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International Tuberculum Sellae Meningioma Study: Preoperative Grading Scale To Predict Outcomes And Propensity-Matched Outcomes By Endonasal Versus Transcranial Approach, Michael Mcdermott Dec 2023

International Tuberculum Sellae Meningioma Study: Preoperative Grading Scale To Predict Outcomes And Propensity-Matched Outcomes By Endonasal Versus Transcranial Approach, Michael Mcdermott

All Publications

Background and objectives: Tuberculum sellae meningiomas are resected via an expanded endonasal (EEA) or transcranial approach (TCA). Which approach provides superior outcomes is debated. The Magill-McDermott (M-M) grading scale evaluating tumor size, optic canal invasion, and arterial involvement remains to be validated for outcome prediction. The objective of this study was to validate the M-M scale for predicting visual outcome, extent of resection (EOR), and recurrence, and to use propensity matching by M-M scale to determine whether visual outcome, EOR, or recurrence differ between EEA and TCA.

Methods: Forty-site retrospective study of 947 patients undergoing tuberculum sellae meningiomas resection. Standard …


Non-Invasive Glucose Detection Using A Triple Pole Csrr Sensor, Chibuike Nnabuife Okika Dec 2023

Non-Invasive Glucose Detection Using A Triple Pole Csrr Sensor, Chibuike Nnabuife Okika

Theses

A compact, low-cost, portable, non-invasive blood glucose sensor has been designed and presented in this paper. The proposed sensor is a triple-pole square Complementary Split Ring Resonator (CSRR) sensor that is etched on an FR4 substrate. At the bottom of the sensor is coupled an etched Microstrip Transmission Line (MTL) with an impedance matching of 50 Ω, which excites the sensor elements. Utilizing the CSRR-based sensor overcomes the disadvantages of pain and discomfort that the traditional method of pricking the skin to measure blood glucose levels could pose. The sensors work in such a way that as the glucose concentration …


Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling In Airway Smooth Muscle, Deepak A. Deshpande, Raymond B. Penn Dec 2023

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling In Airway Smooth Muscle, Deepak A. Deshpande, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.


An Intersectional Approach To Quantifying The Impact Of Geographic Remoteness And Health Disparities On Quality-Adjusted Life Expectancy: Application To Australia, Peter Lee, Steven J. Bowe, Lidia Engel, Erica I. Lubetkin, Nancy Devlin, Lan Gao Dec 2023

An Intersectional Approach To Quantifying The Impact Of Geographic Remoteness And Health Disparities On Quality-Adjusted Life Expectancy: Application To Australia, Peter Lee, Steven J. Bowe, Lidia Engel, Erica I. Lubetkin, Nancy Devlin, Lan Gao

Publications and Research

Objectives

An intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) is a novel method for exploring the interaction between sociodemographic characteristics that affect health outcomes. This study explores the interaction between geographic remoteness and socioeconomic status on health outcomes in Australia from an intersectional perspective.

Methods

Data from a cross-sectional survey were matched with data from the Australian Bureau of Statistics and the Australian Institute of Health and Welfare. To explore the effect of health-related quality of life on life expectancy, quality-adjusted life expectancy (QALE) was estimated through applying utility values derived from the EQ-5D-5L to life table …


Novel Psychophysics Of Cognitive Color Appearance Phenomena, Luke Hellwig Dec 2023

Novel Psychophysics Of Cognitive Color Appearance Phenomena, Luke Hellwig

Theses

Color appearance models can be used as an experimental design and analysis tool to better study high-level color perception involving brightness and chromatic adaptation. We investigate the experimental basis for the Helmholtz-Kohlrausch effect, the contribution of chromatic intensity to our perception of brightness. A new experimental method for measuring the brightness of chromatic colors leads to a model of the Helmholtz-Kohlrausch effect, which we use to extend CIECAM16, the color appearance model recommended by the Commission Internationale de l'Eclairage. The model is tested on high-dynamic-range images. The process of building this model also leads to several improvements in CIECAM16 itself. …


Analysis Of Molecular Dynamics Simulations Relevant To Combining Polarized Neutron Scattering With Nuclear Magnetic Resonance, Stella Van Ness Dec 2023

Analysis Of Molecular Dynamics Simulations Relevant To Combining Polarized Neutron Scattering With Nuclear Magnetic Resonance, Stella Van Ness

Theses

The goal of this thesis is to contribute to the study of combining nuclear magnetic resonance (NMR) and neutron scattering to study liquid structure. NMR could be used to polarize select atoms in a target molecule in a neutron scattering system. Molecular dynamics (MD) was used to simulate a system of thienopyridazine dissolved into deuterated methanol. A robust function was constructed to calculate the scattering cross-sections resulting from this system, as they depend on the polarization and spin states of the hyperpolarizable hydrogen atoms. This function can be used in the future to estimate signal-to-noise characteristics of specific experimental designs.


Lifelong Learning In Spiking Neural Networks Through Neural Plasticity, Nicholas Soures Dec 2023

Lifelong Learning In Spiking Neural Networks Through Neural Plasticity, Nicholas Soures

Theses

Lifelong learning, the ability to learn from continually changing data distributions in real-time, is a significant challenge in artificial intelligence. The central issue is that new learning tends to interfere with previously acquired memories, a phenomenon known as catastrophic forgetting. Surrounding this are several other challenges associated with this, such as knowledge transfer and adaptation, few-shot learning, and processing of noisy data. Since humans do not seem to suffer from this problem, researchers have applied biologically inspired techniques to address it, including metaplasticity, synaptic consolidation and memory replay. Although these approaches have seen some success in traditional neural networks, there …


Prediction Of Unplanned 30-Day Readmission Of Heart Failure Patients Using Lstm, Jesdin Raphael Dec 2023

Prediction Of Unplanned 30-Day Readmission Of Heart Failure Patients Using Lstm, Jesdin Raphael

Theses

In the context of heart failure, a leading cause of hospitalization in the United States, approximately 15\% of patients discharged within 30 days face readmission, contributing to escalated healthcare costs and compromised clinical outcomes. This study leverages a wealth of personal information extracted from Emergency Health Records (EHRs) spanning two decades. This research aims to enhance the predictive capabilities of re-hospitalization for cardiac patients by creating a two-stage LSTM model while incorporating features into regression and time series datasets. A critical aspect of this study involves ensuring the integration of all relevant features across both datasets. Including constant data elements, …


Interactions Between Fitness Components Across The Life Cycle Constrain Competitor Coexistence, Miguel Gómez-Llano, Wade A. Boys, Taylor Ping, Simon P. Tye, Adam M. Siepielski Dec 2023

Interactions Between Fitness Components Across The Life Cycle Constrain Competitor Coexistence, Miguel Gómez-Llano, Wade A. Boys, Taylor Ping, Simon P. Tye, Adam M. Siepielski

Biological Sciences Faculty Publications and Presentations

  1. Numerous mechanisms can promote competitor coexistence. Yet, these mechanisms are often considered in isolation from one another. Consequently, whether multiple mechanisms shaping coexistence combine to promote or constrain species coexistence remains an open question.
  2. Here, we aim to understand how multiple mechanisms interact within and between life stages to determine frequency-dependent population growth, which has a key role stabilizing local competitor coexistence.
  3. We conducted field experiments in three lakes manipulating relative frequencies of two Enallagma damselfly species to evaluate demographic contributions of three mechanisms affecting different fitness components across the life cycle: the effect of resource competition on individual growth …


Detection Of Dsrab Operon Expression In Desulfotalea Psychrophila Cells Subjected To Simulated Martian Conditions Of Temperature And Regolith's Sulphate Minerals Composition, Sergio Mosquera, Mack Ivey, Vincent F. Chevrier Dec 2023

Detection Of Dsrab Operon Expression In Desulfotalea Psychrophila Cells Subjected To Simulated Martian Conditions Of Temperature And Regolith's Sulphate Minerals Composition, Sergio Mosquera, Mack Ivey, Vincent F. Chevrier

Biological Sciences Faculty Publications and Presentations

Discoveries of transient liquid water in the Martian polar caps and the presence of liquid lakes and subsurface oceans in icy satellites have increased the interest of scientists in the capabilities of terrestrial extremophiles to grow and remain metabolically active in these extreme environments. The principal goal of this research is to understand the metabolic capacity of the anaerobic psychrophile, Desulfotalea psychrophila, cultured at subfreezing temperatures in media containing various concentrations of sulphate minerals. In this regard, our experiments focused on the detection of D. psychrophila survival and active metabolism, employing a biochamber that can recreate Martian temperatures. Using …


Utilizing The Genetic Potentials Of Traditional Rice Varieties And Conserving Rice Biodiversity With System Of Rice Intensification Management, Yheni Dwiningsih Dec 2023

Utilizing The Genetic Potentials Of Traditional Rice Varieties And Conserving Rice Biodiversity With System Of Rice Intensification Management, Yheni Dwiningsih

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

The genetic potentials of rice cultivars will need to be expressed to their fullest if global rice production is to be expanded enough by 2050 to meet the increased demand of the expanding population while the availability of land and water per capita dwindles. New and ‘improved’ rice varieties have contributed greatly to increased production over the past 50 years, but the rate of rice yield increase based on genetic changes has declined in recent decades compared with the early years of the Green Revolution. In fact, many rice consumers continue to prefer to consume ‘traditional’ rice varieties (referred to …


Overexpression Of Acetyl Coa Carboxylase 1 And 3 (Accase1 And Accase3), And Cyp81a21 Were Related To Cyhalofop Resistance In A Barnyardgrass Accession From Arkansas, Fidel Gonzalez-Torralva, Jason K. Norsworthy Dec 2023

Overexpression Of Acetyl Coa Carboxylase 1 And 3 (Accase1 And Accase3), And Cyp81a21 Were Related To Cyhalofop Resistance In A Barnyardgrass Accession From Arkansas, Fidel Gonzalez-Torralva, Jason K. Norsworthy

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.] is the most difficult-to-control weed species of rice production systems worldwide. It has evolved resistance to different herbicide sites of action, including the acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. Target-site mutations conferring resistance to ACCase-inhibiting herbicides are well documented; however, the role of the different ACCase genes in conferring resistance to cyhalofop-p-butyl (cyhalofop), an ACCase-inhibiting herbicide, remains poorly understood. This research assessed the contribution of gene amplification and expression of ACCase genes in a cyhalofop-resistant barnyardgrass accession. Additionally, the expression of glutathione-S-transferases (GSTs) and cytochrome P450 monooxygenases (P450s) genes as possible …


Uncertainty In Streamflow Measurements Significantly Impacts Estimates Of Downstream Nitrate Export, Shannon L. Speir, C. Nathan Jones, Arial J. Shogren, Carla L. Atkinson Dec 2023

Uncertainty In Streamflow Measurements Significantly Impacts Estimates Of Downstream Nitrate Export, Shannon L. Speir, C. Nathan Jones, Arial J. Shogren, Carla L. Atkinson

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Across watershed science, two key variables emerge–streamflow and solute concentration–which serve as the basis for efforts ranging from basic watershed biogeochemistry research to policy decisions surrounding watershed management. However, we rarely account for how error in discharge (Q) impacts estimates of downstream nutrient loading. Here, we examined the impact of uncertainty in streamflow measurements on estimates of downstream nitrate export using publicly available data from the U.S. Geological Survey (USGS). We characterized how uncertainty in stage-discharge relationships impacts annual flux estimates across 70 USGS gages. Our results indicate the interquartile range of relative error in Q was 33% across these …


Thermodynamics And Kinetics Analyses Of Clc-Ec1 Dimerization Reaction In Lipid Bilayers, Taeho Lee Dec 2023

Thermodynamics And Kinetics Analyses Of Clc-Ec1 Dimerization Reaction In Lipid Bilayers, Taeho Lee

Arts & Sciences Graduate Student Theses and Dissertations

The efforts of this thesis are directed towards understanding the thermodynamics and kinetics underlying the dimerization reaction of a chloride/proton antiporter membrane protein, CLC-ec1, in lipid membranes. Due to the inherent challenges of working with membrane proteins, thermodynamic and kinetic information for the protein association reactions in membranes has been historically limited. The research presented in this thesis demonstrates the technological advancements for these measurements in a model membrane protein system, thereby setting an important milestone for the field. Since CLC-ec1 dimerizes via a greasy, membrane embedded binding interface, the physical driving forces involved in this reaction were unknown. It …


Bisexuality, Biphobia, And Its Effects On Sexual Identity, Religious Identity And Mental Health: Examining Clinical Implications, Diana Ramirez Dec 2023

Bisexuality, Biphobia, And Its Effects On Sexual Identity, Religious Identity And Mental Health: Examining Clinical Implications, Diana Ramirez

Dissertations

Bisexuality is a sexual orientation, sometimes known as “bi,” that includes sexuality in which certain people are attracted to more than one sex and gender. Bisexuality differs from other sexual- and gender-nonconforming experiences (McInnis et al., 2022). According to Ross et al. (2018), bisexuality is frequently described as an invisible sexual orientation, and only in the last 20 years has research on biphobia and bisexuality increased (McInnis et al., 2022). Experiences unique to bisexuality include bisexual invisibility from a societal level (Dyar et al., 2015), bisexuals are more prone to experience sexual orientation instability (Bostwick et al., 2014), and bisexual …


Chronic Stressors, Obesity Pathogenesis, And The Moderating Effect Of Internalized Weight Stigma; A Quantitative, Illinois Study, Karyn Byrne Dec 2023

Chronic Stressors, Obesity Pathogenesis, And The Moderating Effect Of Internalized Weight Stigma; A Quantitative, Illinois Study, Karyn Byrne

Dissertations

The obesity epidemic is a ‘wicked’ problem with a complex web of determinants and outcomes. While generally higher for minoritized populations, prevalence rates manifest in surprising, nonlinear patterns. There is no consensus regarding treatment protocols or mitigation efforts, except that current efforts remain largely ineffective. Much research evidence that a profusion of determinants of health support obesity pathogenesis through various physiological processes and mechanisms, including the allostatic load, mitochondria functioning, the gut microbiome, and epigenetics. Intervening to support markers of the allostatic load (immunity, inflammation, and metabolic health) may provide a more effective treatment outcomes than traditional approaches, which tend …


"I Think There Is A Place For Small Programs:" Advocating, Implementing, And Sustaining Tpc Programs In Small Us Institutions, Martha Lynn Russell Dec 2023

"I Think There Is A Place For Small Programs:" Advocating, Implementing, And Sustaining Tpc Programs In Small Us Institutions, Martha Lynn Russell

English Theses & Dissertations

Technical and Professional Communication (TPC) programs in small institutions compose of over a third of all programs in the US, yet this space has been understudied by most scholars. To fill this gap, this dissertation presents findings from one-hour interviews with twenty-six TPC program directors in small US institutions with undergraduate populations of less than six thousand. The results of this dissertation include the ways that small institutions are advocating, implementing, and sustaining their TPC program in unique ways with implications for how any TPC programs regardless of size can learn from these findings.


Increasing Emotional Regulation In Young Children With Autism Spectrum Disorder, Bryana Arias Dec 2023

Increasing Emotional Regulation In Young Children With Autism Spectrum Disorder, Bryana Arias

Capstone Projects and Master's Theses

This capstone project focuses on the emotion regulation skills of school-age children (5 to 7 years) on the moderate to severe autism spectrum. Emotional regulation is the process by which a person engages in behaviors with the implicit or explicit goal of altering emotion frequency, intensity, duration, or type (Raugh & Strauss, 2023). Through emotional self-regulation, individuals can control their thoughts, behaviors, and emotions within everyday situations. This process involves the ability to identify one’s emotions and those of other people while developing strategies to constructively manage their reactions to emotional experiences and inhibitory control (Dumont et al., 2019). Autism …


Preschool Children Learn About Regulating Emotions, Elisa Camacho Dec 2023

Preschool Children Learn About Regulating Emotions, Elisa Camacho

Capstone Projects and Master's Theses

This project was done to teach preschool children how to self-regulate, as well as see what they know about self-regulation.


Increasing Social And Emotional Development In Preschoolers, Alondra Susana Cardenas Martinez Dec 2023

Increasing Social And Emotional Development In Preschoolers, Alondra Susana Cardenas Martinez

Capstone Projects and Master's Theses

My project focuses on ways that Hispanic immigrant parents can stimulate their preschool children’s social and emotional development. Many children in the U.S. today are entering kindergarten not being emotionally and socially ready to spend time away from their caregivers and to have interactions with peers. When entering the school system for the first time children need to develop independence and social awareness. Communication and interactions between parent and child as well as the child with other children at a young age will both stimulate them and prepare them for interactions with others and set them a foundation for success. …


Predicting The Spatio-Temporal Response Of Recurrent Glioblastoma Treated With Rhenium-186 Labelled Nanoliposomes, Chase Christenson, Chengyue Wu, David A Hormuth, Shiliang Huang, Ande Bao, Andrew Brenner, Thomas E Yankeelov Dec 2023

Predicting The Spatio-Temporal Response Of Recurrent Glioblastoma Treated With Rhenium-186 Labelled Nanoliposomes, Chase Christenson, Chengyue Wu, David A Hormuth, Shiliang Huang, Ande Bao, Andrew Brenner, Thomas E Yankeelov

Faculty, Staff and Student Publications

Rhenium-186 (186Re) labeled nanoliposome (RNL) therapy for recurrent glioblastoma patients has shown promise to improve outcomes by locally delivering radiation to affected areas. To optimize the delivery of RNL, we have developed a framework to predict patient-specific response to RNL using image-guided mathematical models.

METHODS: We calibrated a family of reaction-diffusion type models with multi-modality imaging data from ten patients (NCR01906385) to predict the spatio-temporal dynamics of each patient's tumor. The data consisted of longitudinal magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) to estimate tumor burden and local RNL activity, respectively. The optimal model from the …


Immune Evasion And Membrane Fusion Of Sars-Cov-2 Xbb Subvariants Eg51 And Xbb23, Julia N Faraone, Panke Qu, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Linda J Saif, Eugene M Oltz, Kai Xu, Daniel Jones, Richard J Gumina, Shan-Lu Liu Dec 2023

Immune Evasion And Membrane Fusion Of Sars-Cov-2 Xbb Subvariants Eg51 And Xbb23, Julia N Faraone, Panke Qu, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Linda J Saif, Eugene M Oltz, Kai Xu, Daniel Jones, Richard J Gumina, Shan-Lu Liu

Faculty, Staff and Student Publications

Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising in circulation - EG.5.1 and XBB.2.3, for their neutralization and syncytia formation. We determined the neutralizing antibody titers in sera of individuals that received a bivalent mRNA vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to a much less extent, two new EG.5.1 and XBB.2.3 variants. In fact, the enhanced neutralization escape of EG.5.1 appeared to be driven by its key …


Multi-Ancestry Genome-Wide Association Study Of Cannabis Use Disorder Yields Insight Into Disease Biology And Public Health Implications, Daniel F Levey, Marco Galimberti, Joseph D Deak, Frank R Wendt, Arjun Bhattacharya, Dora Koller, Kelly M Harrington, Rachel Quaden, Emma C Johnson, Priya Gupta, Mahantesh Biradar, Max Lam, Megan Cooke, Veera M Rajagopal, Stefany L L Empke, Hang Zhou, Yaira Z Nunez, Henry R Kranzler, Howard J Edenberg, Arpana Agrawal, Jordan W Smoller, Todd Lencz, David M Hougaard, Anders D Børglum, Ditte Demontis, Veterans Affairs Million Veteran Program, J Michael Gaziano, Michael J Gandal, Renato Polimanti, Murray B Stein, Joel Gelernter Dec 2023

Multi-Ancestry Genome-Wide Association Study Of Cannabis Use Disorder Yields Insight Into Disease Biology And Public Health Implications, Daniel F Levey, Marco Galimberti, Joseph D Deak, Frank R Wendt, Arjun Bhattacharya, Dora Koller, Kelly M Harrington, Rachel Quaden, Emma C Johnson, Priya Gupta, Mahantesh Biradar, Max Lam, Megan Cooke, Veera M Rajagopal, Stefany L L Empke, Hang Zhou, Yaira Z Nunez, Henry R Kranzler, Howard J Edenberg, Arpana Agrawal, Jordan W Smoller, Todd Lencz, David M Hougaard, Anders D Børglum, Ditte Demontis, Veterans Affairs Million Veteran Program, J Michael Gaziano, Michael J Gandal, Renato Polimanti, Murray B Stein, Joel Gelernter

Faculty, Staff and Student Publications

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within …


Isoform-Level Transcriptome-Wide Association Uncovers Genetic Risk Mechanisms For Neuropsychiatric Disorders In The Human Brain, Arjun Bhattacharya, Daniel D Vo, Connor Jops, Minsoo Kim, Cindy Wen, Jonatan L Hervoso, Bogdan Pasaniuc, Michael J Gandal Dec 2023

Isoform-Level Transcriptome-Wide Association Uncovers Genetic Risk Mechanisms For Neuropsychiatric Disorders In The Human Brain, Arjun Bhattacharya, Daniel D Vo, Connor Jops, Minsoo Kim, Cindy Wen, Jonatan L Hervoso, Bogdan Pasaniuc, Michael J Gandal

Faculty, Staff and Student Publications

Methods integrating genetics with transcriptomic reference panels prioritize risk genes and mechanisms at only a fraction of trait-associated genetic loci, due in part to an overreliance on total gene expression as a molecular outcome measure. This challenge is particularly relevant for the brain, in which extensive splicing generates multiple distinct transcript-isoforms per gene. Due to complex correlation structures, isoform-level modeling from cis-window variants requires methodological innovation. Here we introduce isoTWAS, a multivariate, stepwise framework integrating genetics, isoform-level expression and phenotypic associations. Compared to gene-level methods, isoTWAS improves both isoform and gene expression prediction, yielding more testable genes, and increased power …


Targeted Gene Expression Profiling Predicts Meningioma Outcomes And Radiotherapy Responses, William C Chen, Abrar Choudhury, Mark W Youngblood, Mei-Yin C Polley, Calixto-Hope G Lucas, Kanish Mirchia, Sybren L N Maas, Abigail K Suwala, Minhee Won, James C Bayley, Akdes S Harmanci, Arif O Harmanci, Tiemo J Klisch, Minh P Nguyen, Harish N Vasudevan, Kathleen Mccortney, Theresa J Yu, Varun Bhave, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason W Chan, Haley K Perlow, Joshua D Palmer, Christine Haberler, Anna S Berghoff, Matthias Preusser, Theodore P Nicolaides, Christian Mawrin, Sameer Agnihotri, Adam Resnick, Brian R Rood, Jessica Chew, Jacob S Young, Lauren Boreta, Steve E Braunstein, Jessica Schulte, Nicholas Butowski, Sandro Santagata, David Spetzler, Nancy Ann Oberheim Bush, Javier E Villanueva-Meyer, James P Chandler, David A Solomon, C Leland Rogers, Stephanie L Pugh, Minesh P Mehta, Penny K Sneed, Mitchel S Berger, Craig M Horbinski, Michael W Mcdermott, Arie Perry, Wenya Linda Bi, Akash J Patel, Felix Sahm, Stephen T Magill, David R Raleigh Dec 2023

Targeted Gene Expression Profiling Predicts Meningioma Outcomes And Radiotherapy Responses, William C Chen, Abrar Choudhury, Mark W Youngblood, Mei-Yin C Polley, Calixto-Hope G Lucas, Kanish Mirchia, Sybren L N Maas, Abigail K Suwala, Minhee Won, James C Bayley, Akdes S Harmanci, Arif O Harmanci, Tiemo J Klisch, Minh P Nguyen, Harish N Vasudevan, Kathleen Mccortney, Theresa J Yu, Varun Bhave, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason W Chan, Haley K Perlow, Joshua D Palmer, Christine Haberler, Anna S Berghoff, Matthias Preusser, Theodore P Nicolaides, Christian Mawrin, Sameer Agnihotri, Adam Resnick, Brian R Rood, Jessica Chew, Jacob S Young, Lauren Boreta, Steve E Braunstein, Jessica Schulte, Nicholas Butowski, Sandro Santagata, David Spetzler, Nancy Ann Oberheim Bush, Javier E Villanueva-Meyer, James P Chandler, David A Solomon, C Leland Rogers, Stephanie L Pugh, Minesh P Mehta, Penny K Sneed, Mitchel S Berger, Craig M Horbinski, Michael W Mcdermott, Arie Perry, Wenya Linda Bi, Akash J Patel, Felix Sahm, Stephen T Magill, David R Raleigh

Faculty, Staff and Student Publications

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems …


Fimap A Fast Identity-By-Descent Mapping Test For Biobank-Scale Cohorts, Han Chen, Ardalan Naseri, Degui Zhi Dec 2023

Fimap A Fast Identity-By-Descent Mapping Test For Biobank-Scale Cohorts, Han Chen, Ardalan Naseri, Degui Zhi

Faculty, Staff and Student Publications

Although genome-wide association studies (GWAS) have identified tens of thousands of genetic loci, the genetic architecture is still not fully understood for many complex traits. Most GWAS and sequencing association studies have focused on single nucleotide polymorphisms or copy number variations, including common and rare genetic variants. However, phased haplotype information is often ignored in GWAS or variant set tests for rare variants. Here we leverage the identity-by-descent (IBD) segments inferred from a random projection-based IBD detection algorithm in the mapping of genetic associations with complex traits, to develop a computationally efficient statistical test for IBD mapping in biobank-scale cohorts. …


A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Carla C Winter, Anne Jacobi, Junfeng Su, Leeyup Chung, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He Dec 2023

A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Carla C Winter, Anne Jacobi, Junfeng Su, Leeyup Chung, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He

Faculty, Staff and Student Publications

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad …


Single-Cell Analysis Of Chromatin Accessibility In The Adult Mouse Brain, Songpeng Zu, Yang Eric Li, Kangli Wang, Ethan J Armand, Sainath Mamde, Maria Luisa Amaral, Yuelai Wang, Andre Chu, Yang Xie, Michael Miller, Jie Xu, Zhaoning Wang, Kai Zhang, Bojing Jia, Xiaomeng Hou, Lin Lin, Qian Yang, Seoyeon Lee, Bin Li, Samantha Kuan, Hanqing Liu, Jingtian Zhou, Antonio Pinto-Duarte, Jacinta Lucero, Julia Osteen, Michael Nunn, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Zihan Wang, Jingbo Shang, M Margarita Behrens, Joseph R Ecker, Allen Wang, Sebastian Preissl, Bing Ren Dec 2023

Single-Cell Analysis Of Chromatin Accessibility In The Adult Mouse Brain, Songpeng Zu, Yang Eric Li, Kangli Wang, Ethan J Armand, Sainath Mamde, Maria Luisa Amaral, Yuelai Wang, Andre Chu, Yang Xie, Michael Miller, Jie Xu, Zhaoning Wang, Kai Zhang, Bojing Jia, Xiaomeng Hou, Lin Lin, Qian Yang, Seoyeon Lee, Bin Li, Samantha Kuan, Hanqing Liu, Jingtian Zhou, Antonio Pinto-Duarte, Jacinta Lucero, Julia Osteen, Michael Nunn, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Zihan Wang, Jingbo Shang, M Margarita Behrens, Joseph R Ecker, Allen Wang, Sebastian Preissl, Bing Ren

Faculty, Staff and Student Publications

Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types; however, our understanding of the gene regulatory programs in these cell types is far from complete1-4. Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated by analysing chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1,482 distinct brain cell populations, adding over 446,000 cCREs to the most recent such annotation in the mouse genome. The mouse brain cCREs are …


Molecularly Defined And Spatially Resolved Cell Atlas Of The Whole Mouse Brain, Meng Zhang, Xingjie Pan, Won Jung, Aaron R Halpern, Stephen W Eichhorn, Zhiyun Lei, Limor Cohen, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Xiaowei Zhuang Dec 2023

Molecularly Defined And Spatially Resolved Cell Atlas Of The Whole Mouse Brain, Meng Zhang, Xingjie Pan, Won Jung, Aaron R Halpern, Stephen W Eichhorn, Zhiyun Lei, Limor Cohen, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Xiaowei Zhuang

Faculty, Staff and Student Publications

In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1-3, including several brain regions (for example, refs. 1-11). However, a comprehensive cell atlas of the whole brain is still missing. Here we imaged a panel of more than 1,100 genes in approximately 10 million cells across the …


Single-Cell Dna Methylome And 3d Multi-Omic Atlas Of The Adult Mouse Brain, Hanqing Liu, Qiurui Zeng, Jingtian Zhou, Anna Bartlett, Bang-An Wang, Peter Berube, Wei Tian, Mia Kenworthy, Jordan Altshul, Joseph R Nery, Huaming Chen, Rosa G Castanon, Songpeng Zu, Yang Eric Li, Jacinta Lucero, Julia K Osteen, Antonio Pinto-Duarte, Jasper Lee, Jon Rink, Silvia Cho, Nora Emerson, Michael Nunn, Carolyn O'Connor, Zhanghao Wu, Ion Stoica, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Chongyuan Luo, Jesse R Dixon, Hongkui Zeng, Bing Ren, M Margarita Behrens, Joseph R Ecker Dec 2023

Single-Cell Dna Methylome And 3d Multi-Omic Atlas Of The Adult Mouse Brain, Hanqing Liu, Qiurui Zeng, Jingtian Zhou, Anna Bartlett, Bang-An Wang, Peter Berube, Wei Tian, Mia Kenworthy, Jordan Altshul, Joseph R Nery, Huaming Chen, Rosa G Castanon, Songpeng Zu, Yang Eric Li, Jacinta Lucero, Julia K Osteen, Antonio Pinto-Duarte, Jasper Lee, Jon Rink, Silvia Cho, Nora Emerson, Michael Nunn, Carolyn O'Connor, Zhanghao Wu, Ion Stoica, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Chongyuan Luo, Jesse R Dixon, Hongkui Zeng, Bing Ren, M Margarita Behrens, Joseph R Ecker

Faculty, Staff and Student Publications

Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq)1 technologies to generate 301,626 methylomes and 176,003 chromatin conformation–methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell taxonomy with 4,673 cell groups and 274 …