Medical Specialties Commons^™

Polygenic Risk And Chemotherapy-Related Subsequent Malignancies In Childhood Cancer Survivors: A Childhood Cancer Survivor Study And St Jude Lifetime Cohort Study Report, Cindy Im, Noha Sharafeldin, Yan Yuan, Zhaoming Wang, Yadav Sapkota, Zhanni Lu, Logan G Spector, Rebecca M Howell, Michael A Arnold, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Smita Bhatia, Gregory T Armstrong, Joseph P Neglia, Yutaka Yasui, Lucie M Turcotte

Faculty, Staff and Student Publications

Purpose: Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases.

Patients and methods: SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS …

Cavernous Sinus Hemangioma: Histopathological Spectrum Of 8 Cases, Joshua M Rasband, Rasha Alfattal, Akash J Patel, Gregory N Fuller, Arie Perry, Hsiang-Chih Lu

Faculty, Staff and Students Publications

No abstract provided.

The Underutilization Of Preventive Cardiovascular Measures In Patients With Cancer: An Analysis Of The Behavioural Risk Factor Surveillance System, 2011–22, Ahmed Sayed, Malak Munir, Daniel Addison, Abdelrahman I Abushouk, Susan F Dent, Tomas G Neilan, Anne Blaes, Michael G Fradley, Anju Nohria, Khaled Moustafa, Salim S Virani

Faculty, Staff and Students Publications

AIMS: This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD).

METHODS AND RESULTS: Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011-22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported …

Can The Date Of Last Menstrual Period Be Trusted In The First Trimester? Comparisons Of Gestational Age Measures From A Prospective Cohort Study In Six Low-Income To Middle-Income Countries, Archana Patel, Carla M. Bann, Vanessa R. Thorsten, Sowmya R. Rao, Adrien Lokangaka, Antoinette Tshefu Kitoto, Melissa Bauserman, Lester Figueroa, Nancy F. Krebs, Fabian Esamai, Sherri Bucher, Sarah Saleem, Robert L. Goldenberg, Elwyn Chomba, Waldemar A. Carlo, Shivaprasad Goudar, Richard Derman, Marion Koso-Thomas, Elizabeth Mcclure, Patricia L. Hibberd

Global Health Articles

OBJECTIVES: We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries.

DESIGN: Prospective cohort study SETTING AND PARTICIPANTS: This study included data from the Global Network's population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based …

Standardized Definitions For Efficacy End Points In Neoadjuvant Breast Cancer Clinical Trials: Neosteep, Jennifer K Litton, Meredith M Regan, Lajos Pusztai, Hope S Rugo, Sara M Tolaney, Elizabeth Garrett-Mayer, Laleh Amiri-Kordestani, Reva K Basho, Ana F Best, Jean-Francois Boileau, Carsten Denkert, Jared C Foster, Nadia Harbeck, Heather A Jacene, Tari A King, Ginny Mason, Ciara C O'Sullivan, Tatiana M Prowell, Andrea L Richardson, Karla A Sepulveda, Mary Lou Smith, Judy A Tjoe, Gulisa Turashvili, Wendy A Woodward, Lynn Pearson Butler, Elena I Schwartz, Larissa A Korde

Faculty, Staff and Student Publications

PURPOSE: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points.

METHODS: The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at …

A Proteogenomics Data-Driven Knowledge Base Of Human Cancer, Yuxing Liao, Sara R Savage, Yongchao Dou, Zhiao Shi, Xinpei Yi, Wen Jiang, Jonathan T Lei, Bing Zhang

Faculty, Staff and Students Publications

By combining mass-spectrometry-based proteomics and phosphoproteomics with genomics, epi-genomics, and transcriptomics, proteogenomics provides comprehensive molecular characterization of cancer. Using this approach, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has characterized over 1,000 primary tumors spanning 10 cancer types, many with matched normal tissues. Here, we present LinkedOmicsKB, a proteogenomics data-driven knowledge base that makes consistently processed and systematically precomputed CPTAC pan-cancer proteogenomics data available to the public through ∼40,000 gene-, protein-, mutation-, and phenotype-centric web pages. Visualization techniques facilitate efficient exploration and reasoning of complex, interconnected data. Using three case studies, we illustrate the practical utility of LinkedOmicsKB in providing …

Sedentary Bout Patterns And Metabolic Health In The Hispanic Community Health Study/Study Of Latino Youth (Sol Youth)., Jordan A. Carlson, Paul R. Hibbing, Bethany Forseth, Keith M. Diaz, Daniela Sotres-Alvarez, Carolina M. Bejarano, Andrea T. Duran, Sheila F. Castañeda, Melawhy L. Garcia, Krista M. Perreira, Martha L. Daviglus, Linda Van Horn, Marc D. Gellman, Carmen R. Isasi, Jianwen Cai, Alan M. Delamater, Vincent S. Staggs, John Thyfault, Linda C. Gallo

Manuscripts, Articles, Book Chapters and Other Papers

Background There is limited evidence on the potential negative metabolic health impacts of prolonged and uninterrupted sedentary bouts in structurally disadvantaged youth. This study investigated associations between sedentary bout variables and metabolic health markers in the Hispanic Community Health Study/SOL Youth (Study of Latino Youth). Methods and Results SOL Youth was a population-based cohort of 1466 youth (age range, 8-16 years; 48.5% female); 957 youth were included in the analytic sample based on complete data. Accelerometers measured moderate-to-vigorous physical activity (MVPA), total sedentary time, and sedentary bout patterns (daily time spent in sedentary bouts ≥30 minutes, median sedentary bout duration, …

Progression Of Comorbidities In Youth With Overweight Or Obesity During The Covid-19 Pandemic., Erica Wee, Ashley K. Sherman, Safa Farrukh, Mark A. Clements, Kelsee Halpin, Yun Yan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Childhood obesity rates have continued to increase with the COVID-19 pandemic. However, data are limited on the impact of increasing obesity on associated comorbidities.

METHODS: We evaluated the progression of overweight- or obesity-associated comorbidities by investigating change in laboratory results pre-COVID-19 pandemic and post-COVID-19 pandemic onset in youth with overweight or obesity. We defined progression of comorbidities based on increase in category rather than absolute change in value.

RESULTS: HbA1c progression was seen in 19%, and LDL cholesterol progression was seen in 26%, as defined by categories. HbA1c progression and LDL cholesterol progression were significantly correlated. HbA1c and LDL …

A Comparative Study Of Postnatal Anthropometric Growth In Very Preterm Infants And Intrauterine Growth., Fu-Sheng Chou, Hung-Wen Yeh, Reese H. Clark

Manuscripts, Articles, Book Chapters and Other Papers

Most growth references for very preterm infants were developed using measurements taken at birth, and were thought to represent intrauterine growth. However, it remains unclear whether the goal of approximating an intrauterine growth rate as stated by the American Academy of Pediatrics is attainable by very preterm infants. Using real-world measurement data from very preterm infants born between 2010 through 2020, we develop models to characterize the patterns of postnatal growth, and compare them to intrauterine growth. By assessing the weight growth rate, we show three phases of postnatal growth not evident in intrauterine growth. Furthermore, postnatal length and head …

Abcc1 And Glutathione Metabolism Limit The Efficacy Of Bcl-2 Inhibitors In Acute Myeloid Leukemia, Jessica Ebner, Johannes Schmoellerl, Martin Piontek, Gabriele Manhart, Selina Troester, Bing Z Carter, Heidi Neubauer, Richard Moriggl, Gergely Szakács, Johannes Zuber, Thomas Köcher, Michael Andreeff, Wolfgang R Sperr, Peter Valent, Florian Grebien

Faculty, Staff and Student Publications

The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear. Using CRISPR/Cas9 screening, we find that loss of ABCC1 strongly increases the sensitivity of AML cells to Venetoclax. Genetic and pharmacologic ABCC1 inactivation potentiates the anti-leukemic effects of BCL-2 inhibitors and efficiently re-sensitizes Venetoclax-resistant leukemia cells. Conversely, ABCC1 overexpression induces resistance to BCL-2 inhibitors by reducing intracellular drug levels, and high ABCC1 levels …

A Blood-Based Metabolomic Signature Predictive Of Risk For Pancreatic Cancer, Ehsan Irajizad, Ana Kenney, Tiffany Tang, Jody Vykoukal, Ranran Wu, Eunice Murage, Jennifer B Dennison, Marta Sans, James P Long, Maureen Loftus, John A Chabot, Michael D Kluger, Fay Kastrinos, Lauren Brais, Ana Babic, Kunal Jajoo, Linda S Lee, Thomas E Clancy, Kimmie Ng, Andrea Bullock, Jeanine M Genkinger, Anirban Maitra, Kim-Anh Do, Bin Yu, Brian M Wolpin, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the …

Evaluating Atezolizumab In Patients With Urinary Tract Squamous Cell Carcinoma (Aurora): Study Protocol For A Single Arm, Open-Label, Multicentre, Phase Ii Clinical Trial, Simon Crabb, Robin Wickens, Sarah Jane-Bibby, Denise Dunkley, Megan Lawrence, Allen Knight, Robert Jones, Alison Birtle, Robert Huddart, Mark Linch, Jonathan Martin, Adam Coleman, Konstantinos Boukas, Hannah Markham, Gareth Griffiths

Faculty, Staff and Student Publications

BACKGROUND: Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene …

Deep Learning Integrates Histopathology And Proteogenomics At A Pan-Cancer Level, Joshua M Wang, Runyu Hong, Elizabeth G Demicco, Jimin Tan, Rossana Lazcano, Andre L Moreira, Yize Li, Anna Calinawan, Narges Razavian, Tobias Schraink, Michael A Gillette, Gilbert S Omenn, Eunkyung An, Henry Rodriguez, Aristotelis Tsirigos, Kelly V Ruggles, Li Ding, Ana I Robles, D R Mani, Karin D Rodland, Alexander J Lazar, Wenke Liu, David Fenyö, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated with critical clinical outcomes in cancer. We utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types from CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs. normal (AUROC = 0.995) and tissue-of-origin (AUROC = 0.979). We further investigate predictive power on tasks not normally performed from H&E alone, including TP53 prediction and pathologic stage. Importantly, we describe predictive morphologies not previously utilized in a clinical setting. The incorporation of transcriptomics and proteomics identifies pathway-level …

Sepepquant Enhances The Detection Of Possible Isoform Regulations In Shotgun Proteomics, Yongchao Dou, Yuejia Liu, Xinpei Yi, Lindsey K Olsen, Hongwen Zhu, Qiang Gao, Hu Zhou, Bing Zhang

Faculty, Staff and Students Publications

Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key …

Association Between Alcohol Consumption And Ectopic Fat In The Multi-Ethnic Study Of Atherosclerosis, Richard Kazibwe, Parag A Chevli, Joni K Evans, Matthew Allison, Erin D Michos, Alexis C Wood, Jingzhong Ding, Michael D Shapiro, Morgana Mongraw-Chaffin

Faculty, Staff and Students Publications

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 >(light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and …

A Multicenter Analysis Of Abnormal Chromosomal Microarray Findings In Congenital Heart Disease, Benjamin J Landis, Lindsey R Helvaty, Gabrielle C Geddes, Jiuann-Huey Ivy Lin, Svetlana A Yatsenko, Cecilia W Lo, William L Border, Stephanie Burns Wechsler, Chaya N Murali, Mahshid S Azamian, Seema R Lalani, Robert B Hinton, Vidu Garg, Kim L Mcbride, Jennelle C Hodge, Stephanie M Ware

Faculty, Staff and Students Publications

Background

Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype–phenotype relationships.

Methods and Results

Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers. Highly detailed cardiac phenotypes were systematically classified and analyzed for their association with CMA abnormality. Hierarchical classification of each patient into 1 CHD category facilitated broad analyses. Inclusive classification allowing multiple CHD types per …

Epigenetic Induction Of Smooth Muscle Cell Phenotypic Alterations In Aortic Aneurysms And Dissections, Abhijit Chakraborty, Yanming Li, Chen Zhang, Yang Li, Kimberly R Rebello, Shengyu Li, Samantha Xu, Hernan G Vasquez, Lin Zhang, Wei Luo, Guangyu Wang, Kaifu Chen, Joseph S Coselli, Scott A Lemaire, Ying H Shen

Faculty, Staff and Students Publications

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified.

METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis.

RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of …

Neighborhood Disadvantage And Neural Correlates Of Threat And Reward Processing In Survivors Of Recent Trauma, E. Kate Webb, Timothy D. Ely, Grace E. Rowland, Lauren A.M. Lebois, Sanne J.H. Van Rooij, Steven E. Bruce, Tanja Jovanovic, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Laura T. Germine, Kenneth A. Bollen, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Jennifer S. Stevens, Kerry J. Ressler, Nathaniel G. Harnett

Department of Emergency Medicine Faculty Papers

IMPORTANCE: Differences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.

OBJECTIVE: To investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data …

Associations Between Telomere Attrition, Genetic Variants In Telomere Maintenance Genes, And Non-Small Cell Lung Cancer Risk In The Jammu And Kashmir Population Of North India, Gh Rasool Bhat, Rajeshwer Singh Jamwal, Itty Sethi, Amrita Bhat, Ruchi Shah, Sonali Verma, Minerva Sharma, Hana Q Sadida, Sara K Al-Marzooqi, Tariq Masoodi, Sameer Mirza, Mohammad Haris, Muzafar A Macha, Ammira S Alshabeeb Akil, Ajaz A Bhat, Rakesh Kumar

Faculty, Staff and Student Publications

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk.

METHODS: We …

Age- And Sex-Specific Reference Values Of Biventricular Flow Components And Kinetic Energy By 4d Flow Cardiovascular Magnetic Resonance In Healthy Subjects, Xiaodan Zhao, Ru-San Tan, Pankaj Garg, Ping Chai, Shuang Leng, Jennifer Ann Bryant, Lynette L S Teo, Tee Joo Yeo, Marielle V Fortier, Ting Ting Low, Ching Ching Ong, Shuo Zhang, Rob J Van Der Geest, John C Allen, Teng Hong Tan, James W Yip, Ju Le Tan, Marina Hughes, Sven Plein, Jos J M Westenberg, Liang Zhong

Faculty, Staff and Student Publications

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEi

METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEi

RESULTS: …

A Review Of The Role Of Tendon Stem Cells In Tendon-Bone Regeneration, Junjie Chen, Chuanfeng Jiang, Lu Yin, Yingqi Liu, Yue He, Sen Li, Huarui Shen

Faculty, Staff and Student Publications

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has …

Classification Of Missense Variants In The N-Methyl-D-Aspartate Receptor Grin Gene Family As Gain- Or Loss-Of-Function, Scott J Myers, Hongjie Yuan, Riley E Perszyk, Jing Zhang, Sukhan Kim, Kelsey A Nocilla, James P Allen, Jennifer M Bain, Johannes R Lemke, Dennis Lal, Timothy A Benke, Stephen F Traynelis

Faculty, Staff and Student Publications

Advances in sequencing technology have generated a large amount of genetic data from patients with neurological conditions. These data have provided diagnosis of many rare diseases, including a number of pathogenic de novo missense variants in GRIN genes encoding N-methyl-d-aspartate receptors (NMDARs). To understand the ramifications for neurons and brain circuits affected by rare patient variants, functional analysis of the variant receptor is necessary in model systems. For NMDARs, this functional analysis needs to assess multiple properties in order to understand how variants could impact receptor function in neurons. One can then use these data to determine whether the …

Advance Directives For Patients With Breast Cancer: Applying The Right Info/Right Care/Right Patient/Right Time Oncology Model, Stephanie Ossowski, Liisa Lyon, Elizabeth Linehan, Nancy P Gordon, Olga Egorova, Becky Mark, Kimberly Beringer, Thea Abbe, Aida Shirazi, Christine Weldon, Julia Trosman, Arliene Ravelo, Raymond Liu

Faculty, Staff and Student Publications

Background Advance directives (AD) are an important component of life care planning for patients undergoing treatment for cancer; however, there are few effective interventions to increase AD rates. In this quality improvement project, the authors integrated AD counseling into a novel right info/right care/right patient/right time (4R) sequence of care oncology delivery intervention for breast cancer patients in an integrated health care delivery system. Methods The authors studied two groups of patients with newly diagnosed breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at a single facility. The usual care (UC) cohort (N = 139) received care …

Neurocognitive Outcomes In Adult Survivors Of Neuroblastoma: A Report From The Childhood Cancer Survivor Study, Caroline Hesko, Wei Liu, Deo K Srivastava, Tara M Brinkman, Lisa Diller, Todd M Gibson, Kevin C Oeffinger, Wendy M Leisenring, Rebecca Howell, Gregory T Armstrong, Kevin R Krull, Tara O Henderson

Faculty, Staff and Student Publications

Background: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap.

Methods: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire. Impaired emotional regulation, organization, task efficiency, and memory defined as scores ≥90th percentile of sibling norms. Modified Poisson regression models evaluated associations with treatment exposures, era of diagnosis, and chronic conditions. Analyses were stratified by age at diagnosis (≤1 and >1 year) as proxy for lower versus higher risk disease.

Results: Survivors (N = 837; median …

Is Tegoprazan-Based Triple Therapy Effective In Regions With High Rates Of Clarithromycin Resistance?, Hyun Ho Choi

Faculty, Staff and Student Publications

No abstract provided.

Decoding Depression Severity From Intracranial Neural Activity, Jiayang Xiao, Nicole R Provenza, Joseph Asfouri, John Myers, Raissa K Mathura, Brian Metzger, Joshua A Adkinson, Anusha B Allawala, Victoria Pirtle, Denise Oswalt, Ben Shofty, Meghan E Robinson, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Paul R Schrater, Ankit B Patel, Andreas S Tolias, Kelly R Bijanki, Xaq Pitkow, Sameer A Sheth

Faculty, Staff and Students Publications

BACKGROUND: Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis.

METHODS: We recorded high-density neural activity from intracranial electrodes implanted in depression-relevant prefrontal cortical regions in 3 human subjects with severe depression. Neural recordings were labeled with depression severity scores across a wide dynamic range using an adaptive assessment that allowed sampling with a temporal frequency greater than that possible with typical rating scales. We modeled these data using regularized regression techniques with region selection to decode depression severity from …

Single Cell Multiomics Identifies Cells And Genetic Networks Underlying Alveolar Capillary Dysplasia, Minzhe Guo, Kathryn A Wikenheiser-Brokamp, Joseph A Kitzmiller, Cheng Jiang, Guolun Wang, Allen Wang, Sebastian Preissl, Xiaomeng Hou, Justin Buchanan, Justyna A Karolak, Yifei Miao, David B Frank, William J Zacharias, Xin Sun, Yan Xu, Mingxia Gu, Pawel Stankiewicz, Vladimir V Kalinichenko, Jennifer A Wambach, Jeffrey A Whitsett

Faculty, Staff and Students Publications

Rationale

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal developmental disorder of lung morphogenesis caused by insufficiency of FOXF1 (forkhead box F1) transcription factor function. The cellular and transcriptional mechanisms by which FOXF1 deficiency disrupts human lung formation are unknown.

Objectives

To identify cell types, gene networks, and cell–cell interactions underlying the pathogenesis of ACDMPV.

Methods

We used single-nucleus RNA and assay for transposase-accessible chromatin sequencing, immunofluorescence confocal microscopy, and RNA in situ hybridization to identify cell types and molecular networks influenced by FOXF1 in ACDMPV lungs.

Measurements and Main Results

Pathogenic single-nucleotide variants and copy-number …

N-Terminal Α-Amino Sumoylation Of Cofilin-1 Is Critical For Its Regulation Of Actin Depolymerization, Weiji Weng, Xiaokun Gu, Yang Yang, Qiao Zhang, Qi Deng, Jie Zhou, Jinke Cheng, Michael X Zhu, Junfeng Feng, Ou Huang, Yong Li

Faculty, Staff and Student Publications

Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

The Effectiveness Of Disinfection Protocols In Osteopathic Family Medicine Offices, Riley Phyu, Harrison A Patrizio, Thomas Boyle, Todd Schachter

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Healthcare-associated infections (HAIs) pose a substantial public health threat. Despite significant strides to curb HAIs in hospital environments, outpatient settings have not received the same degree of attention. Given their emphasis on holistic, patient-centered care, osteopathic family medicine offices are pivotal in both disease prevention and comprehensive patient treatment. The importance of simple yet effective disinfection protocols, such as thorough cleaning between patient appointments, cannot be overstated in these settings because they are integral to minimizing disease transmission.

OBJECTIVES: This study aims to assess the effectiveness of the current disinfection protocols in osteopathic family medicine offices.

METHODS: A cross-sectional …