Digital Commons Network^™

The Soft Cluster Score As A Multifaceted Predictive Model For Postoperative Outcomes, Gwendolyn B Henry, Spoorthi Kamepalli, Carter J Burns, Jeremy Birkmire, George Cholankeril, Avegail Flores, John A Goss, Abbas Rana

Faculty, Staff and Students Publications

Background: Consideration of both donor and recipient factors at the time of an organ offer is crucial in achieving the most optimal outcome given the shortage of available donor organs and waitlist mortality risk. Our aim was to achieve a comprehensive risk assessment for liver transplant patients by creating a series of independent risk index equations for 6 distinct posttransplant endpoints in the transplant continuum of care.

Methods: The Survival Outcomes Following Liver Transplantation (SOFT) Cluster score includes risk indices for patient mortality at 90 d, 1 y, 3 y, and 5 y posttransplant, graft failure at 1 y after …

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 …

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 …

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Anti-Egfr Liposomal Drug Delivery System Loaded With Agy2 Potentiates The Anti-Cancer Effect Of Agy2 Against Egfr Expressed Pancreatic Cancer, Raviteja Bulusu, Esther Frimpong, Joy Okoro, Sunil Krishnan, Saunjoo Yoon, Bo Han, Xue Zhu, Edward Agyare

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies worldwide due to late diagnosis, dense stromal barriers, and resistance to existing chemotherapeutics. To address these limitations, we developed a targeted liposomal delivery system that encapsulates AGY2, a newly synthesized, more potent fluoro pyrimidine nucleoside analog. In this study, epidermal growth factor receptor (EGFR) functionalized liposomal nanoparticles (EGFR-AGY2 LNPs) were optimized using Box–Behnken Design to achieve superior physicochemical stability. The optimized formulation demonstrated nanoscale dimensions (∼121 nm), high entrapment efficiency (∼75%), and strong colloidal stability. Surface antibody conjugation was confirmed by Fourier Transform Infrared Analysis (FTIR) and immunofluorescence analysis, …

Higher Sodium Intake Is Associated With Episodic Memory Decline In Cognitively Unimpaired Older Males: A 6-Year Longitudinal Study, Francisca Chuwa, Stephanie R. Rainey-Smith, Hilal Salim Said Al Shamsi, Hamid Sohrabi, Kevin Taddei, Colin L. Masters, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Recent evidence has suggested an association between high sodium intake and development of cognitive impairment. However, while animal studies demonstrate consistent relationships between sodium intake and cognitive impairment, this relationship remains less clear in humans. Our aim was to investigate the relationship between self-reported baseline sodium intake and cognitive decline over 72 months. Cognitively unimpaired participants (n = 1208) from the Australian Imaging, Biomarkers and Lifestyle study were included (70.87 years of age; 41 % male). Participants completed a food frequency questionnaire to quantify sodium intake and underwent comprehensive neuropsychological assessment at baseline and four additional timepoints, 18 months apart. …

Age-Related Increase In Plasma P-Tau217 In Amyloid-Beta–Negative Cognitively Unimpaired Individuals Affects Diagnostic Interpretation, Anna E. Mammel, Fernando Gonzalez-Ortiz, Ali Mousavi, Kelsey Hallett, Mary Encarnacion, Don Biehl, Pradip Gill, Sazan Ismael, Christopher Fowler, James D. Doecke, Larry Ward, Hans Frykman

Research outputs 2022 to 2026

Introduction: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta–negative (Aβ-) individuals. Methods: Plasma p-tau217 was measured in CU Aβ- positron emission tomography–negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60–69, 70–79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. Results: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = …

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 …

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 …

Calcium Signaling And Postsynaptic Density Dynamics: The Roles Of Calmodulin In Synaptic Protein Regulation, Keyaa Dilip Shah, Yonghong Zhang

School of Integrative Biological & Chemical Sciences Faculty Publications

Calcium signaling in neuronal cells is the principal mechanism underlying learning and synaptic plasticity, whereas the postsynaptic density (PSD) is an important center where calcium-dependent processes are organized and regulated. This review explores the roles of calmodulin (CaM) in facilitating calcium-dependent modulation of the activities of synaptic proteins in the PSD. We focus on the molecular processes through which CaM interacts with calcium signals to regulate the function, localization, and interactions of central synaptic proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), membrane-associated guanylate kinases (MAGUKs), and N-methyl-D-aspartate (NMDA) receptors. We aim to summarize recent advances in structural, biochemical, and imaging …

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 …

Decentralizing Dementia Research To The Us–Mexico Border: The Rio Grande Valley Ad-Rcmar As A Model For Translational Equity, Gladys E. Maestre, John Blangero, Eron Manusov, Gabriel A. De Erausquin, Francisco Fernandez, Silvia Mejia-Arango, Vincent P. Diego, Juan C. Lopez-Alvarenga, Claudia Alaniz, Neyra García, Rosa V. Pirela, Andrew Tsin, Michael Mahaney

School of Medicine Publications

Translational equity means ensuring that diagnostics, treatments, care models, and prevention strategies are developed and implemented so they work for populations with the greatest burden and least access to care. In Alzheimer's disease and related dementias (ADRD), where most evidence derives from highly educated, non-Hispanic White participants at large academic centers, translational equity is critical to prevent misclassification, limited access, and widening disparities and to ensure that underrepresented communities shape how new knowledge moves into practice. Hispanic and other populations in the United States are disproportionately affected by ADRD yet remain underrepresented in research, with gaps especially pronounced in high-poverty …

Mitigating Disparities In Diagnosis Of Dementia, Lycia Tramujas Vasconcellos Neumann, Simin Mahinrad, Erin L. Abner, Soo Borson, Goldie S. Byrd, Maria Carrillo, Lindsay Clark, Anthony N. Correro Ii, Kacie D. Deters, Gladys E. Maestre

School of Medicine Publications

The field of Alzheimer's disease and related dementias (AD/ADRD) is undergoing a transformative shift with a better understanding of disease biology, biomarker-based diagnostics, and disease-modifying therapies. Yet, these advancements risk exacerbating existing disparities in diagnosis and care. The 2024 Alzheimer's Association International Conference (AAIC) Advancements: Exploring Equity in Diagnosis convened interdisciplinary experts to address these inequities and chart a path toward population-generalizable research and practice. This article synthesizes key insights from the conference, highlighting considerations for inclusive and representative research design, ethical approaches in diagnostic disclosure, as well as challenges and solutions at individual, community, and systemic levels to advance …

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 …

Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy And Phenotypic Expansions, Sarah Araji, Xiaonan Zhao, Jill A Rosenfeld, Seema R Lalani, Daryl A Scott

Faculty, Staff and Students Publications

Dandy-Walker malformation (DWM) is a rare congenital abnormality of the posterior fossa and the cerebellum and has an incidence of 1 in 10 000 to 30 000 births. Although DWM can present in isolation, it is often associated with other central nervous system (CNS) abnormalities or extra-CNS anomalies (DWM+). A molecular cause is not identified in the majority of individuals with DWM+. This is due, in part, to uncertainty regarding optimal testing strategies and an incomplete understanding of the genetic causes of DWM+. In this study, we analyzed clinical exome sequencing (cES) data from 91 individuals with DWM+ to determine …

Assessing Shifts In Research Priority Areas From The Neurological Community Before And After The Covid-19 Pandemic, Leah Dempsey, Travis Cruickshank, Mitchell Turner, Manja Laws, Danielle Bartlett, Barby Singer, Onno Van Der Groen, Moira Sim, Mandy Stanley

Research outputs 2022 to 2026

Introduction: People living with a neurological condition face many difficulties in daily life, impacting their function and quality of life (QoL). There is currently no cure to many neurological conditions, therefore identifying interventions to improve QoL is of high importance. COVID-19 changed society in many ways and understanding the research priorities from the neurological community post pandemic is urgently needed to ensure resources are used efficiently and aligned with the needs and priorities of the community. To better understand the priority areas, it is essential for individuals with lived experience to have input into priority areas for research. Therefore, the …

Systemic And Metabolic Control Of Liver Regeneration, Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J Cooper, Joao V Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Valentina Santo, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Xiuning Le, Jia Wu, Sinchita Roy-Chowdhuri, Mark J Routbort, P Andrew Futreal, John V Heymach, Mark M Awad, Adam J Schoenfeld, Jianjun Zhang, Biagio Ricciuti, Lei Deng, Natalie I Vokes

Faculty, Staff and Student Publications

The liver possesses a unique regenerative capacity, driven by mechanisms that extend beyond classical growth factor signaling. Recent studies underscore the importance of metabolic reprogramming, mitochondrial adaptation, and signaling metabolites in promoting tissue injury repair. Dynamic crosstalk between hepatocytes, non-parenchymal cells, and other organs governs the regenerative process. Spatial compartmentalization within the liver and systemic cues from adipose tissue, the pancreas, the gut, the brain, skeletal muscle, and other organs play critical roles in shaping regenerative outcomes. In this review we discuss how the liver's tissue microenvironment and inter-organ communication networks regulate liver regeneration, providing new insights into the complex …

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 …

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 …

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 …

Vergence Task-Based Neural Pathways With Binocularly Normal Vision And Comorbid Persistent Post-Concussive Symptoms -Convergence Insufficiency, Ayushi Sangoi

Dissertations

Binocular dysfunctions are more prevalent in the persistent post-concussive symptoms (PPCS) population than in the general population. The most prevalent binocular disorder is convergence insufficiency (CI), affecting 3-17% of the general population and up to 10 times as many people with PPCS. CI makes it difficult to fuse or maintain fusion on targets at near, and its symptoms include double or blurry vision and headaches when performing close-range tasks such as reading, which can exacerbate PPCS symptoms. Given controversy over the subjectivity and effectiveness of diagnostic tools and symptom surveys for both PPCS and CI, understanding why CI has high …

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 …

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 …

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 …

Repeated Head Impacts Establish A Senescent Cranial Bone Marrow Niche That Impairs Brain Metabolism, Patrick J Devlin, Romeesa Khan, Trang H Do, Bryce E West, Janelle M Korf, Gary U Guzman, John Ahn, Alexander Saltzman, Antrix Jain, Chunfeng Tan, Rene Flores, Micheal E Maniskas, Sean P Marrelli, Anna Malovannaya, Erica Underwood, Rodney M Ritzel

Faculty, Staff and Students Publications

Background: Traumatic brain injury (TBI) of any severity is associated with long-term systemic inflammation and increased risk of peripheral comorbidities, yet the mechanisms driving immune dysregulation and accelerated aging after repeated sub-concussive head impacts remain poorly defined. Here, we investigated the acute and chronic effects of repetitive head impacts (RHI) on distal and proximal bone marrow compartments in the femur and calvaria, respectively.

Methods: Using a modified weight-drop mouse model delivering rotational and acceleration-deceleration forces (3 hits/week for up to 16 weeks), RHI produced no mortality, skull fracture, hemorrhage, or brain leukocyte infiltration. Bone marrow stem and progenitor cell proliferation, …

A Remote Intervention To Improve Medication Nonadherence Guided By A Marker Of Risk Derived From The Electronic Health Records Of Adolescent Transplant Recipients, Eyal Shemesh, Ravinder Anand, Rachel A Annunziato, Emily M Fredericks, Jennifer Garcia, Nitika Arora Gupta, Lawrence C Kleinman, Alyssa Kriegermeier, Krupa R Mysore, Vicky L Ng, Steven J Lobritto, Shreena Patel, Emily Rothbaum Perito, Elizabeth B Rand, Rene Romero, Robert S Venick, Sarah Duncan-Park, Jeffrey Mitchell, Sarah G Anderson, Margaret L Stuber, Miguel Reyes-Múgica, George V Mazariegos, Benjamin L Shneider

Faculty, Staff and Students Publications

Improving medication adherence in adolescents who had a liver transplant (iMALT), a prospective, block-randomized, single-blind, controlled multisite study in 13 pediatric transplant centers, used the medication level variability index (MLVI) to identify nonadherent adolescents. It compared a 2-year remote behavioral telemetric intervention (TI) that focused on adherence and addressed barriers to standard of care (SOC). The primary endpoint was the composite incidence of centrally determined (3 masked pathologists) rejection, death, retransplantation, or consent withdrawal. In 148 participants (TI group, n = 72 and the SOC group, n = 76), with a mean age 15.5 years, there were twice as many …

Unveiling Immune-Related Gene Signatures In Triple Negative Breast Cancer Through Integrated Transcriptomic Analysis, Priyanga Paranthaman, Ramanathan Karuppasamy, Shanthi Veerappapillai

BioMedicine

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. Understanding the underlying molecular mechanisms, particularly immune-related gene networks, is critical for identifying novel therapeutic targets. Aim: This study aimed to identify immune-related hub genes involved in TNBC progression by integrating microarray and RNA sequencing data. Methods: We integrated microarray and RNA sequencing datasets from five Gene Expression Omnibus (GEO) studies (GSE36295, GSE37751, GSE61724, GSE38959, and GSE58135) to identify differentially expressed genes (DEGs). Protein–protein interaction (PPI) networks were constructed using the STRING database. Key modules and hub genes were identified through network analysis. …