Digital Commons Network^™

Evidence For Direct And Sleep-Moderated Relationships Between Aquaporin-4 Genetic Variants And Alzheimer's Disease Phenotypes, Tenielle Porter, Ayeisha Milligan Armstrong, Eleanor K. O'Brien, Vincent Doré, Pierrick Bourgeat, Mitchell Turner, Paul Maruff, Christopher C. Rowe, Belinda M. Brown, Victor L. Villemagne, Stephanie R. Rainey-Smith, Simon M. Laws

Research outputs 2022 to 2026

Introduction: Variants in the aquaporin-4 gene (AQP4) have been associated with Alzheimer's disease (AD) diagnosis, cognition, and brain amyloid beta (Aβ) and may affect the sleep and Aβ relationship. Their association with other AD-related phenotypes/disease progression remain largely unknown. Methods: Associations between AQP4 variants, self-reported sleep measures, and AD-related phenotypes in cognitively unimpaired individuals with evidence of Aβ accumulation were examined using data from the Australian Imaging, Biomarkers and Lifestyle study. Results: AQP4 variants were directly associated with regional brain volumes, atrophy, and cognition. They were also associated with differences in regional brain volumes and atrophy in interaction with sleep …

Nlrp3 Inflammasome: A Link Between Systemic Infection And Alzheimer’S Disease, Tatiana Barichello, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

No abstract provided.

Menopause May Partially Explain Age-Related Increased Risk Of Masld Fibrosis: A Causal Mediation Analysis, Itunu O Sokale, Yan Liu, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

No abstract provided.

Generation And Characterization Of Twist1 Acetyl-Mimic And Acetyl-Deficient Mouse Models, Mary Elmeniawi, Xiaobin Yu, Samuel Wen, Gunjan A Bhatia, Lan Liao, Jianming Xu, Walid D Fakhouri

Faculty, Staff and Students Publications

TWIST1 encodes a highly conserved basic helix–loop–helix transcription factor essential for embryonic development from Drosophila to humans. TWIST1 activity is regulated by post‐translational modifications, including phosphorylation during development and cancer metastasis. Recent cancer studies identified acetylation of lysines K73 and K76 as a novel regulatory modification that shifts TWIST1 from a repressive to an activating state during epithelial‐to‐mesenchymal transition (EMT). However, the developmental and in vivo functions of TWIST1 acetylation remain unknown. To investigate the physiological role, we generated the first acetyl‐deficient Twist1 K73,76R K73,76R and acetyl‐mimic Twist1 K73,76Q K73,76Q mouse models using CRISPR/Cas9‐mediated genome editing. Targeted sequencing confirmed substitutions, …

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 …

Author Correction: Biallelic Variants In The Noncoding Rna Gene Rnu4-2 Cause A Recessive Neurodevelopmental Syndrome With Distinct White Matter Changes, Rocio Rius, Alexander J M Blakes, Yuyang Chen, Joachim De Jonghe, François Lecoquierre, Ruebena Dawes, Benjamin Cogne, Hyung Chul Kim, Javeria R Alvi, Florence Amblard, Morad Ansari, Annabelle Arlt, Christina Austin-Tse, Sarah Baer, Meena Balasubramanian, Elsa V Balton, Giulia Barcia, Ana Beleza-Meireles, Jonathan A Bernstein, Jasmin Beygo, Pierre Blanc, Nuria C Bramswig, Frederik Braun, Daniel Buchzik, Daniel G Calame, Jamie Campbell, Charles Coutton, Chloe A Cunningham, Nitsuh Dargie, Christel Depienne, Katrina M Dipple, Anne Dieux, Abhijit Dixit, Lauren Dreyer, Haowei Du, Salima El Chehadeh, Michael Field, Lisa J Ewans, Vanessa Geiger, Richard A Gibbs, Ian Glass, Olivier Grunewald, Paul Gueguen, Tobias B Haack, Hamza Hadj Abdallah, Radu Harbuz, Ingo Helbig, Judit Horvath, Alexander Hustinx, Bertrand Isidor, Marie-Line Jacquemont, Fraser Jamie, Médéric Jeanne, Riley Kessler, Hannah Klinkhammer, G Christoph Korenke, Urania Kotzaeridou, Peter Krawitz, Steven Laurie, Richard J Leventer, Rebecca J Levy, James R Lupski, Pierre Marijon, Kaitlin E Mcginnis, Rodrigo Mendez, Olfa Messaoud, Caroline Nava, Mevyn Nizard, Anne O'Donnell-Luria, Melanie C O'Leary, Simone Olivieri, Amitav Parida, Davut Pehlivan, Anna Jenne Prentice, Jennifer E Posey, Chloe M Reuter, Véronique Satre, Caroline Schluth-Bolard, Thomas Smol, Tipu Sultan, John Taylor, Christel Thauvin-Robinet, Julien Thevenon, Eloise Uebergang, Sandra Ueberberg, Catherine Vincent-Delorme, Evangeline Wassmer, Emma Westwood, Matthew T Wheeler, Elif Yilmaz Gulec, Adeline Vanderver, Arastoo Vossough, Stephan J Sanders, Siddharth Banka, Gregory M Findlay, Daniel G Macarthur, Cas Simons, Nicola Whiffin

Faculty, Staff and Students Publications

No abstract provided.

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 …

Ilae-Yes Global Webinar Series: Integrating Clinical And Basic Science In Epilepsy Research, Cecilie G Nome, Parthvi Ravat, Fabrice Bartolomei, Marco De Curtis, Rossella Di Sapia, Marian Galovic, Maria Gogou, Lukas Imbach, Julia Jacobs, Katja Kobow, Alice D Lam, Christos Panagiotis Lisgaras, Elisa Micalizzi, Eleni Nikalexi, Jeffrey L Noebels, Jeanne T Paz, Avtar Singh Roopra, Sally Shaaban, Laurent Sheybani, Shobi Sivathamboo, Ana Suller Marti, Adam Williamson, Naoto Kuroda

Faculty, Staff and Students Publications

Bridging clinical and basic research is increasingly recognized as a priority in the epilepsy field, yet opportunities for integration remain limited by the time, space, and financial constraints of scientific meetings. To address this gap, the Research Task Force of the Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES) organized a free global webinar series designed to promote translational dialogue and provide accessible research education for early-career clinicians, researchers, and physician-scientists. Based on a preliminary ILAE-YES community survey, eight topics of high interest were selected: (1) epigenetics, (2) EEG biomarkers, (3) ictogenesis, (4) thalamo-cortical network, (5) sudden unexpected …

Hematologic Markers And Machine Learning In Predicting Placenta Accreta: A Case-Control Study, Michael D Jochum, Kelly D Albrecht, Yamely Mendez Martinez, Victoria Zhang, Sanmay Sarada, Brian Burnett, Christina C Reed, Karin A Fox, Amir A Shamshirsaz, Michael A Belfort, Jessian L Munoz, Hennie A Lombaard

Faculty, Staff and Students Publications

Objective: This study aims to enhance antenatal detection of placenta accreta spectrum (PAS) and predict severe hemorrhage at delivery using machine learning by evaluating the association between antenatal hematologic index trends across trimesters, imaging markers, and patient history.

Methods: We retrospectively analyzed 2017-2023 data from a PAS referral center, including demographics, laboratory results, ultrasounds, and outcomes. Patients with confirmed PAS (cases) were compared to those with antenatal risk but no histopathologic evidence of PAS (controls). Statistical analyses and machine learning models were developed to predict PAS. We also used machine learning to predict severe hemorrhage (>1500 mL) in the …

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.

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 …

Anterior Cutaneous Nerve Entrapment Syndrome From Glucagon-Like Peptide-1 Receptor Agonist Injection, Neha Singh, Elisa Chaparro, Jordan Michael Shapiro, Emanuel Narcis Husu

Faculty, Staff and Students Publications

Anterior cutaneous nerve entrapment syndrome (ACNES) is an underdiagnosed cause of abdominal pain. We report the first documented ACNES case following subcutaneous administration of glucagon-like peptide-1 receptor agonist. A 44-year-old man developed focal, neuropathic abdominal pain coinciding with initiation of tirzepatide injections. Clinical examination confirmed ACNES diagnosis, and pain improved after relocating injections away from the abdomen and initiating multimodal pharmacotherapy. This case emphasizes the need to consider ACNES in patients endorsing focal abdominal pain with concurrent use of glucagon-like peptide-1 therapy and highlights injection site modification as a simple, effective management strategy while exercising self-restraint with respect to workup.

Ldm-Morph: Latent Diffusion Model Guided Deformable Image Registration, Jiong Wu, Tinsu Pan, Kuang Gong

Faculty, Staff and Student Publications

Deformable image registration plays an essential role in various medical image tasks. Existing deep learning-based deformable registration frameworks primarily utilize convolutional neural networks (CNNs) or Transformers to learn features to predict the deformations. However, the lack of semantic information in the learned features limits the registration performance. Furthermore, the similarity metric of the loss function is often evaluated only in the pixel space, which ignores the matching of high-level anatomical features and can lead to deformation folding. To address these issues, in this work, we proposed LDM-Morph, an unsupervised deformable registration algorithm for medical image registration. LDM-Morph integrated features extracted …

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 …

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 …

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 …

Public Attitudes Toward Cascade Genetic Screening In The United States, Hadley Stevens Smith, Emilie S Zoltick, Madison R Hickingbotham, Emily S Bonkowski, Stacey Pereira, Tara A Lavelle, David L Veenstra, Amy L Mcguire, Katherine E Bonini, Leila Jamal

Center for Medical Ethics and Health Policy Staff Publications

Introduction: After a patient receives genetic test results that indicate an actionable health condition, cascade genetic screening (CGS) is the process of evaluating the patient's relatives for a potentially elevated genetic risk of disease. The United States primarily relies on patients to communicate with their relatives, resulting in suboptimal rates of risk communication, familial genetic testing uptake, and risk-reducing interventions. There is ongoing debate about whether and how best to inform relatives of a potentially increased genetic risk.

Methods: We conducted a nationally representative survey of US adults to assess attitudes toward informing at-risk relatives, acceptability of system-mediated communication, and …

Rethinking Ethics For An Era Of Trusted Computational Tools, Kristin M Kostick-Quenet, Meghan Hurley, John Herrington, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Computer perception (CP) technologies are poised to deliver near real-time behavioral insights with high precision. As technical barriers recede, our field's ethical focus must shift from "Can we trust the data?" to "Should we use it here, and how?" We propose a contextual ethics framework that: (1) defines the appropriate scope of CP integration; (2) advocates codesigned roadmaps to manage expectations and epistemic conflict; (3) expands evaluation beyond performance metrics to humanistic outcomes; and (4) anticipates future high performance systems to safeguard dignity, empathy, and shared decision-making in clinical care.

Rethinking Flow: The Paradox Of Renoprotection Without Increased Renal Blood Flow In Cardiopulmonary Bypass, Shiksha Mohan, Ronald A Shaju, Sharan Misra, Titiksha Sharma, Veeraj K Sirivolu, Abhinav Rajkumar, Anthony Rodas-Camacho, Aizah Zaidi, Dhruv Dhingra, Ilma Khan, Rishav Bhattacharya, Vishal Pancholy, Shivam Banerjee, Shreyo Ghosh, Shiyi Li, Kenneth K Liao, Carl P Walther, Nandan K Mondal

Faculty, Staff and Students Publications

No abstract provided.

Perinatal Mental Health Screening And Care Among Those With Pregnancy Complications, Alison N Goulding, Terri L Fletcher, Emily S Miller

Faculty, Staff and Students Publications

Perinatal mental health conditions are common and, without effective treatment, can contribute to adverse maternal and child outcomes. In the United States, mental health conditions are a leading cause of maternal morbidity and mortality, contributing to over 20% of pregnancy-related deaths. This expert review aims to assess current literature and provide recommendations regarding mental health care in high-risk patients who experience pregnancy complications. Individuals experiencing pregnancy complications are at increased risk for perinatal mental health conditions, including depression, anxiety, and post-traumatic stress disorder, as compared to those with uncomplicated pregnancies. Despite this increased disease burden, there is limited research on …

Rocatinlimab As A Novel Treatment Strategy For Atopic Dermatitis, Haylee Whyde, Evan Blazek, Macy Davis, Parker George, Alex Lowery, Connor Dains, Brenna Hissong, David Koh

Pharmacy and Wellness Review

Atopic dermatitis is a common chronic inflammatory skin disease that affects millions of children and adults in the United States. Atopic dermatitis is characterized by recurrent pruritus, erythema, and relapsing symptoms that can significantly impair quality of life. The pathophysiology of atopic dermatitis involves epidermal barrier dysfunction, immune dysregulation, and genetic susceptibility. Atopic dermatitis guidelines follow a stepwise approach that begins with a severity assessment, trigger avoidance, and nonpharmacologic and pharmacologic treatments. First-line therapies include topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and emollients. Crisaborole and topical ruxolitinib are used for mild-to-moderate disease when prior therapy has been inadequate. Monoclonal …

Choline Counteracts Pregnancy Undernutrition-Associated Colitis In Sheep By Restoring Microbiota Driven Bile Acid Metabolism, Weibin Wu, Peng Jiao, Yamei Gu, Huizhen Lu, Caiyun Fan, Zheng Sun, Lizhuang Hao, Shengyong Mao, Jianbo Cheng, Yanfeng Xue

Faculty, Staff and Students Publications

High-fertility sheep experience undernutrition during late gestation, which induces body metabolic disruption and intestinal inflammation. Crucially, the gut microbiota-bile acid axis is a promising intestinal inflammation target, but how choline modulates this axis in livestock enteritis is unknown. This study investigated choline's protective mechanisms against undernutrition-induced intestinal inflammation in sheep, focusing on gut microbiota and bile acid regulation. Choline consistently alleviates colitis severity, restores epithelial barrier integrity, and suppresses intestinal inflammation. These protective effects are accompanied by pronounced remodeling of the colonic microbial ecosystem, characterized by the enrichment of Clostridiales bacterium to elevate bile salt hydrolase activity and regulate bile …

Evaluating The Market Withdrawal Of Andexanet Alfa, Jordyn Linfield, Addisyn Cooper, Alexander Defranco, Emma Gerding, Jessica Kelley, Tyler Henney, Connor Dains, Brenna Hissong, Brittany Bates

Pharmacy and Wellness Review

The coagulation cascade comprises intrinsic, extrinsic, and common pathways that converge when thrombin converts fibrinogen (factor I) into fibrin, leading to fibrin mesh formation, stabilization of the platelet plug, and ultimately thrombus formation. Inhibition of the coagulation cascade can be achieved with a variety of anticoagulant medications, including direct oral anticoagulants (DOACs). The mechanism of action of DOACs is to inhibit either factor Xa or thrombin. Reversal of anticoagulation remains an important clinical consideration when managing patients on DOACs who experience serious bleeding events. Andexanet alfa is a recombinant, modified human factor Xa protein previously indicated for patients receiving rivaroxaban …

Toxitarget: A Multi-Omics Database For Toxicant-Responsive Molecular Targets, Ravindra Kumar, Tianyi Fu, Prashant Kumar Kuntala, Benpeng Miao, Shuhua Fu, Daofeng Li, Frederick L Tyson, Marisa S Bartolomei, Cheryl L Walker, Ting Wang, Bo A Zhang

Faculty, Staff and Students Publications

Environmental toxicant exposures can induce widespread alterations in both the transcriptome and epigenome of mammals, and directly contribute to the increased risk of various diseases, including cardiovascular disorders, cancer, and neurological disorders. To evaluate how early-life toxicants produce long-term impacts on the transcriptome and epigenome in mice, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 3607 multi-omics datasets from longitudinal studies in mice. The molecular changes in responding to distinct environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di-2-ethylhexyl phthalate (DEHP), dioxin (TCDD), …

Icam1high Neutrophils Sculpt Tumor Evolution And Metastasis Through Symbiotic Adhesion And Reverse Migration, Ling Wu, Zhan Xu, Jun Wang, Fengshuo Liu, Yunfeng Ding, Yang Gao, Siyue Wang, Jun Liu, Hilda L Chan, Weiguo Wu, Yi-Hsuan Wu, Liqun Yu, Xiaoxin Hao, Xuan Li, David G Edwards, Cher Sha, Tobie D Lee, Nan Guan, Sergio Aguirre, Luis Becerra-Dominguez, Dane Hoffman, Xiang Chen, Charlotte Helena Rivas, Xiaoyuan G Yan, Igor L Bado, Weijie Zhang, Qian Zhu, Arun Sreekumar, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Neutrophils are a prominent component of the tumor microenvironment that can have both pro- and anti-tumor functions. By analyzing neutrophils across different human cancers, we revealed an ICAM1high subset enriched in the tumor microenvironment, which were also observed in murine triple negative breast cancer (TNBC) models. ICAM1high neutrophils exhibited an enhanced capacity for cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion conferred mutual advantages to both cell types. In contrast, cancer cells with mesenchymal-like phenotypes were vulnerable to neutrophil-mediated cytotoxicity due to decreased cell adhesion and elastase resistance. These opposite effects drove tumor evolution toward a …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …