Digital Commons Network^™

Comparison Of Imaging Based Single-Cell Resolution Spatial Transcriptomics Profiling Platforms Using Formalin-Fixed Paraffin-Embedded Tumor Samples, Nejla Ozirmak Lermi, Max Molina Ayala, Sharia Hernandez, Wei Lu, Khaja Khan, Alejandra Serrano, Idania Lubo, Leticia Hamana, Katarzyna Tomczak, Sean Barnes, Jinzhuang Dou, Qingnan Liang, Rti Team, Maria Gabriela Raso, Ximing Tang, Mei Jiang, Beatriz Sanchez-Espiridion, Annikka Weissferdt, John Heymach, Jianjun Zhang, Boris Sepesi, Tina Cascone, Anne Tsao, Mehmet Altan, Reza Mehran, Don Gibbons, Ignacio Wistuba, Cara Haymaker, Ken Chen, Luisa M Solis Soto

Faculty, Staff and Student Publications

Imaging-based spatial transcriptomics (ST) is evolving as a pivotal technology in studying tumor biology and associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. We use serial 5 μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma samples in tissue microarrays to compare the performance of the ST platforms (CosMx, MERFISH, and Xenium (uni/multi-modal)) in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx, and hematoxylin and eosin staining data. In addition to an objective assessment of automatic cell segmentation and phenotyping, we …

Distinct Intrinsic And Extrinsic Factors Differentially Regulate Skeletal Stem Cells In Calvaria Versus Long Bones During Bone Regeneration, Jea Solidum, Kohei Yamasaki, Youngjae Jeong, Laura Ortinau, Francisco Heralde, Dongsu Park

Faculty, Staff and Students Publications

Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not been well elucidated. Here, using an inducible Prx1-CreER-EGFP+/−;Rosa26-tdTomato mouse model, we observed that endogenous Prx1+ Su-SSCs and their orthotopic transplantation into calvarial injury do not form cartilage intermediates at the injury sites, while the transplantation of Prx1+ LB-PSSCs into LB injury induces osteochondrogenic differentiation, respectively. However, the heterotopic transplantation of Prx1+ Su-SSCs (Su-SSCs …

A Novel Self-Inhaled Nicotine Exposure System In Murine Models Reveals Age-Dependent Metabolic Effects Of Nicotine, Xu Xu, Hailan Liu, Meng Yu, Qingzhuo Liu, Yongxiang Li, Yue Deng, Yuxue Yang, Jingjing Cheng, Yutian Liu, Mengjie Wang, Xing Fang, Longlong Tu, Olivia Z Ginnard, Kristine M Mcdermott, Darah Threat, Fuhui Wang, Meixin Sun, Xinming Liu, Jiamin Qiu, Xi Wu, Jinjing Jian, Tong Zhou, Megan E Burt, Sanika V Jossy, Junying Han, Chunmei Wang, Yongjie Yang, Yong Xu, Yuhan Shi

Faculty, Staff and Students Publications

Background: Nicotine is known to influence metabolism and body weight, yet existing murine models of nicotine exposure often fail to replicate human smoking behaviors accurately. To address this gap, we designed a cost-effective, self-administered nicotine inhalation system that allows mice to voluntarily inhale nicotine vapor generated from e-liquid.

Results: Using this system, we investigated the metabolic effects of nicotine exposure in adult and adolescent mice. Adult mice exposed to nicotine vapor for 10 days exhibited significant weight loss, which was rapidly regained upon cessation, paralleling human smoking patterns. In contrast, adolescent mice did not lose weight during nicotine exposure but …

Non-Invasive Detection Of Choroidal Melanoma Via Tear-Derived Protein Corona On Gold Nanoparticles: A Machine Learning Approach, Hakimeh Rakhshandeh, Ahmad Nasiraei, Hamid Riazi-Esfahani, Babak Masoomian, Fariba Ghassemi, Mojtaba Arjmand, Saeed Heidari Keshel, Fatemeh Atyabi, Rassoul Dinarvand

Wills Eye Hospital Papers

This study investigates the feasibility of using tear sample analysis, based on protein corona formation on gold nanoparticles combined with electrospray ionization mass spectrometry (ESI-MS) and machine learning techniques, as a non-invasive approach for the detection of choroidal melanoma. The aim is to assess whether protein-nanoparticle interactions can support early and reliable identification of this ocular condition. Tear samples were collected using Schirmer strips from six healthy individuals and six patients diagnosed with choroidal melanoma, with subsequent augmentation to 18 samples per group. Gold nanoparticles (AuNPs, ~ 20 nm) were synthesized via citrate reduction and incubated with tear samples to …

Smarcal1 Is A New Osteosarcoma Predisposition Gene, Maryam Rafati, Lillian M Guenther, Laura E Egolf, D Matthew Gianferante, Jung Kim, Kevin Wang, Bin Zhu, Logan G Spector, Nathan Anderson, Katherine A Janeway, Donald A Barkauskas, Douglas S Hawkins, Ana Patiño-Garcia, Philip J Lupo, Michael E Scheurer, Lindsay Morton, Gregory T Armstrong, Yadav Sapkota, M Monica Gramatges, Massimo Serra, Claudia Hattinger, Katia Scotlandi, Irene L Andrulis, Jay S Wunder, Mandy L Ballinger, David M Thomas, Meredith Yeager, Michael Dean, Douglas R Stewart, Aurelie Vogt, Jia Liu, Belynda D Hicks, Wen-Yi Huang, Maria Teresa Landi, Adriana Lori, W Ryan Diver, Sharon A Savage, Stephen J Chanock, Lisa Mirabello

Faculty, Staff and Students Publications

Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most cases are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2,119 osteosarcoma cases, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across three osteosarcoma case sets (1.8%, n = 2,119) than in 2,625 comparably sequenced cancer-free controls (0.3%; P <  .001). Cases with SMARCAL1 pathogenic variants had significantly improved overall survival compared to cases without these variants (hazard ratio 0.36, 95% CI 0.14-0.96, P = .034). In the UK Biobank (469,557 exomes), there was a 33-fold increased risk of osteosarcoma in individuals with SMARCAL1 pathogenic variants. These results identify SMARCAL1 as a new osteosarcoma predisposition gene and thus warrant follow-up to identify the mechanisms by which SMARCAL1 contributes to the etiology of osteosarcoma.

Lysosomes Signal Through The Epigenome To Regulate Longevity Across Generations, Qinghao Zhang, Weiwei Dang, Meng C Wang

Faculty, Staff and Students Publications

The epigenome is sensitive to metabolic inputs and crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We find that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate-activated protein kinase (AMPK) or reduction of lysosomal mechanistic-target-of-rapamycin (mTOR) signaling increased expression of a histone H3.3 variant and increased its methylation on K79, leading to lifespan extension across multiple generations. This transgenerational pro-longevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase, and was recapitulated by …

Swollen Lymph Node Metastasis In Gastric Cancer: A Forgotten Prognostic Signal In Need Of Clinical Action, Keykavous Parang, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Gastric cancer (GC) remains a leading cause of cancer mortality. While the extent of nodal involvement is a well-known prognostic factor, the specific entity of swollen lymph node metastasis (SLNM), bulky nodal tumor deposits detectable radiologically or pathologically, has received little attention in staging. Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC. Through robust data and rigorous propensity-matched analyses, SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis, even among patients undergoing curative resection. As precision oncology advances, the …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …

The Impact Of Myopia On Regional Visual Field Loss And Progression In Glaucoma, Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R. Pasquale, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Mohammad Eslami, Tobias Elze, Lucy Q. Shen, Nazlee Zebardast, David S. Friedman, Michael V. Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.

METHODS: We included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope < 0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤-1 decibels (dB)/year; (3) MD fast progression: MD slope ≤-1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤-6.00 diopters [D]).

RESULTS: More negative SE values were associated with worse TD values in the paracentral VF …

Associations Between Adhering To 24-Hour Movement Guidelines And Anxiety Among Adolescents Across Intersectional Identities: Kyrbs 2020-2022., Suryeon Ryu, Eun Young Lee, Zan Gao

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Identifying preventive measures for adolescent mental health is a global public health priority, as poor mental health heightens the risk of early death from related issues, including suicide. This study examined the associations between adherence to the 24-Hour Movement Guidelines and anxiety among a nationally representative sample of South Korean adolescents, using an intersectional identity framework.

METHODS: Data from the 2020-2022 Korea Youth Risk Behavior Surveys were analyzed. Adolescents aged 12-17 years were grouped based on adherence to guidelines: none, physical activity (PA), sedentary behavior (SB), sleep, two guideline combinations, and all three. Anxiety was the mental health outcome. …

Lung Nr3c1+ And Cxcr6high T Cells Distinguish Immunopathogenesis Of Human Emphysema, Yun Zhang, Maor Sauler, David B Corry, Scott A Ochsner, Sarah Perusich, Li-Zhen Song, Joshua Malo, Raul San Jose Estepar, Francesca Polverino, Farrah Kheradmand

Faculty, Staff and Students Publications

There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 …

Pediatric Heart Failure: A Practical Guide For Primary Care Providers Supporting Families Across The Care Continuum, Shahnawaz Amdani, Kriti Puri, Julie Glickstein, Joseph A Spinner, Jonathan N Johnson, Ashraf S Harahsheh, Majd Makhoul, Susan Denfield

Faculty, Staff and Students Publications

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF.

Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF.

Results: HF in children most commonly results from congenital heart disease and …

Monitoring The Hematologic Markers In Patients Undergoing Single-Stage Exchange Arthroplasty For Periprosthetic Joint Infection, Wenbo Mu, Juan D. Lizcano, Boyong Xu, Wentao Guo, Abudousaimi Aimaiti, Xiaogang Zhang, Javad Parvizi, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is a serious complication that necessitates a complex treatment strategy. Single-stage exchange arthroplasty, combined with intravenous and intra-articular antibiotic infusions, has shown high efficacy in treating complex PJIs. However, the impact of this approach on hematologic parameters remains underexplored. This study aims to evaluate the postoperative trends in blood platelet count, white blood cell (WBC) count, and neutrophil count in patients undergoing single-stage exchange arthroplasty.

METHODS: A retrospective analysis was conducted on 313 patients who underwent single-stage revision for PJI between June 2010 and October 2022. Hematologic parameters were monitored for the first seven postoperative …

Practice Patterns In Management Of Low- To Intermediate-Grade Salivary Gland Carcinoma: A Multi-Institutional Study, Mirabelle Sajisevi, Kenny Nguyen, Peter Callas, Andrew Holcomb, Emre Vural, Kyle Davis, Carissa Thomas, John Stein, Ameya Asarkar, Ricardo Aulet, Rebecca Bell, Michael Blasco, Vanessa Bowmaster, Clayton Burruss, Jeffson Chung, Kimberly Chan, Brent Chang, Charles Coffey, David Cognetti, Dylan Cooper, Joehassin Cordero, John Donovan, Yue Jennifer Du, Yusuf Dundar, Rogerio Dedivitis, Heather Edwards, Boban Erovic, Antoine Eskander, Philip Feinberg, Emily Garvey, David Goldstein, Joseph Goodman, Rafael Goulart, Neerav Goyal, Stefan Grasl, Jonathan Giurintano, Nikita Gupta, Andy Habib, Trevor Hackman, Jared Hara, Christina Henson, Michael Hinni, Nadia Hua, Stephanie Johnson-Obaseki, Aditya Juloori, Noah Kalman, Alexandra Kejner, Sobia Khaja, Jamie Ku, Arnaud Lambert, Bao Luu, Kelly Magliocca, Luiz Medina Dos Santos, Cara Michael, Brett Miles, Giulianno De Melo, Michael Moore, Gregoire Morand, Kauê Moura, Hesameddin Noroozi, Rusha Patel, Joseph Paydarfar, Karolina Plonowska-Hirschfeld, Nader Sadeghi, Fabrice Savaria, Nicole Schmitt, Justin Shapiro, Timothy Shaver, Sandro Stoeckli, William Stokes, Anita Sulibhavi, Jason Tasoulas, Varun Vendra, Daniel Vinh, Celina Virgen, Neil Woody, Geoffrey Young, Kiran Kakarala, Danny Enepekides, Michael Hier, Louise Davies, William Ryan

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: To characterize practice patterns and outcomes in the management of low- and intermediate-grade salivary gland carcinoma prior to the existence of treatment guidelines.

METHODS: Analysis of a registry of patients who underwent parotid and submandibular gland resections for low-and intermediate-grade carcinomas between 2010 and 2019.

RESULTS: Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial (n = 384, 53%) or total (n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was …

Synthetic Electrospun Fiber Matrix In The Management Of Acute Wounds Following Excision Of Hidradenitis Suppurativa Lesions: A Prospective Pilot Study, Michael Madueke, Frank Lau

School of Medicine Faculty Publications

Hurley Stage II or III hidradenitis suppurativa (HS) may necessitate surgical excision of diseased skin and subcutaneous fat for symptom control and disease management. These excisions result in open wounds in topographically challenging regions and typically cannot be primarily closed. This study evaluates the use of a synthetic electrospun fiber matrix (SEFM) as a post-resection regeneration template to accelerate re-granulation and improve subsequent skin graft incorporation. This prospective pilot study enrolled Hurley Stage II or III patients undergoing surgical resection of HS lesions. SEFM was applied to the resulting wounds in conjunction with negative pressure wound therapy (NPWT). Patients were …

Understanding Cancer Survivorship Care Needs Using Amazon Reviews: Content Analysis, Algorithm Development, And Validation Study, Liwei Wang, Qiuhao Lu, Rui Li, Taylor B. Harrison, Heling Jia, Ming Huang, Heidi Dowst, Rui Zhang, Hoda Badr, Jungwei W. Fan, Hongfang Liu

Department of Medical Oncology Faculty Papers

BACKGROUND: Complementary therapies are being increasingly used by cancer survivors. As a channel for customers to share their feelings, outcomes, and perceived knowledge about the products purchased from e-commerce platforms, Amazon consumer reviews are a valuable real-world data source for understanding cancer survivorship care needs.

OBJECTIVE: In this study, we aimed to highlight the potential of using Amazon consumer reviews as a novel source for identifying cancer survivorship care needs, particularly related to symptom self-management. Specifically, we present a publicly available, manually annotated corpus derived from Amazon reviews of health-related products and develop baseline natural language processing models using deep …

Adsl Deficiency Is A Secondary Mitochondrial Disease Affecting Organelle Homeostasis And Erk2/Akt Signaling In A Linear Genotype-Phenotype Relation, Matteo Bordi, Beatrice Testa, Claudia Compagnucci, Fiorella Colasuonno, Francesca Cipressa, Elisabetta Betterini, Andrea Mancini, Claudia Carsetti, Illari Salvatori, Caterina Ferraina, Ming Yang, Rossella De Cegli, Eugenio Del Prete, Chiara Veroni, Salvatore Rizza, Sofia Mauri, Elena Ziviani, Marina Macchiaiolo, Davide Vecchio, Filippo Maria Panfili, Teresa Rizza, Gerrit Weber, Rosalba Carrozzo, Alberto Ferri, Silvia Campello, Andrea Ballabio, Christian Frezza, Gianluca Cestra, Marco Tartaglia, Andrea Bartuli, Francesco Cecconi

Duncan NRI Faculty and Staff Publications

Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production. The severity of mitochondrial impairment correlates with ADSLd pathology, especially in mitochondria-dependent tissues. We also identify defects in mitochondrial dynamics and transport linked to ERK2 and AKT suppression. Notably, overexpressing constitutively active ERK2 or supplementing purine intermediates partially rescues the mitochondrial phenotype. These findings suggest an alternative disease mechanism and …

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Sars-Cov-2 Nsp13 Interacts With Tead To Suppress Hippo-Yap Signaling, Fansen Meng, Jong Hwan Kim, Chang-Ru Tsai, Jeffrey D Steimle, Jun Wang, Yufeng Shi, Rich G Li, Bing Xie, Vaibhav Deshmukh, Shijie Liu, Xiao Li, James F Martin

Faculty, Staff and Students Publications

The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into mouse cardiomyocytes suppresses …

Understanding Cancer Survivorship Care Needs Using Amazon Reviews: Content Analysis, Algorithm Development, And Validation Study, Liwei Wang, Qiuhao Lu, Rui Li, Taylor B Harrison, Heling Jia, Ming Huang, Heidi Dowst, Rui Zhang, Hoda Badr, Jungwei W Fan, Hongfang Liu

Faculty, Staff and Students Publications

Background: Complementary therapies are being increasingly used by cancer survivors. As a channel for customers to share their feelings, outcomes, and perceived knowledge about the products purchased from e-commerce platforms, Amazon consumer reviews are a valuable real-world data source for understanding cancer survivorship care needs.

Objective: In this study, we aimed to highlight the potential of using Amazon consumer reviews as a novel source for identifying cancer survivorship care needs, particularly related to symptom self-management. Specifically, we present a publicly available, manually annotated corpus derived from Amazon reviews of health-related products and develop baseline natural language processing models using deep …

Clinical Outcomes Of Neoadjuvant Chemoimmunotherapy Vs. Chemoradiotherapy In Operable Non-Small Cell Lung Cancer, Tal Sherman, Nikta Nair, Marli Meller, Raleigh Anderson, Guillermo Jimenez, Elizaveta Flevora, Charalambos Solomides, Rita Axelrod, Sarah Gordon, Ida Micaily, Maria Werner-Wasik, Sung Whang, Tyler Grenda, Olugbenga Okusanya, Nathaniel R. Evans, Iii, Nilanjan Haldar, Erik Blomain

Department of Radiation Oncology Posters

Introduction

• Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers and remains the leading cause of cancer death.
• Surgery is curative for early-stage disease, but recurrence rates remain high.
• CheckMate-816 trial established neoadjuvant chemo-immunotherapy (chemo-IO) as a new standard for resectable NSCLC, demonstrating improved pathologic response and event-free survival.
• PACIFIC trial showed the survival benefit of consolidative immunotherapy after chemoradiotherapy (chemo-RT) in unresectable stage III NSCLC, highlighting the synergy between radiation and immune checkpoint blockade.
• Despite these advances, there is little comparative data on the role of chemo-IO versus chemo-RT in the neoadjuvant, operable setting.
• Objective: To compare …

Retracted: Idea Density And Grammatical Complexity As Neurocognitive Markers, Diego Iacono, Gloria Feltis

Department of Neurology Faculty Papers

Language, a uniquely human cognitive faculty, is fundamentally characterized by its capacity for complex thoughts and structured expressions. This review examines two critical measures of linguistic performance: idea density (ID) and grammatical complexity (GC). ID quantifies the richness of information conveyed per unit of language, reflecting semantic efficiency and conceptual processing. GC, conversely, measures the structural sophistication of syntax, indicative of hierarchical organization and rule-based operations. We explore the neurobiological underpinnings of these measures, identifying key brain regions and white matter pathways involved in their generation and comprehension. This includes linking ID to a distributed network of semantic hubs, like …

Cerebellar Dysfunction In A Mouse Model Of Childhood-Onset Manganese-Induced Dystonia Parkinsonism, Alexander N Rodichkin, Amanda M Brown, Pavani Devabathini, Jennifer L Mcglothan, Si Chen, Ajith Pattammattel, Yong S Chu, Tao Lin, Daniel D Pontow, Karam Abilmouna, Ritishka Kapoor, Sarah E Hardin, Yulia Pushkar, Roy V Sillitoe, Tomás R Guilarte

Duncan NRI Faculty and Staff Publications

Humans with pathogenic variants of the manganese (Mn) transporter gene SLC39A14 exhibit highly elevated brain Mn concentrations and childhood-onset dystonia-parkinsonism. Here we show that Slc39a14-knockout (KO) mice, a preclinical model of the disease with elevated Mn concentrations in the CB, express deficits in physiological tremor implicating cerebellar (CB) dysfunction. Imaging of intracellular Mn in Purkinje cells (PCs) using synchrotron-based X-ray fluorescence microscopy confirmed highly elevated Mn concentrations in the PCs of Slc39a14-KO mice. To determine biological pathways altered in the CB of Slc39a14-KO mice relative to wildtype (WT), we performed RNA sequencing and discovered significant upregulation of pathways and genes …

Artificial Intelligence In The Management Of Leukemia, Stephanie Koo, Austin P. Runde, Melvin Speisman

School of Medicine

BACKGROUND: Recently, given the demonstrated ability of AI to accurately characterize complex pathologies, AI has been proposed to be of use in the diagnosis, treatment, and monitoring of leukemias given their genetic complexity and subtype heterogeneity, array of treatments, and need for relapse detection. AI has several potential applications in the management of leukemia. First, it can be used to detect leukemia; using AI to detect nuances in lab values can ensure these deadly cancers are never missed. Second, AI can be used to risk-stratify patients and personalize treatments; leukemias are among the most genetically complex cancers with well-characterized risk …

Ybx1-Mediated Activation Of Srebp2 Drives Sorafenib Resistance Via Cholesterol Biosynthesis In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard, Ana Ayala Pazzi, Shaibir Hussain, Salique H. Shaham, Manish Tripathi

Research Colloquium

Background: Hepatocellular carcinoma (HCC) is an aggressive, largely chemo-resistant cancer with a poor prognosis and is the leading cause of cancer-related deaths worldwide. Currently, there is no effective systemic chemotherapy for HCC. Sorafenib is a multikinase inhibitor commonly used as the first-line treatment for advanced HCC. However, acquired drug resistance significantly limits its clinical effectiveness. The Y-box binding protein (YBX1) is an oncogenic RNA-binding protein found to be upregulated in sorafenib-resistant HCC cells and tissues.

Methods: HCC model SK Hep1, YBX1 overexpression, and knockdown cells were prepared by transient transfection with puromycin selection, and stable cell lines were established through …

Implementing A Specific And Standardized Grading Scale For Therapeutic Injection Site Reactions To Improve Adverse Event Reporting, Priya Kale, Kavita Sarin

Research Colloquium

Up to 15.5% of patients taking biologic medication experience injection site reactions (ISRs) leading to morbidity, early discontinuation, and reduced treatment compliance. As biologic medications are increasingly used to treat chronic inflammatory conditions, including psoriasis and atopic dermatitis, there needs to be an improved understanding of ISRs. However, current methods of grading ISRs are nonspecific and unstandardized leading to a lack of understanding of medication-specific ISRs and ambiguity in perceptions of treatment tolerability. Here we aim to develop a standardized ISR grading scale for use in clinical trials. A scoping review was performed to evaluate current ISR grading scales and …

Tc-Ptp Enhances Cordycepin-Induced Apoptosis In Human Pancreatic Cancer Cells, Olivia Samaie, Rodrigo Vidales, Lindsey Shim, Murali M. Yallapu, Subhash C. Chauhan, Mushfiq Hassan Shaikh, Dae Joon Kim

Research Colloquium

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy marked by early metastasis, dense desmoplastic stroma, and profound resistance to conventional therapies. Despite the development of combination regimens such as gemcitabine and FOLFIRINOX, outcomes remain dismal, with median survival under one year for metastatic cases. This underscores the urgent need for novel therapeutic approaches that target multiple pathways simultaneously. T-cell protein tyrosine phosphatase (TC-PTP) is one of nonreceptor PTPs that negatively regulates oncogenic signaling pathways, particularly STAT3 and AKT, both of which are constitutively active in many solid tumors. Cordycepin, a nucleoside analogue derived from Cordyceps militaris, has …

Corticobasal Syndrome With Mixed Pathology In The Absence Of Grn Mutation: A Clinico-Pathological Case Of Ftld-Tdp With Coexisting Alzheimer’S And Lewy Body Pathology, Hugo Zamarron, David Irwin, Jeffery Phillips, Edward Lee, Matthew Tisdall, Corey Mcmillan

Research Colloquium

Background: Corticobasal syndrome (CBS) is a neurodegenerative disorder characterized by often asymmetric fronto-pariteal and extra-pyramidal features that is traditionally associated with tauopathy, but pathological findings are heterogenous, including other forms of frontotemporal lobar degeneration (FTLD) and mixed pathologies of aging. We present clinical, radiographic, and histopathologic features of asymmetry in a unique patient with CBS and underlying FTLD with TDP-43 pathology (FTLD-TDP), co-occurring with other age-related pathologies.

Case Presentation: A 76-year-old man presented with progressive cognitive and motor dysfunction including asymmetric parkinsonism, left-sided dystonia and rigidity, apraxia, visuospatial impairment, and a subtle social disorder including apathy and social withdrawal. The …

From Imaging To Impact: A Multi-Disciplinary T32 Program Framework And Initial Insights For Training In Image-Guided Cancer Therapy, Kari J. Brewer Savannah, Stephen Y. Lai, Clifton D. Fuller, Kristy K. Brock

Advances in Cancer Education and Quality Improvement

As multi-disciplinary image-guided assessment and therapies become increasingly important for precision oncology, the need for comprehensive training opportunities that effectively prepare the next generation of clinician-scientists and scientists is evident. We present an innovative, evidence-based research training framework that integrates the following critical features: 1) intentional and personalized mentoring and career development, 2) immersive research in image-guided cancer therapy, 3) strategic mentored clinical exposure, 4) structured didactic learning and professional development opportunities, and 5) mentored grant writing. Designed to foster scientific rigor, translational thinking, and multi-disciplinary collaboration, the Image-Guided Cancer Therapy T32 Training Program (IGCT-T32) aims to prepare postdoctoral fellows …

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing