Medicine and Health Sciences Commons^™

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Baseline Parp-1 Pet Imaging In Patients With Advanced Solid Tumors With Dna Damage Response Mutations, Tarek Daoud, Jiansong Chen, Peng Wei, Franklin Wong, Timothy A Yap, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Methods: Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before …

A New Era In Advocacy Training: Promoting Safety And Resilience, Elizabeth S Barnert, Lauren Gambill, Sheela Gavvala, Molly K Krager, Lauren Vonholtz, Lois K Lee, Lenore Jarvis

Faculty, Staff and Student Publications

No abstract provided.

Dyadic Associations Between Stress And Sleep Quality And Moderating Effects Of Emotional Intimacy And In Survivors Of Young Adult Cancer And Their Spouses: An Observational Study, Haejeong An, Seokhun Kim, Michael Roth, Kathrin Milbury, Dalnim Cho

Faculty, Staff and Student Publications

Background: Survivors of young adult (YA) cancer often experience substantial stress during the transition to survivorship, which may impair sleep. Although the stress-sleep link is well established, its role within survivor-spouse dyads remains unclear. Emotional intimacy may influence how couples regulate stress and affect sleep. This study examined dyadic associations between stress and sleep among survivors of YA cancer and their spouses and significant others (hereafter spouses) and tested emotional intimacy as a moderator.

Methods: A total of 103 survivor of YA cancer-spouse dyads completed self-reported measures of stress, emotional intimacy, and sleep quality. An actor-partner interdependence moderation model was …

Associations Between Sociodemographic Predictors And Age Of Referral For Autism Spectrum Disorder (Asd) Diagnosis Since The Beginning Of The Covid-19 Pandemic, Mallika Mathur, Ruosha Li, Sandra Mckay, Christine Markham, Deepali K Ernest, Shreela Sharma

Faculty, Staff and Student Publications

Purpose: Sociodemographic characteristics, such as race and ethnicity, are associated with delays in ASD diagnosis. However, limited literature has examined the characteristics associated with delayed diagnosis since the start of the COVID-19 pandemic. This study aimed to identify the individual and aggregate sociodemographic characteristics associated with the age at which a child receives a referral for a diagnosis (from March 2020 to May 2023) and evaluate the impacts of the pandemic on this association.

Methods: Using cross-sectional data obtained from patients' electronic health records and the U.S. Census Bureau, we examined associations using linear regressions (N = 507). A subgroup …

Physical Activity For Public Health In The 21st Century, Deborah Salvo, Inacio Crochemore-Silva, Andrea Wendt, Jakob Tarp, Eric J Shiroma, Richard J Simpson, I-Min Lee, Ulf Ekelund, Ester Cerin, Youssouf Keita, Adrian Bauman, Pedro C Hallal, Andrea Ramirez Varela, Michael Pratt, Rodrigo Reis, Erica Hinckson, Ding Ding, Harold W Kohl, James Sallis

Faculty, Staff and Student Publications

With over 5 million attributed deaths per year, physical inactivity is a major global public health issue. Although the importance of physical activity is well recognized within the scope of obesity and cardiometabolic disease prevention and control, its broader benefits for the health of individuals and societies are yet to be fully harnessed. Furthermore, the role of active leisure, active transport and active labor-primary domains of physical activity-in supporting or hindering social and health equity has been largely overlooked. Here we (1) used a health equity lens to describe global domain-specific physical activity inequalities through an analysis of World Health …

Outcomes After Pulmonary Artery Flow Reducer Implantation In High-Risk Neonates With Congenital Heart Disease And Pulmonary Overcirculation, Cihangir Buyukgoz, Shyam Sathanandam, Neil Tailor, Ashley Molloy, Thomas Spentzas, Karthik Ramakrishnan, Christopher Knott-Craig, Umar Boston

Faculty, Staff and Student Publications

Background: Surgical outcomes in neonates with complex congenital heart disease (CHD) and pulmonary overcirculation (POC) initially palliated with pulmonary flow reducers (PFRs) were evaluated.

Methods: This was a retrospective study conducted between January 1, 2020 and December 31, 2023. Eleven neonates underwent PFR palliation. Fenestrated Medtronic microvascular plugs (PFRs) were delivered into the branch pulmonary artery (PA). The target surgical procedure involved the removal of PFRs and biventricular repair (n = 9) or single-ventricle palliation (n = 2).

Results: Patients were deemed high risk on the basis of prematurity (n = 5), early gestational age (n = 5), heterotaxy (n …

Using Confirmatory Factor Analysis To Identify Symptom Clusters In Individuals With Acquired Disabilities, David S Tulsky, Aaron J Boulton, Pamela A Kisala, Callie E Tyner, Ryan Pohlig, Nancy D Chiaravalloti, Jerry Slotkin, Heather B Taylor, Mark Sherer

Faculty, Staff and Student Publications

Purpose: Acquired disabilities, such as spinal cord injury, traumatic brain injury, limb loss (or other major limb injury/illness), or stroke, are typically accompanied by an array of physical and emotional symptoms and social challenges that interfere with recovery and affect quality of life (QOL). Despite advances in personalized medicine, interrelationships between symptoms remain unclear, and clinicians often treat individual symptoms in isolation. The objective of this study was to identify clusters of symptoms that occur across sudden-onset disability populations, with a long-term goal of identifying targets for clinical intervention.

Methods: Participants were 755 adults who sustained a spinal cord injury, …

Probability Of Fentanyl Adulteration In Cocaine Selectively Decreases Cocaine Demand, Cecilia Nunez, Jin H Yoon, James Mackillop, Margaret C Wardle

Faculty, Staff and Student Publications

Fentanyl-related, cocaine-overdose deaths have drastically increased, yet research on how people who use cocaine perceive fentanyl adulteration is limited. This study developed the novel Adulterated Cocaine Purchasing Task (ACocPT), a modification of the original Cocaine Purchasing Task, to quantify how people respond to fentanyl adulteration in cocaine. In the ACocPT, participants indicated how much cocaine they would purchase when cocaine had no (0%) vs. some (10%) probability of fentanyl adulteration. Study aims were: 1) determine how possible fentanyl adulteration affects cocaine demand, and 2) determine which individual characteristics predict continued demand for cocaine despite fentanyl adulteration. This Amazon Mechanical Turk …

A Treat-To-Target Approach For Obesity Management: A Post Hoc Analysis Of The Surmount-5 Trial., Carel W Le Roux, Luca Busetto, Louis Aronne, Deborah Bade Horn, Georgios K Dimitriadis, Beverly Falcon, Luis-Emilio Garcia-Perez, Elisa Gomez Valderas, Theresa Hunter Gibble, Cagri Senyucel, Julia P Dunn

Faculty, Staff and Student Publications

Introduction: With new advancements in obesity medicine, clarity on goals and expectations for successful disease management is limited. This post hoc analysis assessed application of proposed treat-to-target (TtT) thresholds for obesity to the outcome measures of SURMOUNT-5, which randomised participants with obesity to tirzepatide or semaglutide.

Methods: The proportion of participants in each treatment group reaching proposed TtT thresholds for waist to height ratio (WHtR) < 0.53, body mass index (BMI) < 27 kg/m2, or a combination was evaluated. The associations between the thresholds and achieving low disease activity to remission (meeting goals for at least four of five defined cardiometabolic risk parameters) and normalisation or improvement in SF-36v2 physical component score (PCS) from baseline to week 72 were explored.

Results: About 23.1%-33.9% of participants treated with tirzepatide and 14.2%-20.7% treated with semaglutide reached the TtT thresholds, with greater weight reduction than the overall population. About 77% of participants who reached WHtR < 0.53 achieved low disease activity to remission, with an odds ratio of 2.31 (p < 0.001) compared to those who did not reach this target. The BMI threshold was not statistically associated with the assessed outcomes for SF-36v2 PCS.

Conclusion: In this …

Tumor Flare Reaction With Brentuximab-Vedotin In Mycosis Fungoides, Rishabh Lohray, Seda Purnak, Samruddhi Arkatkar, Madeleine Duvic, Victor Prieto, Carlos Torres-Cabala, Auris Huen

Faculty, Staff and Student Publications

No abstract provided.

Identifying Sorafenib Benefit Among Patients With Hepatocellular Carcinoma: A Transcriptomic And Genomic Approach, Sun Young Yim, Hayeon Kim, Tae Hyung Kim, Sang-Hee Kang, Youngwoo Lee, Eunho Choi, Yang Jae Yoo, Seong Hee Kang, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kyung Suk Yang, Yitao Tang, Bowha Sohn, Yun Seong Jeong, Hyewon Park, Han Liang, Ju-Seog Lee, Ji Hoon Kim

Faculty, Staff and Student Publications

Background & aims: Sorafenib has been a cornerstone of hepatocellular carcinoma (HCC) therapy; however, its efficacy is limited, and identifying patients who will benefit from sorafenib is challenging. We aimed to identify predictive biomarkers of sorafenib benefit in patients with HCC.

Methods: Gene expression data from 33 HCC tumors treated with sorafenib were analyzed to construct a prediction model aimed at identifying patients with greater benefit from sorafenib treatment. The robustness of the predictor was validated using gene expression data from two phase III clinical trials, IMbrave150 and STORM.

Results: The analysis of transcriptome data revealed a 50-gene signature, the …

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Bridging Gaps: Enhancing Sleep And Health Disparities In Latino Families With Young Adults With Autism Using A Culturally Adapted Intervention, Antonio F Pagán, Alejandro L Pagán, Linda Hernandez, Matthew R Cribbet, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

The present study examined the effects of a culturally adapted intervention, ¡Iniciando! la Adultez, on sleep and health-related quality of life (HRQoL) in Latino young adults with autism spectrum disorder (ASD) and their Spanish-speaking parents. The intervention targeted the transition to adulthood, a period associated with increased challenges in sleep and HRQoL, particularly for underserved Latino populations. Participants included 26 young adults and 38 parents who completed assessments at baseline and post-treatment. The results indicated significant improvements in several HRQoL domains for both groups, with young adults reporting enhanced emotional well-being, social functioning, and general health. Parents experienced notable improvements …

Preoperative First-Line Amlodipine In Phaeochromocytoma/Paraganglioma: Perioperative Haemodynamic Instability And Its Predictors, Chandramouli L, Saba Samad Memon, Anurag Ranjan Lila, Manjiri Karlekar, Aditya Phadte, Vijaya Sarathi, Rohit Barnabas, Sailaja Pramod Bijani, Sameer Rege, Yogesh Prabhakar Takalkar, Amala Kudalkar, Aarti Kulkarni, Nalini Shah, Tushar R Bandgar

Faculty, Staff and Student Publications

Objectives: Preoperative alpha blockade is recommended for phaeochromocytomas and paragangliomas (PPGLs), whereas evidence for calcium channel blockers remains limited. This study evaluated perioperative haemodynamic outcomes with first-line amlodipine for preoperative blockade and identified predictors of intraoperative haemodynamic instability (iHDI).

Methods/design: In this monocentric retrospective study, 35 operated PPGL patients who received preoperative first-line amlodipine (July 2021-March 2024) were analysed. Continuous intraoperative arterial pressure recordings were analysed for episodes and duration of hypertension, hypotension, and iHDI. Biochemical phenotype and tumour characteristics were assessed as predictors.

Results: The cohort (median age: 32 years; 60% female) included 32 phaeochromocytomas and 3 sympathetic paragangliomas. …

Factors Associated With Venous Complications In Lower Extremity Free Flap Reconstruction: A Multivariate Analysis, Bora Kahramangil, Ellen Wang, Imran Rizvi, Jessica R Nye, Kylie Swiekatowski, Alexandra Dunker, Kate Liao, Michael H Haydon, Jeffrey G Trost, Mohin A Bhadkamkar

Faculty, Staff and Student Publications

Background: Due to their dependent location, lower extremity (LE) free flaps (FFs) are at increased risk for venous complications. This study analyzes risk factors of venous complications in LE FFs.

Methods: A single-center retrospective review was conducted of adult patients undergoing LE FF reconstruction from 2016 to 2025. Variables included demographics, wound and operative characteristics, and the number of venous anastomoses. The primary outcome was venous complications, defined as a composite variable encompassing venous congestion, flap loss due to venous causes, and flap hematoma.

Results: The cohort consisted of 370 patients undergoing LE FF reconstructions. Single venous anastomosis was used …

Correction: Prospective Trial Of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage Via Lumbar Catheter Extension (Pillar-Xt), Spiros L Blackburn, Marc A Babi, Andrew W Grande, Omar A Choudhri, Erik F Hauck, Christopher P Kellner, Michael C Giordano, Shivanand P Lad, Aaron R Mccabe

Faculty, Staff and Student Publications

This corrects the article "Prospective Trial of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage via Lumbar Catheter Extension (PILLAR-XT)" in volume 43 on page 934.

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Black Equality In Ocd Neurogenomics (Belong): Study Protocol, Iasha J Williams, Dalia Y Marquez, Kara E Lopez-Lengowski, Malini Bommiasamy, Ogechi Cynthia Onyeka, Slayton J Underwood, Juliana E Avery, Jacob Gluckman, Thariana Pichardo, Rhea Chandler, Yulu Brown, Katie Mangen, Emma Grace Choplin, Black Equality In Ocd Neurogenomics (Belong) Study Team, Sonyia C Richardson, Joseph D Buxbaum, Eric A Storch, James J Crowley, Sidney H Hankerson, Dorothy E Grice

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a chronic, serious psychiatric disorder that affects 2%-3% of the population and is associated with high personal and societal costs. Genetic factors are estimated to explain roughly half the risk of developing OCD, and genomic studies are just beginning to identify common and rare genetic variants mediating this risk. A major goal of genomic studies is to yield insights into the etiology of OCD and identify molecular targets for the development of novel therapeutics. However, the overwhelming majority of subjects in existing genetic studies are of European ancestry, limiting the generalizability of these findings. To address …

Ins-17 Acts As A Nutrient Deprivation Signal To Mediate Adult Iis-Regulated Associative Behaviors In C. Elegans, Emily J Leptich, Priyadharshini Vijayakumar, Edward W Pietryk, Meredith I Williams, Rachana Rajupalem, Rachel N Arey

Faculty, Staff and Students Publications

Insulin/Insulin-like growth factor 1 (IGF-1) signaling (IIS) is a pleiotropic signaling pathway that functions across tissues to coordinate phenotypic changes in response to nutrient status. Thus, the ubiquity of the IIS pathway hinders efforts to elucidate the mechanisms driving specific IIS-related phenotypes. Previous research in the nematode worm C. elegans has demonstrated that loss of function of the IIS transmembrane receptor (IR) ortholog, DAF-2, results in a doubled lifespan and enhanced learning and memory behaviors in young and aged animals. However, these findings are the result of reducing DAF-2 receptor function rather than modulating ligand-receptor interactions. In the current study, …

Rethinking "Very High-Risk" Ascvd: Most Patients Qualify, Few Are Distinct?, Michael D Shapiro, Yuzhi Xi, Tammy Jiang, Xiao Zhang, Lori D Bash, Swapnil Rajpathak, Laura Gellis, Robert Hilkert, Erin D Michos, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Long-Term Outcomes Of Left Bundle-Branch Pacing Vs Biventricular Pacing In Heart Failure: The Heartsync-Lbbp Randomized Clinical Trial, Xueying Chen, Xi Liu, Ruogu Li, Zhongkai Wang, Yixiu Liang, Lei Zhang, Wei Wang, Jin Bai, Jingfeng Wang, Shengmei Qin, Weiwei Zhang, Tianbao Yao, Dong Huang, Ting Chen, Xianxian Zhao, Dening Liao, Jingbo Li, Jialiang Mao, Mihail G Chelu, Yangang Su, Kenneth A Ellenbogen, Junbo Ge

Faculty, Staff and Students Publications

Importance: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking.

Objective: To evaluate the long-term clinical outcomes of LBBP and BiVP.

Design, setting, and participants: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 …

Leadless Pacing And The Emerging Era Of Combined Procedures In Adult Congenital Heart Disease, Srikant Das, Brock A Karolcik, Taylor S Howard

Faculty, Staff and Students Publications

No abstract provided.

Influence Of Gut Microbiota On Response To Immune Check Point Inhibitors In Masld Patients With Hcc: Unraveling The Connection, Mazen Elsheikh, Mohamad Ali Ibrahim, Sherry Fares, Megha Bhongade, Karim Adhem, Ximena I Ramirez-Morales, Ahmed O Kaseb, Joseph Petrosino, Manal M Hassan, Prasun K Jalal

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment for various cancers, including advanced hepatocellular carcinoma (HCC). However, a significant proportion of patients with HCC, particularly those with metabolic dysfunction-associated liver disease (MASLD), exhibit resistance to ICI therapy. Studies have revealed that the presence of specific gut bacteria, such as Akkermansia, Bifidobacterium, and Lachnoclostridium, is associated with improved outcomes with ICI-treated HCC patients. Conversely, the overgrowth of bacteria like Enterobacteriaceae is linked to resistance to therapy. This review investigates the role of gut microbiota in shaping immune checkpoint inhibitor responses in MASLD-related hepatocellular carcinoma, focusing on how dysbiosis may …

Investigating Conjunctival Immune Pathways In Sjögren And Non-Sjögren Disease Associated Dry Eye, Kaitlin K Scholand, Laura Schaefer, Jianming Shao, Zhiyuan Yu, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Purpose: Dry eye disease (DED) is classified based on its predominant etiology into aqueous tear-deficient (ATD), evaporative, or mixed. Sjӧgren disease keratoconjunctivitis sicca (SjD-KCS) is a very severe autoimmune form of ATD DED. The purpose of this work was to compare transcriptomic changes in the conjunctiva sampled from patients with ATD, SjD-KCS, and healthy controls (HC) to evaluate distinctions in the immune response on the ocular surface based on diagnosis.

Methods: Impression cytology of the temporal bulbar conjunctiva was collected using the EyePrim device. RNA was extracted and submitted with the Nanostring nCounter Human Immunology V2 panel for gene expression …

Leveraging Untargeted Metabolomics In Combination With Machine Learning To Uncover Novel Insights Into Bladder Cancer, Abu Hena Mostafa Kamal, Vasanta Putluri, Tanmay Gandhi, Chandra Shekar R Ambati, Chandra Sekhar Amara, Karthik Reddy Kami Reddy, Meredith Lauren Spradlin, Amrit Koirala, Sachin B Jorvekar, Sandra L Grimm, Dexue Fu, Krishna Parsawar, Felice De Jong, Chris Beecher, Subrata Sen, Seth P Lerner, M Minhaj Siddiqui, Yair Lotan, Livia S Eberlin, Arun Sreekumar, Cristian Coarfa, Nagireddy Putluri

Faculty, Staff and Students Publications

Background

Untargeted metabolomics has emerged as a powerful approach to uncover metabolic dysregulation associated with cancer progression. When integrated with a machine learning strategy it facilitates the discovery of key metabolic pathways and predictive biomarkers with high diagnostic and prognostic value.

Methods

In this study, we employed liquid chromatography coupled to high-resolution Tribrid Orbitrap mass spectrometry to perform comprehensive metabolic profiling of bladder cancer (BLCA) as well as predict invasiveness of the disease.

Results

By leveraging both in-house retention time-based MS/MS spectral libraries and commercial databases, we robustly identify over 2000 metabolites. In addition, this platform allows identification of novel …

Non-Invasive Intracranial Pressure Estimation In The Intensive Care Unit: Narrative Review Of Methods And Clinical Applications, Edoardo Picetti, Daniele Guerino Biasucci, Elisa Gouvea Bogossian, Sérgio Brasil, Danilo Cardim, Marek Czosnyka, Daniel A Godoy, Gregory W J Hawryluk, Mohammad I Hirzallah, Frank A Rasulo, Carla Bittencourt Rynkowski, Andres M Rubiano, Fabio Silvio Taccone, Chiara Robba

Faculty, Staff and Students Publications

Despite invasive methods are the gold standard for intracranial pressure (ICP) measurement, several non-invasive techniques (nICP) have been proposed as surrogate, although their use remains insufficiently recognized in clinical practice. These include transcranial Doppler blood flow velocity  assessment (arterial or venous), optic nerve sheath diameter (ONSD), automated pupillometry, measurement of skull expansion and compliance, brain imaging, double-depth ophthalmic artery blood flow velocity, and ultrasound time-of-flight. The main limitations of all indirect methods are calibration and zeroing, which constrain the absolute accuracy of non-invasive ICP monitoring. For transcranial Doppler-based methods, the 95% limits of agreement are approximately ± 7-15 mmHg, while …

Efficient In Vivo Pharmacological Inhibition Of Δfosb, An Ap-1 Transcription Factor, In The Brain, Sean Mcneme, Anil Kumar, Yun Young Yim, Brandon W Hughes, Corey St Romain, Yi Li, Ashwani Kumar, Qichao Bao, Molly Estill, Shanghua Fan, Nadeen Takatka, Earnest P Chen, Matthew Rivera, Haiying Chen, Alfred J Robison, Mischa Machius, Stephen J Haggarty, Jeannie Chin, Eric J Nestler, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, an unusually stable member of the AP-1 family of transcription factors, mediates long-term maladaptations that play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesia, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitro in cell-based assays, and one such compound, JPC0661, disrupts ΔFOSB binding to genomic DNA in vivo in the mouse brain with partial efficiency. JPC0661 binds to a groove outside of the DNA-binding cleft of the ΔFOSB/JUND bZIP heterodimer in a cocrystal structure. Here, we generated a …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …