Digital Commons Network^™

Molecular Dynamics Of The Host Response To Streptococcus Pneumoniae Pneumonia In Baboons, Bryan D Kraft, Et Al.

2020-Current year OA Pubs

BACKGROUND: Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

METHODS: We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis …

Peroxisomal Metabolism Of Branched Fatty Acids Regulates Energy Homeostasis, Xuejing Liu, Anyuan He, Dongliang Lu, Donghua Hu, Min Tan, Parniyan Goodarzi, Bilal Ahmad, Brian Kleiboeker, Brian N Finck, Mohamed Zayed, Jonathan R Brestoff, Ali Javaheri, Fong-Fu Hsu, Clay F Semenkovich, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1

Upper And Lower Airway Microbiota Across Infancy And Childhood, Ariel J Hernandez-Leyva, Anne L Rosen, Christopher P Tomera, Elaina E Lin, Elikplim H Akaho, Allison M Blatz, William R Otto, Joey Logan, Lisa R Young, Rebecca M Harris, Samantha A Whiteside, Andrew L Kau, Audrey R Odom John

2020-Current year OA Pubs

BACKGROUND: The upper and lower respiratory tracts feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the nasopharynx and trachea across childhood.

METHODS: We employed V4 16S rRNA gene sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 172 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures over the course of 20 weeks in 2020 from subjects enrolled in a cross-sectional study. After extraction, sequencing, and quality control, we studied the remaining 147 of …

Cyp1b1 Mediates Cigarette Smoke-Induced Lipid Accumulation In Alveolar Type 2 Cells, Yin Zhu, Siddhika Gamare, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like …

Observational Activation Of Anterior Cingulate Cortical Neurons Coordinates Hippocampal Replay In Social Learning, Xiang Mou, Daoyun Ji

Faculty, Staff and Students Publications

Social learning enables a subject to make decisions by observing the actions of another. How neural circuits acquire relevant information during observation to guide subsequent behavior is unknown. Utilizing an observational spatial working memory task, we show that neurons in the rat anterior cingulate cortex (ACC) associated with spatial trajectories during self-running in a maze are reactivated when observing another rat running the same maze. The observation-induced ACC activities are reduced in error trials and are correlated with activities of hippocampal place cells representing the same trajectories. The ACC activities during observation also predict subsequent hippocampal place cell activities during …

Uncovering The Pml::Rara Fusion In Cytogenetically Cryptic And Fish-Negative Acute Promyelocytic Leukemia-A Case Report And Comprehensive Literature Review, Busra Delikkaya, Jaime Eberle-Singh, Arianna Morton, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since …

Economics Of Corneal Cross-Linking For Keratoconus Treatment, Christopher J. Rapuano, Richard L. Lindstrom, Eric Donnenfeld, John P. Berdahl, Vance Thompson, David Kratochvil, John Carter

Wills Eye Hospital Papers

AIM: To optimize the real-world applicability of a health economic model estimating the cost-effectiveness of corneal cross-linking for the treatment of keratoconus in the United States.

MATERIALS AND METHODS: A previously reported discrete-event simulation (DES) model was adapted to reassess the cost-effectiveness of corneal cross-linking (CXL) from the US payer perspective. The simulation of keratoconus progression, which is a key driver of model outcomes, was remodeled to more accurately reflect the real-world relationship between age and the rate of disease progression. All costs were updated to reflect 2025 values. We simulated 4,000 eyes of 2,000 patients diagnosed with keratoconus to …

Motion Impact Score For Detecting Spurious Brain-Behavior Associations, Benjamin P Kay, David F Montez, Scott Marek, Joshua S Siegel, Babatunde Adeyemo, Timothy O Laumann, Athanasia Metoki, Roselyne J Chauvin, Andrew N Van, Vahdeta Suljic, Samuel R Krimmel, Ryland L Miller, Dillan J Newbold, Annie Zheng, Nicole A Seider, Kristen M Scheidter, Julia S Monk, Jarod L Roland, Evan M Gordon, Abraham Z Snyder, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

In-scanner head motion introduces systematic bias to resting-state fMRI functional connectivity (FC) not completely removed by denoising algorithms. Researchers studying traits associated with motion (e.g. psychiatric disorders) need to know if their trait-FC relationships are impacted by residual motion to avoid reporting false positive results. We devised Split Half Analysis of Motion Associated Networks (SHAMAN) to assign a motion impact score to specific trait-FC relationships. SHAMAN distinguishes between motion causing overestimation or underestimation of trait-FC effects. We assessed 45 traits from n = 7270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without …

Comparison Of Authentic Urine N-Ethylpentedrone Metabolites To Predicted In Silico And In Vitro Human Hepatocyte Metabolism, Gloria Daziani, Omayema Taoussi, Diletta Berardinelli, Giulia Bambagiotti, Marilyn A. Huestis, Francesco P. Busardò, Jeremy Carlier

Institute of Emerging Health Professions Faculty Papers

Synthetic cathinones are the second most common class of substances belonging to the category of new psychoactive substances (NPS). N-ethylpentedrone (NEPD) self-administration was reported, making it important to elucidate its metabolic pathway to improve its detection. NEPD is often taken together with other substances; confidently identifying its intake is important for accurate toxicological analysis and understanding its toxicity. NEPD metabolism was studied following incubation with human hepatocytes and analysis by liquid chromatography-high-resolution mass spectrometry paired with Compound Discoverer software (Thermo Fisher Scientific). Prediction of possible metabolites was performed with the online software GLORYx. In vivo NEPD metabolism was evaluated by …

Effects Of Olfactory Enrichment On Perioperative Neurocognitive Disorders In Elderly Patients Undergoing Orthopedic Surgery: A Study Protocol Of A Multi-Center Randomized Controlled Trial, Xinchun Mei, Jiayi Wang, Zihan Ni, Yanyan Wang, Binglei Zhao, Daniel I Sessler, Zhongcong Xie, Yuan Shen

Faculty, Staff and Student Publications

Background: Neurocognitive disorders are prevalent among older surgical patients, yet their underlying mechanisms and effective interventions remain largely unknown. Studies in rodents and patients suggest a connection between olfactory impairment and perioperative neurocognitive disorder (PND). Previous work in mice demonstrates that anesthesia and surgery can lead to both olfactory impairment and cognitive deficits. Olfactory enrichment, which is also referred to as olfactory training (i.e., daily exposure to multiple odorants), may prove helpful. For example, olfactory enrichment appears to reduce PND-like behaviors in mice, possibly by mitigating anesthesia- and surgery-induced reductions in olfactory receptor neurons. Additionally, olfactory enrichment increases the volume …

Genetic Susceptibility To Oral And Atherosclerotic Cardiovascular Diseases Based On Dental And Heart Score Studies, Mariana Bezamat, Dylan J Baxter, Nandita Mukhopadhyay, Anum Saeed, Lei Liu, Lisa De Las Fuentes, Betsy Foxman, John R Shaffer, Daniel W Mcneil, Steven E Reis, Mary L Marazita

2020-Current year OA Pubs

Periodontal disease and dental caries are two oral conditions that have been associated with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if one of the key mechanisms involved in this association could be a shared genetic susceptibility. The goal of this study was to explore whether there is an intersection of genetic loci among individuals with comprehensive oral examinations and subclinical ASCVD screenings. We leveraged data from oral and medical examinations obtained from the Dental and Heart Strategies Concentrating on Risk Evaluation (Dental/Heart SCORE) projects. Genome-wide association studies (GWASs) were performed independently in 552 participants (aged 45-75 years). The …

Dworf Gene Therapy Improves Cardiac Calcium Handling And Mitochondrial Function, Omar Brito-Estrada, Yasuhide Kuwabara, Aaron M Gibson, Keira R Hassel, Michael L Kamradt, Joseph P Verry, N Scott Blair, Michael J Bround, Jiuzhou Huo, Jeffery D Molkentin, Catherine A Makarewich

Faculty, Staff and Students Publications

Background: Calcium (Ca2+) dysregulation is a hallmark of heart failure, impairing excitation-contraction coupling and contributing to pathological remodeling. The sarco/endoplasmic reticulum Ca2+ ATPase isoform 2a (SERCA2a) mediates Ca2+ reuptake into the sarcoplasmic reticulum (SR) during diastole, but its activity declines in failing hearts. DWORF (dwarf open reading frame), a newly identified cardiac microprotein, enhances SERCA2a activity and improves cardiomyocyte Ca2+ cycling and contractility. SR Ca2+ release also influences mitochondrial metabolism and ATP production. Here, we investigated whether DWORF overexpression improves SR Ca2+ handling, augments mitochondrial Ca2+ signaling, and protects against heart failure progression.

Methods: Transgenic and adeno-associated virus approaches were …

Bedside Small-Bowel Challenge Vs. Fluoroscopic Series For Sbo: A Cost Effectiveness Analysis, Aravinda Krishna Ganapathy, Liam Cunningham, M Hunter Lanier, Selasi Nakhaima, Madelyn Thiel, Daniel Hoffman, Obeid Ilahi, David H Ballard, Vincent M Mellnick

2020-Current year OA Pubs

BACKGROUND: Small bowel obstruction (SBO) accounts for 12-16% of surgical hospital admissions and can lead to complications such as bowel ischemia. Traditional management requires transporting patients to the Radiology Department (RD) for a fluoroscopic small bowel series, occupying resources and time. This study evaluates the efficacy and efficiency of the Small Bowel Challenge Exam, a bedside alternative.

METHODS: A retrospective analysis was performed on 85 SBO patients from January 2018 to December 2023 at an academic tertiary care facility, comparing the traditional fluoroscopic series (37 patients) to the bedside Small Bowel Challenge Exam (48 patients). Key metrics analyzed included hospital …

Global, Regional, And National Burden Of Cardiovascular Diseases And Risk Factors In 204 Countries And Territories, 1990-2023, Global Burden Of Cardiovascular Diseases And Risks 2023 Collaborators, Mohammadreza Abbasian

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging.

OBJECTIVES: We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure.

METHODS: The Global Burden of Disease (GBD) 2023 study, a multinational …

Associations Between Adhering To 24-Hour Movement Guidelines And Anxiety Among Adolescents Across Intersectional Identities: Kyrbs 2020-2022., Suryeon Ryu, Eun Young Lee, Zan Gao

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Identifying preventive measures for adolescent mental health is a global public health priority, as poor mental health heightens the risk of early death from related issues, including suicide. This study examined the associations between adherence to the 24-Hour Movement Guidelines and anxiety among a nationally representative sample of South Korean adolescents, using an intersectional identity framework.

METHODS: Data from the 2020-2022 Korea Youth Risk Behavior Surveys were analyzed. Adolescents aged 12-17 years were grouped based on adherence to guidelines: none, physical activity (PA), sedentary behavior (SB), sleep, two guideline combinations, and all three. Anxiety was the mental health outcome. …

Lung Nr3c1+ And Cxcr6high T Cells Distinguish Immunopathogenesis Of Human Emphysema, Yun Zhang, Maor Sauler, David B Corry, Scott A Ochsner, Sarah Perusich, Li-Zhen Song, Joshua Malo, Raul San Jose Estepar, Francesca Polverino, Farrah Kheradmand

Faculty, Staff and Students Publications

There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 …

Association Of Genetic Scores Related To Insulin Resistance With Neurological Outcomes In Ancestrally Diverse Cohorts From The Trans-Omics For Precision Medicine (Topmed) Program, Chloé Sarnowski, Yixin Zhang, Farah Ammous, Lincoln M P Shade, Daniel Dicorpo, Xueqiu Jian, Donna K Arnett, Thomas R Austin, Alexa Beiser, Joshua C Bis, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Charles S Decarli, Harsha Doddapaneni, Josée Dupuis, David W Fardo, Jose C Florez, Stacey Gabriel, Richard A Gibbs, David C Glahn, Namrata Gupta, Hector M González, Kevin A González, Konstantinos Hatzikotoulas, Kathleen M Hayden, Susan R Heckbert, Bertha Hidalgo, Alicia Huerta-Chagoya, Timothy M Hughes, Sharon L R Kardia, Charles L Kooperberg, Lenore J Launer, W T Longstreth, Ravi Mandla, Rasika A Mathias, Andrew P Morris, Thomas H Mosley, Ilya M Nasrallah, Paul Nyquist, Bruce M Psaty, Qibin Qi, Laura M Raffield, Nigel W Rayner, Alexander P Reiner, Claudia L Satizabal, Elizabeth Selvin, Magdalena D R Sevilla-Gonzalez, Albert V Smith, Jennifer A Smith, Kirk Smith, Beverly M Snively, Lorraine Southam, Tamar Sofer, Ken Suzuki, Henry J Taylor, Miriam S Udler, Karine A Viaud-Martinez, Sylvia Wassertheil-Smoller, Alexis C Wood, Lisa R Yanek, Xianyong Yin, Alisa K Manning, Jerome I Rotter, Stephen S Rich, James B Meigs, Myriam Fornage, Sudha Seshadri, Alanna C Morrison, Topmed Neurocognitive Working Group, Topmed Diabetes Working Group

The Brown Foundation: Institute of Molecular Medicine

To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P <  0.002) of the cross-population (P = 1.3 × 10-5) and European (PEA = 3.0 × 10-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P <  0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.

Atrial Fibroblast-Derived Macrophage Migration Inhibitory Factor Promotes Atrial Macrophage Accumulation In Postoperative Atrial Fibrillation, Joshua A Keefe, Jose Alberto Navarro-Garcia, Shuai Zhao, Mihail G Chelu, Xander Ht Wehrens

Faculty, Staff and Students Publications

New study: Blocking MIF protein prevents irregular heartbeats after surgery by reducing harmful immune cell buildup in the atria.

A Community-Engaged Approach To Enhancing Participation In Genomic Research In Rare And Understudied Cancer Populations, Saira Khan, Bailey Martin-Giacalone, Kayla Wallace, Briana Wilson, Christine Marx, Erin Linnenbringer, Jessica Mozersky, Melinda Bachini, Nancy Chollet, Dionne Stalling, Li Ding, Ryan C Fields, Graham A Colditz, Bettina F Drake

2020-Current year OA Pubs

UNLABELLED: Few studies provide insights on how to incorporate community members' perspectives of genomic research during the early phases of study development. Engaging with community members early and consistently throughout the research lifecycle could help identify and mitigate barriers to genomic research participation, particularly among groups with rare and understudied cancers.

METHODS: The Washington University Participant Engagement and Cancer Genome Sequencing (WU-PE-CGS) study formed a Participant Engagement Advisory Board (PEAB) consisting of patients, patient advocates, and patient advocacy organizations who represented the three understudied cancer populations: cholangiocarcinoma, early-onset colorectal cancer in Black Americans, and multiple myeloma in Black Americans. PEAB …

Gata2 Mutation Is Associated With Immune Dysfunction And Increased Mycobacterium Haemophilum Susceptibility In Immunocompromised Individuals, Ananya Gupta, Shail B. Mehta, Abhimanyu, Bruce A. Rosa, John Martin, Mushtaq Ahmed, Shyamala Thirunavukkarasu, Farheen Fatma, Gaya K. Amarasinghe, Makedonka Mitreva, Thomas C. Bailey, David B. Clifford, Shabaana A. Khader

2020-Current year OA Pubs

Infections with nontuberculous mycobacterium (NTM) are on the rise. Here, we investigated an uncommon NTM infection, by M. haemophilum (Mh, n = 4), from a shared geographic location in the United States. All patients had underlying immunosuppressive conditions or treatments. We identified that all these individuals had a nonsynonymous mutation in GATA2 gene, which was absent in healthy controls (HCs, n = 4) from the same geographic area (Missouri, USA). Whole blood from these individuals had attenuated cytokine responses to Mh stimulation for IL-1β, IL-6, IL-8, MIP-1α and MIP-1β, but not to phytohemagglutinin (PHA) or another NTM, M. abscessus. Impaired …

Use Of Amplified Lewy Body Dementia Fibrils And Autoradiography To Characterize Binding Of Radioligand Tg-1-90b To Alpha-Synuclein Fibrils In Postmortem Brain Tissue, Jennifer Y O'Shea, Dhruva D Dhavale, Helen Hwang, Zachary Smith, Thomas J A Graham, Robert H Mach, Paul T Kotzbauer

2020-Current year OA Pubs

Parkinson's disease (PD) and Lewy Body Dementia (LBD) are defined by accumulation of alpha-synuclein (Asyn) fibrils within Lewy bodies (LBs) and Lewy neurites (LNs). The development of a Positron Emission Tomography (PET) tracer for quantifying Asyn fibrils would improve diagnostic accuracy and provide a biomarker for disease progression. We previously described radioligand [

What Is Known About The Fish Intake Of People Living In Disadvantaged Communities In The Uk? A Scoping Review, Sarah Gale, Roseline Aboluwade, Louise Hunt, Clare Pettinger

School of Health Professions

Fish provides essential nutrients, including protein, omega-3 fatty acids (oily fish) and other micronutrients, and may be seen to have a prominent role in protecting against non-communicable diseases, especially cardiovascular disease. Recent UK National Diet and Nutrition Survey analysis suggests people are not meeting their weekly fish intake recommendation of at least two portions per week, of which one should be oily. Lower socioeconomic groups are more likely to eat poor-quality diets, with low fish intake, resulting in poor health outcomes. The aim of this scoping review was to examine the factors influencing fish consumption in people living within ‘disadvantaged …

Trends And Disparities In Acute Coronary Syndrome-Related Mortality In The United States: Implications For Healthcare, Muhammad Khuzzaim Khan, Ibrahim Ahmed Khan, Abdul Moiz Javed, Arslan Wazir, Hira Saleem, Muhammad Zohaib, Faisal Rasheed, Priyanka Mohan Lal, Syeda Laiba Sherazi, Amiaz Karim, Nikhil Duseja, Hussam Al Hennawi

Abington Jefferson Health Papers

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States (US). However, the trends and disparities in ACS mortality are not well understood. This study aimed to analyze the ACS mortality in the US from 1999 to 2020 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. The age-adjusted mortality rates (AAMR) due to ACS were calculated for each year from 1999 to 2020, stratified by sex, race, urbanization, and state. The trends and disparities in AAMR were examined using descriptive statistics and graphical methods. The AAMR due …

Chronic Poppers Maculopathy: Case Report And Literature Comparison Of Chronic And Acute Use, Francesco Cappellani, Caterina Gagliano, Jose S. Pulido

Wills Eye Hospital Papers

RATIONALE: Alkyl nitrites ("poppers") are recreational substances known for their vasodilatory and euphoric effects. Increasing evidence links them to a vision-threatening condition termed poppers maculopathy, characterized by foveal yellow spots and outer retinal changes on optical coherence tomography. While most reports describe acute exposure, little is known about long-term consequences. This case describes one of the longest documented durations of chronic poppers use, combined with a literature review to contextualize the clinical spectrum.

PATIENT CONCERNS: A 68-year-old man with human immunodeficiency virus, type 2 diabetes, hypertension, and depression presented with progressive central vision loss in both eyes persisting for at …

Human Single-Neuron Activity Is Modulated By Intracranial Theta Burst Stimulation Of The Basolateral Amygdala, Justin M Campbell, Shuo Wang, Lawrence N Eisenman, James Swift, Tao Xie, Peter Brunner, Jon Timothy Willie, Et Al.

2020-Current year OA Pubs

Direct electrical stimulation of the human brain has been used for numerous clinical and scientific applications. At present, however, little is known about how intracranial stimulation affects activity at the microscale. In this study, we recorded intracranial EEG data from a cohort of patients with medically refractory epilepsy as they completed a visual recognition memory task. During the memory task, brief trains of intracranial theta burst stimulation (TBS) were delivered to the basolateral amygdala (BLA). Using simultaneous microelectrode recordings, we isolated neurons in the hippocampus, amygdala, orbitofrontal cortex, and anterior cingulate cortex and tested whether stimulation enhanced or suppressed firing …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

Early Blood Pressure Targets In Acute Spinal Cord Injury: A Randomized Clinical Trial, Ruba Sajdeya, N. David Yanez, Michael Kampp, Michael D. Goodman, David Zonies, Brandon Togioka, Andrew Nunn, Robert D. Winfield, Niels D. Martin, Anirudh Kohli, Toan T. Huynh, David O. Okonkwo, Roy A. Poblete, Emily J. Gilmore, Randall M. Chesnut, Aaron E. Bunnell, Tetsu Ohnuma, Mona Hashemaghaie, Miriam M. Treggiari

Department of Surgery Faculty Papers

IMPORTANCE: Early blood pressure management is central to neurologic resuscitation of spinal cord injury; however, the role of augmented blood pressure is unclear.

OBJECTIVE: To compare the efficacy and safety of augmented vs conventional blood pressure on 6-month neurologic outcomes after acute spinal cord injury.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial took place from October 3, 2017, to July 26, 2023, and assessed patients 18 years or older with spinal cord injury followed up for 6 months at 13 large US trauma centers.

INTERVENTIONS: Patients were equally randomized to augmented (>85-90 mm Hg) or conventional ( …

Galntl5 Binds Galnac And Is Required For Migration Through The Uterotubal Junction And Sperm-Zona Pellucida Binding, Taichi Noda, Reika Uriu, Daisuke Mashiko, Hina Shinohara, Yongcun Qu, Ayumu Taira, Ryan M Matzuk, Duri Tahala, Motochika Nakano, Kimi Araki, Zhifeng Yu, Ying Zhang, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Objective: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston.

Methods: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times.

Results: A total of 32,640 stroke admissions from 29 studies …

Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated With Olfactory Dysfunction, Mohammed Aslam Imtiaz, Konstantinos Melas, Adrienne Tin, Valentina Talevi, Honglei Chen, Myriam Fornage, Srishti Shrestha, Martin Gögele, David Emmert, Cristian Pattaro, Peter Pramstaller, Franz Förster, Katrin Horn, Thomas H Mosley, Christian Fuchsberger, Markus Scholz, Monique M B Breteler, N Ahmad Aziz

Faculty, Staff and Student Publications

Background: Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. Therefore, here we aimed to elucidate its genetic architecture through a genome-wide association study meta-analysis (GWMA).

Methods: This GWMA included the participants of European ancestry (N = 22,730) enrolled in four different large population-based studies followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). Olfactory dysfunction was assessed using a 12-item smell identification test.

Results: GWMA revealed a novel genome-wide significant locus (tagged by single nucleotide …

Salvage Therapies For First Relapse Of Shh Medulloblastoma In Early Childhood, Craig Erker, Mohamed S Abdelbaki, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sonic hedgehog (SHH) medulloblastoma is the most common molecular group of infant and early childhood medulloblastoma (iMB) and has no standard of care at relapse. This work aimed to evaluate the post-relapse survival (PRS) and explore prognostic factors of patients with nodular desmoplastic (ND) and/or SHH iMB.

METHODS: This international retrospective study included 147 subjects diagnosed with relapsed ND/SHH iMB between 1995 and 2017, < 6 years old at original diagnosis, and treated without initial craniospinal irradiation (CSI). Univariable and multivariable Cox models with propensity score analyses were used to assess PRS for those in the curative intent cohort.

RESULTS: The 3-year PRS was 61.6% (95% confidence interval [CI], 52.2-69.6). The median age at relapse was 3.4 years (interquartile range [IQR], 2.6-4.1). Those with local relapse (40.8%) more often received salvage treatment with surgery …