Digital Commons Network^™

Tet2-Mutant Myeloid Cells Mitigate Alzheimer’S Disease Progression Via Cns Infiltration And Enhanced Phagocytosis In Mice, Katie A Matatall, Trisha K Wathan, Minh Nguyen, Hu Chen, Alexandra Mcdonald, Guantong Qi, Julia A Belk, Marcus A Florez, Duy T Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M Buttigieg, Chih-Wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E Kennedy, Arushana A Maknojia, Apoorva Thatavarty, Josaura V Fernandez Sanchez, Hind Bouzid, Surabi Veeraragavan, Susan Crocker, Margaret A Goodell, Antony Rodriguez, Siddhartha Jaiswal, Michael J Rauh, Eirini P Papapetrou, Samuele G Marro, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than …

A Multi-Measurement Study Of The Relation Between Deliberation And Volition, Guillaume P. Pech, Emilie A. Caspar, Elisabeth Pacherie, Axel Cleeremans, Uri Maoz

Psychology Faculty Articles and Research

Historically, voluntary action and volition more generally have been investigated through the lens of meaningless decisions. Importantly, these findings have been used in the debate about key notions like free will and moral responsibility. However, more recent claims have challenged the possibility of generalizing findings from a meaningless context to a more meaningful one. The current study investigates the markers of volition, specifically comparing meaningful and meaningless decisions. In an effort to maximize their monetary gain, 50 participants repeatedly deliberated between two options, making either rewarded choices—hard-deliberation decisions (where the options differed along two dimensions) or easy-deliberation decisions (where the …

Adipokines And Transitions In Metabolic Health Over Time: The Atherosclerosis Risk In Communities (Aric) Study, Bige Ozkan, Sui Zhang, Justin B Echouffo-Tcheugui, Roberta Florido, Vijay Nambi, Erin D Michos, Layla A Abushamat, Kunihiro Matsushita, Gary Gerstenblith, Roger S Blumenthal, Ron Hoogeveen, Christie M Ballantyne, Josef Coresh, Elizabeth Selvin, Chiadi E Ndumele

Faculty, Staff and Students Publications

Context: Transitions in metabolic health status over time are strongly linked to risk for cardiovascular events, particularly among individuals with obesity. Adipokines are proteins with metabolic effects, but their role in transitions in metabolic health status over time is unknown.

Objective: To evaluate the associations of adiponectin and leptin with metabolic risk transitions over time.

Methods: Among 8423 individuals who attended ARIC Visits 2 (1990-1992) and 4 (1996-1998), we evaluated prospective associations of Visit 2 levels of the adipokines adiponectin and leptin (per 1-SD higher) with 6-year transitions in metabolic health. Metabolic health was categorized as metabolically "healthy" [no metabolic …

Biomarkers In Renal Cell Carcinoma: A Systematic Review And Immunohistochemical Validation Study, Brett Berezowski, Robert Boothe, Billy Chaplin, Sharon J Del Vecchio, Zakariya Fares, Tyrone L R Humphries, Keng Lim Ng, Taylor Noonan, Hemamali Samaratunga, Aaron Urquhart, David A Vesey, Simon T Wood, Glenda C Gobe, Robert J Ellis

Faculty, Staff and Student Publications

The worldwide incidence of renal cell carcinoma (RCC) rose by 22% between 2012 and 2022. In Australia, RCC accounted for 2.8% of all cancer diagnoses and contributing to 1.8% of cancer-related deaths. Identification of RCC biomarkers may aid in diagnosis and management. Methods: A systematic review of immunohistochemical markers of RCC studies published between 1990 and 2019 was undertaken to select candidate biomarkers of RCC. Immunohistochemical staining of 73 clear cell RCC tumors and paired normal tissue was undertaken using selected markers. Semi-quantitative and quantitative analysis of staining intensity between paired samples was undertaken to evaluate utility as potential …

Dosimetric Evaluation Of Clearsight Bolus Versus Superflab Bolus For Vmat Head And Neck Treatment, Courtney M. Williams

Masters Projects

This study compares the dosimetric performance and fit accuracy of ClearSight and Superflab boluses in head and neck (HN) volumetric modulated arc therapy (VMAT) treatment plans, focusing on dose distribution and air gap volumes. A RANDO anthropomorphic phantom was used to simulate HN VMAT treatment for oral cavity cancer with positive lymph nodes, prescribed 70 Gy in 35 fractions. Four configurations were tested: ClearSight bolus over a thermoplastic mask (CSO), ClearSight under a mask (CSU), Superflab over a mask (SFO), and Superflab under a mask (SFU). Five computed tomography (CT) scans, one without bolus and four with bolus, were performed …

Mri-Based Radiomics For Outcome Stratification In Pediatric Osteosarcoma, Esther Ngan, Dolores Mullikin, Ashok J Theruvath, Ananth V Annapragada, Ketan B Ghaghada, Andras A Heczey, Zbigniew A Starosolski

Faculty, Staff and Students Publications

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. \

Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor …

Association Between Allostatic Load And Accelerated White Matter Brain Aging: Findings From The Uk Biobank, Li Feng, Zhenyao Ye, Zewen Du, Yezhi Pan, Travis Canida, Hongjie Ke, Song Liu, Shuo Chen, L Elliot Hong, Peter Kochunov, Jie Chen, David K Y Lei, Edmond Shenassa, Tianzhou Ma

Faculty, Staff and Student Publications

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting, …

Interactive 3d Segmentation For Primary Gross Tumor Volume In Oropharyngeal Cancer, Mikko Saukkoriipi, Jaakko Sahlsten, Joel Jaskari, Lotta Orsmaa, Jari Kangas, Nastaran Rasouli, Roope Raisamo, Jussi Hirvonen, Helena Mehtonen, Jorma Järnstedt, Antti Mäkitie, Mohamed Naser, Clifton Fuller, Benjamin Kann, Kimmo Kaski

Faculty, Staff and Student Publications

Radiotherapy is the main treatment modality of oropharyngeal cancer (OPC), in which an accurate segmentation of primary gross tumor volume (GTVt) is essential but also challenging due to significant interobserver variability and the time consumed in manual tumor delineation. For such a challenge an interactive deep learning (DL) based approach offers the advantage of automatic high-performance segmentation with the flexibility for user correction when necessary. In this study, we investigate an interactive DL for GTVt segmentation in OPC by introducing a novel two-stage Interactive Click Refinement (2S-ICR) framework and implementing state-of-the-art algorithms. Using the 2021 HEad and neCK TumOR dataset …

Information Theory Optimization Of Signals From Small-Angle Scattering Measurements, Robert P Rambo, John A Tainer

Faculty, Staff and Student Publications

Small-angle X-ray scattering (SAXS) of particles in solution informs on the conformational states and assemblies of biological macromolecules (bioSAXS) outside of cryo- and solid-state conditions. In bioSAXS, the SAXS measurement under dilute conditions is resolution limited, and through an inverse Fourier transform, the measured SAXS intensities directly relate to the physical space occupied by the particles via the P(r)-distribution. Yet, this inverse transform of SAXS data has been historically cast as an ill-posed, ill-conditioned problem requiring an indirect approach. Here, we show that through the applications of matrix and information theories, the inverse transform of SAXS intensity data is a …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Rescue Of Male Infertility By Human Prss55 In Transgenic Mice Establishes A Contraceptive Research Model, Courtney M Sutton, Kohei Umezu, Daisuke Mashiko, Masahito Ikawa, Irina V Larina, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of non-hormonal male contraceptives requires validated preclinical models. This study investigated whether human orthologs of two mouse testis-specific serine proteases, PRSS55 and TMPRSS12, both essential for male fertility in mice, could functionally rescue the infertility phenotypes of their respective knockout mouse lines. We generated transgenic mouse lines expressing human PRSS55 with either an extracellularly or intracellularly positioned C-terminal 3xFLAG tag (RES GPI or RES TM), and a line expressing human TMPRSS12 with a C-terminal 3xFLAG tag (T12 RES), all on their respective mouse null backgrounds. Fertility was assessed through continuous mating trials, and sperm parameters were evaluated. Both …

Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U Rehman, Carol Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W Scherer, Ingo Helbig, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Children with neurodevelopmental disorders exhibit highly penetrant sleep and circadian dysfunction, but the underlying mechanisms are unclear. We asked whether a subset of individuals with neurodevelopmental disorders might have genetic variants in genes known to drive circadian rhythms. Through international collaboration, we identified ten individuals with very rare genetic variants in BMAL1, a core component of the molecular clock. These individuals exhibited overlapping signs and symptoms including developmental delay, autism spectrum disorder, and variably penetrant marfanoid features. We functionally tested the identified BMAL1 variants in cell culture and in vivo and found disrupted BMAL1 function. These findings demonstrate that …

Leishmania In Texas: A Contemporary One Health Scoping Review Of Vectors, Reservoirs, And Human Health, Morgan H Jibowu, Richard Chung, Nina L Tang, Sarah Guo, Leigh-Anne Lawton, Brendan J Sullivan, Dawn M Wetzel, Sarah M Gunter

Faculty, Staff and Students Publications

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to Leishmania mexicana. We conducted a scoping literature review to systematically assess contemporary research on Leishmania in humans, animals, reservoir hosts, or vectors in Texas after 2000. Out of 22 eligible studies, the most prevalent themes were case reports, followed by studies on domestic animals, reservoirs, and vectors, with several studies bridging multiple disciplines. Climate change, urbanization, and habitat encroachment appear to be driving the northward expansion …

Development And Validation Of Venous Thromboembolism-Bidirectional Encoder Representations From Transformers (Vte-Bert) Natural Language Processing Model, Omid Jafari, Shengling Ma, Barbara D Lam, Jun Y Jiang, Emily Zhou, Mrinal Ranjan, Justine Ryu, Raka Bandyo, Arash Maghsoudi, Bo Peng, Christopher I Amos, Abiodun Oluyomi, Nathanael R Fillmore, Jennifer La, Ang Li

Faculty, Staff and Students Publications

Background: Accurate and rapid phenotyping of venous thromboembolism (VTE) in longitudinal studies is important. A natural language processing (NLP) tool externally validated in representative patients is lacking.

Objectives: To train and validate an efficient NLP model to detect incident VTE event.

Methods: We designed a novel NLP platform, NLPMed, to assist thrombosis researchers with data preprocessing, phenotype annotation, language model finetuning, and NLP application. Using clinical notes, discharge summaries, and radiology reports from patients with cancer at 2 healthcare institutions, we finetuned Bio_Clinical Bidirectional Encoder Representations from Transformers (BERT) to develop VTE-BERT. The new model was trained to detect acute …

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

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Integrating Ctdna Analysis And Radiomics For Dynamic Risk Assessment In Localized Lung Cancer, Everett J Moding, Mohammad Shahrokh Esfahani, Cheng Jin, Angela B Hui, Barzin Y Nabet, Yufei Liu, Jacob J Chabon, Michael S Binkley, David M Kurtz, Emily G Hamilton, Aadel A Chaudhuri, Chih Long Liu, Zhe Li, Rene F Bonilla, Alice L Jiang, Brianna C Lau, Pablo Lopez, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing Liao, Millie Das, Kavitha J Ramchandran, Sukhmani K Padda, Joel W Neal, Heather A Wakelee, Michael F Gensheimer, Billy W Loo, Ruijiang Li, Steven H Lin, Ash A Alizadeh, Maximilian Diehn

Faculty, Staff and Student Publications

The complementarity and clinical utility of combining liquid biopsies and radiomic image analysis has not been demonstrated. Circulating tumor DNA (ctDNA) minimal residual disease after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is highly prognostic, but on-treatment biomarkers are needed to enable response-adapted therapies. Here, we analyzed 418 patients with NSCLC undergoing CRT to develop and validate a novel dynamic risk model that accurately predicts ultimate progression-free survival during treatment. We optimize tissue-free variant calling from plasma samples to facilitate ctDNA monitoring and demonstrate the importance of accounting for persistent clonal hematopoiesis variants. We show that mid-CRT ctDNA concentration …

Depletion Of Effector Regulatory T Cells Associates With Major Response To Induction Dual Immune Checkpoint Blockade, Xianli Jiang, Nils-Petter Rudqvist, Bo Jiang, Shengbin Ye, Shan He, Qingnan Liang, Jinzhuang Dou, Michelle D Williams, Joe Dan Dunn, Jason M Johnson, Keiko Akagi, Weihong Xiao, Shaoheng Liang, Satvik Elayavalli, Baohua Sun, Edwin R Parra, Renata Ferrarotto, Adam S Garden, Clifton David Fuller, Jay Reddy, Neil D Gross, Miriam N Lango, Cheuk Hong Leung, Suyu Liu, Diane D Liu, Meng Li, J Jack Lee, Michael A Curran, Jack Phan, Ken Chen, Maura L Gillison

Faculty, Staff and Student Publications

In a phase II trial, patients with local-regionally advanced human papillomavirus-positive oropharyngeal carcinoma (n = 35) received ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1) as induction immunotherapy and concurrently with radiotherapy (NCT03799445). Coprimary endpoints included 6-month complete metabolic response rate (94%) and 2-year progression-free survival (84%). Induction yielded a 46% major histopathologic response rate. Single-cell profiling revealed responders had higher baseline intratumoral CD8+ T cells with a tumor-reactive, tissue-resident memory (TRM) phenotype and a treatment-related decrease in effector regulatory T (eTreg) cells. The eTreg decrease correlated with CD8+ T-cell clonotype transitioning from TRM to effector memory and IFNG+ effector cells. …

Rsph4a-Pcdx: An Index To Predict Lung Function Decline In Primary Ciliary Dyskinesia, Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with

Rna Sequencing And Immunohistochemistry Jointly Improve Tumor Biomarker Interpretation, Vladimir Kushnarev, Danil Stupichev, Suren Davitavyan, Kirill Kriukov, Basavaraja U Shanthappa, Anna Butusova, Sofia Menshikova, Anna Belozerova, Anastasia Shvyrkova, Arina Tkachuk, Olga Khatenkova, Linda Balabanian, Ekaterina Postovalova, Jochen K Lennerz, Funda Meric-Bernstam, Alexander Bagaev

Faculty, Staff and Student Publications

This study aimed to assess the correlation between RNA sequencing (RNA-seq) and immunohistochemistry (IHC) in detecting key cancer biomarkers across solid tumors, and then, to establish RNA-seq thresholds that accurately reflect clinical IHC classifications. Expression levels of nine biomarkers-ESR1, PGR, AR, MKI67, ERBB2, CD274, CDX2, KRT7, and KRT20-were analyzed in 365 formalin-fixed, paraffin-embedded samples from breast, lung, gastrointestinal, and other solid carcinomas. Correlations between RNA-seq data and IHC scores were determined using Spearman's correlation coefficients, with RNA-seq cut-offs established to distinguish positive from negative IHC scores. The results revealed strong correlations for most biomarkers, with coefficients ranging from 0.53 to …

Inhibition Of Epithelial Cell Yap-Tead/Lox Signaling Attenuates Pulmonary Fibrosis In Preclinical Models, Darcy Elizabeth Wagner, Hani N Alsafadi, Nilay Mitash, Aurelien Justet, Qianjiang Hu, Ricardo Pineda, Claudia Staab-Weijnitz, Martina Korfei, Nika Gvazava, Kristin Wannemo, Ugochi Onwuka, Molly Mozurak, Adriana Estrada-Bernal, Juan Cala-Garcia, Katrin Mutze, Rita Costa, Deniz Bölükbas, John Stegmayr, Wioletta Skronska-Wasek, Stephan Klee, Chiharu Ota, Hoeke A Baarsma, Jingtao Wang, John Sembrat, Anne Hilgendorff, Jun Ding, Andreas Günther, Rachel Chambers, Ivan Rosas, Stijn De Langhe, Naftali Kaminski, Mareike Lehmann, Oliver Eickelberg, Melanie Königshoff

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by excessive extracellular matrix deposition. Current IPF therapies slow disease progression but do not stop or reverse it. The (myo)fibroblasts are thought to be the main cellular contributors to excessive extracellular matrix production in IPF. Here we show that fibrotic alveolar type II cells regulate production and crosslinking of extracellular matrix via the co-transcriptional activator YAP. YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells. Pharmacological YAP inhibition via verteporfin reverses fibrotic alveolar type II cell reprogramming and LOX …

Role Of Cardiac Ketone Body Metabolism In Myocardial Perfusion And Exercise Performance., Kara R. Gouwens

Electronic Theses and Dissertations

Cardiorespiratory fitness, a crucial determinant of overall health and a strong predictor of all-cause mortality, is largely dependent on the capacity of the cardiovascular system to deliver oxygen and nutrients. The heart, as the central pump, requires a continuous and adaptable oxygen supply, particularly during increased workload such as occurs with exercise. Impaired myocardial blood flow (MBF) in response to increased demand can lead to ischemia, limiting exercise capacity and potentially causing severe cardiac events. Interestingly, changes in myocardial metabolism and cardiac work correlate with changes in MBF. Therefore, understanding the regulation of MBF, especially the link between local cardiac …

Management Approaches To Spastic Gait Disorders, Sheng Li, Tulsi Pandat, Bradley Chi, Daniel Moon, Manuel Mas

Faculty, Staff and Student Publications

Spastic gait presents clinically as the net mechanical consequence of neurological impairments of spasticity, weakness, and abnormal synergies and their interactions with the ground reaction force in patients with upper motor neuron syndromes and with some neuromuscular diseases. It is critical to differentiate whether the primary problem is weakness or spasticity, thus better understanding different phenotypes of spastic gait disorders. Pelvic girdle abnormality plays a pivotal role in determining the clinical presentation of gait disorders, since it determines the body vector and compensatory kinetic chain reactions in the knee and ankle joints. Knee joint abnormality can be a mechanical compensation …

Do Finances Determine Our Fate?: Understanding The Relationships Between Socioeconomic Status, Inflammation, And Cancer Recurrence Risk, Faith Wilbourne

Master's Theses

Individuals of a low socioeconomic status (SES) are more likely to experience a cancer recurrence relative to individuals with a higher SES. This may be partially explained by the stressors of living with a low SES. These stressors can increase inflammatory markers known to elevate the risk of cancer development. Health-promoting behaviors such as exercise, adequate sleep, and a healthy diet can reduce systemic inflammation. Health behaviors may therefore moderate any potential relationship between SES and cancer recurrence risk. This study explored associations between SES (income, educational attainment) and inflammatory markers related to cancer recurrence while seeking to determine if …

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …

Digital Pathology In Tau Research: A Comparison Of Qupath And Halo, Angelique D. Gonzalez, Yannick Joel Wadop Ngouongo, Benjamin Danner, Kyra M. Clarke, Matthew B. Dopler, Ali Ghaseminejad-Bandpey, Sahana Babu, Julie Parker-Garza, Cole Corbett, Gladys Maestre

School of Medicine Publications

The application of digital pathology tools has expanded in recent years, but non-neoplastic human brain tissue presents unique challenges due to its complexity. This study evaluated HALO and QuPath tau quantification performance in the hippocampus and mid-frontal gyrus across various tauopathies. Percent positivity emerged as the most reliable measure, showing strong correlations with Braak stages and CERAD scores, outperforming object and optical densities. QuPath demonstrated superior correlations with Braak stages, while HALO excelled in aligning with CERAD scoring. However, HALO’s optical density was less consistent. Paired t-tests revealed significant differences in object and optical densities between platforms, though percent positivity …

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, Francesca Taraballi, Claudia Corbo, Julia Enterria-Rosales, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

Rates Of Appropriate Initiation Of Low Dose Aspirin Prophylaxis As Indicated By The Gestosis Score In Early Pregnancy: A Cross-Sectional Study, Mundlapati Usha, Nathasha Hk, Akkamma A. Satyaraddi, Geetanjali M. Katageri

Digital Journal of Clinical Medicine

Introduction: Pre-clampsia is a multisystem disorder in pregnancy. Initiating Low Dose Aspirin (LDA) in early pregnancy is recommended to prevent development of pre-eclampsia in high-risk women. Gestosis score is a simple screening tool for predicting women at risk for developing pre-eclampsia. It can be done by any health care provider even in the periphery. This study highlights the degree of awareness amongst obstetric healthcare providers in prediction and prevention of pre-eclampsia and the rates of appropriate initiation of Aspirin.

Methodology: 134 pregnant women were included in the study. The parameters for calculating the GESTOSIS score were retrieved from …

Does Midbrain Atrophy Distinguish Progressive Supranuclear Palsy From Frontotemporal Dementia?, Mauro César Quintão E Silva Cunningham, Sarah Teixeira Camargos, Vinícius Ribeiro Jeunon, Natalia Pessoa Rocha, Antônio Lúcio Teixeira, Thiago De Oliveira Maciel, Elisa De Paula França Resende, Francisco Eduardo Costa Cardoso, Paulo Caramelli, Leonardo Cruz De Souza

Faculty, Staff and Student Publications

Background: The diagnostic value of midbrain atrophy for distinguishing behavioral variant frontotemporal dementia (bvFTD) from progressive supranuclear palsy (PSP) is unclear.

Objective: To investigate whether measures of midbrain atrophy differentiate PSP from bvFTD.

Methods: We included four groups: healthy controls (n = 19), PSP-Richardson syndrome (n = 20), bvFTD (n = 19) and Parkinson's disease (PD; n = 12). The following quantitative and qualitative measures were calculated: Hummingbird sign rating scale [HBS-RS], global midbrain atrophy [GMA], midbrain area, midbrain/pons ratio, the Magnetic Resonance Parkinsonism Index (MRPI), the MRPI 2.0 and brainstem volume.

Results: Compared to controls, PSP and bvFTD had …

A Systematic Clinical Framework For Postimplantation Monitoring In Thalamic Neuromodulation: Insights From Twiddler's Syndrome, Shalin Shah, Ganne Chaitanya, Jeston Chin, Nicholas Delcimmuto, Jay R Gavvala

Faculty, Staff and Student Publications

This case described a 25-year-old pregnant woman with refractory multifocal epilepsy, diagnosed in 2020 and treated with bilateral thalamic deep brain stimulation (DBS) targeting the centromedian and pulvinar nuclei. Prior to DBS, she experienced daily focal seizures, often progressing to generalized tonic-clonic seizures despite optimal medication. Presurgical evaluations revealed multifocal epilepsy with right hemispheric involvement and diffuse band heterotopia. Given the extensive neurophysiological and radiographic findings, DBS was chosen over resective surgery. Following implantation in December 2023, initial stimulation settings resulted in some seizure control but also development of new symptoms, including shock-like sensations down her neck. After 43 seizure-free …

Associative Coding Of Conditioned Fear In The Thalamic Nucleus Reuniens In Rodents And Humans, Tuğçe Tuna, Michael S Totty, Muhammad Badarnee, Flávio Afonso Gonçalves Mourão, Shaun Peters, Mohammad R Milad, Stephen Maren

Faculty, Staff and Student Publications

The nucleus reuniens (RE) is a midline thalamic structure interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Recent work in both rodents and humans implicates the RE in the adaptive regulation of emotional memories, including the suppression of learned fear. However, the neural correlates of aversive learning in the RE of rodents and humans remain unclear. To address this, we recorded RE activity in humans (BOLD fMRI) and rats (fiber photometry) during Pavlovian fear conditioning and extinction. In both rats and humans, we found that conditioned stimulus (CS)-evoked activity in RE reflects the associative value of the CS. …