Francisco A Blanco, Seyoung Yu, Soeun Rhee, Hui Su Jeong, Isaac Plutzer, Michael B Major, Béatrice Benoit, Christian Poüs, Caleb Heffner, Zoha Kibar, Gyang Markus Bot, Hope Northrup, Kit Sing Au, Madison Strain, Allison E Ashley-Koch, Richard H Finnell, Joan T Le, Hal S Meltzer, Camila Araujo, Helio R Machado, Roger E Stevenson, Anna Yurrita, Sara Mumtaz, Awais Ahmed, Mulazim Hussain Khara, Osvaldo M Mutchinick, José Ramón Medina-Bereciartu, Friedhelm Hildebrandt, Gia Melikishvili, Ahmed I Marwan, Valeria Capra, Mahmoud M Noureldeen, Aida M S Salem, Mahmoud Y Issa, Maha S Zaki, Libin Xu, Ji Eun Lee, Donghyuk Shin, Anna Alkelai, Alan R Shuldiner, Stephen F Kingsmore, Stephen A Murray, Heon Yung Gee, W Todd Miller, Kimberley F Tolias, John B Wallingford, Spina Bifida Sequencing Consortium, Sangwoo Kim, Joseph G Gleeson

Faculty, Staff and Students Publications

Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting. A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained1. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele2. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or …