Medical Sciences Commons^™

Oxytocin Dynamics And Synchrony In Mother-Child Dyads: Long-Term Neuroendocrine Effects Of Maternal Institutionalization, Olga V Burenkova, Ekaterina M Shurdova, Victoria Manasevich, Marina Norkina, Polina E Pashkina, Aleksei A Podturkin, Alena Vodneva, Marina A Zhukova, Elena L Grigorenko

Faculty, Staff and Student Publications

Early institutional care (IC; orphanage) is a severe form of early psychosocial deprivation with documented long-term effects on social and caregiving functioning. Despite longstanding interest in oxytocin (OT) as a key neuroendocrine modulator of affiliative behavior and stress, OT dynamics and synchrony during mother-child interaction among mothers with IC history remain poorly understood. To our knowledge, this is the first study to characterize maternal and child OT responses and dyadic OT covariation in this population. We measured salivary OT in mothers with IC history and mothers raised in biological family care (BFC), and in their children, at baseline and after …

Practice Patterns In Pediatric Cardiothoracic Presurgical Conferences: A Multicenter Survey Study, Britney Reed, Poonam Puranik, Andrew Rodenbarger, Mira Trivedi, Dilachew A Adebo, Gary Beasley, Louis Bezold, M Jay Campbell, Michael R Carr, Joshua Daily, Mark Debrunner, Erica Del Grippo, Carlen G Fifer, Timothy M Hoffman, Susan R Hupp, Joshua D Kurtz, Gira Morchi, Carl Owada, Renuka Peterson, Michael D Puchalski, Ryan A Romans, Arwa Saidi, Rajesh U Shenoy, Anoop K Singh, Robert D Tunks, Thomas M Yohannan, Carolyn M Wilhelm, Jyoti K Patel

Faculty, Staff and Student Publications

Pediatric cardiothoracic surgeries are high-stakes, complex procedures, typically undergoing prior review at multidisciplinary conferences. This study evaluates practice patterns of conferences throughout the United States (US). Surveys were distributed to fellowship program directors or division directors in 124 US pediatric cardiology centers seeking information on conference logistics, fellow roles, quality improvement (QI), and satisfaction. All 47 responding centers (response rate 38%) conduct presurgical conferences, mostly on a weekly basis (92%) lasting 60-120 min (79%). The conferences are solely virtual (19%) or hybrid (81%). High-volume centers (> 300 surgical cases/year) are more likely to hold multiple conferences (13/20 vs 7/27, p <  0.01) and less likely to designate a moderator (11/20 vs 22/26, p = 0.027). Categorical pediatric cardiology fellows at 33 centers present clinical data (97%), echocardiograms (85%), catheterizations (82%), and cross-sectional imaging (39%), typically beginning in their first year. Most centers report that minor (98%) or major changes (51%) are made to patient management at least "sometimes." Responders rate conferences as very important (median 10/10 on a 10-point Likert scale, IQR 9-10), but satisfaction is more modest (median 7/10, IQR 7-9). Only 17% of centers have a formal QI process. Comments from 42 centers reveal positive themes of collaboration (68%) but also concerns about lengthy (30%) or inefficient (36%) discussion. Conclusions: This survey highlights common practices for pediatric cardiothoracic presurgical conferences. Conferences are collaborative and seen as highly impactful. However, satisfaction varies, and QI efforts are infrequent. These findings highlight opportunities for process improvement and standardization.

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 …

Socio-Ecological Models As A Framework For 21st-Century Genetic Counseling, Shana L. Merrill, Rebecca Mueller

College of Life Sciences Faculty Papers

Socio-ecological models and the related concepts of micro-, meso-, and macro-level practice are commonly used in the fields of social work and public health yet have not been thoroughly conceptualized for application to genetic counseling practice, research, and training. The field of genetic counseling is currently undergoing significant expansion with more genetic counseling training programs, greater variation in genetic counselor job roles, and genetic counselors practicing in more globally dispersed regions. It is therefore a critical time to conceptualize and tailor relevant theoretical frameworks to unify and guide the evolving field of genetic counseling. In this paper, we posit that …

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: …

Assessment Of Knee Laxity After Retrograde Intramedullary Nailing For Periprosthetic Distal Femur Fractures: A Cadaveric Study., Joshua P Rainey, Lucas A Anderson, Ian M Duensing, Jeremy M Gililland, Patrick J Kellam

Faculty, Staff and Student Publications

Objectives: Periprosthetic distal femur fractures have grown in volume because the rate of primary total knee arthroplasty (TKA) has increased. These injuries are increasingly treated with intramedullary nailing (IMN), but knee instability after retrograde IMN has not been well studied. A cadaveric study was performed to investigate TKA balance after retrograde femoral IMN. The main hypothesis was that retrograde femoral IMN preparation would lead to increased flexion space laxity.

Methods: A medial parapatellar approach and measured resection TKA technique were performed in 8 cadaveric knees. A tensioner was used to measure the flexion and extension spaces in millimeters and the …

The Wake Of Addiction: Pharmacological Strategies For Sleep Disturbances In Stimulant Use Disorders, A Systematic Review, Isabella G Bourtin, Douglas J Calvillo, Jessica C Badawi, Joy M Schmitz, Scott D Lane, Jin Ho Yoon, Heather E Webber

Faculty, Staff and Student Publications

Background: A systematic review was conducted following PRISMA guidelines to identify human studies investigating pharmacological interventions and reported sleep outcomes among individuals with CUD or MUD.

Methods: PubMed and APA PsycInfo were searched from inception to January 2025 and risk of bias was assessed. Articles were included if they included human participants with either cocaine or methamphetamine dependence, administered a pharmacological treatment, and reported night-time sleep as an outcome using at least one rigorous measurement tool. Articles were excluded if they included animals, did not include pharmacological intervention (e.g., supplements or behavioral treatments), or only assessed baseline sleep or if …

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 …

Steroid Receptor Coactivators In Immunity – From Function To Emerging Translational Opportunities, Yosef Gilad, David M Lonard

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) comprise a family of three paralogous proteins. As transcriptional coactivators SRCs are essential for enabling the full transcriptional output of nuclear receptors (NRs). They regulate the transcriptional activity of nearly all NRs as well as a wide range of non-NR transcription factors. The central role of SRCs in gene regulation is reflected in their broad impact on major physiological and pathological processes, such as development, reproduction, metabolism, immunity and cancer. Although the major impact of SRCs on human health and disease established them as attractive therapeutic targets, their effective pharmacological targeting remained a challenge for nearly …

Mindful Self-Compassion To Reduce Pain Interference Among Adults With Osteogenesis Imperfecta, Amena Sediqi, Roya Al-Khalili, Saunya Dover, Corien Peeters, Adam Khalif, V Reid Sutton, Frank Rauch, Brendan Lee, Eric A Storch, Marie-Eve Robinson

Faculty, Staff and Students Publications

Between 60 and 80% of adults with osteogenesis imperfecta (OI) experience chronic pain and associated interference. Currently available pain therapies often provide marginal efficacy. Mindful self-compassion (MSC) has emerged as a promising intervention for coping with chronic pain. We conducted a single-center 8-week pilot intervention study to assess the feasibility and acceptability of a MSC program among adults with OI and co-occurring chronic pain. Individuals attended the validated MSC course consisting of 8 weekly virtual 2-h sessions. Participants completed a battery of validated questionnaires assessing pain, various aspects of well-being, and physical function at baseline and post-intervention. Participants wore the …

Functional Genomics Studies Of Psychiatric Disorders In Individuals Of Latin American Populations: A Scoping Review, Luz M Porras, Isabelle Rodríguez-Lausell, Gabriel Iglesias-Maldonado, Emily Val F Tuliao, Gabriela Martínez, Chelsey Leveque, Julian Tobon, Rachel Eloy, Sintia Belangero, Cynthia M Bulik, Camila M Loureiro, Carolina Muniz Carvalho, Vanessa Ota, Diego Luiz Rovaris, Eric A Storch, Eva Maria Trujillo-Chi Vacuan, Maria M Velasquez, Latin American Genomics Consortium, Marcos L Santoro, Humberto Nicolini, Elizabeth G Atkinson, Janitza L Montalvo-Ortiz, Paola Giusti-Rodríguez

Faculty, Staff and Students Publications

Over the past 15 years, genetic studies of psychiatric disorders have provided important insight into the contribution of both common variants of small effect, as well as rare exonic and copy number variants with large effect sizes. Genome-wide association studies (GWAS) allow us to understand the intricate polygenicity characteristic of many psychiatric disorders. However, a considerable proportion of single nucleotide polymorphisms (SNPs) implicated in these disorders localize to the non-coding regions of the genome. Unraveling the molecular mechanisms that underlie the etiology of psychiatric illnesses requires integration using functional genomics approaches. Functional genomics methods are critical for developing a mechanistic …

Structural Determinants Of Ligand Response Specificity In The Mast Cell Activating Gpcr, Mrgprx2, Abiodun Adefola R Adeosun, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The mast cell-specific G-protein-coupled receptor (GPCR) MRGPRX2 (Mas-Related G Protein-coupled Receptor X2) has roles in itch and pain, and it mediates clinically relevant allergy-like responses to a diverse assortment of drugs. The varied responses of individuals to MRGPRX2 agonists, leading to drug hypersensitivity reactions in some cases, suggests the presence of consequential variants in the population. However, genetic associations with drug responses are poorly understood. We used heterologously-expressed MRGPRX2 to investigate the effect of 18 naturally occurring non-synonymous single nucleotide polymorphisms on activation by representative compounds from several classes, including neuropeptides, opioid agonists, antibiotics, neuromuscular blocking agents, and polycationic aromatic …

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 …

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.

Prognostic Value Of Stress Perfusion Cardiac Magnetic Resonance Imaging In Kawasaki Disease With Coronary Artery Aneurysms: A 10-Year Retrospective Cohort Study, Alexander J Kiener, S Kristen Sexson Tejtel, Aimee Liou, Carolyn A Altman, Tam T Doan

Faculty, Staff and Students Publications

Background: Kawasaki disease (KD) with coronary artery aneurysms (CAA) places patients at risk for myocardial ischemia and major cardiac events (MCE). While stress perfusion cardiac magnetic resonance imaging (spCMR) is used for surveillance, its prognostic value has not been established.

Methods: We conducted a retrospective cohort study of KD patients (AHA risk levels 3-5) who underwent clinically indicated vasodilator spCMR at a tertiary pediatric center between October 2014 and December 2024. We evaluated inducible perfusion defects, late gadolinium enhancement (LGE), ventricular function, and MCE (myocardial infarction, ventricular dysfunction, arrhythmia, revascularization, transplant, or death). We performed Cox regression and Kaplan-Meier analyses …

A Phase 4, Open-Label, Non-Randomized, Multicenter Study To Evaluate Efficacy (And Safety) Of Intravenous Administration Of Optison For Contrast-Enhanced Echocardiography In Pediatric Patients, Arash Sabati, Shuo Wang, Pushpa Shivaram, Joshua Hawley, David Thompson, Francine Erenberg, Shelby Kutty, Aparna Kulkarni, Tam T Doan, Joshua D Robinson

Faculty, Staff and Students Publications

Contrast-enhanced echocardiography (CE-echo) is commonly used in adult patients to optimize endocardial border delineation (EBD) but there is limited experience in children. A prospective, open-label, non-randomized, multicenter study was performed to evaluate the efficacy of intravenous Optison for CE-echo in pediatric patients and determine the optimal dose of Optison. Subjects ≥ 9 and <  18 years with suboptimal echocardiograms (defined as ≥ 2 contiguous segments that could not be adequately visualized) were enrolled. After a baseline non-contrast echocardiogram (NC-echo), CE-echo was performed with 2 dose levels of Optison based on patient weight. The primary endpoint was visualization of the LV wall segments (LVWS) in apical 2- and 4-chamber views. An EBD score was calculated by assigning a value from 0 (no visualization) to 3 (optimal visualization) for 12 LVWS. 37 subjects across 8 sites completed the study. 30 had complete echocardiograms at both dose levels. 2 patients had usable images at dose 2 only. Mean age was 13.4 years (± 2.6) with 23 males (62%). Mean weight was 73.9 kg (± 36.8) with wide distribution of weight (interquartile range of 42-102 kg). There were 8 patients under 40 kg. Most subjects had a prior medical/surgical history (n = 33, 89%). Both dose levels of Optison CE-echo improved the number of LVWS visualized from 3.7 ± 1.1 on NC-echo to 10.0 ± 0.1 with dose 1 (p <  0.001) and 10.5 ± 0.1 with dose 2 (p <  0.001). EBD score also improved at both dose levels from 11.9 ± 2.5 for NC-echo to 28.5 ± 1.7 for dose 1 (p <  0.001) and 30.2 ± 8.4 for dose 2 (p <  0.001). The number of suboptimal echocardiograms improved from 92.3% ± 10.7 in NC-echo to 26.2% ± 9 with dose 1 (p <  0.001) and 30.8% ± 4.5 with dose 2 (p <  0.001). CE-echo with intravenous Optison in pediatric patients improved the number of LVWS visualized, improved EBD score, and reduced the number of suboptimal echocardiograms at both dosages used in this study. Intravenous Optison can improve LV visualization in pediatric patients with suboptimal echocardiograms.

Myocardial T1 And T2 Values Are Associated With Patient Age In Healthy Pediatric Heart Transplant Recipients, Andrew A Lawson, Robyn G Lottes, Defne Magnetta, Andrada Popescu, Kae Watanabe, Cynthia K Rigsby, Michael Markl, Nazia Husain

Faculty, Staff and Students Publications

Background: In pediatric heart transplant recipients (PHTR), myocardial T1 and T2 values are elevated in the setting of acute rejection and with cardiac allograft vasculopathy. In normal, healthy children, T1 and T2 values vary with patient age. Our goal was to identify associations between T1, extracellular volume fraction (ECV), and T2 values and patient- and donor-characteristics in PHTR without history of significant graft pathology.

Methods: We performed a single-center, retrospective chart review of consecutive cardiac magnetic resonance (CMR) studies in PHTR from 2017 to 2023. Exclusion criteria were a prior CMR during the study period, history of any prior antibody-mediated …

How To … Coach Problem Representation To Strengthen Diagnostic Reasoning In Trainees, Cody Clary, Adam Cohen, Satid Thammasitboon

Faculty, Staff and Students Publications

Problem representation (PR) is a concise synthesis of clinical information that captures the core diagnostic problem in a single statement, often referred to as a 'one-liner'. Although central to diagnostic reasoning, this skill is frequently underdeveloped in medical training. Many trainees struggle to transform clinical data into meaningful representations, which can hinder communication, diagnostic reasoning and patient safety. The Assessment of Reasoning Tool-Reconstructed (ART-R) provides a structured framework that educators can adapt as a coaching rubric to strengthen PR during clinical teaching. Using the ART-R, faculty can guide trainees to refine their PR by focusing on three elements: (1) clarity …

Paid Employment And Ability To Work Among People Receiving Dialysis: A Systematic Review Of Qualitative Studies, Ao Zhang, Adam Martin, Karine Manera, Chandana Guha, Martin Howell, Patrizia Natale, Nicole Scholes-Robertson, Dharshana Sabanayagam, Adeera Levin, Wolfgang Winkelmayer, Kevin F Erickson, Germaine Wong, Allison Jaure, Anita Van Zwieten

Faculty, Staff and Students Publications

Rationale & objective: People receiving dialysis have reduced workforce participation, which can affect mental well-being and exacerbate the financial burden of dialysis. This study describes the experiences and perspectives of people receiving dialysis on employment and their ability to work.

Study design: Systematic review and thematic synthesis of qualitative studies.

Setting & study populations: Adults aged 16 years and over receiving dialysis.

Search strategy & sources: MEDLINE, Embase, and PsycINFO were searched to May 2025 for qualitative and mixed-methods studies that reported the perspectives of people receiving dialysis on employment or ability to work.

Data extraction: Text from results and …

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 …

Kidney Disease And Heart Failure: Recent Advances And Current Challenges: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Carolyn S P Lam, Biykem Bozkurt, David Z I Cherney, Justin A Ezekowitz, Meg J Jardine, Sadiya S Khan, Magdalena Madero, Mark J Sarnak, Jozine M Ter Maaten, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Nisha Bansal

Faculty, Staff and Students Publications

Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, which elevates the risks of hospitalization, disease progression, and death. Despite advances in treating each condition independently, many challenges remain in diagnosing and managing them in combination. In March 2024, Kidney Disease: Improving Global Outcomes (KDIGO) held the Controversies Conference on Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Discussions highlighted the complex, bidirectional relationship between HF and CKD, including shared risk factors and overlapping pathophysiology as well as nuances in interpreting biomarkers such as natriuretic peptides and serum creatinine. Sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and emerging …

Corneal Innervation Research At A Crossroads: A Tool-Driven Roadmap For The Future, Anna Matynia, Ian D Meng, Brian M Davis, Stephen C Pflugfelder, Anat Galor, Victor L Perez, Elizabeth R Felix, Pedram Hamrah, Pantelimon Rompolas, Raul E Ruiz-Lozano, Shamsuddin A Bhuiyan, Kaveh Moghbeli, Evangelia Semizoglou, William Renthal, Harinder Singh, Jishnu Das, Marcin Golczak, Mary Ann Stepp, Catherine W Morgans, Cintia S De Paiva, Carl Y Saab, Igor Spigelman, Rony R Sayegh, Tally M Largent-Milnes, Hao Wu, Wenqin Luo, Sreya Mitra, Heesuk Yoo, Sina Farsiu, Sejiro Littleton, Eden Jacob, Matthew T Mcpheeters, Maryse Lapierre-Landry, Jordan J Smith, Xi Wang, Roxana Florea, Made Airanthi K Widjaja-Adhi, Scott Holmes, Zane Zemborain, Kate E T Laise, Nicholas J Pondelis, Ki-Soo Jeong, Rui Chen, Michael W Jenkins, Vivian Lee, Eric A Moulton, Deborah S Jacobs, Sue A Aicher, Anthony J St Leger, Daniel R Saban

Faculty, Staff and Students Publications

Corneal innervation research has faced long-standing clinical challenges that only recent technological breakthroughs now make tractable. Advances in single-cell analysis, viral vectors, clinical imaging, and artificial intelligence provide integrated approaches for uncovering molecular mechanisms underlying functional outcomes and facilitating clinical applications. The National Eye Institute's U01-funded consortium on ocular surface innervation addresses major knowledge gaps in characterizing corneal-projecting neurons, understanding neuroimmune and epithelial interactions in the cornea, and translating animal model findings to human pathology. The unique properties of the cornea (transparent, avascular, and densely innervated) make it ideal for neurobiology research on peripheral and central sensory processing. Through a …

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 …

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 …

Human Neuronal Firing Varies With The Frequency Of Local Field Potential Oscillations, Zahra Jourahmad, Raissa K Mathura, Layth S Mattar, Melissa C Franch, Danika L Paulo, Mohammed Hasen, Nicole R Provenza, Benjamin Y Hayden, Sameer A Sheth, Eleonora Bartoli, Andrew J Watrous

Faculty, Staff and Students Publications

Neural oscillations play a critical role in shaping neuronal firing patterns. While phase-locked neuronal firing ("phase tuning") has been extensively studied in animal models and human invasive recordings, much less is known about whether neurons show preferential firing at specific oscillatory frequencies, termed frequency tuning. Here, we employ human intracranial recordings across several brain regions including hippocampus, entorhinal cortex, anterior and posterior cingulate cortex, and orbitofrontal cortex to test the hypothesis that neurons exhibit frequency-specific firing. We analyzed 357 single units recorded simultaneously with local field potentials in 19 neurosurgical patients during awake resting. We estimated the instantaneous frequency of …

Comprehensive Proteogenomic Characterization Reveals Clinically Relevant Molecular Subtypes Associated With Medulloblastoma Progression, Seong-Min Park, Kyung-Hee Kim, Jong Hyuk Yoon, Fulvio D'Angelo, Seung Ah Choi, Chan Il Kim, Harim Koo, Seungmin Park, Hyondeog Kim, Sreeja Sundara Raj, Sung Soo Kim, Ae Kyung Park, Eun Jung Koh, Seong-Ik Kim, Yu-Mi Shim, Lee Kwang-Hoon, Eric Eunshik Kim, Ji Hoon Phi, Yeon Suk Jo, Do Hyun Nam, Daehee Hwang, Do Young Hyeon, Sunghyun Huh, Hyung Joon Kwon, Seokjun Ha, Sanha Park, Hyeji Shin, Jeong Taik Kwon, Heon Yoo, Ho-Shin Gwak, Michael D Taylor, Bong Jin Park, Jason K Sa, Youngwook Kim, Antonio Iavarone, Sung-Hye Park, Seung-Ki Kim, Jong Bae Park

Faculty, Staff and Students Publications

Current treatment strategies for medulloblastoma remain ineffective owing to extensive tumor heterogeneity. We generated five platforms of omics data including liquid chromatography and mass spectrometry-based proteome and performed integrated multi-omic characterization to improve the conventional molecular classification of medulloblastoma. We identified seven refined distinct subtypes. The sonic hedgehog (SHH) group was reclassified into two subgroups, SHHα and SHHβ, whereas group 4 was divided into three subgroups, G4α, G4β, and G4γ. SHH and group 4 subtypes exhibit two distinct neuronal differentiation trajectories: granular neuron and unipolar brush cell differentiation (SHHβ and G4γ, respectively), both of which associated with more favorable clinical …

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 …

Comparison Of Different “Familial Chylomicronemia Syndrome” Clinical Diagnosis Scoring Systems In Patients With Persistent Chylomicronemia, Diane Brisson, Miriam Larouche, Nathalie Laflamme, Seyedmohammad Saadatagah, Jean Bergeron, Christie M Ballantyne, Daniel Gaudet

Faculty, Staff and Students Publications

Background: Chylomicronemia is associated with extreme hypertriglyceridemia and an increased risk of acute pancreatitis and cardiometabolic complications. Rarely, chylomicronemia persists despite control of secondary causes and conventional treatments. The most severe form of persistent chylomicronemia (PC) is familial chylomicronemia syndrome (FCS). Diagnosis scoring systems have been developed to help clinicians differentiate FCS from other causes of chylomicronemia.

Objective: To assess the ability of FCS diagnosis scoring systems to discriminate FCS from other forms of PC.

Methods: This study included 413 Caucasians presenting a history of chylomicronemia, among whom 65 (15.7%) met the criteria of PC. The performance of 3 FCS …

Validity And Utility Of A Single-Item Patient-Reported Measure Of Treatment-Related Bother In Rheumatoid Arthritis: A Cross-Sectional Omeract Study, Dorthe B Berthelsen, Tobias Haugegaard, Mohammed M Kamso, Peter Tugwell, Lee S Simon, John P A Ioannidis, Caroline Flurey, Maarten Boers, Marieke Voshaar, Pam Richards, Beverly Shea, Daniel E Furst, Jasvinder A Singh, Randall Stevens, Thasia Woodworth, Susan J Bartlett, Glen S Hazlewood, Robin Christensen

Faculty, Staff and Students Publications

Objectives: To assess the construct validity of a modified single-item measure of bother due to side effects (the GP5 item) from the Functional Assessment of Chronic Illness Therapy (FACIT) system by comparing it to current symptomatic side effects from the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PROCTCAE) reported by patients with rheumatoid arthritis (RA).

Methods: Through a cross-sectional, web-based survey we collected information on the frequency of symptomatic side effects and bother from side effects related to RA medications. We applied multiple correspondence analysis (MCA) to reduce 80 symptomatic side effects into key dimensions (≥5% of …