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Resolution Of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 In Male Miceb, Kiersten Scott, Nabila Boukelmoune, Cullen Taniguchi, A Phillip West, Cobi J Heijnen

Faculty, Staff and Student Publications

Based on previous results showing a pivotal role of endogenous interleukin-10 (IL-10) in the recovery from cisplatin-induced peripheral neuropathy, the present experiments were carried out to determine whether this cytokine plays any role in the recovery from cisplatin-induced fatigue in male mice. Fatigue was measured by decreased voluntary wheel running in mice trained to run in a wheel in response to cisplatin. Mice were treated with a monoclonal neutralizing antibody (IL-10na) administered intranasally during the recovery period to neutralize endogenous IL-10. In the first experiment, mice were treated with cisplatin (2.83 mg/kg/day) for five days and IL-10na (12 μg/day for …

Positive Selection Of Somatically Mutated Clones Identifies Adaptive Pathways In Metabolic Liver Disease, Zixi Wang, Shijia Zhu, Yuemeng Jia, Yunguan Wang, Naoto Kubota, Ruth Gordillo, Min Zhu, Tripti Sharma, Lin Li, Qiyu Zeng, Yu-Hsuan Lin, Meng-Hsiung Hsieh, Purva Gopal, Tao Wang, Matt Hoare, Peter Campbell, Yujin Hoshida, Hao Zhu

Faculty, Staff and Student Publications

Somatic mutations in nonmalignant tissues accumulate with age and injury, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate genes in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to nonalcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side by side. This in vivo tracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes …

Consensus Proposal For Revised International Working Group 2023 Response Criteria For Higher-Risk Myelodysplastic Syndromes, Amer M Zeidan, Uwe Platzbecker, Jan Philipp Bewersdorf, Maximilian Stahl, Lionel Adès, David Bowen, Andrew Brunner, Hetty E Carraway, Naval Daver, Maria Díez-Campelo, Theo De Witte, Amy E Dezern, Fabio Efficace, Guillermo Garcia-Manero, Jacqueline S Garcia, Ulrich Germing, Aristoteles Giagounidis, Elizabeth A Griffiths, Robert P Hasserjian, Eva Hellström-Lindberg, Marcelo Iastrebner, Rami Komrokji, Austin G Kulasekararaj, Luca Malcovati, Yasushi Miyazaki, Olatoyosi Odenike, Valeria Santini, Guillermo Sanz, Phillip Scheinberg, Reinhard Stauder, Arjan A Van De Loosdrecht, Andrew H Wei, Mikkael A Sekeres, Pierre Fenaux

Faculty, Staff and Student Publications

Myelodysplastic syndromes/myelodysplastic neoplasms (MDS) are associated with variable clinical presentations and outcomes. The initial response criteria developed by the International Working Group (IWG) in 2000 have been used in clinical practice, clinical trials, regulatory reviews, and drug labels. Although the IWG criteria were revised in 2006 and 2018 (the latter focusing on lower-risk disease), limitations persist in their application to higher-risk MDS (HR-MDS) and their ability to fully capture the clinical benefits of novel investigational drugs or serve as valid surrogates for longer-term clinical end points (eg, overall survival). Further, issues related to the ambiguity and practicality of some criteria …

Resolution Of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 In Male Mice, Kiersten Scott, Nabila Boukelmoune, Cullen Taniguchi, A Phillip West, Cobi J Heijnen

Faculty, Staff and Student Publications

Based on previous results showing a pivotal role of endogenous interleukin-10 (IL-10) in the recovery from cisplatin-induced peripheral neuropathy, the present experiments were carried out to determine whether this cytokine plays any role in the recovery from cisplatin-induced fatigue in male mice. Fatigue was measured by decreased voluntary wheel running in mice trained to run in a wheel in response to cisplatin. Mice were treated with a monoclonal neutralizing antibody (IL-10na) administered intranasally during the recovery period to neutralize endogenous IL-10. In the first experiment, mice were treated with cisplatin (2.83 mg/kg/day) for five days and IL-10na (12 μg/day for …

Mapping The Functional Interactions At The Tumor-Immune Checkpoint Interface, Behnaz Bozorgui, Elisabeth K Kong, Augustin Luna, Anil Korkut

