Digital Commons Network^™

Individualized Functional And Structural Language Lateralities In Temporal Lobe Epilepsy And Their Impact On Memory, Ankeeta Ankeeta, Qirui Zhang, Sam Sharifzadeh Javidi, Shilpi Modi, Michael R. Sperling, Joseph I. Tracy

Department of Neurology Faculty Papers

The basis and impact of functional asymmetries in the brain, particularly language lateralization, are not fully understood, and the relationship between functional and structural asymmetries remains largely untested. This study investigated the degree to which asymmetries in hemispheric language laterality are concordant with asymmetries in gray matter (GM) structure and whether the hemispheric organization of memory is influenced by functional language asymmetries. Structural and functional MR data was acquired from 261 individuals, including those with unilateral temporal lobe epilepsy (LTLE = 96, RTLE = 69) and matched with healthy participants (HPs = 96). Functional language laterality indices (LIs) were calculated …

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …

Rural Cancer Survivors' Perceived Delays In Seeking Medical Attention, Diagnosis And Treatment: Findings From A Large Qualitative Study, Alyssa Taglieri-Sclocchi, Ingrid Bindicsova, Susannah K. Ayre, Michael Ireland, Sonja March, Fiona Crawford-Williams, Suzanne Chambers, Jeff Dunn, Belinda C. Goodwin, Elizabeth A. Johnston

Research outputs 2022 to 2026

Aims: To investigate rural cancer survivors' self-reported reasons for perceived delays in initial cancer detection and treatment. Methods: Within a cohort study, adult cancer survivors who had travelled > 50 km for cancer care, staying at subsidised accommodation lodges in city centres in Queensland, Australia, were invited to complete a structured interview on perceived delays in: (i) seeking medical attention, (ii) receiving their diagnosis and (iii) commencing treatment. Content analysis was used to map self-reported reasons for perceived delays at each step, which were then categorised based on the perceived source: (i) personal, (ii) healthcare professional, (iii) healthcare system or (iv) …

Fetal Body Composition And Organ Volume Trajectories In Association With Maternal Perceived Stress Or Depressive Symptoms In The Fetal 3d Study, Alexandra Jean-Louis, Jessica L Gleason, Zhen Chen, Kathryn A Wagner, William A Grobman, Roger B Newman, Wesley Lee, Robert Gore-Langton, Seth Sherman, John Owen, Deborah A Wing, Daniel W Skupski, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Objectives: Evaluate associations between maternal perceived stress and depressive symptoms, and fetal body composition and organ volumes.

Methods: In the NICHD Fetal 3D Study (2015-2019; n = 2457), stress and depressive symptoms were assessed at enrollment (10-13 weeks). High stress was defined as a Perceived Stress Scale (PSS) score ≥15 and high depressive symptoms, defined as an Edinburgh Postnatal Depression Scale (EPDS) score ≥10. Fetal body composition and organ volumes (cerebellar, lung, liver, and kidney) were measured up to five times between 15 and 40 weeks using three-dimensional (3D) ultrasound technology. Trajectories of body composition and organ volumes across pregnancy …

Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker

Faculty, Staff and Students Publications

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …

Intracranial Injury Following Nasogastric Tube Placement After Skull Base Surgery: A Case Report And Systematic Review, Gabrielle Wolter, Zain U Naqvi, Ali Jalali, Tran Locke, K Kelly Gallagher, Meha G Fox

Faculty, Staff and Students Publications

Inadvertent intracranial nasogastric tube placement is a recognized risk following skull base fracture, but prior skull base surgery also poses a significant and underrecognized risk for this potentially fatal complication. We report the case of a 75-year-old female admitted with Clostridioides difficile colitis, six months after endoscopic endonasal resection of a pituitary macroadenoma. A systematic review identified 10 prior cases of intracranial tube placement following skull base or sinonasal surgery, including nasotracheal and feeding tube insertions. Literature suggests that using small-bore flexible tubes and preserving anatomical barriers, such as the position of the middle turbinate and intact bony structures like …

Definition And Classification Of Dystonia, Alberto Albanese, Kailash P Bhatia, Victor S C Fung, Mark Hallett, Joseph Jankovic, Christine Klein, Joachim K Krauss, Anthony E Lang, Jonathan W Mink, Sanjay Pandey, Jan K Teller, Marina A J Tijssen, Marie Vidailhet, H A Jinnah

Faculty, Staff and Students Publications

Dystonia is a movement disorder with varied clinical features and diverse etiologies. Here we present a revision of the 2013 consensus definition and classification of dystonia in light of subsequent publications and experience with its application during the last decade. A panel of movement disorder specialists with expertise in dystonia reviewed the original document and proposed some revision. There was broad consensus to retain the definition of dystonia with only minor clarifications to the wording. Dystonia is defined as a movement disorder characterized by sustained or intermittent abnormal movements, postures, or both. Dystonic movements and postures are typically patterned and …

Corrigendum To “Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease” [Progr Retin Eye Res 106 (2025) 101362], Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

No abstract provided.

Genomic Reporting Practices Across 5 Molecular Disciplines: A Study From The College Of American Pathologists, Larissa V Furtado, Annette S Kim, Ann M Moyer, Joel T Moncur, Rena R Xian, Angshumoy Roy, Avni B Santani, Yassmine Akkari, Karl V Voelkerding, Rhona J Souers, Jaimie Halley, Glenn E Palomaki

Faculty, Staff and Students Publications

Context.—: Genomic reports are primarily organized in a narrative and unstructured format with variations in content and format. Regulatory requirements and professional guidelines for genetic test reporting exist but provide little guidance for effective communication of information.

Objective.—: To assess clinical genomic reporting practices across 5 disciplines within molecular diagnostics, including germline, somatic solid tumors, somatic hematologic malignancies, pharmacogenomics, and prenatal cell-free DNA screening.

Design.—: Reporting practices were assessed by using a structured review of clinical genomic reports from multiple laboratories in 5 molecular disciplines spanning different practice settings. Report content was reviewed by the presence/absence of from 27 to …

Functional Assays In Drosophila Facilitate Classification Of Variants Of Uncertain Significance Associated With Rare Diseases, Jung-Wan Mok, Shelley B Gibson, Haley A Dostalik, Shinya Yamamoto

Faculty, Staff and Students Publications

Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Metabolomic Data May Support The Development Of Personalized Nutrition Approaches To Type 2 Diabetes Management, Danielle J Lee, Shragvi Balaji, Jerome I Rotter, Alexis C Wood

Faculty, Staff and Students Publications

Diet is a major modifiable risk factor for type 2 diabetes (T2D), and suboptimal diets continue to contribute substantially to the population burden of T2D. Personalized nutrition proponents argue that specializing recommendations to interindividual differences in diet-health relationships will yield reductions in disease risk. However, how to personalize diet, and to whom, to reduce T2D risk remains unclear. Metabolites offer promise in this respect, as they capture (in part) dietary intake after the processes of digestion, processing, and absorption. The incorporation of metabolite data into diet-health studies therefore offers the opportunity to examine how the effects of food on the …

Fgf21 Promotes Longevity In Diet-Induced Obesity Through Metabolic Benefits Independent Of Growth Suppression, Christy M Gliniak, Ruth Gordillo, Yun-Hee Youm, Qian Lin, Clair Crewe, Zhuzhen Zhang, Bianca C Field, Teppei Fujikawa, Megan Virostek, Shangang Zhao, Yi Zhu, Clifford J Rosen, Tamas L Horvath, Vishwa Deep Dixit, Philipp E Scherer

Faculty, Staff and Students Publications

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis. Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence …

Mechanisms Of Change In Exposure Therapy For Anxiety And Related Disorders: A Research Agenda, Kristen Benito, Andre Pittig, Jonathan Abramowitz, Joanna J Arch, Denise Chavira, Rianne De Kleine, Alessandro S De Nadai, Dirk Hermans, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, Katharina Kircanski, Peter M Mcevoy, Heidi Meyer, Marie-H Monfils, Santiago Papini, Winfried Rief, David Rosenfield, Eric A Storch, Michael J Telch, Michael W Otto, Jasper A J Smits

Faculty, Staff and Students Publications

Anxiety and related disorders are a significant public health burden with rising prevalence in the wake of the COVID-19 pandemic. As demand for effective anxiety treatment increases, so too does the need for strategies to bolster treatment outcomes. Research on the mechanisms of exposure therapy, the frontline behavioral treatment, will be critically important for optimizing clinical outcomes. We outline an initial agenda for future research on the mechanisms of change of exposure therapy, developed in collaboration with a large international team of researchers through the Exposure Therapy Consortium (ETC). Key questions and recommendations for future research focus on five priority …

Quantitative Ultrashort Echo Time Mri For Evaluation Of Sciatic Nerve Degeneration And Regeneration In Rat Models, Yuanshan Wu, Yajun Ma, Xin Cheng, Kaixin Pan, James Lo, Elisabeth Orozco, Junyuan Chen, Saeed Jerban, Michael P Andre, Jiang Du, Eric Y Chang, Sameer B Shah

Faculty, Staff and Students Publications

Background Evaluating peripheral nerve response after injury or repair remains a critical clinical challenge. Current medical imaging approaches provide limited insight into the degenerative or regenerative environment of affected nerves. Purpose To assess the efficacy of ultrashort echo time (UTE) quantitative MRI (qMRI) for evaluating peripheral nerve degeneration and regeneration in rat models of sciatic nerve injury and to assess correlations between UTE qMRI parameters and histologic findings. Materials and Methods In this animal study conducted from November 2022 to December 2023, four experimental groups were created in 6-8-week-old male Lewis rats:

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 …

Author Correction: Autologous T Cell Therapy For Prame+ Advanced Solid Tumors In Hla-A*02+ Patients: A Phase 1 Trial, 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

No abstract provided.

Involved But Not Essential: Cognitive Activity In Periventricular Nodules And Neuropsychological Outcomes Following Their Ablation, Yosefa A Modiano, Oscar Woolnough, Ryan M Mccormack, Kathryn Snyder, Ellery Wheeler, Samden D Lhatoo, Nuria Lacuey, Sandipan Pati, Katherine Harris, Jay Gavvala, Jessica A Johnson, Nitin Tandon

Faculty, Staff and Student Publications

Objective: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development with high rates of epilepsy. The extent to which nodules participate in normal cerebral functions in addition to pathological processes is unclear. The authors assessed the functional utility (i.e., cognitive impacts) of surgically ablated epileptogenic PVNH tissue via comprehensive neuropsychological testing.

Methods: The sample included 32 patients with PVNH who underwent presurgical neuropsychological evaluation and a subsample of 16 patients who underwent MR-guided laser interstitial thermal therapy (MRgLITT) of nodules, with postsurgical neuropsychological testing. In 11 patients in whom intracranial recordings were performed, reading and naming tasks were tested …

Practical Considerations For Using The Tite-Boin Design To Handle Late-Onset Toxicity Or Fast Accrual In Phase I Trials, Kai Chen, Ting-Yu Chen, Yiming Zhang, Ruitao Lin, Ying Yuan

Faculty, Staff and Student Publications

Conducting phase I trials is particularly challenging when dealing with late-onset dose-limiting toxicity (DLT) or when patient accrual is rapid relative to the DLT assessment window. In such cases, a new cohort may be ready for enrollment before the DLT assessments are complete for the current cohort, complicating dose assignment decisions. The time-to-event Bayesian optimal interval (TITE-BOIN) design was developed to address this issue by enabling real-time dose assignment for new cohorts, even when some enrolled patients' DLT data are still pending. This design has been increasingly adopted in practice. Upon reviewing trial protocols utilizing TITE-BOIN, we observed considerable variation …

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: …

Kap1 Promotes Gastric Adenocarcinoma Progression By Activating Hippo/Yap1 Signaling Via Binding To Hnrnpab, Shumei Song, Yibo Fan, Gengyi Zou, Longfei Huo, Janani Kumar, Yuan Li, Ruiping Wang, Enyu Dai, Jiankang Jin, Ailing W Scott, Shan Shao, Melissa Pool Pizzi, Jody V Vykoukal, Hiroyuki Katayama, Samir Hanash, George A Calin, Xing Zhang, Min Gyu Lee, Zhenning Wang, Yuan-Hung Lo, Qiong Gan, Rebecca E Waters, Feng Yin, Linghua Wang, Xiaodong Cheng, Jaffer A Ajani, Shilpa S Dhar

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter …

Semi-Automated Hippocampal Avoidance Whole-Brain Radiotherapy Planning, Dong Joo Rhee, Subha Perni, Kelly J Perrin, Kevin E Casey, Alexandra O Leone, Callistus M Nguyen, Laurence E Court, He Wang, Xin Wang, Eun Young Han

Faculty, Staff and Student Publications

Background: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) is designed to spare cognitive function by reducing radiation dose to the hippocampus during the treatment of brain metastases. Current manual planning methods can be time-consuming and may vary in quality, necessitating the development of automated approaches to streamline the process and ensure consistency.

Purpose: To automate hippocampal avoidance whole-brain radiotherapy (HA-WBRT) planning.

Methods: Our algorithm automatically contours organs-at-risk (OARs) and the hippocampal-avoidance brain target. The algorithm generates planning structures from given contours, utilizing preset beam parameters and dose constraints for optimization. If the dose constraints are unmet, "hotspot" contours will be created to …

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 …

Protocol To Detect M22g Modification On Single Trna Iso-Decoders By Immuno-Northern Blotting, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are highly dynamic and play crucial roles in regulating gene expression. Here, we present an assay for analyzing N2, N2-dimethylguanosine (m22G) modifications on tRNAs using an antibody-based detection approach. We describe steps for isolating tRNAs from human cells via ion-exchange chromatography, capturing specific tRNA iso-decoders on streptavidin magnetic beads, and detecting modifications through immuno-northern blotting. This approach enables researchers to investigate other tRNA modifications using specific antibodies or downstream approaches such as mass spectrometry.

Crem Is A Regulatory Checkpoint Of Car And Il-15 Signalling In Nk Cells, Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander Biederstädt, Mecit Kaplan, Xin Ru Jiang, Inci Biederstädt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M Deyter, Natalie Wall Fowlkes, Abhinav K Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM …

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 …

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 …

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 …

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 …