Digital Commons Network^™

Neurobehavioral Symptom Profiles For The Behavioral Assessment Screening Tool In Chronic Traumatic Brain Injury, Shannon B Juengst, Brittany Wright, Annalyn Demello, Leia Vos, Fedora Biney, Luis Leon Novelo, Michael Williams

Faculty, Staff and Student Publications

Objective: To identify neurobehavioral symptom profiles among persons with chronic traumatic brain injury (TBI) using the Behavioral Assessment Screening Tool (BAST) and to consider participant characteristics that differ between profile groups.

Setting: Community.

Participants: Participants (n = 615) were English-speaking adults (≥18) and had a self-reported history of at least one TBI of any severity.

Design: Secondary analysis of cross-sectional data.

Main measures: The BAST measures neurobehavioral symptoms in the domains of Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, and Substance Misuse.

Results: Using latent profile analysis (LPA), we identified 3 different neurobehavioral profiles. Overall symptom frequency and differences in the …

Infectious Prions In Brains And Muscles Of Domestic Pigs Experimentally Challenged With The Bse, Scrapie, And Cwd Agents, Francisca Bravo-Risi, Fraser Brydon, Angela Chong, Kane Spicker, Justin J Greenlee, Glenn Telling, Claudio Soto, Sandra Pritzkow, Marcelo A Barria, Rodrigo Morales

Faculty, Staff and Student Publications

Experimental studies suggest that animal species not previously described as naturally infected by prions are susceptible to prion diseases affecting sheep, cattle, and deer. These interspecies transmissions may generate prions with unknown host ranges. Pigs are susceptible to prions from different origins, including deer chronic wasting disease (CWD), sheep scrapie, and bovine spongiform encephalopathy (BSE). Here, we studied prions in brains and muscles from pigs previously infected with these different prion sources. Specifically, we measured the total prion protein (PrP) and PK-resistant PrP by western blot. Seeding activity in these tissues was evaluated using the protein misfolding cyclic amplification (PMCA) …

High Beta Power In The Ventrolateral Prefrontal Cortex Indexes Human Approach Behavior: A Case Study, Nicole R Provenza, Sameer V Rajesh, Gabriel Reyes, Kalman A Katlowitz, Lokesha S Pugalenthi, Raphael A Bechtold, Nabeel Diab, Sandesh Reddy, Anthony K Allam, Ajay D Gandhi, Katherine E Kabotyanski, Kasra A Mansourian, Jonathan H Bentley, Jordan R Altman, Saurabh Hinduja, Nisha Giridharan, Garrett P Banks, Mohammed Hasen, Ben Shofty, Sarah R Heilbronner, Jeffrey F Cohn, David A Borton, Eric A Storch, Jeffrey A Herron, Benjamin Y Hayden, Mary L Phillips, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) of the ventral capsule and ventral striatum (VC/VS) is an effective therapy for treatment-resistant obsessive–compulsive disorder (trOCD). DBS initiation often produces acute improvements in mood and energy. These acute behavioral changes, which we refer to as “approach behaviors,” include increased social engagement and talkativeness. We investigated the relationship between stimulation amplitude, spectral power in the ventrolateral prefrontal cortex (vlPFC), and speech rate in one male patient with trOCD implanted with bilateral VC/VS DBS leads and subdural electrodes adjacent to the orbitofrontal cortex and vlPFC. Several times over the first 24 weeks of therapy, we conducted experiments …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Fares Qeadan, Amanda D Henderson, Andrew R Harrison, Giovanni Defazio, Mark Hallett, Gamze Kilic-Berkmen, Laura Wright, Samantha Pentecost, Paul Reyes, Anna Tingin, Joseph Jankovic, Jane Boyd, Charlene Hudgins, Janet Hieshetter, Joel S Perlmutter, Hyder A Jinnah, Sarah Pirio Richardson

Faculty, Staff and Students Publications

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Whole Genome Sequence Analysis Of Low-Density Lipoprotein Cholesterol Across 246 K Individuals, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Eric Van Buren, Sara Haidermota, Darina Postupaka, Whitney Hornsby, Joshua C Bis, Jennifer A Brody, Brian E Cade, Ren-Hua Chung, Joanne E Curran, Scott M Damrauer, Lisa De Las Fuentes, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Mariaelisa Graff, Xiuqing Guo, Bertha A Hidalgo, Lifang Hou, Ryan Irvin, Renae Judy, Rita R Kalyani, Tanika N Kelly, Iain R Konigsberg, Brian G Kral, Lydia Coulter Kwee, Daniel Levy, Changwei Li, Ani W Manichaikul, Lisa Warsinger Martin, May E Montasser, Alanna C Morrison, Take Naseri, Kari E North, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Alex P Reiner, Svati H Shah, Roelof A J Smit, Jennifer A Smith, Kent D Taylor, Hemant Tiwari, Michael Y Tsai, Satupa'itea Viali, Zhe Wang, Yuxuan Wang, Wei Zhao, Donna K Arnett, John Blangero, Eric Boerwinkle, Donald W Bowden, Jenna C Carlson, Yii-Der Ida Chen, Patrick T Ellinor, Myriam Fornage, Jiang He, Nancy Heard-Costa, Robert C Kaplan, Sharon L R Kardia, Charles Kooperberg, William E Kraus, Leslie A Lange, Ruth J F Loos, Braxton D Mitchell, Bruce M Psaty, Daniel J Rader, Susan Redline, Stephen S Rich, Lisa R Yanek, Richard Gibbs, Stacey Gabriel, Karine A Viaud-Martinez, Susan K Dutcher, Soren Germer, Ryan Kim, Jerome I Rotter, Xihong Lin, Gina M Peloso, Pradeep Natarajan

The Brown Foundation: Institute of Molecular Medicine

Background: Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability.

Results: Here, we conduct the largest meta-analysis of whole genome sequencing for low-density lipoprotein cholesterol (LDL-C), a therapeutic target for coronary artery disease, analyzing data from 246 K participants and integrating 1.23B variants from the UK Biobank and the Trans-Omics …

Therapeutic Restoration Of Mitochondria-Endoplasmic Reticulum Cross Talk For Osteoarthritis, Mingzhuang Hou, Yifan Ma, Yaoge Deng, Yubin Wu, Yanrun Zhu, Yang Liu, Xiaoping Li, Lili Yu, Zirui He, Yifan Wang, Shiyan Dong, Xiaowei Xia, Jianfeng Yu, Chenqi Yu, Kang Kang, Yingjie Lu, Lili Sun, Betty Y S Kim, Yuan Yuan, Yijian Zhang, Wen Jiang, Xuesong Zhu

Faculty, Staff and Student Publications

Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitochondrial dysfunction. However, the precise mechanisms of how this affects chondrocyte homeostasis and whether such processes can be explored as therapeutic targets for osteoarthritis remain unclear. Here, we show that impaired mitochondrial function and disrupted cartilage matrix metabolism due to loss of mitofusin-2 (MFN2) expression in chondrocytes leads to the development of osteoarthritis. Sirtuin-3 (SIRT3), a key regulator of mitochondrial function, plays a critical role in modulating MFN2 to restore mitochondrial dynamics, reduce …

Computationally Resolved Neuroprogenitor Cell Biomarkers Associate With Human Disorders, Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić

Duncan NRI Faculty and Staff Publications

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause …

Dissecting The Effect Of Mitochondrial Bcat Inhibition In Methylmalonic Acidemia, Madeline G Hemmingsen, Guo-Fang Zhang, Yunhan Ma, Hannah Marchuk, Kalyani R Patel, Tong Chen, Xinning Li, Mark Chapman, Sabrina Collias, Dolores H Lopez-Terrada, James Beasley, Ashlee R Stiles, Randy J Chandler, Charles P Venditti, Sarah P Young, Mercedes Barzi, Beatrice Bissig-Choisat, Doug Krafte, Christopher B Newgard, Karl-Dimiter Bissig

Faculty, Staff and Students Publications

Methylmalonic acidemia (MMA) is a severe metabolic disorder affecting multiple organs because of a distal block in branched-chain amino acid (BCAA) catabolism. Standard of care is limited to protein restriction and supportive care during metabolic decompensation. Severe cases require liver/kidney transplantation, and there is a clear need for better therapy. Here, we investigated the effects of a small molecule branched-chain amino acid transaminase (BCAT) inhibitor in human MMA hepatocytes and an MMA mouse model. Mitochondrial BCAT is the first step in BCAA catabolism, and reduction of flux through an early enzymatic step is successfully used in other amino acid metabolic …

Defining Breast Epithelial Cell Types In The Single-Cell Era, G Kenneth Gray, Eric G Carlson, Tatyana Lev, Bailey Marshall, Austin D Reed, Alex P Sánchez-Covarrubias, Alecia-Jane Twigger, Aleix Puig-Barbe, Aatish Thennavan, Ayodele Omotoso, Lyndsay M Murrow, Deeptiman Chatterjee, Siyuan He, Sara Pensa, Brian Aevermann, Norbert K Tavares, Natalie Chen, Jason A Hilton, Kerrigan Blake, Yunlong Liu, Kiet Phong, Zev J Gartner, Devon A Lawson, Alexander Swarbrick, Camila O Dos Santos, Sophia H L George, Joan S Brugge, Mark A Labarge, Harikrishna Nakshatri, Nicholas Navin, Kai Kessenbrock, Walid T Khaled

Faculty, Staff and Student Publications

Single-cell studies on breast tissue have contributed to a change in our understanding of breast epithelial diversity that has, in turn, precipitated a lack of consensus on breast cell types. The confusion surrounding this issue highlights a possible challenge for advancing breast atlas efforts. In this perspective, we present our consensus on the identities, properties, and naming conventions for breast epithelial cell types and propose goals for future atlas endeavors. Our proposals and their underlying thought processes aim to catalyze the adoption of a shared model for this tissue and to serve as guidance for other investigators facing similar challenges.

Impacts Of Environmental Distractions And Interruptions On Unsupervised Digital Cognitive Assessments In Older Adults: Cognitive Ecological Momentary Assessment Study, Matthew Welhaf, Hannah Wilks, Andrew J Aschenbrenner, Samhita Katteri, John C Morris, Jason J Hassenstab

2020-Current year OA Pubs

BACKGROUND: Unsupervised cognitive assessments are becoming commonly used in studies of aging and neurodegenerative diseases. As assessments are completed in everyday environments and without a proctor, there are concerns about how common distractions may impact performance and whether these distractions may differentially impact those experiencing the earliest symptoms of dementia.

OBJECTIVE: We examined the impact of self-reported interruptions, testing location, and social context during testing on remote cognitive assessments in older adults.

METHODS: Participants from the Ambulatory Research in Cognition smartphone study were classified as cognitively normal (n=380) or as having very mild dementia (n=37). Participants completed daily tests of …

Gene Context Drift Identifies Drug Targets To Mitigate Cancer Treatment Resistance, Amir Jassim, Birgit V Nimmervoll, Sabrina Terranova, Erica Nathan, Linda Hu, Jessica T Taylor, Katherine E Masih, Lisa Ruff, Matilde Duarte, Elizabeth Cooper, Gunjan Katyal, Melika Akhbari, Reuben J Gilbertson, Jennifer C Coleman, Joseph S Toker, Colton Terhune, Gabriel Balmus, Stephen P Jackson, Hailong Liu, Tao Jiang, Michael D Taylor, Kui Hua, Jean E Abraham, Mariella G Filbin, Anthony Hill, Anarita Patrizi, Neil Dani, Aviv Regev, Maria K Lehtinen, Richard J Gilbertson

Faculty, Staff and Students Publications

Cancer treatment often fails because combinations of different therapies evoke complex resistance mechanisms that are hard to predict. We introduce REsistance through COntext DRift (RECODR): a computational pipeline that combines co-expression graph networks of single-cell RNA sequencing profiles with a graph-embedding approach to measure changes in gene co-expression context during cancer treatment. RECODR is based on the idea that gene co-expression context, rather than expression level alone, reveals important information about treatment resistance. Analysis of tumors treated in preclinical and clinical trials using RECODR unmasked resistance mechanisms -invisible to existing computational approaches- enabling the design of highly effective combination treatments …

Co-Occurrence Of Congenital Anomalies And Childhood Brain Tumors In 22 Million Live Births, Thanh T Hoang, Jeremy M Schraw, Charles Shumate, Tania A Desrosiers, Wendy N Nembhard, Mahsa Yazdy, Eirini Nestoridi, Amanda E Janitz, Russell S Kirby, Jason L Salemi, Jean Paul Tanner, Tiffany M Chambers, Michael D Taylor, Chad D Huff, Sharon E Plon, Philip J Lupo, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs.

Methods: We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the …

Identification Of Cobra And Viper Bites In Southern India Using Enzyme-Linked Immunosorbent Assay, Tejeswara Rao Asuru, Raskin Erusan Rajagopal, Albert Rajendran, Gulistan Parveen, Anushka Das, Pabitha Devi, Swapan K Dasgupta, Shantaraman Kalyanaraman, Prasenjit Guchhait, Perumal Thiagarajan

Faculty, Staff and Students Publications

Introduction: Snakebite-related deaths are major concerns in populations worldwide that lack access to medical care. Current treatment of snakebites includes administration of polyspecific and polyvalent heterologous equine antiserum. Swift diagnosis of the species of snake responsible is essential to initiate a specific treatment.

Methods: We generated murine monoclonal and rabbit polyclonal antibodies against the venom of the 3 most common venomous snakes in southern India: the Russell viper, the saw-scaled viper, and the Indian cobra. We developed an enzyme-linked immunosorbent assay to distinguish the snake by analyzing the exudates from the snakebite wound.

Results: Monoclonal antibody EC3 reacts specifically with …

Integrative Analysis Of Lung Adenocarcinoma Across Diverse Ethnicities And Exposures, Shankha Satpathy, Natalie M Clark, Yi-Ju Chen, Noshad Hosseini, Ya-Hsuan Chang, Yi Hsiao, Jonathan T Lei, Francesca Petralia, Jin-Shing Chen, Yifat Geffen, David I Heiman, Indranil Paul, Hanbyul Cho, Michelle Hollenberg, Giacomo B Marino, Kuen-Tyng Lin, Rahul Mannan, C Jackson White, Joe Allen, Shayan C Avanessian, M Harry Kane, Ashley Wolfe, Miloni Kinarivala, Wenke Liu, Shankara Anand, Mong-Wei Lin, Moe Haines, Erik J Bergstrom, Grant Hussey, Ginny Xiaohe Li, Deepak C Mani, Hao Fang, Eric J Jaehnig, Hasmik Keshishian, Brecca Miller, Kang-Yi Su, Yi-Jing Hsiao, Hsao-Hsun Hsu, Min-Shu Hsieh, Kuo-Hsuan Hsu, Alexi Monovoukas, Simone Gohsman, John R Thorup, Yamei Deng, Yo Akiyama, Eden Deng, Eric Sheng-Wen Chen, Azra Krek, Rodrigo Espinoza, Weiping Ma, Daniel Charytonowicz, Robert Sebra, Jyun-Hong Lin, Yan-Si Chen, Yin-Chen Hsu, Ze-Shiang Lin, Kun-Chieh Chen, Chang-Wei Yeh, Yu-Tai Wang, Alexander J Lazar, Mehdi Mesri, Eunkyung An, Xu Zhang, Karl R Clauser, David Fenyö, Arul M Chinnaiyan, Bing Zhang, Li Ding, Kelly Ruggles, Chelsea Newton, Hui Zhang, Pei Wang, Galen Hostetter, Gilbert S Omenn, Chandan Kumar-Sinha, Mathangi Thiagarajan, Ramaswamy Govindan, Paul Paik, Abhijit Parolia, Qing K Li, Avi Ma'ayan, Gad A Getz, Saravana M Dhanasekaran, Ana I Robles, Gee-Chen Chang, Pan-Chyr Yang, Sung-Liang Yu, Hsuan-Yu Chen, Alexey I Nesvizhskii, Steven A Carr, D R Mani, Marcin P Cieslik, Yu-Ju Chen, Michael A Gillette, Taiwan Cancer Moonshot Program, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Lung adenocarcinomas (LUAD) are a pressing global health problem with enduring lethality and rapidly shifting epidemiology. Proteogenomic studies integrating proteomics and post-translational modifications with genomics can identify clinical strata and oncogenic mechanisms, but have been underpowered to examine effects of ethnicity, smoking and environmental exposures, or sex on this heterogeneous disease. This comprehensive proteogenomic analysis of LUAD tumors and matched normal adjacent tissues from 406 patients across diverse geographic and demographic backgrounds explores the impact of understudied driver mutations, prognostic role of chromosomal instability, patterns of immune signaling, differential and sex-specific effects of endogenous mutagens and environmental carcinogens, and pathobiology …

Modeling The Impact Of Mmr Vaccination Strategies On Measles Outbreaks In Texas, Kaiming Bi, Thuy Nguyen, Boya Peng, Trudy Krause, Cecilia Ganduglia Cazaban, Janelle Rios, Cici Bauer, Catherine Troisi, Eric Boerwinkle, Aanand D Naik

Faculty, Staff and Student Publications

No abstract provided.

Identifying Bio-Behavioural Signatures Of Persistent Opioid Use Risk In Trauma Injury Patients: A Protocol For A Prospective Cohort Study, Joy M Schmitz, Jin Ho Yoon, Bruno Kluwe-Schiavon, John A Harvin, Preethi H Gunaratne, Darrion Mouton, Kandice Motley, Erin E Fox, Jessica Vincent, Megan Tarbet, Consuelo Walss-Bass

Faculty, Staff and Student Publications

Introduction: Exposure to prescription opioids following traumatic injury can increase the risk of developing tolerance, persistent opioid use and opioid use disorder. The mechanisms underlying opioid tolerance or dependence are not well understood, and no biomarkers predict risk. Opioid exposure causes epigenetic modifications, including alterations in microRNA (miRNA) expression. Several miRNAs, which regulate synaptic plasticity, are hypothesised to underlie substance use disorders and influence µ-opioid receptor levels, modulating opioid tolerance. This project aims to develop a bio-behavioural signature to predict persistent opioid use and chronic pain up to 6 months post-discharge.

Methods and analysis: The study will use a prospective …

Upper Gastrointestinal Symptoms And Gulf War Illness In A Clinical Cohort Of Us Veterans: A Retrospective, Cross-Sectional Study, Abdelrahman Yousef, Sarah T Ahmed, Theresa H Nguyen Wenker, Alice B S Nono-Djotsa, Stephen H Boyle, Elizabeth J Gifford, Deeksha Malhotra, Helena Chandler, Sandhya Bandi, Drew A Helmer

Faculty, Staff and Students Publications

Objective: Approximately 30% of the 700 000 US Gulf War Veterans (GWVs) report symptoms collectively termed Gulf War Illness (GWI), a multisymptom illness of uncertain pathophysiology. Prior studies in GWI focus on overlap with irritable bowel syndrome. This study examines the associations between upper gastrointestinal (UGI) symptoms, GWI and specialty GI care.

Methods: This cross-sectional study analysed GWVs referred to a Veterans Health Administration clinical War-Related Illness and Injury Study Center (2008-2020). Symptoms, demographics, military service and clinical history were obtained from self-reported intake packets. GWI was defined by the Centers for Disease Control and Prevention criteria requiring moderate-to-severe symptoms …

Establishing Best Practices Guidelines For Collaborative Research In Global Surgery: Developing A Delphi Survey, Ramitha Eshan Ruwanpathirana, Swati Deshpande, Sophia Abdulhai, Mathilde Djeneba Billau, Sumeja Catic, Theresa L Chin, Julia N Harrison, Pratyush Kumar, Maria Cecilia T Leyson, Helen W Li, Katayoun S Madani, Arthur Serumaga, Margaret Tarpley, Grayson Wright, Nia N Zalamea, Joshua S Ng-Kamstra

Faculty, Staff and Students Publications

Background: Collaborative research in global surgery has resulted in the rapid development of the field via knowledge creation and dissemination, research capacity building, and direct improvements in the delivery of clinical care. Yet the establishment and maintenance of trans-boundary collaborations carries significant risk to health systems, clinicians, patients, and researchers, particularly if such collaborations are not developed thoughtfully and with appropriate guardrails. In recent years, there has been significant growth in the literature on the pervasiveness and impact of neocolonialism on global health research.

Methods: To harness the benefits of global surgery research collaboration while mitigating these risks, we reviewed …

Human Papillomavirus Integration Induces Oncogenic Host Gene Fusions In Oropharyngeal Cancers, Nusrat Khan, Keiko Akagi, Shiming Jiang, Joe Dan Dunn, Bo Jiang, Weihong Xiao, Madison P O'Hara, Li Shen, Qi Wang, Vakul Mohanty, Jing Wang, Sara Goodwin, Jamie L Hutchins, Kevin R Coombes, Jagannadha K Sastry, David E Symer, Maura L Gillison

Faculty, Staff and Student Publications

HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host fusion genes, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of …

Dissecting Microbial Communities With Single-Cell Transcriptome Analysis, Andrew W Pountain, Itai Yanai

Faculty, Staff and Student Publications

Revealing insights into the function of microbial communities requires moving beyond measuring bulk taxonomic composition to detecting interactions between subpopulations. Following the transformative impact of single-cell gene expression profiling techniques on numerous fields of human biology, recent years have seen increased application to microbes. We review progress in the development of these techniques and discuss challenges in applying them to microbial communities. We highlight applications for dissecting the microbiome in human health and disease that reveal functional heterogeneity within gut communities, antibiotic responses, and the dynamics of mobile genetic elements. As single-cell gene expression technologies continue to develop, they are …

Lewy Body Dementia Promotion By Air Pollutants, Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao

Faculty, Staff and Student Publications

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and …

Detection Of Cancers Three Years Prior To Diagnosis Using Plasma Cell-Free Dna, Yuxuan Wang, Corinne E Joshu, Samuel D Curtis, Christopher Douville, Vernon A Burk, Meng Ru, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Josef Coresh, Eric Boerwinkle, Anna Prizment, Chetan Bettegowda, Kenneth W Kinzler, Nickolas Papadopoulos, Elizabeth A Platz, Bert Vogelstein

Faculty, Staff and Student Publications

To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six …

Implementing A Training Resource For Large-Scale Genomic Data Analysis In The All Of Us Researcher Workbench, Jasmine Baker, Erik Stricker, Julie Coleman, Shamika Ketkar, Taotao Tan, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Debra Murray, Brendan Lee, Kim C Worley, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

A lack of representation in genomic research and limited access to computational training create barriers for many researchers seeking to analyze large-scale genetic datasets. The All of Us Research Program provides an unprecedented opportunity to address these gaps by offering genomic data from a broad range of participants, but its impact depends on equipping researchers with the necessary skills to use it effectively. The All of Us Biomedical Researcher (BR) Scholars Program at Baylor College of Medicine aims to break down these barriers by providing early-career researchers with hands-on training in computational genomics through the All of Us Evenings with …

The Causal Pivot: A Structural Approach To Genetic Heterogeneity And Variant Discovery In Complex Diseases, Chad A Shaw, C J Williams, Taotao Tan, Daniel Illera, Nicholas Di, Joshua M Shulman, John W Belmont

Center on Aging Staff Publications

We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages an established causal factor or factors to detect the contribution of additional suspected causes. Specifically, polygenic risk scores (PRSs) serve as known causes, while rare variants (RVs) or RV ensembles are evaluated as candidate causes. The CP incorporates outcome-induced association by conditioning on disease status. We derive a conditional maximum-likelihood procedure for binary and quantitative traits and develop the Causal Pivot likelihood ratio test (CP-LRT) to detect causal signals. Through simulations, we demonstrate the CP-LRT’s robust power and …

Social Determinants Of Health In Lesbian, Gay, Bisexual, Transgender, Queer, And Other Sexual And Gender Minority (Lgbtq+) Older Adults: Impact Of Socioeconomic Disadvantage On Inpatient Hospitalizations, Jennifer T. May Phd, Rn, Anp-Bc, Devon Noonan, Susan G. Silva

Publications

Introduction

Little is known about the impact of socioeconomic disadvantage on lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) older adults (≥50 years). The aim of this study is to determine whether the distribution of LGBTQ+ inpatient hospitalizations are related to structural socioeconomic factors.

Methods

A secondary analysis of retrospective electronic health record data for LGBTQ+ older adults hospitalized from 2018 to 2022 was conducted at one large health system. The average county area deprivation index where the patient resided was calculated.

Results

The analysis included 2270 LGBTQ+ older adult inpatient hospitalizations, with 1508 (66.4%) from …

An Allele-Agnostic Mutant-Kras Inhibitor Suppresses Tumor Maintenance Signals And Reprograms Tumor Immunity In Pancreatic Cancer, Kathleen M Mcandrews, Francesca Paradiso, Clint A Stalnecker, Benson S Chellakkan, Fredrik I Thege, David H Peng, Barbara A Moreno Diaz, Hikaru Sugimoto, Sarah I Patel, Krishnan K Mahadevan, Michelle L Kirtley, Danielle Wills, Amari M Sockwell, Andre Luis F Fonseca, Yunhe Liu, Kimal I Rajapakshe, Nathaniel G Yee, Phuong Thao Tran, Huda Alchikh Omar, Antonio Tedeschi, Fiorella Schischlik-Siegl, Andrew S Boghossian, Matthew G Rees, Melissa M Ronan, Jennifer A Roth, Dorothea Rudolph, Martin Aichinger, Florian Ebner, Artem V Artemov, Jesse Lipp, Laura Pisarsky, Valerie Laura Herrmann, John Park, Jörg F Rippmann, Otmar Schaaf, Vanessa Chandler, Mariah Williams, Charles E Deckard, Linghua Wang, Channing J Der, Christopher Vellano, Paola A Guerrero, Timothy P Heffernan, Raghu Kalluri, Anirban Maitra

Faculty, Staff and Student Publications

KRAS is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluate the pre-clinical efficacy of BI-2493 a panKRASi, a first-in-class allele agnostic mutant KRAS inhibitor, in pancreatic ductal adenocarcinoma (PDAC). We report effective tumor growth suppression across a broad range of models, including cell lines, patient-derived xenografts (PDXs), syngeneic orthotopic models, and prolonged survival in genetically engineered mouse …

Amoxicillin Vs Ceftriaxone To Treat Pneumonia Caused By Amoxicillin-Non-Susceptible Streptococcus Pneumoniae, Daniel M Musher

Faculty, Staff and Students Publications

Although the article by J Càmara, I Grau, A González-Díaz, N Santos, et al. (Antimicrob Agents Chemother 69:e00237-25, 2025, https://doi.org/10.1128/aac.00237-25) suggests that ceftriaxone is greatly superior to amoxicillin in treating pneumonia due to pneumococci with an MIC > 2 mg/L, much of the difference in efficacy of the two drugs may have been due to dosage, route, and times of administration of the amoxicillin.

Cardiomyocyte Regeneration Therapy And Its Effect On Lvef And Scar Size- A Systematic Review And Meta-Analysis, Mahnoor Mahnoor, Syed Irtaza Hassan, Muhammad Bakhtiar, Salal Sharjeel, Roha Daneyal, Muhammad Ibrahim, Raheel Iftikhar

Kimmel Cancer Center Faculty Papers

BACKGROUND: Myocardial infarction (MI) results in loss of cardiomyocytes leading to heart failure. Despite advancements in pharmacotherapy and interventions such as revascularization, ischemic heart failure remains a challenge. Recent advancements in stem cell therapies, genetic engineering and bioengineering have shown to improve cardiac function and quality of life.

METHODOLOGY: Following PRISMA guidelines, randomized controlled trials clinical trials from last 12 years were systematically reviewed. All the patients included in these studies had ischemic heart failure and were subjected to different types of stem cell therapies. Protocol for this meta-analysis is registered on PROSPERO (Registration no: CRD42023399263). Data extraction and Quality …

Gellan Gum Formulations Containing Natural Polyphenolic Compounds To Treat Oral Candidiasis, Narchonai Ganesan, Lewis Oscar Felix, Biswajit Mishra, Liyang Zhang, Charilaos Dellis, Fadi Shehadeh, Danielle Wu, Lissette A Cruz, R M Arce, Eleftherios Mylonakis

Faculty, Staff and Student Publications

Oral candidiasis (OC) is caused by Candida albicans, targeting immunocompromised individuals and developing drug resistance, highlighting the need for advanced therapeutics. Polyphenols such as caffeic acid phenethyl ester (CAPE) and ellagic acid (EA) display antifungal and immune-modulating properties. Incorporating CAPE and EA in gellan gum (GG) formulation enhances their applicability and effectiveness against OC. We developed GG-based formulations loaded with CAPE (1,000 µg/mL), EA (1,000 µg/mL), or CAPE + EA (1,000 µg/mL each) against C. albicans. GG formulations containing gellan (0.6% and 1.0%), genipin (5 mM), polyethylene glycol 400 (0.5%), and sorbitan monooleate 80 (0.5%) demonstrated enhanced release …

Periprocedural Results And Right Ventricular Outcomes Of Computer Assisted Vacuum Thrombectomy Treatment Of Acute Pulmonary Embolism: Interim Analysis Of 300 Patients From The Strike-Pe Study, John M. Moriarty, Brian J. Schiro, Suhail Y. Dohad, Houman Tamaddon, Hugh C. Davis, David M. Shavelle, George S. Chrysant, Elias A. Iliadis, David J. Dexter, Juan J. Ciampi Dopazo, Andrew Holden, Frances M. West, Brent Keeling, Andrew S. P. Sharp, Ido Weinberg

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Pulmonary embolism (PE) can be a life-threatening condition. Endovascular treatment is emerging as a promising treatment to restore hemodynamic stability and reverse right ventricular (RV) dysfunction in PE; however, more studies are needed to elucidate the effects on the right ventricle after endovascular treatment. This analysis reports the effects of computer assisted vacuum thrombectomy on RV function.

METHODS: Eligible patients for the single-arm, prospective, international, multicenter STRIKE-PE (A Prospective, Multicenter Study of the Indigo Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism) cohort study are adults with acute PE with symptoms for ≤14 …