Faculty, Staff and Student Publications

The interactions between tumor intrinsic processes and immune checkpoints can mediate immune evasion by cancer cells and responses to immunotherapy. It is, however, challenging to identify functional interactions due to the prohibitively complex molecular landscape of the tumor-immune interfaces. We address this challenge with a statistical analysis framework, immuno-oncology gene interaction maps (ImogiMap). ImogiMap quantifies and statistically validates tumor-immune checkpoint interactions based on their co-associations with immune-associated phenotypes. The outcome is a catalog of tumor-immune checkpoint interaction maps for diverse immune-associated phenotypes. Applications of ImogiMap recapitulate the interaction of SERPINB9 and immune checkpoints with interferon gamma (IFNγ) expression. Our analyses …

Experiencing Moral Distress Within The Intimate Partner Violence & Sexual Assault Workforce, Leila Wood

Faculty, Staff and Student Publications

PURPOSE: Moral distress (MD) refers to the psychological disequilibrium that emerges when institutional policies and/or practices conflict with an individual's professional values and ethics. MD has been interrogated frequently in health care and ancillary medical settings, and has been identified as a critical barrier to enhanced organizational climate and patient care. However, little work has investigated experiences of MD among members of the intimate partner violence (IPV) and sexual violence (SV) workforce.

METHODS: This study investigates MD in a sample of IPV and SV service providers via secondary analysis of 33 qualitative interviews conducted with service providers in the summer …

Ms 192 Guide To The Curtis C. Mooney Papers (2015), Curtis C. Mooney (1947-2000)

Manuscript Finding Aids

Oral histories on community mental health in Texas created during Curtis Mooney’s dissertation research. See more at MS 192.

Covid-19 Severity Scale For Claims Data Research, Regina M Hansen

Faculty, Staff and Student Publications

OBJECTIVE: to create and validate a methodology to assign a severity level to an episode of COVID-19 for retrospective analysis in claims data.

DATA SOURCE: Secondary data obtained by license agreement from Optum provided claims records nationally for 19,761,754 persons, of which, 692,094 persons had COVID-19 in 2020.

STUDY DESIGN: The World Health Organization (WHO) COVID-19 Progression Scale was used as a model to identify endpoints as measures of episode severity within claims data. Endpoints used included symptoms, respiratory status, progression to levels of treatment and mortality.

DATA COLLECTION/EXTRACTION METHODS: The strategy for identification of cases relied upon the February …

Cloning A Profibrotic Stem Cell Variant In Idiopathic Pulmonary Fibrosis, Justin Li, Tinne C J Mertens, Harry Karmouty-Quintana, Christopher P Crum, Mark L Metersky, David A Schwartz, Peter J A Davies, Clifford Stephan, Soma S K Jyothula, Ajay Sheshadri, Erik Eddie Suarez, Howard J Huang, John F Engelhardt, Burton F Dickey, Kalpaj R Parekh, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of lung alveoli with dense fibrotic matrices. Although the mechanisms initiating IPF remain unclear, rare and common alleles of genes expressed in lung epithelia, combined with aging, contribute to the risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified lung basal cell heterogeneity in IPF that might be pathogenic. We used single-cell cloning technologies to generate "libraries" of basal stem cells from the distal lungs of 16 patients with IPF and 10 controls. We identified a major stem cell …

Effectors And Effects Of Arginine Methylation, Yalong Wang, Mark T Bedford

Faculty, Staff and Student Publications

Arginine methylation is a ubiquitous and relatively stable post-translational modification (PTM) that occurs in three types: monomethylarginine (MMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Methylarginine marks are catalyzed by members of the protein arginine methyltransferases (PRMTs) family of enzymes. Substrates for arginine methylation are found in most cellular compartments, with RNA-binding proteins forming the majority of PRMT targets. Arginine methylation often occurs in intrinsically disordered regions of proteins, which impacts biological processes like protein-protein interactions and phase separation, to modulate gene transcription, mRNA splicing and signal transduction. With regards to protein-protein interactions, the major 'readers' of methylarginine marks are …

Hica Toxin-Based Counterselection Marker For Allelic Exchange Mutations In Fusobacterium Nucleatum, Bibek Gc, Peng Zhou, Chenggang Wu

