Digital Commons Network^™

Spatial Clustering Of Immunosuppressive Macrophages In Papillary Renal Cell Carcinoma, Mitchell T. Hayes, Jose Laborde, Alex Soupir, Anders Berglund, Jamie K. Teer, Kirill Sabitov, Nicholas H. Chakiryan, Taylor C. Peak, Jonathan Nguyen, Carlos Moran-Segura, Daryoush Saeed-Vafa, Neale Lopez-Blanco, Martina Molgora, Paola M. Ramos-Echevarria, Christopher Guske, Jodi Balasi, Jasreman Dhillon, Youngchul Kim, James Mule, Brooke L. Fridley, Brandon J. Manley

Manuscripts, Articles, Book Chapters and Other Papers

Background

Papillary renal cell carcinoma (pRCC) is the second most common kidney cancer subtype, yet our understanding of its tumor immune microenvironment (TIME) remains limited.

Objective

We utilized multiplex immunofluorescence (mIF) and spatial transcriptomics (ST) to evaluate immune cell architecture in pRCC contrasted with clear cell RCC (ccRCC).

Methods

Localized RCC tumors (16 pRCC, 70 ccRCC) underwent mIF using markers for T cells, B cells, and tumor-associated macrophages (TAMs). Spatial data in both tumor and stromal compartments of the TIME were collected. A post hoc recurrence free survival analysis (RFS) was performed using Cox proportional hazard models. Single-cell ST was …

Germline And Somatic Changes Associated With The Development Of Inherited And De Novo Pediatric Acute Myeloid Leukemia., Scott C. Smith, Lei Zhang

Manuscripts, Articles, Book Chapters and Other Papers

Acute myeloid leukemia (AML) accounts for only about 15-20% of pediatric leukemia and an overall incidence of 1.4 cases per 200,000 children under the age of 15 years. The majority of pediatric AML occurs de novo, often as the result of somatic first hits in utero. A minority of pediatric AML occurs in response to a predisposition syndrome, such as a bone marrow failure syndrome, or other inherited mutations and copy number changes. While the overall survival of pediatric patients with AML is approximately 70%, survival at the individual level is dependent on the abnormality detected either through cytogenomic analyses …

Pathologist-Read Vs Ai-Driven Assessment Of Tumor-Infiltrating Lymphocytes In Melanoma, Thazin N Aung, Matthew Liu, David Su, Saba Shafi, Ceren Boyaci, Sanna Steen, Nikolaos Tsiknakis, Joan Martinez Vidal, Nigel Maher, Goran Micevic, Samuel X Tan, Matthew D Vesely, Saeed Nourmohammadi, Yalai Bai, Dijana Djureinovic, Pok Fai Wong, Katherine Bates, Nay N N Chan, Niki Gavirelatou, Mengni He, Sneha Burela, Robert Barna, Martina Bosic, Konstantin Bräutigam, Irineu Illabochaca, Zhou Chenhao, Joao Gama, Bianca Kreis, Reka Mohacsi, Nir Pillar, Joao Pinto, Christos Poulios, Maria Angeliki Toli, Evangelos Tzoras, Yadriel Bracero, Francesca Bosisio, Gábor Cserni, Alis Dema, Francesco Fortarezza, Mercedes Solorzano Gonzalez, Irene Gullo, Francisco Javier Queipo Gutiérrez, Ezgi Hacihasanoglu, Viktor Jovic, Bianca Lazar, Maria Olinca, Christina Neppl, Rui Caetano Oliveira, Federica Pezzuto, Daniel Gomes Pinto, Vanda Plotar, Ovidiu Pop, Tilman Rau, Kristijan Skok, Wenwen Sun, Ezgi Dicle Serbes, Wiebke Solass, Olga Stanowska, Marcell Szasz, Krzysztof Szymonski, Franziska Thimm, Danielle Vignati, Alon Vigdorovits, Victor Prieto, Tobias Sinnberg, James Wilmott, Shawn Cowper, Jonathan Warrell, Yvonne Saenger, Johan Hartman, Jasmine Plummer, Iman Osman, David L Rimm, Balazs Acs

Faculty, Staff and Student Publications

Importance: Tumor-infiltrating lymphocytes (TILs) are a provocative biomarker in melanoma, influencing diagnosis, prognosis, and immunotherapy outcomes; however, traditional pathologist-read TIL assessment on hematoxylin and eosin-stained slides is prone to interobserver variability, leading to inconsistent clinical decisions. Therefore, development of newer TIL scoring approaches that produce more reliable and consistent readouts is important.

Objective: To evaluate the analytical and clinical validity of a machine learning algorithm for TIL quantification in melanoma compared with traditional pathologist-read methods.

Design, setting, and participants: This multioperator, global, multi-institutional prognostic study compared TIL scoring reproducibility between traditional pathologist-read methods and an artificial intelligence (AI)-driven approach. The …

Adtnorm: Robust Integration Of Single-Cell Protein Measurement Across Cite-Seq Datasets, Ye Zheng, Daniel P Caron, Ju Yeong Kim, Seong-Hwan Jun, Yuan Tian, Florian Mair, Kenneth D Stuart, Peter A Sims, Raphael Gottardo

Faculty, Staff and Student Publications

Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) enables paired measurement of surface protein and mRNA expression in single cells using antibodies conjugated to oligonucleotide tags. Due to the high copy number of surface protein molecules, sequencing antibody-derived tags (ADTs) allows for robust protein detection, improving cell-type identification. However, variability in antibody staining leads to batch effects in the ADT expression, obscuring biological variation, reducing interpretability, and obstructing cross-study analyses. Here, we present ADTnorm, a normalization and integration method designed explicitly for ADT abundance. Benchmarking against 14 existing scaling and normalization methods, we show that ADTnorm accurately aligns populations …

Image-Based Mandibular And Maxillary Parcellation And Annotation Using Computed Tomography (Impact): A Deep Learning-Based Clinical Tool For Orodental Dose Estimation And Osteoradionecrosis Assessment, Laia Humbert-Vidan, Austin H Castelo, Renjie He, Lisanne V Van Dijk, Dong Joo Rhee, Congjun Wang, He C Wang, Kareem A Wahid, Sonali Joshi, Parshan Gerafian, Natalie West, Zaphanlene Kaffey, Sarah Mirbahaeddin, Jaqueline Curiel, Samrina Acharya, Amal Shekha, Praise Oderinde, Alaa M S Ali, Andrew Hope, Erin Watson, Ruth Wesson-Aponte, Steven J Frank, Carly E A Barbon, Kristy K Brock, Mark S Chambers, Muhammad Walji, Katherine A Hutcheson, Stephen Y Lai, Clifton D Fuller, Mohamed A Naser, Amy C Moreno, Opc-Survivor Program, Md Anderson Head And Neck Cancer Symptom Working Group

Faculty, Staff and Student Publications

Background and purpose: Accurate delineation of orodental structures on radiotherapy computed tomography (CT) images is essential for dosimetric assessment and dental decisions. We propose a deep-learning (DL) auto-segmentation framework for individual teeth and mandible/maxilla sub-volumes aligned with the ClinRad osteoradionecrosis staging system.

Materials and methods: Mandible and maxilla sub-volumes were manually defined on simulation CT images from 60 clinical cases, differentiating alveolar from basal regions; teeth were labelled individually. For each task, a DL segmentation model was independently trained. A Swin UNETR-based model was used for mandible sub-volumes. For smaller structures (e.g., teeth and maxilla sub-volumes) a two-stage model first …

The Evolution Of Multidisciplinary Head And Neck Cancer Treatment, Kevin J Contrera, Pooja D Reddy, Vanessa Helou, Jeffrey N Myers, Heath D Skinner, Renata Ferrarotto, Eugene N Myers

Faculty, Staff and Student Publications

Objective: The management of head and neck squamous cell carcinoma (HNSCC) has substantially changed over the past two centuries. This review explores the historical progression of HNSCC management focusing on the multidisciplinary treatment paradigm.

Data sources: This review synthesizes data from historical and current clinical trials, books, scientific reports, public documents, and other written material relevant to HNSCC management.

Review methods: Historical review.

Results: Although surgery was initially the only treatment available, radiation, chemotherapy, and immunotherapy have expanded the treatment landscape for HNSCC. Despite continuous evolution, modern treatment of HNSCC remains rooted in a multidisciplinary, personalized approach. This review highlights …

Liger-Hn Phase Iii Trials Of Petosemtamab + Pembrolizumab And Petosemtamab Monotherapy In Recurrent Or Metastatic Hnscc, Jean-Pascal Machiels, Jérôme Fayette, Robert Haddad, Douglas Adkins, Maura Gillison, Kevin J Harrington, Sung-Bae Kim, Christophe Le Tourneau, Amanda Psyrri, Ari Rosenberg, Lillian L Siu, Makoto Tahara, William N William, Jim Ford, Shekeab Jauhari, Rebecca Pyle, Yu-Ming Shen, David Yao, Fabian Zohren, Everett Vokes

Faculty, Staff and Student Publications

Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, especially when their cancer is resistant to standard treatments like anti-programmed cell death protein 1 and platinum-based therapies. Petosemtamab - a human, common light chain, bispecific antibody with enhanced antibody-dependent cellular cytotoxicity targeting epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) - demonstrated antitumor activity in r/m HNSCC. In many tumor types, including HNSCC, EGFR is an oncogenic driver, while LGR5 is upregulated. LGR5 can potentiate the wingless-type integration site (WNT)/β-catenin signaling pathway in response to …

Mutation Dynamics From Diagnosis To Relapse In Acute Myeloid Leukemia With Chromosomal 7 Deletions, Eitan Kugler, Enes Dasdemir, Alex Bataller, Bofei Wang, Courtney D Dinardo, Naval Daver, Musa Yilmaz, Nicholas J Short, Gautam Borthakur, Tapan M Kadia, Koji Sasaki, Danielle Hammond, Alexandre Bazinet, Ehsan Irajizad, Beenu Thakral, Sherry Pierce, Patrick Reville, Farhad Ravandi, Hussein A Abbas

Faculty, Staff and Student Publications

Monosomy 7 and 7q deletions (-7/del(7q)) are the most common adverse cytogenetic event in acute myeloid leukemia (AML), linked to high relapse rates. We analyzed 115 AML patients with -7/del(7q) who achieved remission after induction therapy to characterize the mutational landscape from diagnosis to relapse. Median overall survival (OS) was 10.4 months, with improved survival in patients without TP53 mutation (13.04 vs. 8.6 months) or complex karyotype (12.4 vs. 8.6 months). TP53 mutations were most frequent (67% of cases at diagnosis) and persisted in 97% of patients at relapse. At time of relapse, patients with TP53 mutations had fewer co-occurring …

A Visual-Omics Foundation Model To Bridge Histopathology With Spatial Transcriptomics, Weiqing Chen, Pengzhi Zhang, Tu N Tran, Yiwei Xiao, Shengyu Li, Vrutant V Shah, Hao Cheng, Kristopher W Brannan, Keith Youker, Li Lai, Longhou Fang, Yu Yang, Nhat-Tu Le, Jun-Ichi Abe, Shu-Hsia Chen, Qin Ma, Ken Chen, Qianqian Song, John P Cooke, Guangyu Wang

Faculty, Staff and Student Publications

Artificial intelligence has revolutionized computational biology. Recent developments in omics technologies, including single-cell RNA sequencing and spatial transcriptomics, provide detailed genomic data alongside tissue histology. However, current computational models focus on either omics or image analysis, lacking their integration. To address this, we developed OmiCLIP, a visual-omics foundation model linking hematoxylin and eosin images and transcriptomics using tissue patches from Visium data. We transformed transcriptomic data into 'sentences' by concatenating top-expressed gene symbols from each patch. We curated a dataset of 2.2 million paired tissue images and transcriptomic data across 32 organs to train OmiCLIP integrating histology and transcriptomics. Building …

Blood Bacterial Dna Signatures In A Prospective Cohort Of Patients With Masld Cirrhosis, Suet-Ying Kwan, Lillian I Dolapchiev, Caren I Sanchez, Tiffany L Calderone, Jessica I Sanchez, Megha B Bhongade, Ahmed El Sabagh, Darrel W Cleere, Nakul Gupta, Prasun K Jalal, David W Victor, Laura Beretta

Faculty, Staff and Student Publications

Background: Predictive biomarkers are needed to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), at high risk for HCC. Our study aimed to determine whether the detection of circulating bacterial DNA could be associated with HCC development in MASLD patients with liver cirrhosis.

Methods: We developed a multicenter prospective cohort of patients with cirrhosis undergoing surveillance for HCC by contrast-enhanced magnetic resonance imaging. In a nested cohort study, we performed 16S rRNA sequencing of cell-free DNA extracted from 343 longitudinal plasma samples collected from 151 MASLD patients with cirrhosis. Among the 151 patients, 25 developed HCC during follow-up.

Results: …

Impacts Of Radiation On Metabolism And Vascular Cell Senescence, Junichi Abe, Khanh Chau, Anahita Mojiri, Guangyu Wang, Masayoshi Oikawa, Venkata S K Samanthapudi, Abigail M Osborn, Keila C Ostos-Mendoza, Karla N Mariscal-Reyes, Tammay Mathur, Abhishek Jain, Joerg Herrmann, Syed Wamique Yusuf, Sunil Krishnan, Anita Deswal, Steven H Lin, Sivareddy Kotla, John P Cooke, Nhat-Tu Le

Faculty, Staff and Student Publications

Significance: This review investigates how radiation therapy (RT) increases the risk of delayed cardiovascular disease (CVD) in cancer survivors. Understanding the mechanisms underlying radiation-induced CVD is essential for developing targeted therapies to mitigate these effects and improve long-term outcomes for patients with cancer.

Recent Advances: Recent studies have primarily focused on metabolic alterations induced by irradiation in various cancer cell types. However, there remains a significant knowledge gap regarding the role of chronic metabolic alterations in normal cells, particularly vascular cells, in the progression of CVD after RT.

Critical Issues: This review centers on RT-induced metabolic alterations in vascular cells …

Heat Shock Induces Alternative Polyadenylation Through Dynamic Dna Methylation And Chromatin Looping, Emily E Fink, Yi Zhang, Briana Santo, Anwita Siddavatam, Rosie Ou, Vishal Nanavaty, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood. Previously, we elucidated a DNA methylation-regulated APA mechanism, in which gene body DNA methylation enhances distal poly(A) isoform expression by blocking CCCTC-binding factor (CTCF) binding and chromatin loop formation at APA control regions. We hypothesized that DNA methylation-regulated APA is one mechanism cells employ to induce proteostasis-promoting poly(A) isoforms. At the DNAJB6 cochaperone locus, acute heat shock resulted in binding of stress response transcription factors heat shock factor 1, ATF6, and YY1 at …

Powerest: Statistical Power Estimation For Spatial Transcriptomics Experiments To Detect Differentially Expressed Genes Between Two Conditions, Lan Shui, Anirban Maitra, Ying Yuan, Ken Lau, Harsimran Kaur, Liang Li, Ziyi Li

Faculty, Staff and Student Publications

Recent advancements in spatial transcriptomics (ST) have significantly enhanced biological research in various domains. However, the high cost for current ST data generation techniques restricts the large-scale application of ST. Consequently, maximization of the use of available resources to achieve robust statistical power for ST data is a pressing need. One fundamental question in ST analysis is detection of differentially expressed genes (DEGs) under different conditions using ST data. Such DEG analyses are performed frequently, but their power calculations are rarely discussed in the literature. To address this gap, we developed PoweREST, a power estimation tool designed to support the …

Tumour And Microenvironment Crosstalk In Nsclc Progression And Response To Therapy, Zahraa Rahal, Roy El Darzi, Seyed Javad Moghaddam, Tina Cascone, Humam Kadara

Faculty, Staff and Student Publications

The treatment landscape of non-small-cell lung cancer (NSCLC) is evolving rapidly, driven by advances in the development of targeted agents and immunotherapies. Despite this progress, some patients have suboptimal responses to treatment, highlighting the need for new therapeutic strategies. In the past decade, the important role of the tumour microenvironment (TME) in NSCLC progression, metastatic dissemination and response to treatment has become increasingly evident. Understanding the complexity of the TME and its interactions with NSCLC can propel efforts to improve current treatment modalities, overcome resistance and develop new treatments, which will ultimately improve the outcomes of patients. In this Review, …

1d Thermoembolization Model Using Ct Imaging Data For Porcine Liver, Rohan Amare, Danielle Stolley, Steve Parrish, Megan Jacobsen, Rick R Layman, Chimamanda Santos, Beatrice Riviere, Natalie Fowlkes, David Fuentes, Erik Cressman

Faculty, Staff and Student Publications

Innovative therapies such as thermoembolization are expected to play an important role in improving care for patients with diseases such as hepatocellular carcinoma. Thermoembolization is a minimally invasive strategy that combines thermal ablation and embolization in a single procedure. This approach exploits an exothermic chemical reaction that occurs when an acid chloride is delivered via an endovascular route. However, comprehension of the complexities of the biophysics of thermoembolization is challenging. Mathematical models can aid in understanding such complex processes and assisting clinicians in making informed decisions. In this study, we used a Hagen-Poiseuille 1D blood flow model to predict the …

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

A Follow-Up Study On The Novel Use Of Contrast-Enhanced Susceptibility-Weighted Imaging For Extremity Desmoid Fibromatosis Response Assessment, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Ken-Pin Hwang, Jingfei Ma, R Jasson Stafford, Ravin Ratan, John E Madewell, Dejka Araujo, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Desmoid tumors are rare mesenchymal neoplasms characterized by a clonal proliferation of fibroblasts and myofibroblasts. Using the novel contrast-enhanced susceptibility-weighted imaging (CE-SWI) for characterizing desmoid tumors can enhance the separation between fibrous T2-hypointense and cellular T1-enhancing components. We aim to evaluate the effectiveness of the CE-SWI signal, volumetric, and radiomics-derived features in assessing desmoid treatment response. This IRB-approved study included 17 single-lesion extremity desmoid fibromatosis patients who underwent standard-of-care MRI, including CE-SWI, from March 2021 to February 2024. Measurements of maximum diameter, volume, and the modified Choi (m-Choi: tumor/muscle T2 ratio) were computed based on CE-SWI and T2-STIR volumetric tumor …

Cross-Continental Analysis Shows That Disturbance Effects On Reptile Body Condition Do Not Predict Abundance Responses, Kristina J. Macdonald, Don A. Driscoll, Michael D. Craig, Robert A. Davis, Steven J. Hromada, C. M. Gienger, Lee A. Fitzgerald, Daniel J. Leavitt, Danielle K. Walkup, Rickard Abom, Adrian F. Wayne, Gordon R. Friend, Brent Johnson, Danielle Stokeld, Chris R. Dickman, Scott A. Thompson, Graham G. Thompson, Daniel F. Bohórquez Fandiño, Christopher K. Woolley, Annabel L. Smith, Calum Irvine, Tim S. Jessop, Jade E. Keehn, Chris R. Feldman, Xavier Santos, Josabel Belliure

Research outputs 2022 to 2026

Ecological disturbances are discrete events that alter or transform the physical, chemical, or biological characteristics of ecosystems. Disturbance can cause animal populations to decline and, according to the risk-disturbance hypothesis and population collapse framework, these declines can be predicted by declines in animal body condition. However, no research has empirically examined the general relationship between body condition and abundance, nor their relationship in response to disturbance. We used a combined dataset representing 33 studies and > 42,000 observations of 75 species from Australia, New Zealand, Spain and the United States of America to test predictions relating to the relationship between reptile …

Wnt-Directed Cxcl12-Expressing Apical Papilla Progenitor Cells Drive Tooth Root Formation, Mizuki Nagata, Gaurav T Gadhvi, Taishi Komori, Yuki Arai, Hiroaki Manabe, Angel Ka Yan Chu, Ramandeep Kaur, Meer Ali, Yuntao Yang, Chiaki Tsutsumi-Arai, Yuta Nakai, Yuki Matsushita, Nicha Tokavanich, W Jim Zheng, Joshua D Welch, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

The tooth root is a critical component of the tooth anchored to surrounding alveolar bones. Tooth root formation is driven by cells in the apical papilla (AP) that generate new dentin-forming odontoblasts at the root-forming front. Mesenchymal stem cells have been isolated from AP for regenerative use; however, how AP cells physiologically coordinate tooth root formation remains undefined. We find that CXCL12+ cells emerge in AP under hypoxic environments at the onset of tooth root formation. Using Cxcl12-creER-based cell-lineage analysis, we further find that CXCL12+ AP cells contribute not only to odontoblasts but also to cementum-forming cementoblasts of the elongating …

Cdemapper: Enhancing National Institutes Of Health Common Data Element Use With Large Language Models, Yan Wang, Jimin Huang, Huan He, Vincent Zhang, Yujia Zhou, Xubing Hao, Pritham Ram, Lingfei Qian, Qianqian Xie, Ruey-Ling Weng, Fongci Lin, Yan Hu, Licong Cui, Xiaoqian Jiang, Hua Xu, Na Hong

Faculty, Staff and Student Publications

Objective: Common Data Elements (CDEs) standardize data collection and sharing across studies, enhancing data interoperability and improving research reproducibility. However, implementing CDEs presents challenges due to the broad range and variety of data elements. This study aims to develop a CDE mapping tool to bridge the gap between local data elements and National Institutes of Health (NIH) CDEs.

Methods: We propose CDEMapper, a large language model (LLM)-powered mapping tool designed to assist in mapping local data elements to NIH CDEs. CDEMapper has 3 core modules: (1) CDE indexing and embeddings. NIH CDEs were indexed and embedded to support semantic search; …

Effect Of Tai Chi Practice On The Adaptation To Sensory And Motor Perturbations While Standing In Older Adults, Arion Dey, Huiyeong Chang, Laila Shaaban, Armaan Suga, Genavieve Braden, Andres Bustamante, Jisang Park, Shenhua Zhang, Yang Hu, Manuel E. Hernandez

Faculty Research, Scholarly, and Creative Activity

Tai Chi provides an age-appropriate exercise to decrease fall risks in older adults. However, the exact mechanism underlying the benefits of Tai Chi practice remains an open question. Thus, this study examined how aging and Tai Chi practice impact adaptation to sensory and motor perturbations while standing. We hypothesized that older Tai Chi practitioners would exhibit a decreased reliance on visual processes as sensory and motor perturbations increased, relative to naive healthy older adults. Using rambling and trembling decompositions of the center of pressure (COP) and frequency-domain features, we examined changes in low (0–0.3 Hz), medium (0.3–1 Hz), and high …

Quantifying Marine Carbon Dioxide Removal Via Alkalinity Enhancement Across Circulation Regimes Using Ecco-Darwin And 1d Models, Kay Suselj, Dustin Carroll, Daniel Whitt, Bridget Samuels, Dimitris Menemenlis, Hong Zhang, Nate Beatty, Anna Savage

Faculty Research, Scholarly, and Creative Activity

Ocean Alkalinity Enhancement (OAE) is emerging as a viable method for removing anthropogenic (Formula presented.) emissions from the atmosphere to mitigate climate change. To achieve substantial carbon reductions, OAE would need to be deployed at scale across the global ocean. Hence, there is a need to quantify how the efficiency of OAE varies globally across a range of space-time scales in preparation for field deployments. Here we develop a marine carbon dioxide removal (mCDR) efficiency evaluation framework based on the data-assimilative ECCO-Darwin ocean biogeochemistry model, which separates and quantifies two key factors over seasonal to multi-annual timescales: (a) mCDR potential, …

Paving The Way For Improved Representation Of Coupled Physical And Biogeochemical Processes In Arctic River Plumes—A Case Study Of The Mackenzie Shelf, Clément Bertin, Dustin Carroll, Dimitris Menemenlis, Stephanie Dutkiewicz, Hong Zhang, Melissa Schwab, Raphaël Savelli, Atsushi Matsuoka, Manfredi Manizza, Charles E Miller, Simon Bowring, Bertrand Guenet, Vincent Le Fouest

Faculty Research, Scholarly, and Creative Activity

Processes affecting the transformation of riverine dissolved organic carbon (DOC) across the land-to-ocean aquatic continuum are still poorly constrained in Arctic models, leading to large uncertainties in simulated air–sea CO2 fluxes of the coastal periphery. Here we use the ECCO-Darwin regional configuration of the Southeastern Beaufort Sea to analyze the sensitivity of simulated carbon cycling to (1) the model vertical discretization and (2) different parameterizations of Mackenzie River carbon discharge. We show that riverine DOC lifetime rather than its volume largely modulates Mackenzie River plume air–sea CO2 fluxes, leading to the Southeastern Beaufort Sea (SBS) being either a source (0.03 …

Sex Differences In Motor Unit Behavior In Patients With Parkinson's Disease, Yuichi Nishikawa, Kohei Watanabe, Aleš Holobar, Tetsuya Takahashi, Noriaki Maeda, Hirofumi Maruyama, Allison Hyngstrom

Physical Therapy Faculty Research and Publications

The aim of this study was to determine whether there are sex differences in motor unit firing behavior in patients with Parkinson's disease. Twenty-seven patients with Parkinson's disease (females = 14 [age = 71.1 ± 6.8], males = 13 [age = 69.2 ± 10.3], Unified Parkinson's Disease Rating Scale Part III score; females = 10.8 ± 4.8, males = 11.4 ± 1.4) performed a contraction at 30% of the maximal voluntary contraction. For each participant, motor unit spike trains were decomposed from high-density surface electromyography data recorded from bilateral vastus lateralis muscles via blind source separation algorithms. In addition to …

Graph Convolutional Networks Enable Fast Hemorrhagic Stroke Monitoring With Electrical Impedance Tomography, J. Toivanen, V. Kolehmainen, A. Paldanius, A. Hänninen, A. Hauptmann, Sarah J. Hamilton

Mathematical and Statistical Science Faculty Research and Publications

Objective: To develop a fast image reconstruction method for stroke monitoring with electrical impedance tomography with image quality comparable to computationally expensive nonlinear model-based methods. Methods: A post-processing approach with graph convolutional networks is employed. Utilizing the flexibility of the graph setting, a graph U-net is trained on linear difference reconstructions from 2D simulated stroke data and applied to fully 3D images from realistic simulated and experimental data. An additional network, trained on 3D vs. 2D images, is also considered for comparison. Results: Post-processing the linear difference reconstructions through the graph U-net significantly improved the image quality, resulting in images …

Seasonal And Landscape-Driven Variations In Forage Resources Of Apis Mellifera Scutellata: Implications For Pollination Sustainability And Colony Health In Taita Taveta County, Kenya, Mary Chege, Mbatha B. Wambua, Wambua J. Kilonzo, Sevgan Subramanian, Beatrice T. Nganso

All Peer-Reviewed Publications

Seasonality and land-use change are key factors influencing forage availability for managed honey bee colonies, yet knowledge of forage identity and how these factors influence forage availability remains limited in Africa. To address these gaps, we used DNA metabarcoding to identify nectar and pollen plant species supporting the nutrition of the African savannah honey bee, Apis mellifera scutellata, across different land-use/land cover types and seasons in Taita Taveta County, Kenya. We identified 224 forage plant species from 65 families, with Asteraceae, Fabaceae, and Myrtaceae being the top contributors. Forage availability was significantly influenced by landscape and season, with honey bees …

Enhancing Phenotyping Accuracy For Selection Of Urochloa Spp. Tolerant Genotypes To Red Spider Mite (Oligonychus Trichardti), Paula Espitia-Buitrago, José Miguel Cotes Torres, Luis Miguel Hernández, Juan Andres Cardoso, Frank Chidawanyika, Rosa N. Jauregui

All Peer-Reviewed Publications

The red spider mites are a major biotic limitation to productivity for Brachiaria (Urochloa spp.) grasses in tropical Eastern Africa, causing severe economic losses mainly in the dry seasons. However, due to the lack of reports of integrated pest management strategies, genetic resistance can play a crucial role in Brachiaria-based livestock systems, minimising the impact of this pest. The objective of this study was to develop and validate a methodology for accurately categorising resistance responses in Urochloa genotypes to identify potential sources of resistance to the Western Kenya red spider mite Oligonychus trichardti (Meyer 1974). Accordingly, 25 genotypes of Urochloa …

Meeting Report On An Integrated Research Agenda For Mosquito-Borne Arboviruses, Angela K. Ulrich, Nicolina M. Moua, Alison Mack, Natsuko Imai-Eaton, J. Erin Staples, Angela J. Mehr, Julia T. Ostrowsky, Tabitha Leighton, Ana Cehovin, Petra C. Fay, Josephine P. Golding, Emma Maynard, Luke Alphey, Diana P. Rojas Alvarez, Lark L. Coffey, Nuno R. Faria, Rafael Maciel-De-Freitas, Kevin Maringer, Kris A. Murray, Henrik Salje, Rosemary Sang, Pedro F.C. Vasconcelos, Yee Sin Leo, Steven P. Sinkins, Jocelyne Neto De Vasconcelos, Samuel K. Dadzie, Eva Harris, Thais H. Dos Santos, Raman Velayudhan

All Peer-Reviewed Publications

The emergence and re-emergence of mosquito-borne arbovirus (MBV) diseases pose a rapidly expanding global health threat fueled by the convergence of multiple ecologic, economic, and social factors, including climate change, land use, poverty, deficiencies of water storage and sanitation, and limitations of vector control programs. On December 6, 2023, the Wellcome Trust and the University of Minnesota's Center for Infectious Disease Research and Policy held a meeting titled "An integrated approach to mosquito-borne arboviruses: a priority research agenda."The meeting comprised presentations, panels, and facilitated discussions aimed at describing the state of the field, highlighting recent accomplishments, identifying novel strategies, and …

Autologous T Cell Therapy For Prame, Martin Wermke, Dejka M Araujo, Manik Chatterjee, Apostolia M Tsimberidou, Tobias A W Holderried, Amir A Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J Luke, Cedrik M Britten

Faculty, Staff and Student Publications

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02+ patients with PRAME+ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose …

Memantine Inhibits Calcium-Permeable Ampa Receptors, Elisa Carrillo, Alejandra Montaño Romero, Cuauhtemoc U Gonzalez, Andreea L Turcu, Santiago Vázquez, Edward C Twomey, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Memantine is an US Food and Drug Administration (FDA) approved drug that is thought to selectively inhibit NMDA-subtype of ionotropic glutamate receptors (NMDARs). NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine …