Digital Commons Network^™

Genetic Architecture Of White Matter Microstructure Captured By Unsupervised Deep Representation Learning Of Fractional Anisotropy Maps, Xingzhong Zhao, Ziqian Xie, Wei He, Hyun Yong Koh, Bohong Guo, Han Chen, Myriam Fornage, Degui Zhi

The Brown Foundation: Institute of Molecular Medicine

Fractional anisotropy (FA) from diffusion MRI is a widely used marker of white matter (WM) integrity, but conventional FA-based genetic studies typically rely on tract- or atlas-defined averages that may obscure spatially distributed WM variation and limit genetic discovery. Here, we propose a deep learning framework, termed unsupervised deep representation of WM (UDR-WM), which uses voxel-wise FA maps to derive brain-wide unsupervised deep imaging phenotypes (UDIP-FA) without prior anatomical assumptions. Compared with traditional FA phenotypes, UDIP-FA shows greater sensitivity to aging and substantially higher SNP-based heritability. Multivariate GWAS identified 939 lead SNPs across 586 loci, mapping to 3,480 UDIP-FA-associated genes. …

Transgenic Hookworm Secretes Anti-Tetrodotoxin Human Single Chain Antibody, Kumar Sachin Singh, Suman Bharti, Bruce A Rosa, Mahdiyeh Bigham, Samuel C Uzoechi, Young-Jun Choi, John C Martin, Danielle Kemper, Slavica Pavlovic Djuranovic, Darren A Pickering, Rachael Ryan, Bethany K Bracken, Maria Elena Bottazzi, Eric C Carnes, Wannaporn Ittiprasert, Matthew Moyle, Paul J Brindley, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies across a broad range of indications. However, parenteral administration and the need for frequent dosing increase costs and limit compliance, creating an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustained biologics in situ within the host. Here, we describe a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo. As proof of concept, we engineer the Ancylostoma ceylanicum secretome by inserting a human single-chain variable fragment antibody (s16-HuScFv) into its genome. Transgene expression does not perturb …

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the

A Cross-Sectional Analysis Of The Vaginal Microenvironment In Rheumatoid Arthritis, Marlyd E Mejia, Savannah Bowman, Jessica Lee, Ali El-Halwagi, Keshia Ferguson, Maryjo Maliekel, Yixuan Zhou, Camille Serchejian, Clare M Robertson, Mallory B Ballard, Lee B Lu, Sobia Khan, Olubunmi O Oladunjoye, Shixia Huang, Sandeep K Agarwal, Kathryn A Patras

Faculty, Staff and Students Publications

The human microbiota is implicated in the development and progression of rheumatoid arthritis (RA). Given the increased RA burden in women and well-known correlations between the vaginal microbiota and local inflammation, we seek to understand the vaginal microenvironment in the context of RA pathology. Self-collected vaginal swabs and questionnaires on dietary, menstrual, and health information were obtained from 36 RA and 50 demographically-matched control women, 18–63 years of age. Medication regimen, along with disease activity and severity, was captured for the RA cohort. Vaginal swabs were subjected to long-read 16S rRNA gene sequencing, multiplex cytokine analyses, and quantification of rheumatoid …

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 …

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

Faculty, Staff and Students Publications

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

Transient Yap Activation Uncovers The Neurogenic Potential Of Proliferative Mammalian Müller Glia, English J Laserna, Irina V Saltykova, Benjamin M Hall, Xuefei Tong, Justin S Dhindsa, Borna Sarker, Ayrea E Hurley, Paul G Swinton, William R Lagor, Nicholas M Tran, James F Martin, Ross A Poché

Faculty, Staff and Students Publications

The Hippo pathway effector YAP promotes spontaneous proliferation of Müller glia (MG), suggesting that bypassing Hippo signaling and activating YAP could enhance retinal regeneration. However, whether proliferative adult MGs retain meaningful neurogenic competence remains unclear. Here, using viral delivery of a Hippo-resistant YAP variant to wild-type adult MGs, we achieved transient YAP activation in adult MGs, inducing proliferation followed by cell-cycle withdrawal and differentiation. Intersectional genetic lineage tracing and EdU labeling, combined with transcriptomic analyses, revealed that YAP-activated MGs predominantly regenerate MGs, whereas only a subset gives rise to bipolar cell-like neurons. These results indicate that proliferative MGs acquire a …

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 …

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

Faculty, Staff and Students Publications

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

Systematic Identification Of Cell-Cell Interactions Associated With The Severity Of Patients With Alzheimer’S Disease, Zijian Zhang, Naail Chowdhury, Jing Dong, Lang Wu, Chao Cheng

Faculty, Staff and Students Publications

Background

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder involving dysfunction across multiple brain regions. While accumulating evidence has implicated the roles of diverse cell types, including neurons, glia, and vascular cells in AD pathogenesis, it is still poorly understood how cell type interactions drive or respond to the disease progression and severity.

Objective

This study aimed to systematically characterize cell-type–specific alterations and intercellular communication changes associated with AD progression.

Methods

We leveraged the transcriptome profiling and a previously established statistical framework to present a comprehensive mapping of the cellular interaction landscape in the human brain of AD.

Results …

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

Faculty, Staff and Students Publications

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

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

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

Center for Medical Ethics and Health Policy Staff Publications

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

Association Of Insulin Resistance And Fracture Risk In The Osteoporotic Fractures In Men (Mros) Cohort, Jeonghoon Ha, Li-Yung Lui, Kristine Ensrud, Qian Xiao, Andrew R Hoffman, Joy Y Wu

Faculty, Staff and Student Publications

Context: Insulin resistance (IR) is more prevalent in men than in women, but evidence directly linking IR to fracture risk in older men remains limited.

Objective: To evaluate the association between insulin resistance (IR), estimated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the triglyceride-glucose (TyG) index, and fracture risk in older men.

Methods: Data from 5994 men (≥65 years) in the MrOS cohort were analyzed. A total of 5416 participants were included in the HOMA-IR analysis and 5384 in the TyG index analysis. Fractures were self-reported and confirmed radiographically. Participants were grouped into quartiles based on IR …

Age And Sex Affect The Prevalence And Severity Of Periodontal Conditions In An Academic Setting, Karo Parsegian, Nikolaos Soldatos, Tonia C Carter, Nikola Angelov, Neel Shimpi, Krishna Kumar Kookal, David K Okano, Effie Ioannidou

Faculty, Staff and Student Publications

Background: The aim of the present study was to examine whether age and sex affected the prevalence and severity of periodontal conditions in patients attending an academic dental clinic.

Methods: Electronic health record (EHR) data on the demographic characteristics and periodontal conditions of patients presented for a comprehensive periodontal evaluation were extracted from the institutional dental EHR database. Retrospective analysis of independent associations of age, sex, and other subject characteristics with periodontal conditions was determined using multinomial logistic regression. The null hypothesis stating that age and sex were not associated with the increased prevalence and/or severity of periodontal conditions was …

Cytosignal Detects Locations And Dynamics Of Ligand-Receptor Signaling At Cellular Resolution From Spatial Transcriptomic Data, Jialin Liu, Hiroaki Manabe, Weizhou Qian, Shion Orikasa, Javid Ghaemmaghami, Yichen Wang, Yichen Gu, Angel Ka Yan Chu, Gaurav Gadhvi, Yuxuan Song, Patrick Mcclinden, Vibha N Lama, Noriaki Ono, Joshua D Welch

Faculty, Staff and Student Publications

Cells communicate through ligand-receptor (LR) signaling interactions, but identifying when and where these interactions are active remains challenging. We developed CytoSignal to infer the locations and dynamics of cell-cell communication at cellular resolution from spatial transcriptomic data. Here we show that our cellular resolution, spatially resolved signaling scores enable several important analyses-identifying spatial gradients in signaling strength, quantifying the locations of contact-dependent and diffusible interactions, detecting signaling-associated genes and identifying differential signaling across multisample data. Additionally, we can predict the temporal dynamics of a signaling interaction at each spatial location. We experimentally validate our results in situ by proximity ligation …

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

Faculty, Staff and Student Publications

No abstract provided.

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

Faculty, Staff and Students Publications

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

Whole Genome Sequencing Analysis Of Over 3500 Individuals Dementia-Free Over 85 Years Old, Gina M Peloso, Dongyu Wang, Sabrina M Abbruzzese, Joshua C Bis, Seung Hoan Choi, Alexa Beiser, Jan Bressler, Josée Dupuis, Alison E Fohner, Mohsen Ghanbari, Richard A Gibbs, Nancy Heard-Costa, M Arfan Ikram, Paul Lacaze, Quentin Le Grand, Oscar L Lopez, Thomas H Mosley, Moeen Riaz, Aïcha Soumaré, Amber Yaqub, Eric Boerwinkle, Bruce M Psaty, Myriam Fornage, Sudha Seshadri, Anita L Destefano

Faculty, Staff and Students Publications

BACKGROUND:

Identifying genetic variants conferring resilience to Alzheimer’s disease and related dementia (ADRD) may hold promise for developing therapeutics.

OBJECTIVE:

To determine genetic associations with being dementia-free at age 85 (DF85).

METHODS:

We examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF≤1%) coding and non-coding variants in DF85 participants (n=3,657) against individuals who were not DF85 (n=20,010). We verified associations using a stricter control set who developed dementia before age 85 (n=5,552).

RESULTS: …

Disease-Specific Growth Charts Capture Characteristic Growth Patterns In Children With Pmm2 – Cdg, Kyriakie Sarafoglou, Christina Lam, Andrew C Edmondson, Andrea Miller, Rodrigo T Starosta, Aziza Zeighami, Seishu Horikoshi, Hayden Vreugdenhil, Fernando Scaglia, Tamas Kozicz, Queenie K G Tan, Bradley S Miller, Iván Martínez-Duncker, Gerard T Berry, Peter Mcwilliams, Eva Morava, Yaw Addo

Faculty, Staff and Students Publications

Background: Growth faltering is prevalent in 96% of children with Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG). Published long-term growth data is extremely limited. Growth and weight patterns of PMM2-CDG children differ from the general population limiting the utility of existing normative growth charts to track development trajectory in comparison to peers with PMM2-CDG.

Objective: Create PMM2-CDG disease-specific height-, weight-, and BMI-for-age reference growth charts (0-20 years).

Methods: De-identified growth data was provided by Frontiers in Congenital Disorders of Glycosylation Consortium, CDG Care, Minnesota Partnership for Biotechnology and Medical Genomics, and Glycomine, Inc. Semi-parametric modeling techniques were used to develop PMM2-CDG-specific …

Plasticity And Language In The Anaesthetized Human Hippocampus, Kalman A Katlowitz, Eric R Cole, Elizabeth A Mickiewicz, Shraddha Shah, Melissa Franch, Joshua A Adkinson, James L Belanger, Raissa K Mathura, Domokos Meszéna, Matthew Mcginley, William Muñoz, Garrett P Banks, Sydney S Cash, Chih-Wei Hsu, Angelique C Paulk, Nicole R Provenza, Andrew J Watrous, Ziv Williams, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Sarah R Heilbronner, Robert Kim, Nuttida Rungratsameetaweemana, Benjamin Y Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

Consciousness is a fundamental component of cognition1, but the degree to which higher-order pattern recognition relies on it remains disputed2,3. Here we demonstrate the persistence of oddball discrimination, semantic processing and online prediction in individuals under general-anaesthesia-induced loss of consciousness4,5. Using high-density Neuropixels microelectrodes6 to record both single-unit and local-field-potential neural activity in the human hippocampus while playing a series of tones to anaesthetized patients, we found that hippocampal neurons and local oscillations retained some detection of oddball tones. This effect size grew over the course of the experiment …

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

Faculty, Staff and Students Publications

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

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

Faculty, Staff and Students Publications

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

Full-Body Ai Agent: A Perspective On Multi-Scale Collaborative Ai For Systemic Biology And Precision Medicine., Aoqi Wang, Jiajia Liu, Jianguo Wen, Yangyang Luo, Zhiwei Fan, Liren Yang, Xi Hu, Ruihan Luo, Yankai Yu, Sophia Li, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Artificial intelligence (AI) is increasingly applied to biomedical research, but most current systems remain limited to specific tasks, data types, or biological scales. This makes it difficult to connect molecular alterations, organelle dysfunction, cellular behavior, tissue remodeling, organ physiology, systemic regulation, and whole-body phenotypes into coherent biological reasoning. In this Perspective, we propose the Full-Body AI Agent as a hypothetical multi-agent framework and conceptual blueprint for future systemic biology and precision medicine, rather than a fully implemented software platform. This framework envisions a supervisory Full-Body AI Agent coordinating seven biological-level agents, namely Molecule, Organelle, Cell, Tissue, Organ, Organ System, and …

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

Faculty, Staff and Student Publications

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

Triple Tracer Heterogeneity In Dual Neoplasia: The "Three Musketeers" In Discerning Squamous Cell Carcinoma And Paraganglioma In The Same Patient, Shyam Kumar Ravada, Gaurav Malhotra, Aaditya Daga, Anurag R Lila, Saba Memon, Tushar Bandgar

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma of unknown primary (HNSCCUP) comprises 2%-5% of head and neck squamous cell cancers (HNSCC). Its coexistence with abdominal paraganglioma is exceedingly rare. We report a unique case of a 48-year-old male with HNSCCUP presenting as cervical lymphadenopathy and a coexisting abdominal paraganglioma. 18 F-FDG showed uptake in both lesions, while 68 Ga-DOTATATE was avid only in paraganglioma, and 68 Ga-DOTA-FAPI-04 was avid only in cervical nodes. These differential uptake patterns reflect distinct tumor biology and underscore the potential for tailoring theranostic treatment strategies with 177 Lu/ 90 Y isotopes for FAPI-avid squamous cell cancers …

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Student Publications

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

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

A Trans-Omics Gene-Smoking Interaction Study Of Lung Cancer Based On Consortium Data, Ning Xie, Xiaowen Xu, Yanru Wang, Aoxuan Wang, Xiang Wang, Xuan Wang, Mengsheng Zhao, Jiacheng Zhou, Yongyue Wei, Manel Esteller, Zhibin Hu, Hongbing Shen, Rayjean J Hung, Christopher I Amos, Yi Li, David C Christiani, Feng Chen, Yang Zhao, Ruyang Zhang

Faculty, Staff and Students Publications

Rationale: Genetically predicted molecular traits provide a cost-effective approach for identifying biomarkers and uncovering underlying biological mechanisms. We extended this framework to investigate gene-smoking interactions in lung cancer susceptibility.

Objectives: To identify trans-omics gene-smoking interactions affecting lung cancer risk and to assess how biomarkers modify effect of smoking.

Methods: We conducted the first trans-omics gene-smoking interaction study of lung cancer by integrating consortium-scale individual genotype data (27 737 cases vs 449 910 noncases) from the International Lung Cancer OncoArray Consortium (ILCCO-OncoArray), Transdisciplinary Research Into Cancer of the Lung (TRICL), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the …

Malaria In Children At 9 Us Hospitals: 2016-2023, Sesh Alexander Sundararaman, Brianne Roper, Amy K F Davis, Karen L Hanze Villavicencio, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Ziyi Wang, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Objectives: This study set out to describe imported pediatric malaria in the United States over an 8-year period, including patient demographics, clinical outcomes, and risk factors for severe disease.

Methods: A retrospective descriptive study of pediatric patients treated for malaria at 9 hospitals in the United States from 2016 to 2023 was conducted to analyze patient demographics, clinical outcomes, and risk factors for severe malaria.

Results: A total of 171 children were treated across the 9 US hospitals included in this study from 2016 to 2023. Most patients had traveled to West Africa to visit friends and relatives. Fever was …