Medical Specialties Commons^™

Targeting The Mtor Pathway For The Prevention Of Er-Negative Breast Cancer, Abhijit Mazumdar, William M Tahaney, Jamal L Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, Jing Qian, Alejandro Contreras, Michelle I Savage, Lana A Vornik, Shizuko Sei, Altaf Mohammed, Powel H Brown

Faculty, Staff and Student Publications

Our results show that everolimus delays mammary tumor formation in multiple mouse models, suggesting that mTOR inhibitors will be useful for the prevention of ER-negative and triple-negative breast cancer in humans. See related Spotlight, p. 787.

Fulminant Lung Fibrosis In Non-Resolvable Covid-19 Requiring Transplantation, Soma S K Jyothula, Andrew Peters, Yafen Liang, Weizhen Bi, Pooja Shivshankar, Simon Yau, Puneet S Garcha, Xiaoyi Yuan, Bindu Akkanti, Scott Collum, Nancy Wareing, Rajarajan A Thandavarayan, Fernando Poli De Frias, Ivan O Rosas, Bihong Zhao, L Maximilian Buja, Holger K Eltzschig, Howard J Huang, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.

METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We …

Genome Protection By Dna Polymerase Θ, Richard D Wood, Sylvie Doublié

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ) is a DNA repair enzyme widely conserved in animals and plants. Pol θ uses short DNA sequence homologies to initiate repair of double-strand breaks by theta-mediated end joining. The DNA polymerase domain of Pol θ is at the C terminus and is connected to an N-terminal DNA helicase-like domain by a central linker. Pol θ is crucial for maintenance of damaged genomes during development, protects DNA against extensive deletions, and limits loss of heterozygosity. The cost of using Pol θ for genome protection is that a few nucleotides are usually deleted or added at the …

Avpcancerfree: Impact Of A Digital Behavior Change Intervention On Parental Hpv Vaccine –Related Perceptions And Behaviors, Ross Shegog, Lara S Savas, C Mary Healy, Erica L Frost, Sharon P Coan, Efrat K Gabay, Sharice M Preston, Stanley W Spinner, Mathew Wilbur, Elisabeth Becker, Travis Teague, Sally W Vernon

Faculty, Staff and Student Publications

Parent hesitancy contributes to reduced HPV vaccination rates. The HPVcancerfree app (HPVCF) was designed to assist parents in making evidence-based decisions regarding HPV vaccination. This study examined if parents of vaccine-eligible youth (11-12 yrs.) who use HPVCF in addition to usual care demonstrate significantly more positive intentions and attitudes toward HPV vaccination and greater HPV vaccination rates compared to those not using HPVCF. Clinics (n = 51) within a large urban pediatric network were randomly assigned to treatment (HPVCF + usual care) or comparison (usual care only) conditions in a RCT conducted between September 2017 and February 2019. Parents completed …

An Ai-Driven Clinical Care Pathway To Reduce 30-Day Readmission For Chronic Obstructive Pulmonary Disease (Copd) Patients, Lin Wang, Guihua Li, Chika F Ezeana, Richard Ogunti, Mamta Puppala, Tiancheng He, Xiaohui Yu, Solomon S Y Wong, Zheng Yin, Aaron W Roberts, Aryan Nezamabadi, Pingyi Xu, Adaani Frost, Robert E Jackson, Stephen T C Wong

Faculty, Staff and Student Publications

Healthcare regulatory agencies have mandated a reduction in 30-day hospital readmission rates and have targeted COPD as a major contributor to 30-day readmissions. We aimed to develop and validate a simple tool deploying an artificial neural network (ANN) for early identification of COPD patients with high readmission risk. Using COPD patient data from eight hospitals within a large urban hospital system, four variables were identified, weighted and validated. These included the number of in-patient admissions in the previous 6 months, the number of medications administered on the first day, insurance status, and the Rothman Index on hospital day one. An …

Hdac2 In Primary Sensory Neurons Constitutively Restrains Chronic Pain By Repressing Α2Δ-1 Expression And Associated Nmda Receptor Activity, Jixiang Zhang, Shao-Rui Chen, Meng-Hua Zhou, Daozhong Jin, Hong Chen, Li Wang, Ronald A Depinho, Hui-Lin Pan

Faculty, Staff and Student Publications

α2δ-1 (encoded by the Cacna2d1 gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin) frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), …

Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis, Mingjie Zheng, Rich G Li, Jia Song, Xiaolei Zhao, Li Tang, Shannon Erhardt, Wen Chen, Bao H Nguyen, Xiao Li, Min Li, Jianxin Wang, Sylvia M Evans, Vincent M Christoffels, Na Li, Jun Wang

Faculty, Staff and Student Publications

BACKGROUND: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.

METHODS: We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases

RESULTS: We …

Optimal Construction Of A Functional Interaction Network From Pooled Library Crispr Fitness Screens, Veronica Gheorghe, Traver Hart

Faculty, Staff and Student Publications

BACKGROUND: Functional interaction networks, where edges connect genes likely to operate in the same biological process or pathway, can be inferred from CRISPR knockout screens in cancer cell lines. Genes with similar knockout fitness profiles across a sufficiently diverse set of cell line screens are likely to be co-functional, and these "coessentiality" networks are increasingly powerful predictors of gene function and biological modularity. While several such networks have been published, most use different algorithms for each step of the network construction process.

RESULTS: In this study, we identify an optimal measure of functional interaction and test all combinations of options …

Genetic And Small-Molecule Modulation Of Stat3 In A Mouse Model Of Crohn's Disease, Prema Robinson, Emily Magness, Kelsey Montoya, Nikita Engineer, Thomas K Eckols, Emma Rodriguez, David J Tweardy

Faculty, Staff and Student Publications

Crohn's disease (CD), is an inflammatory bowel disease that can affect any part of the gastro-intestinal tract (GI) and is associated with an increased risk of gastro-intestinal cancer. In the current study, we determined the role of genetic and small-molecule modulation of STAT3 in a mouse model of CD. STAT3 has 2 isoforms (α, β) which are expressed in most cells in a 4:1 ratio (α: β). STAT3α has pro-inflammatory and anti-apoptotic functions, while STAT3β has contrasting roles. We used an animal model of CD consisting of intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid and examined the severity of CD in …

The Fate Of Early Perichondrial Cells In Developing Bones, Yuki Matsushita, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Shion Orikasa, Mizuki Nagata, Sunny Y Wong, Joshua D Welch, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid …

Inactivation Of Lats1/2 Drives Luminal-Basal Plasticity To Initiate Basal-Like Mammary Carcinomas, Joseph G Kern, Andrew M Tilston-Lunel, Anthony Federico, Boting Ning, Amy Mueller, Grace B Peppler, Eleni Stampouloglou, Nan Cheng, Randy L Johnson, Marc E Lenburg, Jennifer E Beane, Stefano Monti, Xaralabos Varelas

Faculty, Staff and Student Publications

Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of Krt14 and Sox9-expressing basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Gene expression analyses of …

Glial Interference: Impact Of Type I Interferon In Neurodegenerative Diseases, Ethan Roy, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Interventions For Preventing And Ameliorating Cognitive Deficits In Adults Treated With Cranial Irradiation, Matthew A Kirkman, Julia Day, Karin Gehring, Karolis Zienius, David Grosshans, Martin Taphoorn, Jing Li, Paul D Brown

Faculty, Staff and Student Publications

BACKGROUND: Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.

OBJECTIVES: To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.

SEARCH METHODS: For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 …

Oxphos Promotes Apoptotic Resistance And Cellular Persistence In Th17 Cells In The Periphery And Tumor Microenvironment, Hanna S Hong, Nneka E Mbah, Mengrou Shan, Kristen Loesel, Lin Lin, Peter Sajjakulnukit, Luis O Correa, Anthony Andren, Jason Lin, Atsushi Hayashi, Brian Magnuson, Judy Chen, Zhaoheng Li, Yuying Xie, Li Zhang, Daniel R Goldstein, Shannon A Carty, Yu Leo Lei, Anthony W Opipari, Rafael J Argüello, Ilona Kryczek, Nobuhiko Kamada, Weiping Zou, Luigi Franchi, Costas A Lyssiotis

Faculty, Staff and Student Publications

T cell proliferation and cytokine production are bioenergetically and biosynthetically costly. The inability to meet these metabolic demands results in altered differentiation, accompanied by impaired effector function, and attrition of the immune response. Interleukin-17-producing CD4 T cells (TH17s) are mediators of host defense, autoimmunity, and antitumor immunity in the setting of adoptive T cell therapy. TH17s are long-lived cells that require mitochondrial oxidative phosphorylation (OXPHOS) for effector function in vivo. Considering that TH17s polarized under standardized culture conditions are predominately glycolytic, little is known about how OXPHOS regulates TH17 processes, such as their ability to persist and thus contribute to …