Faculty, Staff and Student Publications

The study of fusobacterial virulence factors has dramatically benefited from the creation of various genetic tools for DNA manipulation, including galK-based counterselection for in-frame deletion mutagenesis in Fusobacterium nucleatum, which was recently developed. However, this method requires a host lacking the galK gene, which is an inherent limitation. To circumvent this limitation, we explored the possibility of using the hicA gene that encodes a toxin consisting of a HicAB toxin-antitoxin module in Fusobacterium periodonticum as a new counterselective marker. Interestingly, the full-length hicA gene is not toxic in F. nucleatum, but a truncated hicA gene version lacking the first …

Bridging Clinic And Wildlife Care With Ai-Powered Pan-Species Computational Pathology, Khalid Abduljabbar, Simon P Castillo, Katherine Hughes, Hannah Davidson, Amy M Boddy, Lucia Minoli, Elizabeth P Murchison, Trevor A Graham, Simon Spiro, Carlo C Maley, Luca Aresu, Chiara Palmieri, Yinyin Yuan

Faculty, Staff and Student Publications

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves …

Overcoming Adaptive Resistance To Anti-Vegf Therapy By Targeting Cd5l, Christopher J Lafargue, Paola Amero, Kyunghee Noh, Lingegowda S Mangala, Yunfei Wen, Sujanitha Umamaheswaran, Santosh K Dasari, Cristina Ivan, Sunila Pradeep, Wonbeak Yoo, Chunhua Lu, Nicholas B Jennings, Vinod Vathipadiekal, Wei Hu, Anca Chelariu-Raicu, Zhiqiang Ku, Hui Deng, Wei Xiong, Hyun-Jin Choi, Min Hu, Takae Kiyama, Chai-An Mao, Rouba Ali-Fehmi, Michael J Birrer, Jinsong Liu, Ningyan Zhang, Gabriel Lopez-Berestein, Vittorio De Franciscis, Zhiqiang An, Anil K Sood

Faculty, Staff and Student Publications

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. …

Barriers To Care In Juvenile Localized And Systemic Scleroderma: An Exploratory Survey Study Of Caregivers’ Perspectives, Christina Loccke, Erin Moriarty Wade, Pamela Pour, Kaveh Ardalan, Peter Chira, Ingrid M Ganske, Daniel Glaser, Gloria Higgins, Nadia Luca, Katharine F Moore, Vidya Sivaraman, Katie Stewart, Natalia Vasquez-Canizares, Raegan D Hunt, Renata S Maricevich, Kathryn S Torok, Suzanne C Li, Childhood Arthritis, Rheumatology Research Alliance (Carra) Scleroderma Workgroup

Faculty, Staff and Students Publications

BACKGROUND: Juvenile localized scleroderma (LS) and systemic sclerosis (SSc) are rare pediatric conditions often associated with severe morbidities. Delays in diagnosis are common, increasing the risk for permanent damage and worse outcomes. This study explored caregiver perspectives on barriers they encountered while navigating diagnosis and care for their child's scleroderma.

METHODS: In this cross-sectional study, caregivers of juvenile LS or SSc patients were recruited from a virtual family scleroderma educational conference and a juvenile scleroderma online interest group. The survey queried respondents about their child's condition and factors affecting diagnosis and treatment.

RESULTS: The response rate was 61% (73/120), with …

Analysis Of Adsorbed Polyphosphate Changes On Milled Titanium Dioxide, Using Low-Field Relaxation Nmr And Photoelectron Spectroscopy, Ali Hassanpour, John Robb, John L Edwards, Stephen Sutcliffe, Timothy N Hunter

Faculty, Staff and Students Publications

In this study, changes in the adsorbed amount and surface structure of sodium hexametaphosphate (SHMP) were investigated for aluminum-doped TiO2 pigment undergoing milling. Relaxation NMR was utilized as a potential at-line technique to monitor the effect of milling on surface area and surface chemistry, while XPS was used primarily to consider the dispersant structure. Results showed that considerable amounts of weakly adsorbed SHMP could be removed with washing, and the level of dispersant removal increased with time, highlighting destructive effects of sustained high-energy milling. Nonetheless, there were no significant chemical changes to the dispersant, although increases to the bridging oxygen …

Framing The Family: A Qualitative Exploration Of Factors That Shape Family-Level Experience Of Pediatric Genomic Sequencing, Hadley Stevens Smith, Emily S Bonkowski, Madison R Hickingbotham, Raymond Belanger Deloge, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS …

Multi-Center Retrospective Study Of Children With Sickle Cell Disease Admitted To Pediatric Intensive Care Units In The United States, Titilope Fasipe, Julie Katkin, Saleh Bhar, Gladstone Airewele, Arun Saini, Venée N Tubman

Faculty, Staff and Students Publications

Data on outcomes and interventions for children with sickle cell disease (SCD) admitted to a pediatric intensive care units (PICU) are unknown. We provide the first comprehensive multi-center report on PICU interventions associated with death, the need for invasive respiratory support or stroke among critically ill children with SCD. We collected retrospective multi-center cohort data from January 1, 2012 to December 31, 2019 utilizing the Virtual Pediatric Systems, LLC database. We identified 3388 unique children with SCD, accounting for a total of 5264 PICU admissions from 138 PICUs. The overall mortality rate for the PICU admissions cohort was 1.8% (95/5264 …

Bone Marrow Endosteal Stem Cells Dictate Active Osteogenesis And Aggressive Tumorigenesis

Faculty, Staff and Student Publications

The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR)+ perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear. Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 (Fgfr3) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. These Fgfr3-creER-marked endosteal stromal …

Framing The Family: A Qualitative Exploration Of Factors That Shape Family-Level Experience Of Pediatric Genomic Sequencing, Hadley Stevens Smith, Emily S Bonkowski, Madison R Hickingbotham, Raymond Belanger Deloge, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS …

Point-Of-Care Ultrasound In Airway Evaluation And Management: A Comprehensive Review, Jennifer Walker, Yi-Hsuan Yen, Ching-Fang Tiffany Tzeng, Eric H Chou

Faculty, Staff and Student Publications

Airway management is a common and critical procedure in acute settings, such as the Emergency Department (ED) or Intensive Care Unit (ICU) of hospitals. Many of the traditional physical examination methods have limitations in airway assessment. Point-of-care ultrasound (POCUS) has emerged as a promising tool for airway management due to its familiarity, accessibility, safety, and non-invasive nature. It can assist physicians in identifying relevant anatomy of the upper airway with objective measurements of airway parameters, and it can guide airway interventions with dynamic real-time images. To date, ultrasound has been considered highly accurate for assessment of the difficult airway, confirmation …

Cdk5-Prmt1-Wdr24 Signaling Cascade Promotes Mtorc1 Signaling And Tumor Growth, Shasha Yin, Liu Liu, Lauren E Ball, Yalong Wang, Mark T Bedford, Haizhen Wang

Faculty, Staff and Student Publications

The mammalian target of rapamycin complex1 (mTORC1) is a central regulator of metabolism and cell growth by sensing diverse environmental signals, including amino acids. The GATOR2 complex is a key component linking amino acid signals to mTORC1. Here, we identify protein arginine methyltransferase 1 (PRMT1) as a critical regulator of GATOR2. In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cytoplasm and lysosome, which in turn methylates WDR24, an essential component of GATOR2, to activate the mTORC1 pathway. Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation …

Modelling Radiation Cancer Treatment With A Death-Rate Term In Ordinary And Fractional Differential Equations, Nicole Wilson, Corina S Drapaca, Heiko Enderling, Jimmy J Caudell, Kathleen P Wilkie

Faculty, Staff and Student Publications

Fractional calculus has recently been applied to the mathematical modelling of tumour growth, but its use introduces complexities that may not be warranted. Mathematical modelling with differential equations is a standard approach to study and predict treatment outcomes for population-level and patient-specific responses. Here, we use patient data of radiation-treated tumours to discuss the benefits and limitations of introducing fractional derivatives into three standard models of tumour growth. The fractional derivative introduces a history-dependence into the growth function, which requires a continuous death-rate term for radiation treatment. This newly proposed radiation-induced death-rate term improves computational efficiency in both ordinary and …

Bone Marrow Endosteal Stem Cells Dictate Active Osteogenesis And Aggressive Tumorigenesis, Yuki Matsushita, Jialin Liu, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Mizuki Nagata, Wanida Ono, Thomas L Saunders, Joshua D Welch, Noriaki Ono

Faculty, Staff and Student Publications

The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR)+ perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear. Here we show that bone marrow endosteal SSCs are defined by fibroblast growth factor receptor 3 (Fgfr3) and osteoblast-chondrocyte transitional (OCT) identities with some characteristics of bone osteoblasts and chondrocytes. These Fgfr3-creER-marked endosteal stromal cells contribute to …

Nothing About Us Without Us: The Roles Of Diverse Stakeholders In Scientific Publishing

Faculty, Staff and Student Publications

No abstract provided.

Tumor Suppressor Candidate 2 (Tusc2): Discovery, Functions, And Cancer Therapy

Faculty, Staff and Student Publications

Tumor Suppressor Candidate 2 (TUSC2) was first discovered as a potential tumor suppressor gene residing in the frequently deleted 3p21.3 chromosomal region. Since its discovery, TUSC2 has been found to play vital roles in normal immune function, and TUSC2 loss is associated with the development of autoimmune diseases as well as impaired responses within the innate immune system. TUSC2 also plays a vital role in regulating normal cellular mitochondrial calcium movement and homeostasis. Moreover, TUSC2 serves as an important factor in premature aging. In addition to TUSC2's normal cellular functions, TUSC2 has been studied as a tumor suppressor gene that …

Rapid Escape Of New Sars-Cov-2 Omicron Variants From Ba2-Directed Antibody Responses, Chang Liu, Piyada Supasa, Muneeswaran Selvaraj, Thushan I De Silva, Megan Plowright, Thomas A H Newman, Hailey Hornsby, Alexander J Mentzer, Donal Skelly, Thomas G Ritter, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J Dunachie, Optic Consortium, Cornelius Roemer, Thomas P Peacock, Neil G Paterson, Mark A Williams, David R Hall, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton

Faculty, Staff and Student Publications

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent …

Saturated Fatty Acids Dampen The Immunogenicity Of Cancer By Suppressing Sting, Blake R Heath, Wang Gong, Hülya F Taner, Luke Broses, Kohei Okuyama, Max Jin, Andriana Manousidaki, Yuesong Wu, Shaoping Zhang, Haitao Wen, Steven B Chinn, Eric Bartee, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show …

Immune Cellular Patterns Of Distribution Affect Outcomes Of Patients With Non-Small Cell Lung Cancer, Edwin Roger Parra, Jiexin Zhang, Mei Jiang, Auriole Tamegnon, Renganayaki Krishna Pandurengan, Luisa Solis, John Victor Heymach, Cesar Moran, Jack J Lee, Don Gibbons, Ignacio Ivan Wistuba

Faculty, Staff and Student Publications

Studying the cellular geographic distribution in non-small cell lung cancer is essential to understand the roles of cell populations in this type of tumor. In this study, we characterize the spatial cellular distribution of immune cell populations using 23 makers placed in five multiplex immunofluorescence panels and their associations with clinicopathologic variables and outcomes. Our results demonstrate two cellular distribution patterns-an unmixed pattern mostly related to immunoprotective cells and a mixed pattern mostly related to immunosuppressive cells. Distance analysis shows that T-cells expressing immune checkpoints are closer to malignant cells than other cells. Combining the cellular distribution patterns with cellular …

Review Of The Tumor Microenvironment In Basal And Squamous Cell Carcinoma, Elizabeth Chiang, Haleigh Stafford, Jane Buell, Uma Ramesh, Moran Amit, Michael Migden

Faculty, Staff and Student Publications

It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively. However, further investigation of the TME will provide …

Spatiotemporally Distributed Frontotemporal Networks For Sentence Reading, Zachary J Roccaforte

Faculty, Staff and Student Publications

Reading a sentence entails integrating the meanings of individual words to infer more complex, higher-order meaning. This highly rapid and complex human behavior is known to engage the inferior frontal gyrus (IFG) and middle temporal gyrus (MTG) in the language-dominant hemisphere, yet whether there are distinct contributions of these regions to sentence reading is still unclear. To probe these neural spatiotemporal dynamics, we used direct intracranial recordings to measure neural activity while reading sentences, meaning-deficient Jabberwocky sentences, and lists of words or pseudowords. We isolated two functionally and spatiotemporally distinct frontotemporal networks, each sensitive to distinct aspects of word and …