Medicine and Health Sciences Commons^™

Therapeutic Effect Of Recombinant Echinococcus Granulosus Antigen B Subunit 2 Protein On Sepsis In A Mouse Model, Ya-Yun Qian, Fei-Fei Huang, Si-Yu Chen, Wei-Xiao Zhang, Yin Wang, Peng-Fei Du, Gen Li, Wen-Bo Ding, Lei Qian, Bin Zhan, Liang Chu, Dong-Hui Jiang, Xiao-Di Yang, Rui Zhou

Faculty, Staff and Students Publications

BACKGROUND: Sepsis is a potentially fatal systemic inflammatory response syndrome (SIRS) that threatens millions of lives worldwide. Echinococcus granulosus antigen B (EgAgB) is a protein released by the larvae of the tapeworm. This protein has been shown to play an important role in modulating host immune response. In this study we expressed EgAgB as soluble recombinant protein in E. coli (rEgAgB) and explored its protective effect on sepsis.

METHODS: The sepsis model was established by cecal ligation and puncture (CLP) procedure in BALB/c mice. The therapeutic effect of rEgAgB on sepsis was performed by interperitoneally injecting 5 µg rEgAgB in …

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …

Outcomes Of Patients With Acute Myeloid Leukemia And Bone Marrow Fibrosis, Samuel Urrutia, Et Al.

2020-Current year OA Pubs

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics …

Identifying Barriers To Hepatitis B And Delta Screening, Prevention, And Linkage To Care Among People Who Use Drugs In Philadelphia, Pennsylvania, Usa, Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Amy Jessop, Rachel Holbert, Fiona Borondy-Jenkins, Quinn Plunkett, Chari Cohen

Student Papers, Posters & Projects

BACKGROUND: People who use drugs (PWUD) are at increased risk for blood-borne viruses, including hepatitis B (HBV) and delta (HDV). Despite the public health threats both viruses present, awareness remains low among at-risk communities and providers who serve them. This study assessed barriers to HBV and HDV prevention, diagnosis, and linkage to care, evaluated existing levels of knowledge, and identified educational needs and preferences among both PWUD and service providers.

METHODS: For this mixed-methods study, data were collected through an anonymous online provider-focused survey, and interviews with PWUD, non-medical staff, and healthcare providers at a harm reduction organization in Philadelphia, …

A Novel Machine Learning Model To Predict Revision Acl Reconstruction Failure In The Mars Cohort, Kinjal Vasavada, Vrinda Vasavada, Jay Moran, Sai Devana, Changhee Lee, Sharon L. Hame, Laith M. Jazrawi, Orrin H. Sherman, Laura J. Huston, Amanda K. Haas, Christina R. Allen, Daniel E. Cooper, Thomas M. Deberardino, Kurt P. Spindler, Michael J. Stuart, Annunziato Ned Amendola, Christopher C. Annunziata, Robert A. Arciero, Bernard R. Bach, Champ L. Baker, Arthur R. Bartolozzi, Keith M. Baumgarten, Jeffrey H. Berg, Geoffrey A. Bernas, Stephen F. Brockmeier, Robert H. Brophy, Charles A. Bush-Joseph, J. Brad Butler V, James L. Carey, James E. Carpenter, Brian J. Cole, Jonathan M. Cooper, Charles L. Cox, R. Alexander Creighton, Tal S. David, Warren R. Dunn, David C. Flanigan, Robert W. Frederick, Theodore J. Ganley, Charles J. Gatt, Steven R. Gecha, James Robert Giffin, Jo A. Hannafin, Norman Lindsay Harris, Keith S. Hechtman, Elliott B. Hershman, Rudolf G. Hoellrich, David C. Johnson, Timothy S. Johnson, Morgan H. Jones, Christopher C. Kaeding, Ganesh V. Kamath, Thomas E. Klootwyk, Bruce A. Levy, C. Benjamin Ma, G. Peter Maiers, Robert G. Marx, Matthew J. Matava, Gregory M. Mathien, David R. Mcallister, Eric C. Mccarty, Robert G. Mccormack, Bruce S. Miller, Carl W. Nissen, Daniel F. O'Neill, Brett D. Owens, Richard D. Parker, Mark L. Purnell, Arun J. Ramappa, Michael A. Rauh, Arthur C. Rettig, Jon K. Sekiya, Kevin G. Shea, James R. Slauterbeck, Matthew V. Smith, Jeffrey T. Spang, Steven J. Svoboda, Timothy N. Taft, Joachim J. Tenuta, Edwin M. Tingstad, Armando F. Vidal, Darius G. Viskontas, Richard A. White, James S. Williams, Michelle L. Wolcott, Brian R. Wolf, Rick W. Wright, James J. York

Rothman Institute Papers

BACKGROUND: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights.

PURPOSE: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure.

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

METHODS: The authors prospectively recruited patients undergoing rACLR from the MARS cohort and obtained preoperative radiographs, surgeon-reported intraoperative findings, and 2- and 6-year follow-up …

In Vivo Evaluation Of Complex Polyps With Endoscopic Optical Coherence Tomography And Deep Learning During Routine Colonoscopy: A Feasibility Study, Haolin Nie, Hongbo Luo, Vladimir Lamm, Shuying Li, Sanskar Thakur, Chao Zhou, Thomas Hollander, Daniel Cho, Erika Sloan, Jingxia Liu, Pooja Navale, Ahmad N Bazarbashi, Juan Pablo Reyes Genere, Vladimir M Kushnir, Quing Zhu

2020-Current year OA Pubs

Standard-of-care (SoC) imaging for assessing colorectal polyps during colonoscopy, based on white-light colonoscopy (WLC) and narrow-band imaging (NBI), does not have sufficient accuracy to assess the invasion depth of complex polyps non-invasively during colonoscopy. We aimed to evaluate the feasibility of a custom endoscopic optical coherence tomography (OCT) probe for assessing colorectal polyps during routine colonoscopy. Patients referred for endoscopic treatment of large colorectal polyps were enrolled in this pilot clinical study, which used a side-viewing OCT catheter developed for use with an adult colonoscope. OCT images of polyps were captured during colonoscopy immediately before SoC treatment. A deep learning …

Racial And Ethnic Disparities In Perceived Health Status Among Patients With Cardiovascular Disease, Marjan Zakeri, Lincy S Lal, Susan M Abughosh, Shubhada Sansgiry, E James Essien, Sujit S Sansgiry

Faculty, Staff and Students Publications

Introduction: Understanding health outcomes among people with cardiovascular disease (CVD) is crucial for improving treatment strategies and patient quality of life. This study investigated racial and ethnic disparities in perceived health status among non-Hispanic Black, Hispanic, and non-Hispanic White adults with CVD.

Methods: The study had a retrospective cross-sectional design and used data from the Medical Expenditure Panel Survey spanning 8 calendar years (2014-2021). The study population consisted of adults diagnosed with various CVDs. We used ordinal logistic regression models adjusted for demographic and socioeconomic characteristics, CVD severity, comorbidities, and health care expenditures to assess racial and ethnic differences in …

Knowledge, Attitudes, And Concerns About Psilocybin And Mdma As Novel Therapies Among Us Healthcare Professionals, Erin Wang, David S Mathai, Natalie Gukasyan, Sandeep Nayak, Albert Garcia-Romeu

Center for Medical Ethics and Health Policy Staff Publications

Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to …

Underutilization Of Influenza Antiviral Treatment Among Children And Adolescents At Higher Risk For Influenza-Associated Complications - United States, 2023-2024., Aaron M. Frutos, Haris M. Ahmad, Dawud Ujamaa, Alissa C. O'Halloran, Janet A. Englund, Eileen J. Klein, Danielle M. Zerr, Melanie Crossland, Holly Staten, Julie A. Boom, Leila C. Sahni, Natasha B. Halasa, Laura S. Stewart, Olla Hamdan, Tess Stopczynski, William Schaffner, H Keipp Talbot, Marian G. Michaels, John V. Williams, Melissa Sutton, M Andraya Hendrick, Mary A. Staat, Elizabeth P. Schlaudecker, Brenda L. Tesini, Christina B. Felsen, Geoffrey A. Weinberg, Peter G. Szilagyi, Bridget J. Anderson, Jemma V. Rowlands, Murtada Khalifa, Marc Martinez, Rangaraj Selvarangan, Jennifer E. Schuster, Ruth Lynfield, Melissa Mcmahon, Sue Kim, Val Tellez Nunez, Patricia A. Ryan, Maya L. Monroe, Yun F. Wang, Kyle P. Openo, James Meek, Kimberly Yousey-Hindes, Nisha B. Alden, Isaac Armistead, Suchitra Rao, Shua J. Chai, Pam Daily Kirley, Ariana P. Toepfer, Fatimah S. Dawood, Heidi L. Moline, Timothy M. Uyeki, Sascha Ellington, Shikha Garg, Catherine H. Bozio, Samantha M. Olson

Manuscripts, Articles, Book Chapters and Other Papers

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents agedattended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. …

Predictors Of Study Dropout In Cognitive-Behavioural Therapy With A Trauma Focus For Post-Traumatic Stress Disorder In Adults: An Individual Participant Data Meta-Analysis, Simonne Wright, Eirini Karyotaki, Pim Cuijpers, Jonathan Bisson, Davide Papola, Anke B Witteveen, Sudie E Back, Dana Bichescu-Burian, Liuva Capezzani, Marylene Cloitre, Grant J Devilly, Thomas Elbert, Marcelo Mello, Julian D Ford, Damion Grasso, Pedro Gamito, Richard Gray, Moira Haller, Nigel Hunt, Rolf J Kleber, Julia König, Claire Kullack, Jonathan Laugharne, Rachel Liebman, Christopher William Lee, Jeannette Lely, John C Markowitz, Candice Monson, Mirjam J Nijdam, Sonya B Norman, Miranda Olff, Tahereh Mina Orang, Luca Ostacoli, Nenad Paunovic, Eva Petkova, Patricia Resick, Rita Rosner, Maggie Schauer, Joy M Schmitz, Ulrich Schnyder, Brian N Smith, Anka A Vujanovic, Yinyin Zang, Érica Panzani Duran, Francisco Lotufo Neto, Soraya Seedat, Marit Sijbrandij

Faculty, Staff and Student Publications

Background: Available empirical evidence on participant-level factors associated with dropout from psychotherapies for post-traumatic stress disorder (PTSD) is both limited and inconclusive. More comprehensive understanding of the various factors that contribute to study dropout from cognitive-behavioural therapy with a trauma focus (CBT-TF) is crucial for enhancing treatment outcomes.

Objective: Using an individual participant data meta-analysis (IPD-MA) design, we examined participant-level predictors of study dropout from CBT-TF interventions for PTSD.

Methods: A comprehensive systematic literature search was undertaken to identify randomised controlled trials comparing CBT-TF with waitlist control, treatment-as-usual or another therapy. Academic databases were screened from conception until 11 January …

The Il-1Β Inhibitor Canakinumab In Previously Treated Lower-Risk Myelodysplastic Syndromes: A Phase 2 Clinical Trial, Juan Jose Rodriguez-Sevilla, Vera Adema, Kelly S Chien, Sanam Loghavi, Feiyang Ma, Hui Yang, Guillermo Montalban-Bravo, Xuelin Huang, Xavier Calvo, Joby Joseph, Kristy Bodden, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells' (HSPCs') aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had …

Behavioral And Neural Mechanisms Of Face-Specific Attention During Goal-Directed Visual Search, Jie Zhang, Xiaocang Zhu, Huihui Zhou, Shuo Wang

2020-Current year OA Pubs

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. …

Evaluation Of Prognostic Factors In Patients With High-Risk Classical Hodgkin Lymphoma Undergoing Autologous Transplantation, Narendranath Epperla, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

There are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or …

Dilated Cardiomyopathy-Associated Skeletal Muscle Actin (Acta1) Mutation R256h Disrupts Actin Structure And Function And Causes Cardiomyocyte Hypocontractility, Ankit Garg, Silvia Jansen, Lina Greenberg, Rui Zhang, Kory J Lavine, Michael J Greenberg

2020-Current year OA Pubs

Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1's high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how a mutation in an actin isoform expressed at low levels in cardiomyocytes can cause cardiomyopathy by focusing on a unique ACTA1 variant, R256H. We previously identified this variant in a family with dilated cardiomyopathy, who had reduced systolic function without clinical skeletal …

Associations Between Dietary Patterns And Quality Of Life In A Longitudinal Cohort Of Colorectal Cancer Survivors, Kristen S Smith, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

PURPOSE: To characterize dietary patterns and examine associations with cross-sectional and longitudinal changes in quality of life (QOL) over approximately one year after colorectal cancer (CRC) diagnosis.

METHODS: The ColoCare Study is an international, multi-center, prospective cohort study of newly diagnosed CRC survivors of any stage. A subset of participants with CRC in the United States completed patient-reported outcome measures at 6- and 12-months post-enrollment, including the Food Frequency Questionnaire (FFQ) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Dietary patterns at 6 months (around the time of treatment completion) were identified …

Genetic Variants In Canonical Wnt Signaling Pathway Associated With Pediatric Immune Thrombocytopenia, Taylor Olmsted Kim, Jennifer M Geris, Jonathan M Flanagan, Rachael F Grace, Michele P Lambert, Candelaria O'Farrell, Melissa J Rose, Kristin A Shimano, Omar Niss, Cindy Neunert, Taizo A Nakano, Derek Macmath, Bogdan Dinu, Susan E Kirk, Ellis J Neufeld, Jenny M Despotovic, Michael E Scheurer, Amanda B Grimes

Center for Medical Ethics and Health Policy Staff Publications

Through the use of genetic sequencing, molecular variants driving autoimmunity are increasingly identified in patients with chronic and refractory immune cytopenias. With the goal of discovering genetic variants that predispose to pediatric immune thrombocytopenia (ITP) or increase risk for chronic disease, we conducted a genome-wide association study in a large multi-institutional cohort of pediatric patients with ITP. A total of 591 patients were genotyped using an Illumina Global Screening Array BeadChip. Six variants met genome-wide significance in comparison between children with ITP and a cohort of healthy children. One variant in NAV2 was inversely associated with ITP (adjusted odds ratio …

Length Of Hospital And Intensive Care Unit Stay In Patients With Invasive Candidiasis And/Or Candidemia Treated With Rezafungin: A Pooled Analysis Of Two Randomised Controlled Trials, Patrick M Honoré, Matteo Bassetti, Oliver A Cornely, Herve Dupont, Jesús Fortún, Marin H Kollef, Peter Pappas, John Pullman, Jose Vazquez, Inga Bielicka, Sara Dickerson, Nick Manamley, Taylor Sandison, George R Thompson

2020-Current year OA Pubs

BACKGROUND: Invasive candidiasis/candidemia (IC/C) is associated with a substantial health economic burden driven primarily by prolonged hospital stay. The once-weekly IV echinocandin, rezafungin acetate, has demonstrated non-inferiority to caspofungin in the treatment of IC/C. This paper reports a post hoc pooled exploratory analysis of length of stay (LoS) for hospital and intensive care unit (ICU) stays in two previously published clinical trials (ReSTORE [NCT03667690] and STRIVE [NCT02734862], that compared rezafungin with daily IV caspofungin (stable patients in the caspofungin group who met relevant criteria could step down to fluconazole after 3 days or more).

METHODS: LoS outcomes were analysed descriptively …

Regulatory T Cells Require Peripheral Ccl2-Ccr2 Signaling To Facilitate The Resolution Of Medication Overuse Headache-Related Behavioral Sensitization, Sun Ryu, Jintao Zhang, Roli Simoes, Xuemei Liu, Zhaohua Guo, Li Feng, Jacqueline Unsinger, Richard S Hotchkiss, Yu-Qing Cao

2020-Current year OA Pubs

BACKGROUND: Medication overuse headache (MOH) is the most common secondary headache disorder, resulting from chronic and excessive use of medication to treat headaches, for example, sumatriptan. In a recent study, we have shown that the peripheral C-C motif ligand 2 (CCL2), C-C motif chemokine receptor 2 (CCR2) and calcitonin-gene-related peptide (CGRP) signaling pathways interact with each other and play critical roles in the development of chronic migraine-related behavioral and cellular sensitization. In the present study, we investigated whether CCL2-CCR2 and CGRP signaling pathways play a role in the development of sumatriptan overuse-induced sensitization, and whether they are involved in its …

Understanding Faculty Perspectives On Health Equity Curriculum Implementation In Graduate Medical Education: A Qualitative Study, Krys Foster, Dhruvi Shah, Quinn Plunkett, Randa Sifri

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Despite increased awareness of persistent healthcare disparities, integrating health equity education into medical residency curricula needs urgent expansion. The Accreditation Council for Graduate Medical Education (ACGME) mandates addressing healthcare disparities and social determinants of health, but implementation remains insufficient due to pervasive barriers.

OBJECTIVE: To explore residency faculty perspectives at one institution surrounding implementing a health equity curriculum within their programs.

METHODS: Between November 2022 and April 2023, qualitative interviews and focus groups were conducted with residency faculty participants (n = 13) from a large academic medical institution. Participants were recruited via an internal email list directory of program …

Effectiveness Of Mailed Outreach And Patient Navigation To Promote Hcc Screening Process Completion: A Multicentre Pragmatic Randomised Clinical Trial, Amit G Singal, Manasa Narasimman, Darine Daher, Sruthi Yekkaluri, Yan Liu, Minjae Lee, Vanessa Cerda, Aisha Khan, Karim Seif El Dahan, Jennifer Kramer, Purva Gopal, Caitlin Murphy, Ruben Hernaez

Faculty, Staff and Students Publications

Background: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis.

Methods: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the …

Addition Of Metastasis-Directed Therapy To Systemic Therapy For Oligometastatic Pancreatic Ductal Adenocarcinoma (Extend): A Multicenter, Randomized Phase Ii Trial, Ethan B Ludmir, Alexander D Sherry, Bryan M Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N Medina-Rosales, Alexandre Reuben, Emma B Holliday, Grace L Smith, Sonal S Noticewala, Sarah Nicholas, Tracy R Price, Rachael M Martin-Paulpeter, Luis A Perles, Sunyoung S Lee, Michael S Lee, Brandon G Smaglo, Ryan W Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M Taniguchi, Eugene J Koay, Matthew H G Katz, Robert A Wolff, Prajnan Das, Shubham Pant, Albert C Koong, Chad Tang

Faculty, Staff and Student Publications

Purpose: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

Methods: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response …

Dna Methylation Classifier To Diagnose Pancreatic Ductal Adenocarcinoma Metastases From Different Anatomical Sites, Teodor G Calina, Eilís Perez, Elena Grafenhorst, Jamal Benhamida, Simon Schallenberg, Adrian Popescu, Ines Koch, Tobias Janik, Baoqing Chen, Jana Ihlow, Stephanie Roessler, Benjamin Goeppert, Bruno Sinn, Marcus Bahra, George A Calin, Eliane T Taube, Uwe Pelzer, Christopher C M Neumann, David Horst, Erik Knutsen, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.

Methods: For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the …

Microglia Drive Diurnal Variation In Susceptibility To Inflammatory Blood-Brain Barrier Breakdown, Jennifer H. Lawrence, Asha Patel, Melvin W. King, Collin J. Nadarajah, Richard Daneman, Erik S. Musiek

2020-Current year OA Pubs

The blood-brain barrier (BBB) is critical for maintaining brain homeostasis but is susceptible to inflammatory dysfunction. While transporter-dependent efflux of some lipophilic substrates across the BBB shows circadian variation due to rhythmic transporter expression, basal transporter-independent permeability and leakage is nonrhythmic. Whether daily timing influences BBB permeability in response to inflammation is unknown. Here, we induced systemic inflammation through repeated LPS injections either in the morning (ZT1) or evening (ZT13) under standard lighting conditions; we then examined BBB permeability to a polar molecule that is not a transporter substrate, sodium fluorescein. We observed clear diurnal variation in inflammatory BBB permeability, …

Evaluation Of A Trauma-Informed Care (Tic) Training Program Across Community Health Centers In Texas: A Qualitative Study, Jihye Choi, Efrat K Gabay, Aimee Rachel, Aniela Brown, Roxana Cruz, Qiheng Yan, Paula M Cuccaro

Faculty, Staff and Student Publications

BACKGROUND: In April 2019, Texas Association of Community Health Centers launched the Trauma-Informed Care (TIC) program in community health centers across Texas. This initiative aimed to transform organizational culture for consistent delivery of TIC by providing training and coaching opportunities for Trainers and Champions in each health center. This study is an interim qualitative evaluation to gain participants' insights into their experiences of and perceptions about TIC training as part of the TIC initiative.

METHODS: We conducted semi-structured key informant interviews via Zoom with Trainers across four cohorts of participating health centers between February 2020 and April 2023. We used …

The Rna Receptor Rig-I Binding Synthetic Oligodeoxynucleotide Promotes Pneumonia Survival, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleóngarcía, Michael K Longmire, Mathilde Lethier, Stephen Cusack, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in TLR9, the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, …

Multi-Organ Gene Expression Analysis And Network Modeling Reveal Regulatory Control Cascades During The Development Of Hypertension In Female Spontaneously Hypertensive Rat, Eden Hornung, Sirisha Achanta, Alison Moss, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hypertension is a multifactorial disease with stage-specific gene expression changes occurring in multiple organs over time. The temporal sequence and the extent of gene regulatory network changes occurring across organs during the development of hypertension remain unresolved. In this study, female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were used to analyze expression patterns of 96 genes spanning inflammatory, metabolic, sympathetic, fibrotic, and renin-angiotensin (RAS) pathways in five organs, at five time points from the onset to established hypertension. We analyzed this multi-dimensional dataset containing ~15,000 data points and developed a data-driven dynamic network model that accounts for …

Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease …

Association Of Neighborhood-Level Disadvantage Beyond Individual Sociodemographic Factors In Patients With Or At Risk Of Knee Osteoarthritis, Jessica Peoples, Jared J Tanner, Emily J Bartley, Lisa H Domenico, Cesar E Gonzalez, Josue S Cardoso, Catalina Lopez-Quintero, Elizabeth A Reynolds Losin, Roland Staud, Burel R Goodin, Roger B Fillingim, Ellen L Terry

2020-Current year OA Pubs

OBJECTIVE: Lower socioeconomic status (SES) is a risk factor for poorer pain-related outcomes. Further, the neighborhood environments of disadvantaged communities can create a milieu of increased stress and deprivation that adversely affects pain-related and other health outcomes. Socioenvironmental variables such as the Area Deprivation Index, which ranks neighborhoods based on socioeconomic factors could be used to capture environmental aspects associated with poor pain outcomes. However, it is unclear whether the ADI could be used as a risk assessment tool in addition to individual-level SES.

METHODS: The current study investigated whether neighborhood-level disadvantage impacts knee pain-related outcomes above sociodemographic measures. Participants …

Real-World Impact Of Differences In The Who And Icc Classifications Of Non-Hodgkin Lymphoma: A Leo Cohort Study Analysis, Brooj Abro, Matthew J Maurer, Thomas M Habermann, W Richard Burack, Jennifer R Chapman, Jonathon B Cohen, Jonathan W Friedberg, Giorgio Inghirami, Brad S Kahl, Melissa C Larson, Brian K Link, Izidore S Lossos, Peter Martin, Timothy J Mcdonnell, Loretta J Nastoupil, Shaun M Riska, Sergei Syrbu, Francisco Vega, Kiran R Vij, Christopher R Flowers, James R Cerhan, David L Jaye, Andrew L Feldman

Faculty, Staff and Student Publications

Recent introduction of 2 different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will affect < 1% of non-Hodgkin lymphomas.

Probabilistic Presurgical Language Fmri Atlas Of Patients With Brain Tumors, Jian Ming Teo, Vinodh A Kumar, Jina Lee, Rami W Eldaya, Ping Hou, Mu-Lan Jen, Kyle R Noll, Peng Wei, Sherise D Ferguson, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background and purpose: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

Materials and methods: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, …