Digital Commons Network^™

Body Mass Index, Clinical Outcomes, And Mortality In Heart Failure: A Mendelian Randomization Study, Nicholas Sunderland, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Excess adiposity, most commonly indexed through body mass index (BMI), is strongly associated with the development of heart failure (HF). Weight loss therapies improve outcomes in patients with obesity and HF with preserved left ventricular ejection fraction (LVEF), but their effects in HF with reduced LVEF remain unclear.

OBJECTIVES: The aim of this work is to determine whether higher BMI is associated with adverse clinical outcomes in patients with HF and whether there is effect modification by LVEF subgroup.

METHODS: Two-sample Mendelian randomization (MR) was used, with genome-wide significant loci associated with BMI as instrumental variables and outcome data …

Garlic-Derived Metabolite Activates Lkb1, Promotes Adipose Enampt Secretion, And Improves Age-Related Muscle Function Via Hypothalamic Signaling, Jun-Ichiro Suzuki, Kiyoshi Yoshioka, Masahiro Kurita, Takumi Sugimoto, Takahiro Eguchi, Naoki Ito, Aoi Kodama, Yasutomi Kamei, Masahiro Ohtani, Toshiaki Matsutomo, Shin-Ichiro Imai

2020-Current year OA Pubs

Garlic (Allium sativum L.) and its aged extract contain many bioactive compounds that can bring health benefits to humans. Among them, S-1-propenyl-L-cysteine (S1PC) has recently drawn significant attention in the field of nutriceutical research. However, the mechanism of its molecular action has remained poorly understood. Here, we show that S1PC significantly activates liver kinase B1 (LKB1) through enhancing its tertiary complex formation with STRAD and MO25, leading to stimulating the phosphorylation of a mammalian NAD

Adjunctive Psychosocial Interventions And Opioid Abstinence Among Patients Receiving Buprenorphine: A Randomized Clinical Trial., Michelle R. Lent, Emily E Hurstak, Kevin G Lynch, Emily Loscalzo, Kimberly Mazur, Helen L Lugo, Karen L Dugosh

PCOM Scholarly Works

IMPORTANCE: Adjunctive psychosocial treatments are recommended for many using medications for opioid use disorder (MOUD), but it is unclear which approaches can best enhance treatment outcomes.

OBJECTIVES: To evaluate the comparative effectiveness of 2 psychosocial treatments, peer recovery support (PRS) and cognitive-behavioral therapy (CBT), on opioid abstinence when used as adjunctive therapies to office-based buprenorphine treatment in adults with opioid use disorder (OUD).

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included US adults diagnosed with OUD referred for care at 5 federally qualified health centers with office-based addiction treatment programs by their clinicians from 2020 to 2024. Participants were …

Polygenic Risk Scores And Hla Class Ii Variants Are Biomarkers Of Corticosteroid Response In Childhood Nephrotic Syndrome., Tiffany Tu, Alejandro Ochoa, Amika Sood, Ashley Dabrik, Megan Chryst-Stangl, Brandon Lane, Guanghong Wu, Frank Donovan, Ursula Harper, Settara Chandrasekharappa, Christopher Esezobor, Adaobi Solarin, David Hooper, Christine Sethna, Sandra Amaral, Mahmoud Kallash, Michelle Rheault, Priya Verghese, Vikas Dharnidharka, Eloise Salmon, Patricia Weng, Tarak Srivastava, Michael E Seifert, Cozumel Pruette, David Selewski, Keisha Gibson, Tracy Hunley, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arvind Bagga, Aditi Sinha, Nicholas Webb, Larry Greenbaum, Ali Gharavi, Krzysztof Kiryluk, Matthias Kretzler, Lisa Guay-Woodford, Simone Sanna-Cherchi, Agnieszka Bierzynska, Ania Koziell, Gavin Welsh, Moin Saleem, Charles Rotimi, Eileen Chambers, Cliburn Chan, Curegn Consortium, Pnrc Glomerular Disease Group, Cibmtr/Nmdp Consortium, Annette Jackson, Adebowale Adeyemo, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are no current reliable predictors of therapy response at initial clinical presentation.

METHODS: To evaluate predictors, we conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 children (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched control individuals.

RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were …

Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease., Mike Seed, Dawn Ilardi, Valerie Rofeberg, Cynthia Ortinau, Caren Goldberg, Garrett Reichle, Lauren Bush, Justin Elhoff, Amy Jo Lisanti, Jennifer Butcher, Caitlin Rollins, Andrew Van Bergen, Shabnam Peyvandi, Emily Bucholz, Stephanie Cox, Lyla Hampton, Jacqueline Sanz, Sonia Monteiro, Shruti Tewar, Kiona Allen, Caroline Lee, Kristi Glotzbach, Nneka Alexander, Laurel Bear, Corinne Anton, Renee Sananes, Linh Ly, Gina Boucher, Kelly Wolfe, Lindsay Edwards, Elizabeth J. Willen, Alexander Tan, Christina Ortega, Erica Sood, Anjali Sadhwani, Kari Crawford Plant, Lauren Quigley, Jessica Pliego, Elizabeth Valles, Abbey Hines, David Wypij, Thomas Miller

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Neurodevelopmental impairments are common in children with congenital heart disease.

OBJECTIVES: To compare neurodevelopmental outcomes by cardiac diagnosis and identify associations between medical and social factors and early neurodevelopmental outcomes among children with congenital heart disease.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used neurodevelopmental follow-up data obtained between May 1, 2019, and June 30, 2022, and entered into the Cardiac Neurodevelopmental Outcome Collaborative (CNOC) registry, with linkage to the Pediatric Cardiac Critical Care Consortium registry. Children younger than 30 months from 25 CNOC sites were studied. Data analysis was performed between January 2023 and December 2024.

EXPOSURES: Patients …

An Obligatory Role For Agrp Neurons In Maintaining Body Temperature During Time-Restricted Feeding, Cunjin Su, Jing Cai, Yuanzhong Xu, Benjamin R Arenkiel, Qingchun Tong

The Brown Foundation: Institute of Molecular Medicine

Homeotherms maintain a steady body temperature through thermoregulation, a process critical for survival during fasting, in which the brain has to defend energy-costly body temperature while reducing energy expenditure to conserve energy reserve; however, the neural basis for defending body temperature remains unclear. Here, we demonstrated that AgRP neuron lesion led to lethality during time-restricted feeding on chow but not on HFD, and caused no obvious impact on HFD-induced obesity or obesity-reducing responses to glucagon-like peptide-1 receptor agonism. The lesion disrupted adaptive feeding behaviors during time-restricted feeding and reduced motivational feeding on chow. Notably, the lethality was caused by hypothermia …

Silk Vista Baby Versus Pipeline Embolization Device For Unruptured Distal Anterior Cerebral Artery Aneurysms: A Multicenter Propensity-Weighted Comparative Study., Valerio Da Ros, Frédéric Clarençon, Adam A. Dmytriw, Pascal Jabbour Md, Marios Psychogios, Peter Sporns, Ajit S. Puri, Ameer E. Hassan, Oktay Algin, Markus A. Möhlenbruch, Mauro Bergui, Oded Goren, Gregoire Boulouis, Takeshi Morimoto, Raoul Pop, Joanna Wk Ho, Virginia Pujol Lereis, Jared Cooper, Giancarlo Salsano, Alessandro Sgreccia, Arturo Consoli, Eytan Raz, Julien Burel, Khawaja Muhammad Baqir Hassan, Zhe Ji, Riitta Rautio, Maria Ruggiero, Federico Sabuzi, Stefania Proietti, Joseph Domenico Gabrieli, Michael Levitt, Antonio Armando Caragliano, Christophe Cognard, Gaultier Marnat, Nicola Limbucci, Mariangela Piano, Alexis Guedon, Andrea Romi, Fortunato Di Caterino, Mykola Vyval, Adrien Guenego, Mohamad Abdalkader, Thanh Nguyen, Vitor Mendes Pereira, Ocilio Ribeiro Goncalves, Erwah Kalsoum, Alessandro Pedicelli, Andrea M Alexandre, Luca Scarcia

Department of Neurosurgery Faculty Papers

BACKGROUND: Flow diversion is effective for unruptured distal anterior cerebral artery (DACA) aneurysms, yet comparative data between the Silk Vista Baby (SVB) and Pipeline Embolization Device (PED) in this challenging territory remain scarce.

METHODS: We conducted a retrospective multicenter study using the CRETA Registry, including consecutive patients with unruptured DACA aneurysms treated with SVB or PED. The primary endpoint was complete angiographic occlusion (O'Kelly-Marotta grade D). Secondary outcomes included procedural characteristics, clinical outcome (modified Rankin Scale), and complications. Overlap weighting was applied to account for non-randomized treatment allocation. Predictors of occlusion were explored using penalized logistic regression. A sensitivity analysis …

Exploring Racial And Ethnic Diversity Trajectories And Diabetes Prevalence In The United States, Jiue-An Yang, Calvin P Tribby, Anna Dmowska, Qian Xiao, Marta M Jankowska

Faculty, Staff and Student Publications

This study investigates whether long-term changes in neighborhood racial and ethnic diversity are associated with adult diabetes prevalence across the contiguous United States. We calculated diversity indexes for US census tracts (n = 72,033) using decennial census data from 1990 to 2020. Five diversity trajectory clusters were identified using K-means clustering. Diabetes prevalence in 2019 was obtained from the CDC's PLACES dataset. Linear mixed models (LMMs) assessed global associations between diversity trajectories and diabetes prevalence, adjusting for age, sex, poverty, marital status, and public insurance. Geographically weighted regression (GWR) examined local variations in these associations. Compared to the reference group …

Dental Care Utilization Among Sexual And Gender Minority Individuals, Ishita Singh, Oladipo Afolayan, Sarah S Jackson, Irene Tamí-Maury

Faculty, Staff and Student Publications

Objectives: Sexual and gender minority (SGM) individuals can experience notable health disparities, including higher HIV prevalence, social isolation, substance abuse, lack of culturally competent providers, and poorer health outcomes compared to heterosexuals due to stigma and discrimination. This study aims to identify predictors of dental care utilization across sexual minorities using the 2023 TEXAS PRIDE Survey.

Methods: We analyzed data from 517 SGM individuals, assessing sociodemographic characteristics, health behaviors, and recent medical and dental visits. Multivariable logistic regression identified predictors of dental care utilization (i.e., a dental visit in the past year).

Results: Among sexual orientation groups, reported dental care …

Trust In Cancer Information Sources And Awareness Of Human Papillomavirus As A Cause Of Cervical Cancer Among Us Adults, Olajumoke Ope Oladoyin, Paula Cuccaro, Lara S Savas, Robert Yu, Joel Fokom Domgue, Sheryl Mccurdy, Sanjay Shete

Faculty, Staff and Student Publications

Importance: Religiosity, trust in physicians, and trust in government health agencies influence individual decision-making and behavior toward public health programs. However, trust in information about cancer from these sources and their association with public awareness of human papillomavirus (HPV) as a cause of cervical cancer remain understudied.

Objective: To assess the association of trust in cancer information sources with awareness that HPV causes cervical cancer among US adults.

Design, setting, and participants: This cross-sectional study used the nationally representative 2022 Health Information National Trends Survey (HINTS) data on noninstitutionalized US adults aged 18 years or older collected between March 7 …

Age And Sex Affect The Prevalence And Severity Of Periodontal Conditions In An Academic Setting, Karo Parsegian, Nikolaos Soldatos, Tonia C Carter, Nikola Angelov, Neel Shimpi, Krishna Kumar Kookal, David K Okano, Effie Ioannidou

Faculty, Staff and Student Publications

Background: The aim of the present study was to examine whether age and sex affected the prevalence and severity of periodontal conditions in patients attending an academic dental clinic.

Methods: Electronic health record (EHR) data on the demographic characteristics and periodontal conditions of patients presented for a comprehensive periodontal evaluation were extracted from the institutional dental EHR database. Retrospective analysis of independent associations of age, sex, and other subject characteristics with periodontal conditions was determined using multinomial logistic regression. The null hypothesis stating that age and sex were not associated with the increased prevalence and/or severity of periodontal conditions was …

Parent Perspectives On Neonatal Research Without Prior Consent: A Mixed-Methods Interview Study., Stephanie A. Kraft, Abigail Brickler, Abril Beretta, Rishabh Jain, Andrea Kelsh, Kaashif A. Ahmad, Justin T. Clapp, Neal W. Dickert, Rebecca A. Dorner, Katherine F. Guttmann, Anup C. Katheria, Stephanie Kukora, Benjamin A. Mooso, Elliott Mark Weiss, Fam-Connect Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Recruitment for clinical research in the neonatal intensive care unit (NICU) is difficult, which may lead to low enrollment rates, systematically skewed samples, and nongeneralizable results. Research without prior consent (RWPC), defined as obtaining consent only after infants have been randomized to a treatment arm, may improve enrollment but raises ethical challenges. There is a need to better understand how parents with lived experience of having an infant in the NICU consider RWPC’s impact on critical ethical values related to informed consent, including decision-making, respect, and trust. This mixed-methods study aimed to describe parental perceptions of the acceptability and …

Lymph Node Dissection And Postoperative Complications After Lung Cancer Resection, Isheeta Madeka, Khaled Noueihed, Jacob Woodroof, Shale Mack, Hamza Rshaidat, Gregory L Whitehorn, Sneha Alaparthi, Scott H. Koeneman, Tyler R. Grenda, Nathaniel R. Evans, Iii, Olugbenga T. Okusanya

Department of Surgery Faculty Papers

Importance: Current lung cancer guidelines recommend lymph node sampling (LNS) with the 3 + 1 rule, which recommends station-based sampling with at least 3 N2 (mediastinal) and 1 N1 (hilar) nodal stations. Although there is oncologic benefit to rigorous LNS, potential negative impacts on surgical outcomes have not been well investigated. As adoption of the 3 + 1 rule increases given its formalization as guideline-concordant care, associations with adverse outcomes are crucial to characterize.

Objective: To evaluate whether satisfying the 3 + 1 rule is associated with increased postoperative complications.

Design, setting, and participants: This retrospective cohort study used the …

Chronic Conditions And Mortality In Medicare Beneficiaries Before And After The Covid-19 Pandemic, R J Waken, Fengxian Wang, Jose F Figueroa, Rishi K Wadhera, Khavya Avula, E John Orav, Anne Mobley Butler, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: There were well-documented changes in health care use during the COVID-19 pandemic. Little is known about whether there were any associated decreases in claims-based comorbidity ascertainment that might have relevance to health services and policy research.

OBJECTIVE: To quantify differences in claims-based comorbidity assessment in Medicare beneficiaries pre- vs post-COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the 30 Chronic Conditions Warehouse 1- or 2-year lookback claims algorithms to ascertain each comorbidity with exact date ranges for all fee-for-service (FFS) and Medicare Advantage (MA) beneficiaries. Data were analyzed from April 2025 to April 2026.

EXPOSURES: The …

Alcohol Consumption And Molecular Subtypes Of Colorectal Cancer: Pooled Observational And Mendelian Randomization Analyses, Christos V Chalitsios, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alcohol consumption is associated with colorectal cancer (CRC) risk, yet its association with distinct molecular subtypes remains unclear. Clarifying this could reveal insights into alcohol's carcinogenic mechanisms.

OBJECTIVES: We examined the association between alcohol consumption and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, BRAF, and KRAS mutations.

METHODS: Pooled observational (n

RESULTS: Among drinkers, each additional 14 g/d of alcohol was associated with a 10% higher CRC risk [odds ratio (OR) = 1.10; 95% confidence interval (CI): 1.07, 1.13], but this association …

Triple Tracer Heterogeneity In Dual Neoplasia: The "Three Musketeers" In Discerning Squamous Cell Carcinoma And Paraganglioma In The Same Patient, Shyam Kumar Ravada, Gaurav Malhotra, Aaditya Daga, Anurag R Lila, Saba Memon, Tushar Bandgar

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma of unknown primary (HNSCCUP) comprises 2%-5% of head and neck squamous cell cancers (HNSCC). Its coexistence with abdominal paraganglioma is exceedingly rare. We report a unique case of a 48-year-old male with HNSCCUP presenting as cervical lymphadenopathy and a coexisting abdominal paraganglioma. 18 F-FDG showed uptake in both lesions, while 68 Ga-DOTATATE was avid only in paraganglioma, and 68 Ga-DOTA-FAPI-04 was avid only in cervical nodes. These differential uptake patterns reflect distinct tumor biology and underscore the potential for tailoring theranostic treatment strategies with 177 Lu/ 90 Y isotopes for FAPI-avid squamous cell cancers …

Plasma Biomarkers Of Brain Injury In Critically Ill Children Receiving Extracorporeal Membrane Oxygenation, Matthew L Friedman, Michael J Bell, Bonnie A Brooks, Adam S Himebauch, Asavari Kamerkar, Kerri Larovere, Laura L Loftis, Jose A Pineda, Ahmed Said, Hitesh S Sandhu, Martin Stengelin, Catherine Demos, Mark S Wainwright, Alina N West, Allan Barnes, Allen D Everett, Ryan J Felling, Sue J Hong, Jennifer L Roem, Cynthia F Salorio, Derek K Ng, Melania M Bembea

Faculty, Staff and Students Publications

Importance: Timely identification of acute brain injury (ABI) in children receiving extracorporeal membrane oxygenation (ECMO) support is critical for early neuroprotective interventions.

Objectives: To determine if elevations in plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and tau levels in children receiving ECMO precede new ABI confirmed by neuroimaging, and if they are associated with mortality and functional outcomes.

Design, setting, and participants: This was a prospective observational cohort study conducted from 2019 to 2023, with 18-month follow-up completed in 2025. Children aged 2 days to younger than 18 years at ECMO cannulation were recruited from 11 US …

Association Of Infection Frequency And Incident Clonal Hematopoiesis Of Indeterminant Potential, Ajibike Lapite, Vernon A Burk, James Decuir, Junichi Ishigami, Seyedmohammad Saadatagah, Pradeep Natarajan, Christie M Ballantyne, Elizabeth A Platz, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis of indeterminant potential (CHIP) is an age-related phenomenon associated with increased risk of hematologic malignancy. Preclinical studies have shown that infection is a driver of CHIP; clinical studies in people living with HIV suggest a relationship between chronic infection and CHIP, but the association between infection frequency and incident CHIP in the general population remains unknown. We leveraged the atherosclerosis risk in communities study to design a closed prospective cohort study. CHIP was determined based on whole-exome sequencing at 2 time points 20 years apart. Included were 3,367 individuals without cancer or CHIP at time 1 and without …

Matching-Adjusted Indirect Comparison Of Acoltremon Ophthalmic Solution 0.003% And Cyclosporine 0.05% Ophthalmic Emulsion For Increased Tear Production In Patients With Dry Eye Disease, Stephen Pflugfelder, Tony Okoro, Margaret Ainslie-Garcia, Anja Haltner, Emily K Prentiss, Elizabeth M Salvo-Halloran, Nikethana Srikanth, Michelle Senchyna, Esen K Akpek

Faculty, Staff and Students Publications

No abstract provided.

Barrett’S Esophagus-Associated Genetic Loci In African Americans: A Case-Control Study Using The All Of Us Research Program, Ashwin Rao, Jinyoung Byun, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

Background and aims: Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program.

Methods: We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We …

Whole Genome Sequencing Analysis Of Over 3500 Individuals Dementia-Free Over 85 Years Old, Gina M Peloso, Dongyu Wang, Sabrina M Abbruzzese, Joshua C Bis, Seung Hoan Choi, Alexa Beiser, Jan Bressler, Josée Dupuis, Alison E Fohner, Mohsen Ghanbari, Richard A Gibbs, Nancy Heard-Costa, M Arfan Ikram, Paul Lacaze, Quentin Le Grand, Oscar L Lopez, Thomas H Mosley, Moeen Riaz, Aïcha Soumaré, Amber Yaqub, Eric Boerwinkle, Bruce M Psaty, Myriam Fornage, Sudha Seshadri, Anita L Destefano

Faculty, Staff and Students Publications

BACKGROUND:

Identifying genetic variants conferring resilience to Alzheimer’s disease and related dementia (ADRD) may hold promise for developing therapeutics.

OBJECTIVE:

To determine genetic associations with being dementia-free at age 85 (DF85).

METHODS:

We examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF≤1%) coding and non-coding variants in DF85 participants (n=3,657) against individuals who were not DF85 (n=20,010). We verified associations using a stricter control set who developed dementia before age 85 (n=5,552).

RESULTS: …

Disease-Specific Growth Charts Capture Characteristic Growth Patterns In Children With Pmm2 – Cdg, Kyriakie Sarafoglou, Christina Lam, Andrew C Edmondson, Andrea Miller, Rodrigo T Starosta, Aziza Zeighami, Seishu Horikoshi, Hayden Vreugdenhil, Fernando Scaglia, Tamas Kozicz, Queenie K G Tan, Bradley S Miller, Iván Martínez-Duncker, Gerard T Berry, Peter Mcwilliams, Eva Morava, Yaw Addo

Faculty, Staff and Students Publications

Background: Growth faltering is prevalent in 96% of children with Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG). Published long-term growth data is extremely limited. Growth and weight patterns of PMM2-CDG children differ from the general population limiting the utility of existing normative growth charts to track development trajectory in comparison to peers with PMM2-CDG.

Objective: Create PMM2-CDG disease-specific height-, weight-, and BMI-for-age reference growth charts (0-20 years).

Methods: De-identified growth data was provided by Frontiers in Congenital Disorders of Glycosylation Consortium, CDG Care, Minnesota Partnership for Biotechnology and Medical Genomics, and Glycomine, Inc. Semi-parametric modeling techniques were used to develop PMM2-CDG-specific …

Plasticity And Language In The Anaesthetized Human Hippocampus, Kalman A Katlowitz, Eric R Cole, Elizabeth A Mickiewicz, Shraddha Shah, Melissa Franch, Joshua A Adkinson, James L Belanger, Raissa K Mathura, Domokos Meszéna, Matthew Mcginley, William Muñoz, Garrett P Banks, Sydney S Cash, Chih-Wei Hsu, Angelique C Paulk, Nicole R Provenza, Andrew J Watrous, Ziv Williams, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Sarah R Heilbronner, Robert Kim, Nuttida Rungratsameetaweemana, Benjamin Y Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

Consciousness is a fundamental component of cognition1, but the degree to which higher-order pattern recognition relies on it remains disputed2,3. Here we demonstrate the persistence of oddball discrimination, semantic processing and online prediction in individuals under general-anaesthesia-induced loss of consciousness4,5. Using high-density Neuropixels microelectrodes6 to record both single-unit and local-field-potential neural activity in the human hippocampus while playing a series of tones to anaesthetized patients, we found that hippocampal neurons and local oscillations retained some detection of oddball tones. This effect size grew over the course of the experiment …

Spatial Transcriptomics Reveals Coordinated Endothelial And Epithelial Activator Protein-1 Activation In Chronic Lung Allograft Dysfunction, Yasufumi Goda, Tatsuhiko Naito, Mudassir M Banday, Andrew S Potter, Igor Odintsov, Kapil Patel, Nicole Davis, Stefi Lee, Amit Gaggar, Ivan Rosas, Gabriel Loor, Don Hayes, Nirmal S Sharma

Faculty, Staff and Students Publications

Chronic lung allograft dysfunction (CLAD) limits long-term lung graft survival, yet its specific gene expression profiles remain unclear. We performed comprehensive spatial transcriptomic analyses of human lungs from CLAD patients, non-CLAD transplant recipients, and non-transplanted controls. In CLAD, AP-1 target genes, including JUNB and FOS, were significantly upregulated in both the epithelium and endothelium, whereas anti-fibrotic genes such as A2M and surfactant proteins (SFTPA1,2) were upregulated in non-CLAD. The lymphocyte population in CLAD was predominantly composed of T cells, with elevated JAK3-IL7R signaling. TNF and IL-17 signaling pathways were commonly activated in both the epithelium and endothelium, with JUNB and …

Systematic Identification Of Cell-Cell Interactions Associated With The Severity Of Patients With Alzheimer’S Disease, Zijian Zhang, Naail Chowdhury, Jing Dong, Lang Wu, Chao Cheng

Faculty, Staff and Students Publications

Background

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder involving dysfunction across multiple brain regions. While accumulating evidence has implicated the roles of diverse cell types, including neurons, glia, and vascular cells in AD pathogenesis, it is still poorly understood how cell type interactions drive or respond to the disease progression and severity.

Objective

This study aimed to systematically characterize cell-type–specific alterations and intercellular communication changes associated with AD progression.

Methods

We leveraged the transcriptome profiling and a previously established statistical framework to present a comprehensive mapping of the cellular interaction landscape in the human brain of AD.

Results …

A Trans-Omics Gene-Smoking Interaction Study Of Lung Cancer Based On Consortium Data, Ning Xie, Xiaowen Xu, Yanru Wang, Aoxuan Wang, Xiang Wang, Xuan Wang, Mengsheng Zhao, Jiacheng Zhou, Yongyue Wei, Manel Esteller, Zhibin Hu, Hongbing Shen, Rayjean J Hung, Christopher I Amos, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang

Faculty, Staff and Students Publications

Rationale: Genetically predicted molecular traits provide a cost-effective approach for identifying biomarkers and uncovering underlying biological mechanisms. We extended this framework to investigate gene-smoking interactions in lung cancer susceptibility.

Objectives: To identify trans-omics gene-smoking interactions affecting lung cancer risk and to assess how biomarkers modify effect of smoking.

Methods: We conducted the first trans-omics gene-smoking interaction study of lung cancer by integrating consortium-scale individual genotype data (27 737 cases vs 449 910 noncases) from the International Lung Cancer OncoArray Consortium (ILCCO-OncoArray), Transdisciplinary Research Into Cancer of the Lung (TRICL), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the …

Malaria In Children At 9 Us Hospitals: 2016-2023, Sesh Alexander Sundararaman, Brianne Roper, Amy K F Davis, Karen L Hanze Villavicencio, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Ziyi Wang, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Objectives: This study set out to describe imported pediatric malaria in the United States over an 8-year period, including patient demographics, clinical outcomes, and risk factors for severe disease.

Methods: A retrospective descriptive study of pediatric patients treated for malaria at 9 hospitals in the United States from 2016 to 2023 was conducted to analyze patient demographics, clinical outcomes, and risk factors for severe malaria.

Results: A total of 171 children were treated across the 9 US hospitals included in this study from 2016 to 2023. Most patients had traveled to West Africa to visit friends and relatives. Fever was …

Early Neurodevelopmental Outcomes In Children With Congenital Heart Disease, Mike Seed, Cynthia Ortinau, Caroline Lee, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Neurodevelopmental impairments are common in children with congenital heart disease.

OBJECTIVES: To compare neurodevelopmental outcomes by cardiac diagnosis and identify associations between medical and social factors and early neurodevelopmental outcomes among children with congenital heart disease.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used neurodevelopmental follow-up data obtained between May 1, 2019, and June 30, 2022, and entered into the Cardiac Neurodevelopmental Outcome Collaborative (CNOC) registry, with linkage to the Pediatric Cardiac Critical Care Consortium registry. Children younger than 30 months from 25 CNOC sites were studied. Data analysis was performed between January 2023 and December 2024.

EXPOSURES: Patients …

Cabozantinib Plus Nivolumab And Ipilimumab In Previously Untreated, Advanced Renal Cell Carcinoma: Final Results And Biomarker Analyses From The Phase Iii Cosmic-313 Study, R J Motzer, M A Reimers, Et Al.

2020-Current year OA Pubs

BACKGROUND: Primary results from COSMIC-313 demonstrated significantly longer progression-free survival (PFS) with first-line cabozantinib plus nivolumab and ipilimumab versus placebo plus nivolumab and ipilimumab in patients with advanced renal cell carcinoma. Final efficacy and safety results, as well as data from exploratory biomarker analyses, are reported here.

PATIENTS AND METHODS: The design, participants, and primary-endpoint PFS outcomes have been reported previously for this phase III, double-blind, randomized (1 : 1) study of cabozantinib or placebo plus nivolumab and ipilimumab in adults with previously untreated, advanced clear cell renal cell carcinoma. The secondary endpoint was overall survival (OS) in the intention-to-treat …

Initial Injury Type And Violent Reinjury, Nicholas Szoko, Daphne Lew, Taylor Kaser, Zoe M Miller, Matt Vogel, Michael A Mancini, Lindsay M Kranker, Christopher Behr, Vicki Moran, Rachel Ancona, Kristen Mueller

2020-Current year OA Pubs

IMPORTANCE: Violent injuries are the leading cause of death among children and young adults in the United States. Violent injury may increase the risk of subsequent injury (ie, violent reinjury), but it is unclear how this risk varies across different injury types (eg, blunt assault, stabbing, firearm).

OBJECTIVE: To describe patterns of violent reinjury across different injury types to inform tailored prevention strategies.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study included patients who presented with violent injuries to 2 adult and 2 pediatric level I trauma centers in St Louis, Missouri, from January 2016 to December 2023.

EXPOSURES: Violent …