Digital Commons Network^™

Leveraging Preclinical Models Of Metastatic Breast Cancer, Diego A Pedroza, Yang Gao, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women that present to the clinic with established breast cancer metastases have limited treatment options. Yet, the majority of preclinical studies are actually not directed at developing treatment regimens for established metastatic disease. In this review we will discuss the current state of preclinical macro-metastatic breast cancer models, including, but not limited to syngeneic GEMM, PDX and xenografts. Challenges within these models which are often overlooked include fluorophore-immunogenic neoantigens, differences in experimental vs spontaneous metastasis and tumor heterogeneity. Furthermore, due to cell plasticity in the tumor immune microenvironment (TIME) of the metastatic landscape, the treatment efficacy of newly approved immune …

Stereo-Electroencephalography-Guided Network Neuromodulation For Psychiatric Disorders: The Neurophysiology Monitoring Unit, Anusha B Allawala, Kelly R Bijanki, Joshua Adkinson, Denise Oswalt, Evangelia Tsolaki, Sanjay Mathew, Raissa K Mathura, Eleonora Bartoli, Nicole Provenza, Andrew J Watrous, Jiayang Xiao, Victoria Pirtle, Madaline M Mocchi, Sameer Rajesh, Nabeel Diab, Jeffrey F Cohn, David A Borton, Wayne K Goodman, Nader Pouratian, Sameer A Sheth

Faculty, Staff and Students Publications

Background and objectives: Recent advances in stereotactic and functional neurosurgery have brought forth the stereo-electroencephalography approach which allows deeper interrogation and characterization of the contributions of deep structures to neural and affective functioning. We argue that this approach can and should be brought to bear on the notoriously intractable issue of defining the pathophysiology of refractory psychiatric disorders and developing patient-specific optimized stimulation therapies.

Methods: We have developed a suite of methods for maximally leveraging the stereo-electroencephalography approach for an innovative application to understand affective disorders, with high translatability across the broader range of refractory neuropsychiatric conditions.

Results: This article …

X-Linked Genetic Associations In Sporadic Thoracic Aortic Dissection, Fadi I Musfee, Goo Jun, Laura E Mitchell, Han Chen, Dongchuan Guo, Siddharth K Prakash, Shaunak Sanjay Adkar, Megan L Grove, Ryan Bohyun Choi, Derek Klarin, Million Veteran Program, Eric Boerwinkle, Dianna M Milewicz

Faculty, Staff and Students Publications

The male predominance in sporadic thoracic aortic aneurysm and dissection (TAD) suggests that the X chromosome contributes to TAD, but this has not been tested. We investigated whether X-linked variation-common (minor allele frequency [MAF] ≥0.01) and rare (MAF < 0.01)-was associated with sporadic TAD in three cohorts of European descent (Discovery: 364 cases, 874 controls; Replication: 516 cases, 440,131 controls, and ARIC [Atherosclerosis Risk in Communities study]: 753 cases, 2247 controls). For analysis of common variants, we applied a sex-stratified logistic regression model followed by a meta-analysis of sex-specific odds ratios. Furthermore, we conducted a meta-analysis of overlapping common variants between the Discovery and Replication cohorts. For analysis of rare variants, we used a sex-stratified optimized sequence kernel association test model. Common variants results showed no statistically significant findings in the Discovery cohort. An intergenic common variant near SPANXN1 was statistically significant in the Replication cohort (p = 1.81 × 10-8). The highest signal from the meta-analysis of the Discovery and Replication cohorts was a ZNF182 intronic common variant (p = 3.5 × 10-6). In rare variants results, RTL9 reached statistical significance (p = 5.15 × 10-5). Although most of our results were statistically insignificant, our analysis is the most comprehensive X-chromosome association analysis of sporadic TAD to date.

Potentially Functional Variants Of Chmp4a And Panx1 In The Pyroptosis-Related Pathway Predict Survival Of Patients With Non-Oropharyngeal Head And Neck Squamous Cell Carcinoma, Xiaozhun Tang, Huiling Wang, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Qingyi Wei

Faculty, Staff and Students Publications

Background: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC).

Methods: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the …

Loss Of Periostin Function Impairs Ligament Fibroblast Activity And Facilitates Ros-Mediated Cellular Senescence, Muhammad Farooq Rai, Xin Duan, Mingming Yan, Robert H Brophy, Lei Cai

2020-Current year OA Pubs

Anterior cruciate ligament (ACL) injuries pose a significant challenge due to their limited healing potential, often resulting in premature arthritis. The factors and mechanisms contributing to this inadequate healing process remain elusive. During the acute phase of injury, ACL tissues express elevated periostin levels that decline over time. The functional significance of periostin in ligament biology remains understudied. In this study, we investigated the functional and mechanistic implications of periostin deficiency in ACL biology, utilizing ligament fibroblasts derived from patients and a murine model of ACL rupture. Our investigations unveiled that periostin knockdown compromised fibroblast growth characteristics, hindered the egress …

Barriers And Facilitators To Administering Burn Pit Registry Exams In Vha Facilities, Patricia V Chen, Israel C Christie, Kyler M Godwin, Jaehwan Han, Nisha Jani, Anays Sotolongo, Asma Ali, Drew A Helmer

Faculty and Staff Publications

Introduction: The Veterans Health Administration (VHA) established the Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014 to address exposure concerns for veterans who have served in military operations in Southwest Asia and Afghanistan. By 2021, over 236,086 veterans completed the online questionnaire and 60% requested an AHOBPR examination. Of those requesting an exam, only 12% had an exam recorded in their medical record. This article summarizes barriers and facilitators to delivering AHOBPR exams and shares lessons learned from facilities who have successfully implemented burn pit exams for veterans.

Materials and methods: We (I.C.C and J.H.) constructed a key …

Micronuclear Collapse From Oxidative Damage, Melody Di Bona, Yanyang Chen, Albert S Agustinus, Alice Mazzagatti, Mercedes A Duran, Matthew Deyell, Daniel Bronder, James Hickling, Christy Hong, Lorenzo Scipioni, Giulia Tedeschi, Sara Martin, Jun Li, Aušrinė Ruzgaitė, Nadeem Riaz, Parin Shah, Edridge K D'Souza, D Zack Brodtman, Simone Sidoli, Bill Diplas, Manisha Jalan, Nancy Y Lee, Alban Ordureau, Benjamin Izar, Ashley M Laughney, Simon Powell, Enrico Gratton, Stefano Santaguida, John Maciejowski, Peter Ly, Thomas M Jeitner, Samuel F Bakhoum

Faculty, Staff and Student Publications

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood. In this study, we found that mitochondria-derived reactive oxygen species (ROS) disrupt micronuclei by promoting a noncanonical function of charged multivesicular body protein 7 (CHMP7), a scaffolding protein for the membrane repair complex known as endosomal sorting complex required for transport III (ESCRT-III). ROS retained CHMP7 in micronuclei while disrupting its interaction with other ESCRT-III components. ROS-induced cysteine oxidation stimulated CHMP7 oligomerization and …

Identification Of A0 Minimum Ablative Margins For Colorectal Liver Metastases: Multicentre, Retrospective Study Using Deformable Ct Registration And Artificial Intelligence-Based Autosegmentation, Iwan Paolucci, Jessica Albuquerque Marques Silva, Yuan-Mao Lin, Gregor Laimer, Valentina Cignini, Francesca Menchini, Marcio Meira, Alexander Shieh, Caleb O'Connor, Kyle A Jones, Carlo Gazzera, Paolo Fonio, Kristy K Brock, Marco Calandri, Marcos Menezes, Reto Bale, Bruno C Odisio

Faculty, Staff and Student Publications

Background: Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting.

Methods: This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour …

Persistent Mri Findings Unique To Blast And Repetitive Mild Tbi: Analysis Of The Cenc/Limbic Cohort Injury Characteristics, David F Tate, Benjamin S C Wade, Carmen S Velez, Erin D Bigler, Nicholas D Davenport, Emily L Dennis, Carrie Esopenko, Sidney R Hinds, Jacob Kean, Eamonn Kennedy, Kimbra Kenney, Andrew R Mayer, Mary R Newsome, Carissa L Philippi, Mary J Pugh, Randall S Scheibel, Brian A Taylor, Maya Troyanskaya, John K Werner, Gerald E York, William Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

Introduction: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements.

Material and methods: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium …

Contrast Enhanced Ultrasound Of Liver Lesions In Patients Treated For Childhood Malignancies., Ayatullah Mostafa, Zachary Abramson, Mina Ghbrial, Som Biswas, Sherwin S. Chan, Himani Darji, Jessica Gartrell, Seth E. Karol, Yimei Li, Daniel A. Mulrooney, Tushar Patni, Tarek M. Zaghloul, M Beth Mccarville

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients treated for cancer have a higher incidence of focal liver lesions than the general population and there is often concern for a malignant etiology. This can result in patient, caregiver and physician anxiety and is managed by a "wait and watch" approach, or immediate additional imaging, or biopsy, depending on the degree of clinical concern. Because it is a low-cost, easily accessible, radiation and sedation free modality, we investigated the value of contrast enhanced ultrasound (CEUS) to accurately distinguish benign from malignant liver lesions in patients treated for childhood malignancies.

METHODS: We performed an IRB approved retrospective study …

A Non-Parametric Approach To Predict The Recruitment For Randomized Clinical Trials: An Example In Elderly Inpatient Settings, Alejandro Villasante-Tezanos, Yong-Fang Kuo, Christopher Kurinec, Yisheng Li, Xiaoying Yu

Faculty, Staff and Student Publications

BACKGROUND: Accurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement.

METHODS: We create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was …

Detection Of Distant Relatedness In Biobanks To Identify Undiagnosed Cases Of Mendelian Disease As Applied To Long Qt Syndrome, Megan C Lancaster, Hung-Hsin Chen, M Benjamin Shoemaker, Matthew R Fleming, Teresa L Strickland, James T Baker, Grahame F Evans, Hannah G Polikowsky, David C Samuels, Chad D Huff, Dan M Roden, Jennifer E Below

Faculty, Staff and Student Publications

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.

RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In India: A Convergent Parallel Mixed Methods Study, Anubha Agarwal, Raji Devarajan, Salva Balbale, Aashima Chopra, Dorairaj Prabhakaran, Mark D Huffman, Lisa R Hirschhorn, Padinhare P Mohanan

2020-Current year OA Pubs

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally.

METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated …

Creating A Modified Version Of The Cambridge Multimorbidity Score To Predict Mortality In People Older Than 16 Years: Model Development And Validation, Debasish Kar, Kathryn S. Taylor, Mark Joy, Sudhir Venkatesan, Wilhelmine Meeraus, Sylvia Taylor, Sneha N. Anand, Filipa Ferreira, Gavin Jamie, Xuejuan Fan, Simon De Lusignan

Peninsula Medical School

Background: No single multimorbidity measure is validated for use in NHS (National Health Service) England’s General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR), the nationwide primary care data set created for COVID-19 pandemic research. The Cambridge Multimorbidity Score (CMMS) is a validated tool for predicting mortality risk, with 37 conditions defined by Read Codes. The GDPPR uses the more internationally used Systematized Nomenclature of Medicine clinical terms (SNOMED CT). We previously developed a modified version of the CMMS using SNOMED CT, but the number of terms for the GDPPR data set is limited making it impossible to …

Loss Of Symmetric Cell Division Of Apical Neural Progenitors Drives Dennd5a-Related Developmental And Epileptic Encephalopathy., Emily Banks, Vincent Francis, Sheng-Jia Lin, Fares Kharfallah, Vladimir Fonov, Maxime Lévesque, Chanshuai Han, Gopinath Kulasekaran, Marius Tuznik, Armin Bayati, Reem Al-Khater, Fowzan S. Alkuraya, Loukas Argyriou, Meisam Babaei, Melanie Bahlo, Behnoosh Bakhshoodeh, Eileen Barr, Lauren E. Bartik, Mahmoud Bassiony, Miriam Bertrand, Dominique Braun, Rebecca Buchert, Mauro Budetta, Maxime Cadieux-Dion, Daniel G. Calame, Heidi Cope, Donna Cushing, Stephanie Efthymiou, Marwa Abd Elmaksoud, Huda G. El Said, Tawfiq Froukh, Harinder K. Gill, Joseph G. Gleeson, Laura Gogoll, Elaine S-Y Goh, Vykuntaraju K Gowda, Tobias B. Haack, Mais O. Hashem, Stefan Hauser, Trevor L. Hoffman, Jacob S. Hogue, Akimoto Hosokawa, Henry Houlden, Kevin Huang, Stephanie Huynh, Ehsan G. Karimiani, Silke Kaulfuß, G Christoph Korenke, Amy Kritzer, Hane Lee, James R. Lupski, Elysa J. Marco, Kirsty Mcwalter, Arakel Minassian, Berge A. Minassian, David Murphy, Juanita Neira-Fresneda, Hope Northrup, Denis M. Nyaga, Barbara Oehl-Jaschkowitz, Matthew Osmond, Richard Person, Davut Pehlivan, Cassidy Petree, Lynette G. Sadleir, Carol J. Saunders, Ludger Schoels, Vandana Shashi, Rebecca C. Spillmann, Varunvenkat M. Srinivasan, Paria N. Torbati, Tulay Tos, Undiagnosed Diseases Network, Maha S. Zaki, Dihong Zhou, Christiane Zweier, Jean-François Trempe, Thomas M. Durcan, Ziv Gan-Or, Massimo Avoli, Cesar Alves, Gaurav K. Varshney, Reza Maroofian, David A. Rudko, Peter S. Mcpherson

Manuscripts, Articles, Book Chapters and Other Papers

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells …

Loss Of Symmetric Cell Division Of Apical Neural Progenitors Drives Dennd5a-Related Developmental And Epileptic Encephalopathy, Emily Banks, Vincent Francis, Sheng-Jia Lin, Fares Kharfallah, Vladimir Fonov, Maxime Lévesque, Chanshuai Han, Gopinath Kulasekaran, Marius Tuznik, Armin Bayati, Reem Al-Khater, Fowzan S Alkuraya, Loukas Argyriou, Meisam Babaei, Melanie Bahlo, Behnoosh Bakhshoodeh, Eileen Barr, Lauren Bartik, Mahmoud Bassiony, Miriam Bertrand, Dominique Braun, Rebecca Buchert, Mauro Budetta, Maxime Cadieux-Dion, Daniel G Calame, Heidi Cope, Donna Cushing, Stephanie Efthymiou, Marwa Abd Elmaksoud, Huda G El Said, Tawfiq Froukh, Harinder K Gill, Joseph G Gleeson, Laura Gogoll, Elaine S-Y Goh, Vykuntaraju K Gowda, Tobias B Haack, Mais O Hashem, Stefan Hauser, Trevor L Hoffman, Jacob S Hogue, Akimoto Hosokawa, Henry Houlden, Kevin Huang, Stephanie Huynh, Ehsan G Karimiani, Silke Kaulfuß, G Christoph Korenke, Amy Kritzer, Hane Lee, James R Lupski, Elysa J Marco, Kirsty Mcwalter, Arakel Minassian, Berge A Minassian, David Murphy, Juanita Neira-Fresneda, Hope Northrup, Denis M Nyaga, Barbara Oehl-Jaschkowitz, Matthew Osmond, Richard Person, Davut Pehlivan, Cassidy Petree, Lynette G Sadleir, Carol Saunders, Ludger Schoels, Vandana Shashi, Rebecca C Spillmann, Varunvenkat M Srinivasan, Paria N Torbati, Tulay Tos, Maha S Zaki, Dihong Zhou, Christiane Zweier, Jean-François Trempe, Thomas M Durcan, Ziv Gan-Or, Massimo Avoli, Cesar Alves, Gaurav K Varshney, Reza Maroofian, David A Rudko, Peter S Mcpherson

Faculty, Staff and Student Publications

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells …

Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events …

Transcriptome Profiling Of Pediatric Extracranial Solid Tumors And Lymphomas Enables Rapid Low-Cost Diagnostic Classification, Kofi B Opoku, Teresa Santiago, Priya Kumar, Sophia M Roush, Yuri Fedoriw, Tamiwe Tomoka, Vasiliki Leventaki, Larissa V Furtado, Nickhill Bhakta, Thomas B Alexander, Jeremy R Wang

Faculty, Staff and Student Publications

Approximately 80% of pediatric tumors occur in low- and middle-income countries (LMIC), where diagnostic tools essential for treatment decisions are often unavailable or incomplete. Development of cost-effective molecular diagnostics will help bridge the cancer diagnostic gap and ultimately improve pediatric cancer outcomes in LMIC settings. We investigated the feasibility of using nanopore whole transcriptome sequencing on formalin-fixed paraffin embedded (FFPE)-derived RNA and a composite machine learning model for pediatric solid tumor diagnosis. Transcriptome cDNA sequencing was performed on a heterogenous set of 221 FFPE and 32 fresh frozen pediatric solid tumor and lymphoma specimens on Oxford Nanopore Technologies' sequencing platforms. …

Needs Of Family Caregivers Of Hospitalised Adults With Dementia During Care Transitions: A Qualitative Study In A Us Department Of Veterans Affairs Hospital, Molly J Horstman, Tracy L Evans, Crystal Guo, Mandi Sonnenfeld, Aanand D Naik, Alan Stevens, Mark E Kunik

Faculty, Staff and Student Publications

OBJECTIVE: To identify the needs of caregivers of hospitalised adults with dementia in the hospital and during care transitions.

DESIGN: Pragmatic qualitative inquiry with semi-structured interviews.

SETTING: Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, USA.

PARTICIPANTS: 12 family caregivers (family member (n=11); friend (n=1)) and 15 health professionals (hospital medicine physicians (n=4), inpatient nurse case managers (n=2), social workers (n=4), outpatient geriatrics providers (n=2), a primary care provider (n=1), geriatric psychiatrists (n=2)) were interviewed. Caregivers were recruited while their care recipient was hospitalised and were interviewed at least 2 weeks after the care recipient was discharged from …

Influence Of Pathophysiologic Patterns Of Coronary Artery Disease On Immediate Percutaneous Coronary Intervention Outcomes, Carlos Collet, Daniel Munhoz, Takuya Mizukami, Jeroen Sonck, Hitoshi Matsuo, Toshiro Shinke, Hirohiko Ando, Brian Ko, Simone Biscaglia, Fernando Rivero, Thomas Engstrøm, Ketina Arslani, Antonio Maria Leone, Lokien X Van Nunen, William F Fearon, Evald Høj Christiansen, Stephane Fournier, Liyew Desta, Andy Yong, Julien Adjedj, Javier Escaned, Masafumi Nakayama, Ashkan Eftekhari, Frederik M Zimmermann, Koshiro Sakai, Tatyana Storozhenko, Bruno R Da Costa, Gianluca Campo, Nick E J West, Tom De Potter, Ward Heggermont, Dimitri Buytaert, Jozef Bartunek, Colin Berry, Damien Collison, Thomas Johnson, Tetsuya Amano, Divaka Perera, Allen Jeremias, Ziad Ali, Nico H J Pijls, Bernard De Bruyne, Nils P Johnson

Faculty, Staff and Student Publications

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes.

Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI.

Results: A total of …

The Complex Molecular Epileptogenesis Landscape Of Glioblastoma, Victoria Soeung, Ralph B Puchalski, Jeffrey L Noebels

Faculty, Staff and Students Publications

The cortical microenvironment surrounding malignant glioblastoma is a source of depolarizing crosstalk favoring hyperexcitability, tumor expansion, and immune evasion. Neosynaptogenesis, excess glutamate, and altered intrinsic membrane currents contribute to excitability dyshomeostasis, yet only half of the cases develop seizures, suggesting that tumor and host genomics, along with location, rather than mass effect, play a critical role. We analyzed the spatial contours and expression of 358 clinically validated human epilepsy genes in the human glioblastoma transcriptome compared to non-tumor adult and developing cortex datasets. Nearly half, including dosage-sensitive genes whose expression levels are securely linked to monogenic epilepsy, are strikingly enriched …

A Systematic Review Of Oral Vertical Dyskinesia ("Rabbit" Syndrome), Jamir Pitton Rissardo, Krish Kherajani, Nilofar Murtaza Vora, Venkatesh Yatakarla, Ana Letícia Fornari Caprara, Jeffrey Ratliff, Md, Stanley N Caroff

Department of Neurology Faculty Papers

Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as “rabbit” syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical–epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among …

Discovery And Generalization Of Tissue Structures From Spatial Omics Data, Zhenqin Wu, Ayano Kondo, Monee Mcgrady, Ethan A G Baker, Benjamin Chidester, Eric Wu, Maha K Rahim, Nathan A Bracey, Vivek Charu, Raymond J Cho, Jeffrey B Cheng, Maryam Afkarian, James Zou, Aaron T Mayer, Alexandro E Trevino

Staff and Researcher Publications

Tissues are organized into anatomical and functional units at different scales. New technologies for high-dimensional molecular profiling in situ have enabled the characterization of structure-function relationships in increasing molecular detail. However, it remains a challenge to consistently identify key functional units across experiments, tissues, and disease contexts, a task that demands extensive manual annotation. Here, we present spatial cellular graph partitioning (SCGP), a flexible method for the unsupervised annotation of tissue structures. We further present a reference-query extension pipeline, SCGP-Extension, that generalizes reference tissue structure labels to previously unseen samples, performing data integration and tissue structure discovery. Our experiments demonstrate …

Patient And Family Contributions To Improve The Diagnostic Process Through The Ourdx Electronic Health Record Tool: A Mixed Method Analysis, Sigall K Bell, Kendall Harcourt, Joe Dong, Catherine Desroches, Nicholas J Hart, Stephen K Liu, Long Ngo, Eric J Thomas, Fabienne C Bourgeois

Faculty, Staff and Student Publications

Background: Accurate and timely diagnosis relies on sharing perspectives among team members and avoiding information asymmetries. Patients/Families hold unique diagnostic process (DxP) information, including knowledge of diagnostic safety blindspots-information that patients/families know, but may be invisible to clinicians. To improve information sharing, we co-developed with patients/families an online tool called 'Our Diagnosis (OurDX)'. We aimed to characterise patient/family contributions in OurDX and how they differed between individuals with and without diagnostic concerns.

Method: We implemented OurDX in two academic organisations serving patients/families living with chronic conditions in three subspecialty clinics and one primary care clinic. Prior to each visit, patients/families …

Redoma: Bayesian Random-Effects Dose-Optimization Meta-Analysis Using Spike-And-Slab Priors, Cheng-Han Yang, Evan Kwiatkowski, J Jack Lee, Ruitao Lin

Faculty, Staff and Student Publications

The rise of cutting-edge precision cancer treatments has led to a growing significance of the optimal biological dose (OBD) in modern oncology trials. These trials now prioritize the consideration of both toxicity and efficacy simultaneously when determining the most desirable dosage for treatment. Traditional approaches in early-phase oncology trials have conventionally relied on the assumption of a monotone relationship between treatment efficacy and dosage. However, this assumption may not hold valid for novel oncology therapies. In reality, the dose-efficacy curve of such treatments may reach a plateau at a specific dose, posing challenges for conventional methods in accurately identifying the …

Complexity Organization Of Resting-State Functional-Mri Networks, Gabriel Trevino, John J Lee, Joshua S Shimony, Patrick H Luckett, Eric C Leuthardt

2020-Current year OA Pubs

Entropy measures are increasingly being used to analyze the structure of neural activity observed by functional magnetic resonance imaging (fMRI), with resting-state networks (RSNs) being of interest for their reproducible descriptions of the brain's functional architecture. Temporal correlations have shown a dichotomy among these networks: those that engage with the environment, known as extrinsic, which include the visual and sensorimotor networks; and those associated with executive control and self-referencing, known as intrinsic, which include the default mode network and the frontoparietal control network. While these inter-voxel temporal correlations enable the assessment of synchrony among the components of individual networks, entropic …

An Accurate And Rapidly Calibrating Speech Neuroprosthesis, Nicholas S Card, Matthew F Glasser, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy.

METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted …