Medicine and Health Sciences Commons^™

Excellent Outcomes In Feasibility Study Of Radiation-Free Conditioning And Transplant In Pediatric Severe Aplastic Anemia, Mithra Lakshmi Narasimhan, Irem Eldem, Jeffrey J Bednarski, Ginny L Schulz, Robert J Hayashi, Shalini Shenoy

2020-Current year OA Pubs

Severe aplastic anemia (SAA) is treated with a hematopoietic cell transplant (HCT) in the presence of an HLA-matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), graft-versus-host disease (GVHD), and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes …

A Single-Cell Atlas Characterizes Dysregulation Of The Bone Marrow Immune Microenvironment Associated With Outcomes In Multiple Myeloma, William C Pilcher, Lijun Yao, Yizhe Song, Kazuhito Sato, Julia T Wang, Reyka G Jayasinghe, Jennifer A Foltz, Mark A Fiala, Chiang I-Ling, Julie Fortier, Michael Slade, Stephen T Oh, Michael P Rettig, John F Dipersio, Shaji Kumar, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune …

A Catecholamine-Independent Pathway Controlling Adaptive Adipocyte Lipolysis, Xiao Zhang, Sreejith S Panicker, Jordan M Bollinger, Anurag Majumdar, Rami Kheireddine, Lila F Dabill, Clara Kim, Brian Kleiboeker, Fengrui Zhang, Kristann L Magee, Adam Kepecs, Gretchen A Meyer, Irfan J Lodhi, Erica L Scheller, Et Al.

2020-Current year OA Pubs

Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent …

Defining Radiological Healing In Perianal Fistulizing Crohn's Disease: A Topclass Global Expert Delphi Consensus, Easan Anand, Jalpa Devi, David H Ballard, Shivani Joshi, Phil Tozer, Ailsa Hart, Anna Antoniou, Parakkal Deepak, Jaap Stoker, Phillip Lung, Topclass Collaborative Authors

2020-Current year OA Pubs

BACKGROUND & AIMS: Perianal fistulising Crohn's disease (pfCD) affects one-fifth of patients with Crohn's disease (CD), significantly affecting their quality of life. Magnetic resonance imaging is the gold standard for evaluating fistula healing in pfCD, but variability in radiological definitions hampers meaningful clinical interpretation and consistent trial design. This study aimed to establish an international consensus on the definition of radiological healing in pfCD.

METHODS: The study was conducted in 2 phases. Phase 1 involved a systematic review to identify magnetic resonance imaging-based variables and indices used to define healing in pfCD, assessing methodological quality using the COnsensus-based Standards for …

Atomic Models Of The Toxoplasma Cell Invasion Machinery, Jianwei Zeng, Yong Fu, Pengge Qian, Wei Huang, Qingwei Niu, Wandy L Beatty, Alan Brown, L David Sibley, Rui Zhang

2020-Current year OA Pubs

Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal …

Dysregulated Lactate Metabolism Synergizes With Als Genetic Risk Factors To Accelerate Motor Decline, Shweta Tendulkar, Tong Wu, Amy Strickland, Amber R. Hackett, Yurie Sato-Yamada, Xianrong Mao, Yo Sasaki, Jeffrey Milbrandt, A. Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Neurons rely on glial 'lactate shuttling' for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional …

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

Maxgrnet: A Multi-Axis Vision Transformer With Improved Generalization For Eye Disease Classification Using Explainable Ai With Insertion-Deletion Operations On Fundus Images, Md Mehedi Hasan Santo, Fuyad Hasan Bhoyan, Fuad Ibne Jashim Farhad, Fahmid Al Farid, Sovon Chakraborty, Md Humaion Kabir Mehedi, Jia Uddin, Hezerul Bin Abdul Karim

Computer Science Faculty Publications

Eye diseases, including diabetic retinopathy (DR), glaucoma, and cataracts, represent a major global health concern and can lead to severe visual impairment or blindness if not identified in a timely manner. This study proposes a novel eye disease classification framework based on a multi-axis vision transformer (MaxViT) applied to color fundus images with Explainable Artificial Intelligence (XAI) techniques to enhance model transparency. The proposed architecture integrates transformer-based attention mechanisms with Global Response Normalization (GRN)-based multi-layer perceptron (MLP) layers to capture complex spatial and contextual relationships within fundus images effectively. The model was evaluated on a publicly available eye disease classification …

Privacy-Preserving Federated Learning With Optimized Ensemble Weighting And Knowledge Distillation For Covid-19 Detection From Non-Iid Medical Imaging Data, Richard Annan, Hong Qin, Robert Newman, Madhuri Siddula, Letu Qingge

Computer Science Faculty Publications

Medical imaging enables rapid and accurate diagnosis of COVID-19, with CT scans proving especially effective. However, data privacy concerns limit collaborative model development across hospitals. To address this issue, we introduce a novel federated learning framework. It is referred to as Independent Knowledge Distillation with post-Ensemble Federated Learning (IKDEFL). Differential Privacy (DP) is integrated into the framework to improve privacy guarantees. Three DP mechanisms are evaluated. These include Fixed Gaussian, Gaussian Adaptive, and Tree Adaptive. The evaluation has been conducted on heterogeneous and Non-Independent and Identically Distributed (Non-IID) datasets. These datasets reflect real-world hospital scenarios. Results show that IKDEFL significantly …

Isotropic Shrinkage Of Patterned Vacancies Enables Three-Dimensional Nanoprecise Metastructures For Visible Light Applications, Quansan Yang, Gaojie Yang, Takahiro Nambara, Hiroyuki Kusaka, Yuichiro Kunai, Alex C. Matlock, Corban Swain, Brett Pryor, Yannick Salamin, Daniel Oran, Hasindu Kariyawasam, Ramith Hettiarachchi, Dushan Wadduwage, Marin Soljačić, Peter T. C. Soflaei, Edward S. Boyden

Computer Science Faculty Publications

Three-dimensional metastructures with nanoscale feature sizes exhibit unique properties compared with structures with larger feature sizes, but are difficult to fabricate. Here we introduce implosion carving (ImpCarv), a method for photopatterning vacancies of complex geometry throughout materials, followed by isotropic shrinkage (>10-fold). ImpCarv works by photoactivating sensitizers to generate reactive oxygen species that cleave a swollen hydrogel at defined points, followed by controlled shrinkage via dehydration. ImpCarv creates three-dimensional metastructures where the refractive index of each point throughout a material can be specified with nanoscale precision via material presence or absence. By leveraging refractive index programmability for precise phase …

An Investigation Of Federated Gnns Under Aggregation, Data Poisoning, And Differential Privacy For Icu Length-Of-Stay Prediction, Shakib Mahmud Dipto, Soumya Banerjee, Sandip Roy, Ahmad F. Al Musawi, Preetam Ghosh, Sachin Shetty, Pratip Rana

Computer Science Faculty Publications

Accurate prediction of ICU Length of Stay (LoS) is essential for clinical decision-making and healthcare resource management. Graph Neural Networks (GNNs), such as GraphSAGE, offer a natural fit by capturing patient data from Electronic Health Records (EHRs) through graph structures. However, the distributed and sensitive nature of this data raises both privacy and legal concerns regarding the aggregation and training of GNN models. This additionally leads to issues with data imbalance and model robustness. In this study, we perform an analysis of the Federated Graph Neural Network (GNN-FL) framework to enable decentralized learning on EHRs derived from the MIMIC-III dataset. …