Digital Commons Network^™

Transcriptomic Signature-Guided Depletion Of Intermediate Alveolar Epithelial Cells Ameliorates Pulmonary Fibrosis In Mice, Fei Peng, Chun-Sun Jiang, Zhen Zheng, Shahram Aliyari, Dan Shan, Aaryan Sabharwal, Qinyan Yin, Shigeki Saito, Chao He, Ivan O Rosas, Joseph A Lasky, Victor J Thannickal, Yong Zhou

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has identified intermediate epithelial states in pulmonary fibrosis, including KRT5-/KRT17+ aberrant basaloid cells in humans and Krt8+ alveolar differentiation intermediates (ADIs) in mice. Their functional contributions to fibrogenesis, however, remain unclear. Here, we introduce an RNA-sensing-dependent protein translation technology that enables selective targeting of Krt8+ ADI cells in vitro and in vivo. Transcriptomic analysis revealed Small Proline-Rich Protein 1 A (SPRR1A) mRNA as a shared marker of murine Krt8+ ADIs and human KRT5-/KRT17+ basaloid cells, distinguishing them from other lung cell populations. Using programmable RNA sensors, we demonstrated selective EGFP-labeling of Krt8+ ADI cells in vivo, …

Maternal Immunization With Vp8* Mrna Vaccine Yields Superior Passive Transfer Of Rotavirus-Neutralizing Antibodies To Foals, Karin E R Borba, Rebecca M Legere, Nathan M Canaday, Jill W Skrobarczyk, Zachary W T Arnold, Elena Cotton-Betteridge, Cristina Poveda, Michael F Criscitiello, Angela I Bordin, Luc R Berghman, Jeroen B K Pollet, Noah D Cohen

Faculty, Staff and Students Publications

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection.

Methods: Pregnant mares (n = 12 per group) were …

Primary Cortical Neurons Precipitate And Extrude Large Mitochondria-Associated Calcium-Phosphate Sheets With A Bone-Precursor-Like Ultrastructure, Erik D Anderson, Christopher A Cronkite, Philip R Baldwin, Carlota P Abella, Joseph G Duman, Ashleigh N Simmonds, M Neal Waxham, Kimberley F Tolias, Steven J Ludtke

Faculty, Staff and Students Publications

Calcium-phosphate (CaP) is a ubiquitous inorganic compound that plays an important structural role in healthy bone and teeth formation, but its pathologic buildup can occur in dyshomeostatic calcium disorders like Alzheimer's disease and Leigh syndrome. The nexus of pathologic extracellular CaP in the nervous system is not well understood, but prior evidence suggests mitochondria could be a source. We have observed mitochondria-sized sheet-like CaP aggregates within functional wild type cortical neuron cultures at 1 and 20 days in vitro. Neurons were extracted from embryonic day 18 (E18) rat embryos following standard protocols to study neuronal structure and function. We have …

Longitudinal Observation Of Children With Achondroplasia: Findings From A Global Natural History Study (Achieve), Ciara Mcdonnell, Hanne Buciek Hove, Melita Irving, Klane K White, Cesar G Fontecha, Janet M Legare, Wolfgang Högler, Daniel G Hoernschemeyer, Dirk Schnabel, Sheila Unger, Carlos Alberto Bacino, Paul Hofman, Yongguo Yu, Huamei Ma, Chunxiu Gong, Xiaoping Luo, T Andrew Burrow, Geneviève Baujat, Stefano Mora, Melissa Fiscaletti, Carol Zhao, Michael A Makara, Aimee D Shu, Ravi Savarirayan

Faculty, Staff and Students Publications

Introduction: The ACHieve study assessed growth velocity, body proportionality, and clinical events in children with achondroplasia not receiving growth-promoting therapy.

Methods: ACHieve was a global, longitudinal, prospective, observational study. Children ≤8 years old with achondroplasia were enrolled and evaluated every 6 months for anthropometric parameters and clinical events.

Results: ACHieve enrolled 259 children in 15 countries, including 83 from China. Median follow-up was 21 months; median age of diagnosis was approximately 52 weeks in China and 2 weeks elsewhere. Growth parameters were similar regardless of region. Mean annualized growth velocity was 9.3 cm/year for males and 10.4 cm/year for females …

Pathways, Outputs And Impact Of Nih-Supported Bioinformatics And Genomics Graduate Trainees In Africa, Daudi Jjingo, Andrew Walakira, Suhaila Hashim, Cisse Cheickna, Ronald Galiwango, Caleb Kibet, Florence N Kivunike, Gerald Mboowa, Fredrick Elishama Kakembo, Babajide Ayodele, Jean-Baka Domelevo Entfellner, Santie De Villiers, Karen Wambui, Segun Fatumo, Tinashe Chikowore, John Mukisa, Alfred Ssekagiri, Nicholas Bbosa, Julius Mulindwa, Samuel Kyobe, Mike Nsubuga, Grace Kebirungi, Eric Katagirya, Savannah Mwesigwa, Ibra Lujumba, Rogers Kamulegeya, Samuel Kirimunda, Stephen Kanyerezi, Shahiid Kiyaga, Ivan Sserwadda, Davis Kiberu, Bernard S Bagaya, Julius Okwir, Patricia Nabisubi, Grace Nabakooza, Mugume Twinamatsiko Atwine, Ricard Sserunjogi, Rolanda Julius, Mariam Quiñones, Meghan Mccarthy, Phillip Cruz, Karlynn Noble, Christopher J Whalen, Darrell Hurt, Maria Y Giovanni, Michael Tartakovsky, Deogratius Ssemwanga, John M Kitayimbwa, Steven J Reynolds, Christopher C Whalen, Andrew Kambugu, Neil A Hanchard, Li Jian, Peter Amoako-Yirenkyi, Graeme Mardon, I King Jordan, Samson Pandam Salifu, Mamadou Wele, Ezekiel Adebiyi, Jeffrey G Shaffer, Seydou Doumbia, David Patrick Kateete, Michelle Skelton, Nicola Mulder, Jonathan K Kayondo, Daniel Masiga, H3africa Consortium

Faculty, Staff and Students Publications

Global biomedical and health research is increasingly relying on genomic and computational approaches, largely driven by the increasing volumes of nucleic acid sequencing. Concurrently, epidemiological studies and clinical records are generating enormous amounts of data amenable to disease modeling, machine learning, and artificial intelligence techniques. Bioinformatics and data science expertise is therefore essential for improved population health. Accordingly, in 2012, the US National Institutes of Health (NIH) in partnership with the Wellcome Trust, and with support from the African Society for Human Genetics, initiated the H3Africa (Human Heredity and Health in Africa) consortium. One of its key goals was to …

Machine Learning-Based Multimodal Biomarkers Enable Accurate Diagnosis And Early Detection Of Pancreatic Ductal Adenocarcinoma, Tsung-Hung Yao, Warapen Treekitkarnmongkol, Nagireddy Putluri, Deivendran Sankaran, Tristian Nguyen, Seetharaman Balasenthil, Mark W Hurd, Meng Chen, Randall E Brand, Paul D Lampe, Abu Hena M Kamal, Vasanta Putluri, Tony Y Hu, Anirban Maitra, Eugene J Koay, Ann M Killary, Subrata Sen, Suprateek Kundu

Faculty, Staff and Students Publications

While there has been some progress on discovering clinically validated biomarkers for early detection in pancreatic ductal adenocarcinoma (PDAC), several challenges remain. Most approaches rely on single-modality biomarkers with limited sensitivity and/or specificity. Using data from a multicenter study with an age-matched cohort (n = 203 with healthy controls n = 46, pancreatitis controls n = 36, and diagnosed cases n = 121), we developed a machine learning approach integrating 2,096 microRNAs, 125 metabolites, and CA19-9. Our method performs unsupervised selection of an optimal subset of biomarkers with maximal discriminatory power for diagnosis and early detection. In training data, the …

Harnessing Microbial Tools: Escherichia Coli As A Vehicle For Neuropeptide Functional Analysis In Caenorhabditis Elegans, Elizabeth M Diloreto, Shruti Shastry, Emily J Leptich, Douglas K Reilly, Rachel N Arey, Jagan Srinivasan

Faculty, Staff and Students Publications

Animals respond to changes in their environment and internal states via neuromodulation. Neuropeptides modulate neural circuits with flexibility because 1 gene can produce either multiple copies of the same neuropeptide or different neuropeptides. However, with this architectural complexity, the function of discrete and active neuropeptides is muddled. Here, we design a genetic tool that facilitates functional analysis of individual peptides. We engineered Escherichia coli bacteria to express active peptides, fed loss-of-function Caenorhabditis elegans, and rescued the activity of genes with varying lengths and functions: pdf-1, flp-3, ins-6, and ins-22. Some peptides were functionally redundant, while others exhibit unique and previously …

Spatially Resolved Integrative Analysis Of Transcriptomic And Metabolomic Changes In Tissue Injury Studies, Eleanor C Williams, Lovisa Franzén, Martina Olsson Lindvall, Gregory Hamm, Steven Oag, Muntasir Mamun Majumder, James Denholm, Azam Hamidinekoo, Javier Escudero Morlanes, Marco Vicari, Joakim Lundeberg, Laura Setyo, Trevor M Godfrey, Livia S Eberlin, Aleksandr Zakirov, Jorrit J Hornberg, Marianna Stamou, Patrik L Ståhl, Anna Ollerstam, Jennifer Y Tan, Irina Mohorianu

Faculty, Staff and Students Publications

Recent developments in spatially resolved -omics have enabled the joint study of gene expression, metabolite levels and tissue morphology, offering greater insights into biological pathways. Integrating these modalities from matched tissue sections to probe spatially-coordinated processes, however, remains challenging. Here we introduce MAGPIE, a framework for co-registering spatially resolved transcriptomics, metabolomics, and tissue morphology from the same or consecutive sections. We show MAGPIE's generalisability and scalability on spatial multi-omics data from multiple tissues, combining Visium with MALDI and DESI mass spectrometry imaging. MAGPIE was also applied to new multi-modal datasets generated with a specialised sampling strategy to characterise the metabolic …

Erratum For Nachman Et Al., “Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors”, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

No abstract provided.

Neuronal Subtype Governs Amyloid Structure, Cellular Response, And Cognitive Outcome In Genetically Targeted App Mouse Models, Gabriella A Perez, Zoe Lai, George A Edwards Iii, Jacob M Dundee, Shannon N Leahy, Chuangye Qi, Yanyan Qi, Ye-Jin Park, Tzu-Chiao Lu, M Danish Uddin, Rong Zhao, Hui Zheng, Hongjie Li, Joanna L Jankowsky

Faculty, Staff and Students Publications

Pathological heterogeneity is increasingly appreciated in Alzheimer’s disease, yet we do not know how distinct aggregate conformations arise or influence cognitive outcomes. In an amyloid mouse model, we found that different brain regions formed structurally distinct Aβ deposits, prompting us to test whether neuronal subtypes shape aggregate conformation. To address this, we created transgenic mice expressing the same APP construct in either glutamatergic or GABAergic neurons. APP expression in GABAergic neurons resulted in diffuse plaques with high Aβ42/Aβ40 ratios and minimal gliosis, while glutamatergic expression produced neuritic plaques with activated glia. Despite similar Aβ levels, only mice with neuritic plaques …

Predicting Sepsis In Heart Failure Patients Supported By Left Ventricular Assist Devices: The Role Of Ve-Cadherin And Adam10, Shiyi Li, Iván Murrieta-Álvarez, Ismael Garcia, Katherine V Nordick, Rishav Bhattacharya, Shreyo Ghosh, Ronald A Shaju, Adel M Hassan, Carl P Walther, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Vascular endothelial cadherin (VE-Cadherin) is a major endothelial adhesion molecule and can be cleaved explicitly by metalloproteinase domain-containing protein 10 (ADAM10). Vascular hyperpermeability may contribute to a greater susceptibility to sepsis in left ventricular assist device (LVAD) support patients. We aim to evaluate the efficacy of VE-Cadherin and ADAM10 for predicting sepsis in LVAD patients. We prospectively recruited 50 patients with advanced heart failure receiving LVAD therapy. Baseline and weekly postoperative blood samples (weeks 1-4) were collected, and plasma VE-cadherin and ADAM10 levels were measured. Sepsis occurred in 9 of 50 patients (18.0%). Across all sampling points, plasma VE-cadherin and …

Performance Of A Rapid, Highly Multiplexed Nucleic Acid Detection Assay For Identification Of Viral And Bacterial Pathogens From Upper Respiratory Tract Specimens, Coreen L Johnson, James J Dunn

Faculty, Staff and Students Publications

Background: Accurate and timely identification of upper respiratory tract pathogens can improve patient management by decreasing unnecessary additional testing, reducing the cost of care, and informing antimicrobial stewardship. We evaluated the FDA-cleared Diasorin LIAISON PLEX® Respiratory Flex (RSP Flex), a highly multiplexed, rapid nucleic acid detection assay that can identify 14 viral and 5 bacterial respiratory pathogens.

Methods: In total, 215 residual patient upper respiratory tract specimens were tested using the RSP Flex assay and results compared to standard-of-care (SOC) molecular testing.

Results: Positive percentage agreement (PPA) was 100% for the following targets: adenovirus, human coronavirus, Bordetella pertussis, Bordetella parapertussis, …

Neurodevelopmental Outcomes Following Hematopoietic Cell Transplantation For Patients With Severe Combined Immunodeficiency (Scid): A Pidtc Study, Virdette L Brumm, Sharon A Kidd, Brent R Logan, Farheen Chunara, Jennifer Heimall, Linda M Griffith, Donald B Kohn, Lauren Sanchez, Jeffrey J Bednarski, Caridad Martinez, Mark Vander Lugt, Neena Kapoor, Nicola Wright, Barbara Spitzer, Joseph H Oved, Sharat Chandra, Deepak Chellapandian, Christen L Ebens, Aleks Petrovic, Ahmad Rayes, Hilary L Haines, Hannah Lust, Hannah-Lise Tirado Schofield, Lauren Christopher, Lynnette L Harris, Lisa Forbes Satter, Lauri Burroughs, Christopher C Dvorak, Elie Haddad, Jennifer W Leiding, Rebecca A Marsh, Luigi D Notarangelo, Sung Yun Pai, Michael A Pulsipher, Jennifer M Puck, Morton J Cowan, Ami J Shah

Faculty, Staff and Students Publications

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe combined immunodeficiency (SCID). Since the initiation of newborn screening (NBS), survival rates have improved significantly, but the impact of HCT upon neurodevelopment for patients with SCID requires more investigation. We performed a cross-sectional study of subjects with SCID in North America to assess the impact of NBS, transplant conditioning regimen, and genotype on neurodevelopmental outcomes after HCT. 69 subjects with SCID from 17 PIDTC centers (excluding those with ADA deficiency), ages 6-16 years, received comprehensive standardized neurodevelopmental testing of cognitive, behavioral, and emotional function. Compared with the normative population, …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, G Michelle Ducasa, Rebecca A Marsh, Ali Mojebi, Hsi-En Ho, Charlotte Cunningham-Rundles, Lisa Forbes Satter, Elena W Y Hsieh, Sinisa Savic, Marta Dafne Cabañero-Navalón, Hector Balastegui-Martin, Joud Hajjar, Gulbu Uzel, Kevin S Thorneloe, Jocelyn R Farmer

Faculty, Staff and Students Publications

Noninfectious manifestations of common variable immunodeficiency (CVID) are not formally summarized. We performed a systematic literature review to generate a comprehensive reference for the field. Splenomegaly was the most reported manifestation across 53 publications, occurring in a median of 35.2% of patients. Frequently reported digestive system manifestations included diarrhea (median 27.8%; 21 publications), hepato(spleno)megaly (median, 21.0%; 19 publications), portal hypertension (median 21.0%; 3 publications), nodular lymphoid hyperplasia (median, 17.0%; 9 publications), and enteropathy (median, 16.0%; 34 publications). Other notable manifestations included interstitial lung disease (median, 8.7%; 32 publications) and autoimmune cytopenias (median 18.0%; 21 publications). Steroids and rituximab were the …

Vacmap: An Accurate Long-Read Aligner For Unraveling Complex Genomic Rearrangements, Hongyu Ding, Fritz J Sedlazeck, Christos Proukakis, Caoimhe Morley, Marco Toffoli, Anthony Hv Schapira, Zhirui Liao, Lianrong Pu, Shanfeng Zhu

Faculty, Staff and Students Publications

Sequence alignment is essential for genomic research and clinical diagnostics, yet detecting complex rearrangements such as inversions, duplications, and gene conversions remains challenging due to allele complexity and limitations of current methods. We introduce VACmap, a non-linear mapping approach to enhance the detection and representation of all genetic variations. VACmap improves duplication detection from 20% to 90% in the Challenging Medically-Relevant Genes (CMRG) benchmark and improves characterization of complex inversions in repetitive regions and gene conversion events. It improves resolving clinically significant loci, including the LPA gene (with repetitive KIV-2 units linked to coronary heart disease), GBA1 and STRC genes …

Machine Learning Models Predict Long Covid Outcomes Based On Baseline Clinical And Immunologic Factors, Naresh Doni Jayavelu, Hady Samaha, Sonia Tandon Wimalasena, Annmarie Hoch, Jeremy P Gygi, Gisela Gabernet, Al Ozonoff, Shanshan Liu, Carly E Milliren, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Joanna Schaenman, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuit, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Linda N Gen, Ana Fernandez Sesma, Viviana Simon, Florian Krammer, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Charles R Langelier, Leying Guan, Holden T Maecker, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman

Faculty, Staff and Students Publications

Background: The post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID, remain a significant health issue that is incompletely understood. Predicting which acutely infected individuals will develop long COVID is challenging due to the absence of established biomarkers, clear disease mechanisms, or well-defined sub-phenotypes. Machine learning (ML) models may address this gap by leveraging clinical data to enhance diagnostic precision.

Methods: Clinical data, including antibody titers and viral load measurements collected at the time of hospital admission, are used to predict the likelihood of acute COVID-19 progressing to long COVID. Machine learning models are trained and evaluated for predictive …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

Layers To Leaves: A Suite Of Modular 3d Printed Hydroponics Components For Research And Education, Ethan A Shaw, Suraj K Chandramouli, Michael P Dzakovich

Faculty, Staff and Students Publications

Hydroponics is a widely utilized technique to precisely control the plant growing environment and maximize productivity. In some cases, hydroponics systems can be expensive and require specialized expertise to build and maintain. Here, we present a suite of 3D-printed devices that can be constructed into a single or double tower hydroponics system of variable height and composition. This system is easily scalable to fit the needs of a user and can be implemented in a variety of research and educational contexts. Components in this suite can be made from inexpensive plastic filament using household-grade 3D printers. The vertical design of …

Once-Weekly Navepegritide In Children With Achondroplasia: The Approach Randomized Clinical Trial, Ravi Savarirayan, Ciara Mcdonnell, Carlos A Bacino, Daniel G Hoernschemeyer, Janet M Legare, M Jennifer Abuzzahab, Paul L Hofman, Philippe M Campeau, Josep Maria De Bergua Domingo, Leanne M Ward, Kevin Smit, Alden Smith, Meng Mao, Michael S Ominsky, Lærke C Freiberg, Aimee D Shu, Hanne B Hove

Faculty, Staff and Students Publications

Importance: Historically considered a skeletal dysplasia characterized by disproportionate short stature, achondroplasia is a condition with multisystemic effects due to the widespread expression of the fibroblast growth factor receptor 3 variant throughout the body, impacting muscle, neurological function, cardiorespiratory health, and health-related quality of life.

Objective: To evaluate the efficacy, safety, and tolerability of once-weekly navepegritide, an investigational prodrug of C-type natriuretic peptide, while assessing benefits beyond growth that may have important implications for complications and health-related quality of life in children with achondroplasia.

Design, setting, and participants: Enrollment for this pivotal phase 2b, randomized, double-blind, placebo-controlled trial (APPROACH) was …

The Words Community Dwelling, Spanish-Preferring Mexican/Mexican American Adults Use To Talk About Alzheimer’S Disease And Genetic Testing: Implications For Education And Outreach, Jamie C Fong, Fatima I Chavez, Karla Silos, Mirna L Arroyo-Miranda, Gabriela Castro Castro, Mark E Kunik, Joshua M Shulman, Luis D Medina

Faculty, Staff and Students Publications

Introduction: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

Methods: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting …

Proceedings Of The 13th Annual Deep Brain Stimulation Think Tank: The Evolving Landscape, Chance R Fleeting, Eduardo M Moraud, Kamil Uğurbil, Doris D Wang, Wolf-Julian Neumann, Andrea A Kühn, Valerie Voon, Victor Pikov, Marie-Laure Welter, Michael D Fox, John D Rolston, Mahsa Malekmohammadi, Yagna J Pathak, Lyndahl M Himes, David Greene, Abbey S Holt-Becker, Gabriel Lázaro-Muñoz, Alexander W Charney, Amanda R Merner, Martijn Figee, Katherine W Scangos, Timothy Denison, Kent Leyde, Aysegul Gunduz, Helen M Bronte-Stewart, James C Beck, Nora Vanegas-Arroyave, Marta San Luciano, Norbert Brüggemann, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XIII was held September 2-4th, 2025, in Gainesville, Florida, at the Norman Fixel Institute for Neurological Diseases at the University of Florida. The theme was "The Evolving Landscape of DBS: New Indications, New Goals." This theme was a continuation of the DBS Think Tank XI and XII, which were focused on emerging technology and pushing the horizon of indications. Since its founding in 2012, the DBS Think Tank has provided a global forum for leading clinicians, engineers, and researchers in both in industry and academia to present, discuss, and debate the current state …

Amino Acids And Lean Mass Accretion In Preterm Neonates, Antonio C Ramos Dos Santos, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Purpose of review: This review evaluates recent evidence on how total protein and energy intake, amino acid composition, and nutrient delivery modality influence protein synthesis in preterm neonates, with the goal of informing nutritional strategies to support optimal lean mass accretion and growth.

Recent findings: Preterm neonates exhibit anabolic resistance to feeding due to impaired insulin and amino acid signaling in skeletal muscle. Enteral nutrition, especially fortified human milk, supports better lean mass accretion and neurodevelopment than parenteral nutrition. Intermittent bolus feeding and pulsatile leucine supplementation during continuous feeding further enhance mTORC1-dependent translation initiation signaling and protein synthesis efficiency in …

Highly Effective Combination Of Brg1/Brm Inhibitor With Bet Inhibitor Or Decitabine For High-Risk Mecom-Rearranged Aml, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, John A Davis, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Jian Wang, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Ruud Delwel, Kapil N Bhalla

Faculty, Staff and Students Publications

In AML with 3q26.2 rearrangements (r) the distal GATA2 hematopoietic enhancer becomes aberrantly relocated leading to activation of EVI1 expression. EVI1 is a transcriptional regulator that plays a role in proliferation and maintenance of a stem cell-like phenotype in AML. BRG1 (SMARCA4) and BRM (SMARCA2) are the mutually exclusive ATPases of the BAF (BRG1/BRM-associated factor) chromatin remodeling complexes. They regulate access to enhancers/promoters and gene-expressions orchestrating AML stem/progenitor cell proliferation and differentiation. AML with 3q26.2 rearrangements are clinically challenging and prognosis remains very poor. FHD-286 is an orally bioavailable, selective inhibitor of BRG1/BRM under clinical development in AML. Present studies …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Astrocytic Sox9 Overexpression In Alzheimer’S Disease Mouse Models Promotes Aβ Plaque Phagocytosis And Preserves Cognitive Function, Dong-Joo Choi, Sanjana Murali, Wookbong Kwon, Junsung Woo, Eun-Ah Christine Song, Yeunjung Ko, Debosmita Sardar, Brittney Lozzi, Yi-Ting Cheng, Michael R Williamson, Teng-Wei Huang, Kaitlyn Sanchez, Joanna Jankowsky, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes …

3d Geometric Modelling And Clinical Validation Of Lower Limb And Preliminary 2-Year Post-Operative Clinical Outcomes Of Neutral Boundary Alignment In Total Knee Arthroplasty, Bruno Violante, Lorenzo Deveza, Francesco Pollara, Giovanni Rusconi, Gianroberto Ferreri, Alessandro Annibaldi, Ilwhan Park

Faculty, Staff and Students Publications

Purpose: To introduce a novel three-dimensional (3D) modelling concept for lower limb alignment in total knee arthroplasty (TKA), termed neutral boundary alignment (NBA) and to present preliminary clinical data supporting this physics-based custom alignment strategy.

Methods: NBA is defined as the alignment at which the knee joint line is parallel to the ground during the mid-stance phase of gait, achieving static equilibrium with the NBA axis aligned to gravity. A theoretical geometric model of the lower limb was developed, integrating principles of physics to describe this condition. Preliminary clinical validation was performed using radiographic data from an initial cohort of …

Lessons Learned From An Epic Transformation Of A Radiation Oncology Department In Guatemala: Keys To Success, Edgar Ruiz, Hiram A Gay, Milton Ixquiac, Angel Velarde, Baozhou Sun, Jose García-Ramirez, Eric Laugeman, Benjamin Li, Jeff Michalski, Vicky De Falla, Geoff Hugo, Jacaranda Van Rheenen

Faculty, Staff and Students Publications

Purpose: We describe the radical modernization of a radiation oncology department in a developing country, Guatemala, from 2015 to the beginning of 2024. The Instituto de Cancerología y Hospital Dr. Bernardo del Valle S (INCAN) is the only public radiotherapy clinic serving patient referrals from the Ministry of Public Health and Social Assistance program.

Methods and materials: We describe the state of the radiation oncology department in 2015 versus 2024 while chronicling its gradual transformation. This multifaceted collaboration involved academic centers, government agencies, International Atomic Energy Agency (IAEA), industry, and nonprofits and continues to this day. We analyze the infrastructure, …

Predictors Of Inpatient Rn Turnover In Rural And Urban Vha Hospitals, Katherine G Bay, Chase S Eck, Melissa K Knox, Paras Mehta, Laura A Petersen

Faculty, Staff and Students Publications

Background: The rising demand for health care delivery and an aging workforce is of particular concern in rural areas, where health care access depends upon an adequate nursing workforce. To address this shortage and optimize care, it is essential to measure when registered nurses (RN) leave inpatient direct care positions (ie, inpatient RN turnover) and identify modifiable factors correlated with RN turnover.

Objectives: Apply a novel method for characterizing inpatient RN turnover to understand factors associated with variation in RNs leaving inpatient positions at rural and urban Veterans Health Administration (VHA) hospitals.

Project design: Retrospective cohort study.

Subjects: Direct care …

Hypothyroidism Is Associated With Higher Healthcare Utilisation And Higher Need For Blood Transfusion After Primary Total Knee Arthroplasty (Tka) In Patients With Osteoarthritis: A National Inpatient Sample Analysis, Sumanth R Chandrupatla, Kranti C Rumalla, Jasvinder A Singh

Faculty, Staff and Students Publications

Purpose: To examine the association of hypothyroidism with primary total knee arthroplasty (TKA) outcomes in adults with primary underlying diagnosis of osteoarthritis (OA).

Methods: We identified a prospective cohort of patients in the 2016-2020 national inpatient sample (NIS) that received primary TKA with an underlying diagnosis of OA, identified using International Classification of Diseases, Tenth Revision, Common Modification (ICD-10-CM) and Procedure Coding System (ICD-10-PCS) codes in the primary procedure and diagnosis positions, respectively. We performed multivariable-adjusted regression analyses for healthcare utilisation (length of hospital stay, hospital charges and discharge destination) and clinical outcomes (blood transfusion; prosthetic fracture, dislocation or infection; …

Healthcare Transition In Spina Bifida: A National Mixed Method Study, Betsy Hopson, Kathy H Huen, Molly B Richardson, Rhonda G Cady, Jennifer T Queally, Judy Thibadeau, Ellen Fremion

Faculty, Staff and Students Publications

Introduction: Adolescents and young adults (AYA) with spina bifida (SB) face substantial challenges during the transition from pediatric to adult healthcare, including fragmented systems, limited adult provider availability, and gaps in self-management readiness. Despite national guidelines, little is known about how transition practices are implemented across the Spina Bifida Association (SBA) Clinical Care Partner (CCP) network. This study examined clinician perspectives on current practices, barriers, facilitators, and definitions of successful healthcare transition (HCT).

Methods: Using an explanatory sequential mixed methods design, we first conducted a 47-item survey with clinicians from SBA CCP clinics (n = 20/32; 62.5 % response rate). …