A Retrospective Comparative Study Of Sodium Fluoride Na18f-Pet/Ct And 68ga-Psma-11 Pet/Ct In The Bone Metastases Of Prostate Cancer Using A Volumetric 3-D Radiomic Analysis, Kalevi Kairemo, Aki Kangasmäki, Srinivasan Cheenu Kappadath, Timo Joensuu, Homer A Macapinlac

Faculty, Staff and Student Publications

Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). …

Coating Formulation Change Leads To Inferior Performance Of Long-Lasting Insecticidal Nets In Papua New Guinea, Nakei Bubun, Evodia Anetul, Melanie Koinari, Timothy W Freeman, Stephan Karl

Faculty, Staff and Student Publications

BACKGROUND: Long-lasting insecticidal nets (LLINs) play a key role in reducing malaria transmission in endemic countries. In a previous study, the authors demonstrated a substantial decrease in the bioefficacy of LLINs for malaria prevention delivered to Papua New Guinea (PNG) between 2013 and 2019. This coincided with a rise in malaria cases in the country. The present study was aimed at determining the underlying cause of the reduced bioefficacy observed in these LLINs. The main hypothesis was that a change in the coating formulation of the respective LLIN product was responsible, and had led to significantly altered product properties and …

Validation Of Prediction Rules For Computed Tomography Use In Children With Blunt Abdominal Or Blunt Head Trauma: Protocol For A Prospective Multicenter Observational Cohort Study, Irma T Ugalde, Pradip P Chaudhari, Mohamed Badawy, Paul Ishimine, Kevan A Mccarten-Gibbs, Kenneth Yen, Nisa S Atigapramoj, Allyson Sage, Donovan Nielsen, P David Adelson, Jeffrey Upperman, Daniel Tancredi, Nathan Kuppermann, James F Holmes

Faculty, Staff and Student Publications

BACKGROUND: Traumatic brain injuries (TBIs) and intra-abdominal injuries (IAIs) are 2 leading causes of traumatic death and disability in children. To avoid missed or delayed diagnoses leading to increased morbidity, computed tomography (CT) is used liberally. However, the overuse of CT leads to inefficient care and radiation-induced malignancies. Therefore, to maximize precision and minimize the overuse of CT, the Pediatric Emergency Care Applied Research Network (PECARN) previously derived clinical prediction rules for identifying children at high risk and very low risk for IAIs undergoing acute intervention and clinically important TBIs after blunt trauma in large cohorts of children who are …

The Innate Immune System In Cardiovascular Diseases And Its Role In Doxorubicin-Induced Cardiotoxicity, Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release …

Genomic Profiling For Clinical Decision Making In Myeloid Neoplasms And Acute Leukemia, Eric J Duncavage, Adam Bagg, Robert P Hasserjian, Courtney D Dinardo, Lucy A Godley, Ilaria Iacobucci, Siddhartha Jaiswal, Luca Malcovati, Alessandro M Vannucchi, Keyur P Patel, Daniel A Arber, Maria E Arcila, Rafael Bejar, Nancy Berliner, Michael J Borowitz, Susan Branford, Anna L Brown, Catherine A Cargo, Hartmut Döhner, Brunangelo Falini, Guillermo Garcia-Manero, Torsten Haferlach, Eva Hellström-Lindberg, Annette S Kim, Jeffery M Klco, Rami Komrokji, Mignon Lee-Cheun Loh, Sanam Loghavi, Charles G Mullighan, Seishi Ogawa, Attilio Orazi, Elli Papaemmanuil, Andreas Reiter, David M Ross, Michael Savona, Akiko Shimamura, Radek C Skoda, Francesc Solé, Richard M Stone, Ayalew Tefferi, Matthew J Walter, David Wu, Benjamin L Ebert, Mario Cazzola

Faculty, Staff and Student Publications

Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome …

Spatially Aware Dimension Reduction For Spatial Transcriptomics, Lulu Shang, Xiang Zhou

Faculty, Staff and Student Publications

Spatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. Here, we develop a spatially-aware dimension reduction method, SpatialPCA, that can extract a low dimensional representation of the spatial transcriptomics data with biological signal and preserved spatial correlation structure, thus unlocking many existing computational tools previously developed in single-cell RNAseq studies for tailored analysis of spatial transcriptomics. We illustrate the benefits of SpatialPCA for …

Triple Blockade Of Ido-1, Pd-L1 And Mek As A Potential Therapeutic Strategy In Nsclc, Carminia Maria Della Corte, Vincenza Ciaramella, Kavya Ramkumar, Giovanni Vicidomini, Alfonso Fiorelli, Valerio Nardone, Salvatore Cappabianca, Immacolata Cozzolino, Federica Zito Marino, Gaetano Di Guida, Qi Wang, Robert Cardnell, Carl Michael Gay, Davide Ciardiello, Erika Martinelli, Teresa Troiani, Giulia Martini, Stefania Napolitano, Jing Wang, Lauren Averett Byers, Fortunato Ciardiello, Floriana Morgillo

Faculty, Staff and Student Publications

BACKGROUND: Despite the recent progress in the treatment and outcome of Non Small Cell Lung Cancer (NSCLC), immunotherapy has still significant limitations reporting a significant proportion of patients not benefiting from therapy, even in patients with high PD-L1 expression. We have previously demonstrated that the combined inhibition of MEK and PD-L1 in NSCLC patients derived three dimensional cultures exerted significant synergistic effect in terms of immune-dependent cancer cell death. However, subsequent experiments analyzing the expression of Indoleamine 2,3-dioxygenase-1 (Ido-1) gene expression demonstrated that Ido-1 resulted unaffected by the MEK inhibition and even increased after the combined inhibition of MEK and …

Low Rates Of Structured Advance Care Planning Documentation In Electronic Health Records: Results Of A Single-Center Observational Study, Adela Wu, Robert J Huang, Gabriela Ruiz Colón, Chris Zembrzuski, Chirag B Patel

Faculty, Staff and Student Publications

BACKGROUND: Proper advance care planning (ACP) documentation both improves patient care and is increasingly seen as a marker of high quality by governmental payers. The transition of most medical documentation to electronic health records (EHR) allows for ACP documents to be rapidly disseminated across diverse ambulatory practice settings. At the same time, the complexity and heterogeneity of the EHR, as well as the multiple potential storage locations for documentation, may lead to confusion and inaccessibility. There has been movement to promote structured ACP (S-ACP) documentation within the EHR.

METHODS: We performed a retrospective cohort study at a single, large university …

Phase Ii Study Of Venetoclax Added To Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine In Older Patients With Newly Diagnosed Acute Myeloid Leukemia, Tapan M Kadia, Patrick K Reville, Xuemei Wang, Caitlin R Rausch, Gautam Borthakur, Naveen Pemmaraju, Naval G Daver, Courtney D Dinardo, Koji Sasaki, Ghayas C Issa, Maro Ohanian, Guillermo Montalban-Bravo, Nicholas J Short, Nitin Jain, Alessandra Ferrajoli, Kapil N Bhalla, Elias Jabbour, Koichi Takahashi, Rashmi Malla, Kelly Quagliato, Rashmi Kanagal-Shamanna, Uday R Popat, Michael Andreeff, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

PURPOSE: The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

METHODS: This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with …

Bob: Bayesian Optimal Design For Biosimilar Trials With Co-Primary Endpoints, Xiaohan Chi, Zhangsheng Yu, Ruitao Lin

Faculty, Staff and Student Publications

For regulatory approval of a biosimilar product, extensive evaluations should be performed by rigorous clinical trials to establish the similarity between the reference product and the proposed biosimilar in terms of both efficacy and safety. Existing designs for biosimilar trials often use a single primary efficacy endpoint in trial monitoring, and then separately evaluate the safety of the biosimilar product in a secondary analysis at the trial completion. However, ignoring the safety endpoint and the correlation between safety and efficacy in trial monitoring may lead to a high false positive rate, or it may delay the termination of the trial …

Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder, Jiayu Chen, Zening Fu, Juan R Bustillo, Nora I Perrone-Bizzozero, Dongdong Lin, Jose Canive, Godfrey D Pearlson, Julia M Stephen, Andrew R Mayer, Steven G Potkin, Theo G M Van Erp, Peter Kochunov, L Elliot Hong, Bhim M Adhikari, Ole A Andreassen, Ingrid Agartz, Lars T Westlye, Jing Sui, Yuhui Du, Fabio Macciardi, Faith M Hanlon, Rex E Jung, Jessica A Turner, Jingyu Liu, Vince D Calhoun

Faculty, Staff and Student Publications

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway.

STUDY DESIGNS: Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial …

Fine-Tuned Local Coordination Environment Of Pt Single Atoms On Ceria Controls Catalytic Reactivity, Wei Tan, Shaohua Xie, Duy Le, Weijian Diao, Meiyu Wang, Ke-Bin Low, Dave Austin, Sampyo Hong, Fei Gao, Lin Dong, Lu Ma, Steven N Ehrlich, Talat S Rahman, Fudong Liu

Faculty, Staff and Student Publications

Constructing single atom catalysts with fine-tuned coordination environments can be a promising strategy to achieve satisfactory catalytic performance. Herein, via a simple calcination temperature-control strategy, CeO2 supported Pt single atom catalysts with precisely controlled coordination environments are successfully fabricated. The joint experimental and theoretical analysis reveals that the Pt single atoms on Pt1/CeO2 prepared at 550 °C (Pt/CeO2-550) are mainly located at the edge sites of CeO2 with a Pt-O coordination number of ca. 5, while those prepared at 800 °C (Pt/CeO2-800) are predominantly located at distorted Ce substitution sites on CeO2 terrace with a Pt-O coordination number of ca. …

Chronic Exposure To Carbon Black Ultrafine Particles Reprograms Macrophage Metabolism And Accelerates Lung Cancer, Cheng-Yen Chang, Ran You, Dominique Armstrong, Ashwini Bandi, Yi-Ting Cheng, Philip M Burkhardt, Luis Becerra-Dominguez, Matthew C Madison, Hui-Ying Tung, Zhimin Zeng, Yifan Wu, Lizhen Song, Patricia E Phillips, Paul Porter, John M Knight, Nagireddy Putluri, Xiaoyi Yuan, Daniela C Marcano, Emily A Mchugh, James M Tour, Andre Catic, Laure Maneix, Bryan M Burt, Hyun-Sung Lee, David B Corry, Farrah Kheradmand

Faculty, Staff and Student Publications

Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A-dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non-small cell lung cancers. Adoptive transfer of lung APCs …

Scale-Up Of A Rh-Catalyzed Asymmetric Sp3–Sp2 Suzuki–Miyaura-Type Reaction, Laura Cunningham, Mireia Sidera Portela, Stephen P Fletcher

Faculty, Staff and Student Publications

Csp²–Csp² Suzuki–Miyaura couplings (SMCs) are ubiquitous in the synthesis of small molecules, but analogous Csp²–Csp³ bond-forming SMCs are rare, especially asymmetric variants. Recently, we developed a series of Rh-catalyzed couplings between racemic sp³-hybridized allyl chlorides and heteroaryl boronic acids. Here, we demonstrate that these catalytic asymmetric reactions can be scaled-up to give over 100 g of a product. The reaction we chose to test couples a heteroaromatic boronic acid derivative and a racemic bicyclic electrophile to give a product with three contiguous stereogenic centers. The SMC product was obtained as a single …

Intervening On Impostor Phenomenon: Prospective Evaluation Of A Workshop For Health Science Students Using A Mixed-Method Design, Shine Chang, Hwa Young Lee, Cheryl Anderson, Kava Lewis, Devasmita Chakraverty, Melinda Yates

Faculty, Staff and Student Publications

BACKGROUND: Unaddressed impostor feelings that impede developing interest in science and self-efficacy in conducting research have a dispiriting effect that perpetuates unsatisfactory diversity in the health science workforce when such feelings are experienced more by those historically underrepresented in the workforce. This warrants effective interventions to reduce the impact of impostor feelings and related factors that diminish career resilience. We examined the effects of a 90-minute workshop on impostor perceptions and growth mindset to raise awareness of impostor phenomenon (IP) and develop skills to manage IP successfully for students attending a 10-week summer research experience program.

METHODS: Using a convergent …

Environmental Drivers Of The First Major Animal Extinction Across The Ediacaran White Sea-Nama Transition, Scott D Evans, Chenyi Tu, Adriana Rizzo, Rachel L Surprenant, Phillip C Boan, Heather Mccandless, Nathan Marshall, Shuhai Xiao, Mary L Droser

Faculty, Staff and Student Publications

The Ediacara Biota-the oldest communities of complex, macroscopic fossils-consists of three temporally distinct assemblages: the Avalon (ca. 575-560 Ma), White Sea (ca. 560-550 Ma), and Nama (ca. 550-539 Ma). Generic diversity varies among assemblages, with a notable decline at the transition from White Sea to Nama. Preservation and sampling biases, biotic replacement, and environmental perturbation have been proposed as potential mechanisms for this drop in diversity. Here, we compile a global database of the Ediacara Biota, specifically targeting taphonomic and paleoecological characters, to test these hypotheses. Major ecological shifts in feeding mode, life habit, and tiering level accompany an increase …