Digital Commons Network^™

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 …

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 …

Developing Reference Plans For Evaluating Global Clinical Trials Credentialing And Psqa Systems, Fre'etta M D Brooks, Mohammad Hussein, Jessica Lye, Christopher L Nelson, Nakamura Mitsuhiro, Mallory C Glenn, Patricia Diez, Rushil Patel, Maddison Shaw, Ileana Silvestre Patallo, Miriam Barry, Catharine H Clark, Joerg Lehmann, Stephen F Kry

Faculty, Staff and Student Publications

Purpose: To develop a practical framework for creating a diverse set of validated reference plans (varying in complexity) and implement a workflow to introduce beam modeling, calibration, and delivery errors into the reference cohort to test and compare various dosimetry audit methodologies.

Methods: Sixteen IMRT and VMAT reference plans were created, using RayStation software, for four phantom geometries based on established credentialing cases from participating Global Harmonization Group (GHG) members. These reference plans were first validated in a multi-ion-chamber phantom. Nine dosimetric errors (perturbations) were introduced into the plans by modifying beam model and/or delivery parameters (MLC-offset, MLC-transmission, leaf-tip-width, PDD, …

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 …

Bayesian Inference Of Fitness Landscapes Via Tree-Structured Branching Processes, Xiang Ge Luo, Jack Kuipers, Kevin Rupp, Koichi Takahashi, Niko Beerenwinkel

Faculty, Staff and Student Publications

Motivation: The complex dynamics of cancer evolution, driven by mutation and selection, underlies the molecular heterogeneity observed in tumors. The evolutionary histories of tumors of different patients can be encoded as mutation trees and reconstructed in high resolution from single-cell sequencing data, offering crucial insights for studying fitness effects of and epistasis among mutations. Existing models, however, either fail to separate mutation and selection or neglect the evolutionary histories encoded by the tumor phylogenetic trees.

Results: We introduce FiTree, a tree-structured multi-type branching process model with epistatic fitness parameterization and a Bayesian inference scheme to learn fitness landscapes from single-cell …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

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 …

Assessment Of Bg-Pro (Biogent Ag) And Silver Bullet 2.1 (Lumin8) Uv-Light Traps Efficiency For Surveillance Of Malaria Vectors In Western Kenya, Billy L. Amugune, Richard Tamre, Dylan Mogaka, Oscar Mbare, Tullu Bukhari, Ulrike Fillinger, Margaret M. Njoroge

All Peer-Reviewed Publications

The Centers for Diseases Control (CDC) light trap is widely used for malaria vector surveillance, but its acquisition logistics pose challenges in Africa. Evaluating new traps can improve surveillance tools. This study compared the efficiency of the BG-Pro UV and Silver Bullet 2.1 UV (SB 2.1 UV) against the UV LED CDC trap in western Kenya’s rice irrigation area. The traps were tested indoors in eight houses over 64 nights. Light properties and fan speed were analyzed using spectrometry and an anemometer. The BG-Pro UV trap performed better than the UV LED CDC trap for An. gambiae s.l. (RR 2.0, …

In Vivo Pulse-Chase In Caenorhabditis Elegans Reveals Intestinal Histone Turnover Changes Upon Starvation, Christopher Borchers, Kara Osburn, Hyun Cheol Roh, Scott T. Aoki

Faculty Work Comprehensive List

The ability to study protein dynamics and function in the authentic context of a multicellular organism is paramount to better understand biological phenomena in animal health and disease. Pulse-chase of self-labeling fusion protein tags provides the opportunity to label proteins of interest and track those proteins over time. There are currently several challenges associated with performing in vivo protein pulse-chase in animals, such as cost, reproducibility, and accurate detection methods. The Caenorhabditis elegans model organism has attributes that alleviate many of these challenges. This work tests the feasibility of applying the Halo modified enzyme (HaloTag) for in vivo protein pulse-chase …

Cytidine Triphosphate Specifically Modulates Parb-Mediated Dna Compaction: Insights From Single-Molecule Analysis And Parb C-Terminal Lysine Mutagenesis, Lois Akosua Serwaa

Theses and Dissertations

ParB is a central player in bacterial chromosome segregation, and cytidine triphosphate (CTP) is known to modulate its DNA compaction activity. This study explored whether CTP’s regulatory effect is due to specific molecular interactions beyond its known CTP-binding pocket. Using single-molecule flow-stretching and TIRF microscopy, we showed that CTP significantly reduces DNA compaction by wild-type Bacillus subtilis ParB, while ATP has no effect, supporting the hypothesis that CTP acts through specific recognition rather than general charge. CTP’s modulatory effect persisted across C-terminal domain (CTD) lysine mutants. Compaction was reduced in wild-type and K255A but abolished in K252A and K259A. The …

Evaluating The Effects Of Row Spacing, Legume Intercropping, Fertilizer Source, And Fertilizer Timing On Intermediate Wheatgrass In Eastern Nebraska, Madeline M. Johnston

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Kernza^® is the trademarked name of the perennial crop intermediate wheatgrass (Thinopyrum intermedium). In addition to its potential for dual-use as a grain and forage crop, Kernza is marketed to provide needed environmental services by increasing crop biodiversity, sequestering soil carbon, and reducing nitrate leaching. However, more work is needed in cultivar selection and crop management to increase total grain yields and prevent long-term grain yield decline. Furthermore, research in quantifying and understanding Kernza’s ability to affect soil properties and water dynamics is limited.

Two field experiments were conducted at the Eastern Nebraska Research Extension and Education …

Evaluating Biodegradable Mulch As A Soil Conservation Tool And The Impact On Soil Properties And Yield In Soybean (Glycine Max) Cropping Systems In Eastern Nebraska, Ana Clara Gomes

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

This study, conducted during the 2024 growing season, evaluated short-term effects of soil management practices on greenhouse gas (GHG) emissions, soil microclimate, nitrogen dynamics, weed suppression, and soybean (Glycine max) yield. In addition to conventional tillage and no-till, this research included cereal rye (Secale cereale) cover cropping and a novel sprayable biodegradable mulch (BioWRAP®) to assess emerging strategies for sustainable soybean systems under contrasting moisture regimes.

Field trials were established at two eastern Nebraska locations: Havelock (dryland, silty clay loam) and ENREEC (irrigated, clay loam). A strip-block randomized design with four replications tested six soil management …

Pollination And Essential Oil Production Of Lavandula Angustifolia Mill. (Lamiaceae), Riley B. Jackson, Tyler M. Wilson, Joseph S. Wilson, Zabrina Ruggles, Lindsey Topham Wilson, Chris Packer, Jacob G. Young, Christopher R. Bowerbank, Richard E. Carlson

Biology Faculty Publications

Lavandula angustifolia Mill., lavender, is an aromatic plant in the Lamiaceae family. Lavender, which is native to the Mediterranean region but cultivated throughout the world, is an important economic plant. Several studies have investigated two aspects of this aromatic plant: (1) which pollinators, particularly bees, pollinate lavender, and (2) the composition of lavender essential oil. However, little research has been conducted to investigate how pollination affects either the yield or phytochemistry of lavender. The current study, which was conducted in North America, investigates which bee species visit lavender and how pollination affects plant chemistry, specifically the essential oil produced by …

Graduate School Blog - July 2025 Volume 1, Cynthia Haynes

UofM Grad School Blog

The July 2025 UofM Graduate School Blog – Volume 1 continues the Cost of Graduate School Guide with a deep dive into hidden and variable expenses such as residency-based tuition differences, program-specific fees, and differential tuition. The blog provides practical tips for prospective students on how to ask the right financial questions when comparing programs. It also features a student spotlight on Billy Brooks, a dual MHA/MBA candidate motivated to transform healthcare access and equity. Upcoming events include a Virtual Fall 2025 Open House with Financial Aid and USBS, a Dissertation Writers Retreat, and both in-person and virtual Graduate Student …

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

Cazyme Gene Cluster Diversity In Human Gut Microbiome, Yi Xing

Department of Food Science and Technology: Dissertations, Theses, and Student Research

In gut microbiome research, carbohydrate-active enzyme gene clusters (CGCs) have emerged as key functional units for understanding microbial glycan degradation. Unlike taxonomic or broad pathway annotations, CGCs offer gene-cluster-level resolution and capture substrate-specific microbial functions. However, their diversity and distribution in relation to host metabolic phenotypes, such as obesity, remain poorly characterized. This study tests the hypothesis that the composition and abundance of fiber-targeting CGCs vary between obese and healthy human gut microbiomes, reflecting distinct microbial carbohydrate utilization strategies. To examine this, we constructed a high-quality reference CGC dataset comprising 94,019 clusters from the Unified Human Gastrointestinal Genome and profiled …

Assessment Of Spatial Autocorrelation And Scalability In Fine-Scale Wildfire Random Forest Prediction Models, Madeleine Pascolini-Campbell, Joshua B. Fisher, Kerry Cawse-Nicholson, Christine M. Lee, Natasha Stavros

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Wildfire prediction models that can be applied across diverse regions at fine scales (<  100 m) are critical for wildfire management. Remote sensing offers a path forward by providing heterogeneous and dynamic measurements of fuel load, type, and flammability. Machine learning methods such as random forests provide an empirical framework that are high-accuracy, computationally efficient, interpretable and able to model complex ecological relationships. Here we use high resolution (70 m, every 3–5 days) remote sensing observations of evapotranspiration and evaporative stress index, which represent plant water stress, from Ecosystem Spaceborne Thermal Radiometer on Space Station (ECOSTRESS), as well as topography and weather data, to predict burn severity and occurrence for 8 large wildfires that burned 3715 km² from 2021 and 2022 in New Mexico, USA. These fires ranged from low to high burn intensity, and covered a diverse range of ecoregions (deserts, grasslands, forests), plant species, and topographies. We used a single model to predict the burn severity of all wildfires one week before occurrence. The prediction accuracy was greatest when using all predictors (ECOSTRESS, weather, topography) (R² = 0.77). We assessed the role of spatial autocorrelation in driving model performance by: (1) increasing the sample spacing of our dataset, (2) …

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …

Clonal Evolution Of Hematopoietic Stem Cells After Autologous Stem Cell Transplantation, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Linda Zhang, Jennifer Padilla, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Satoko Ogata, Sarah Hanache, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal-Shamanna, Carlos Bueso-Ramos, Daisuke Nakada, Gheath Al-Atrash, Jeffery Molldrem, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi

Faculty, Staff and Student Publications

The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other chemotherapeutic agents had minimal effects. Consequently, the clonal diversity and architecture of post-treatment HSPCs resemble those observed in normal elderly individuals, particularly through the progression of oligoclonal hematopoiesis, thereby suggesting that chemotherapy accelerates clonal aging. Integrated …

Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal …

Thriving Hives: Making Products With Honey - Skincare And Food Recipes, Brynn Meredith, Teresa Hunsaker, Andree' Walker Bravo

All Current Publications

While keeping bees is beneficial for many reasons, one of the most notable benefits is producing honey and wax, which have many practical uses. This fact sheet provides information on honey's properties and how to make creamed honey to control crystallization. It also provides instructions on how to make skincare and various food products using honey.

Germination Time: Impact On Nutritional, Thermal, And Paste Properties Of Red Rice, Thauana Heberie, Lucas Avila Do Nascimento, Ya-Jane Wang, Rosana Colussi, Jaqueline Ferreira De Souza, Andre Ricardo Fajardo, Marcia Foster Mesko

Food Science Faculty Publications and Presentations

BACKGROUNDThe study investigates how varying germination times affect the nutritional, thermal, and pasting properties of red rice. Germination was conducted over 32 h, with aliquots collected every 2 h starting from 18 h for property evaluation.RESULTSAt all evaluated germination times, the red rice samples exhibited low to intermediate amylose levels, while resistant starch content remained relatively constant (approximately 15-20%). Structural changes in the starch were observed: the peak viscosity decreased, maximum gelatinization of the granules occurred at 76 degrees C, and spectroscopic bands characteristic of this polysaccharide were detected at 3400 cm-1 (O-H stretching) and within the 1150-1000 cm-1 range …

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; …

Evaluating Large Language Model Performance To Support The Diagnosis And Management Of Patients With Primary Immune Disorders, Nicholas L Rider, Yingya Li, Aaron T Chin, Daniel V Digiacomo, Cullen Dutmer, Jocelyn R Farmer, Kirk Roberts, Guergana Savova, Mei-Sing Ong

Faculty, Staff and Student Publications

Background: Generative artificial intelligence (GAI) is transforming health care in a variety of ways; however, the present utility of GAI for supporting clinicians who treat rare disease such as primary immune disorders (PIs) is not well studied. We evaluated the ability of 6 state-of-the-art large language models (LLMs) for providing clinical guidance about PIs.

Objective: To quantitatively and qualitatively measure the utility of current, open-source LLMs for diagnosing and providing helpful clinical decision support about PIs.

Methods: Five expert clinical immunologists each provided 5 real-world, anonymized PI case vignettes via multi-turn prompting to 6 LLMs (OpenAI GPT-4o, Llama-3.1-8B-Instruct, Llama-3.1-70B-Instruct, Mistral-7B-Instruct-v0.3, …

Non-Invasive Tools For Analysis Of Plasma Membrane Protein Topology In Living Cells, Daria Savenkova, Leysan Bulatova, Vera Skripova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane protein topology studies offer guidance to membrane protein structure, folding, and function, serving as a credible scaffold for designing site-directed mutagenesis and biochemical experiments, helping to identify functionally significant extracellular and intracellular regions, modeling three-dimensional structures, and building reliable mechanistic models. Membrane protein structure as a function of given lipid composition and physiological state of the cell is best probed in whole intact cells. A described simple and advanced immunofluorescence protocol applied to the transmembrane orientation of extramembrane domains permits a topology analysis of plasma membrane proteins in their native state in living unperturbed eucaryotic cells. The accessibility of …

Long Akap18 Isoforms Anchor Ubiquitin Specific Proteinases And Coordinate Calcium Reuptake At The Sarcoplasmic Reticulum, Taeyeop Park, Katherine Forbush, Yong Li, Oscar Vivas, Kacey J Rosenthal, Jerome Falcone, Cassandra J Wong, James E Bruce, Claudia Moreno, Carmen W Dessauer, John D Scott

Faculty, Staff and Student Publications

Subcellular targeting of signaling enzymes influences where and when various modes of intracellular communication operate. Macromolecular complexes of signal transduction and signal termination elements favor reversible control of repetitive processes. This includes adrenergic stimulation of excitation–contraction coupling in the heart. Long isoforms of A-kinase anchoring protein 18 (AKAP18γ and δ) modulate this process via regulation of calcium uptake into the sarcoplasmic reticulum through the Ca2+ATPase 2a (SERCA2a). AKAP18 proximity-proteomic screening in cardiomyocytes identifies networks for protein kinase A (PKA) and ubiquitin-specific proteinases (USPs). A 2′phosphoesterase domain on AKAP18 interfaces with the USP4 isoform at the Z bands of sarcomeres. PKA …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison B Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth F Sutton, Pamela M Simmons, George R Saade, Antonio Saad, Luis D Pacheco, Esther Park-Hwang, Antonina I Frolova, Ebony B Carter, Ai-Ris Y Collier, Daniel G Kiefer, Vincenzo Berghella, Rupsa C Boelig, Michal A Elovitz, Cynthia Gyamfi-Bannerman, Joseph R Biggio, Kara Rood, William A Grobman, Carrie Haverty, Morten Rasmussen

Faculty, Staff and Student Publications

Importance: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

Objective: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

Design, setting, and participants: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

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 …

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 …