Medical Specialties Commons^™

Ccl4 Functions As A Biomarker Of Type 2 Airway Inflammation, Yoshiki Kobayashi, Hanh Hong Chu, Akira Kanda, Yasutaka Yun, Masami Shimono, Linh Manh Nguyen, Akitoshi Mitani, Kensuke Suzuki, Mikiya Asako, Hiroshi Iwai

Faculty, Staff and Student Publications

Eosinophilic airway inflammatory disease is associated with bronchial asthma, with eosinophilic chronic rhinosinusitis (ECRS) typical of refractory type 2 airway inflammation. CCL4 produced at local inflammatory sites is involved in them via the accumulation and activation of type 2 inflammatory cells, including eosinophils. The detailed mechanism of CCL4 production remains unclear, and also the possibility it could function as a biomarker of type 2 airway inflammation remains unresolved. In this study, we evaluated CCL4 mRNA expression and production via the TSLP receptor (TSLPR) and toll-like receptors (TLRs) or proteinase-activated receptor-2 (PAR2) in BEAS-2B bronchial epithelial cells co-incubated with purified eosinophils …

Characteristics Of Eating Behavior Profiles Among Preschoolers With Low-Income Backgrounds: A Person-Centered Analysis, Jennifer Orlet Fisher, Sheryl O Hughes, Alison L Miller, Mildred A Horodynski, Holly E Brophy-Herb, Dawn A Contreras, Niko Kaciroti, Karen E Peterson, Katherine L Rosenblum, Danielle Appugliese, Julie C Lumeng

Children’s Nutrition Research Center Staff Publications

Background: Individual differences in eating behaviors among young children are well-established, but the extent to which behaviors aggregate within individuals to form distinct eating behavior profiles remains unknown. Our objectives were to identify eating behavior profiles among preschool-aged children and evaluate associations with temperament and weight.

Methods: A secondary, cross-sectional analysis of baseline data from 2 cohort studies was conducted involving 1004 children aged 3-4 years and their parents with low-income backgrounds. Children's eating behaviors and temperament were assessed by parental report. Body mass index z-scores and weight status were calculated using measured heights and weights. Latent profile analysis (LPA) …

Molecular Profiles Of Serum-Derived Extracellular Vesicles In High-Grade Serous Ovarian Cancer, Li Zhao, Sara Corvigno, Shaolin Ma, Joseph Celestino, Nicole D Fleming, Richard A Hajek, Adrian Lankenau Ahumada, Nicholas B Jennings, Erika J Thompson, Hongli Tang, Shannon N Westin, Amir A Jazaeri, Jianhua Zhang, P Andrew Futreal, Anil K Sood, Sanghoon Lee

Faculty, Staff and Student Publications

Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified …

The Rsph4a Gene In Primary Ciliary Dyskinesia, Ron Nates, Mattan Arazi, Liza Grosman-Rimon, Roy Israel, Jacob Gohari, Leonid Sternik, Erez Kachel

Faculty, Staff and Student Publications

INTRODUCTION: There is no consensus as to which patients should undergo Non-Contrast Chest Computerized Tomography (NCCCT) and carotid arteries Doppler (CD) prior to cardiac surgery. The objective of this study was to examine whether preoperative imaging modalities provide clinical benefits and a change in surgical strategy.

METHODS: We routinely performed NCCCT and CD in all non-urgent cardiac surgery patients. Major NCCCT/CD findings related to cardiovascular findings (aortic calcification/atherosclerosis, carotid artery plaque/stenosis), or other incidental findings (lung kidney, thyroid, adrenal, gastrointestinal sites etc.) were documented. The results were divided into 3 categories: (A) findings requiring both changes in surgical strategy and …

Two-Pore Channel Blockade By Phosphoinositide Kinase Inhibitors Ym201636 And Pi-103 Determined By A Histidine Residue Near Pore-Entrance, Canwei Du, Xin Guan, Jiusheng Yan

Faculty, Staff and Student Publications

Human two-pore channels (TPCs) are endolysosomal cation channels and play an important role in NAADP-evoked Ca2+ release and endomembrane dynamics. We found that YM201636, a PIKfyve inhibitor, potently inhibits PI(3,5)P2-activated human TPC2 with an IC50 of 0.16 μM. YM201636 also effectively inhibits NAADP-activated TPC2 and a constitutively-open TPC2 L690A/L694A mutant channel; whereas it exerts little effect when applied in the channel's closed state. PI-103, a YM201636 analog and an inhibitor of PI3K and mTOR, also inhibits human TPC2 with an IC50 of 0.64 μM. With mutational, virtual docking, and molecular dynamic simulation analyses, we found that YM201636 and PI-103 directly …

Clinical Factors Associated With Non-Obese Nonalcoholic Fatty Liver Disease Detected Among Us Adults In The Nhanes 2017-2018, Zayd Adnan Razouki, Xiaotao Zhang, Jessica P Hwang, Natalia I Heredia

Faculty, Staff and Student Publications

NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017−2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0−15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1−7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7−8.5), and …

Influenza Activity And Composition Of The 2022-23 Influenza Vaccine - United States, 2021-22 Season, Angiezel Merced-Morales, Peter Daly, Anwar Isa Abd Elal, Noreen Ajayi, Ekow Annan, Alicia Budd, John Barnes, Arielle Colon, Charisse N Cummings, A Danielle Iuliano, Juliana Dasilva, Nick Dempster, Shikha Garg, Larisa Gubareva, Daneisha Hawkins, Amanda Howa, Stacy Huang, Marie Kirby, Krista Kniss, Rebecca Kondor, Jimma Liddell, Shunte Moon, Ha T Nguyen, Alissa O'Halloran, Catherine Smith, Thomas Stark, Katie Tastad, Dawud Ujamaa, Dave E Wentworth, Alicia M Fry, Vivien G Dugan, Lynnette Brammer

Faculty, Staff and Student Publications

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing …

Tdp1-Independent Pathways In The Process And Repair Of Top1-Induced Dna Damage, Huimin Zhang, Yun Xiong, Dan Su, Chao Wang, Mrinal Srivastava, Mengfan Tang, Xu Feng, Min Huang, Zhen Chen, Junjie Chen

Faculty, Staff and Student Publications

Anticancer drugs, such as camptothecin (CPT), trap topoisomerase I (TOP1) on DNA and form TOP1 cleavage complexes (TOP1cc). Alternative repair pathways have been suggested in the repair of TOP1cc. However, how these pathways work with TDP1, a key repair enzyme that specifically hydrolyze the covalent bond between TOP1 catalytic tyrosine and the 3'-end of DNA and contribute to the repair of TOP1cc is poorly understood. Here, using unbiased whole-genome CRISPR screens and generation of co-deficient cells with TDP1 and other genes, we demonstrate that MUS81 is an important factor that mediates the generation of excess double-strand breaks (DSBs) in TDP1 …

Sirpα Mediates Igf1 Receptor In Cardiomyopathy-Induced By Chronic Kidney Disease, Sandhya S Thomas, Jiao Wu, Giovanni Davogustto, Michael W Holliday, Kristin Eckel-Mahan, Daniela Verzola, Giacomo Garibotto, Zhaoyong Hu, William E Mitch, Heinrich Taegtmeyer

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease (CKD) is characterized by increased myocardial mass despite near-normal blood pressure, suggesting the presence of a separate trigger. A potential driver is SIRPα (signal regulatory protein alpha)-a mediator impairing insulin signaling. The objective of this study is to assess the role of circulating SIRPα in CKD-induced adverse cardiac remodeling.

METHODS: SIRPα expression was evaluated in mouse models and patients with CKD. Specifically, mutant, muscle-specific, or cardiac muscle-specific SIRPα KO (knockout) mice were examined after subtotal nephrectomy. Cardiac function was assessed by echocardiography. Metabolic responses were confirmed in cultured muscle cells or cardiomyocytes.

RESULTS: We demonstrate that …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma, Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Center for Medical Ethics and Health Policy Staff Publications

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

A Phospholipid Mimetic Targeting Lrh-1 Ameliorates Colitis, Suzanne G Mays, Emma H D'Agostino, Autumn R Flynn, Xiangsheng Huang, Guohui Wang, Xu Liu, Elizabeth J Millings, C Denise Okafor, Anamika Patel, Michael L Cato, Jeffery L Cornelison, Diana Melchers, René Houtman, David D Moore, John W Calvert, Nathan T Jui, Eric A Ortlund

Faculty, Staff and Students Publications

Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery. Therefore, we constructed a set of molecules with elements of natural phospholipids appended to a synthetic LRH-1 agonist. We show that the phospholipid-mimicking groups interact with the targeted residues in crystal structures and improve binding affinity, LRH-1 transcriptional activity, …

Unexpected Movement Of The Esophagus Across The Aorta, Hyun Ho Choi, Soo-Yoon Sung, Yoon Ho Ko

Faculty, Staff and Student Publications

Tumor regression throughout treatment would induce organ movement, but little is known of this in the esophagus. To achieve successful tumor regression, radiation therapy requires several weeks of radiation to be delivered accurately to the tumor. Usually, a 5-10 mm margin is allowed for set-up error and internal organ motion. Our case exhibited an unexpectedly large movement of the esophagus across the aorta with tumor regression that extended outside the margin and thus outside the radiotherapy field. These movements may affect subsequent invasive procedures or treatment during cancer therapy. After the unexpected large movement of the esophagus due to tumor …

Paclitaxel And Urolithin A Prevent Histamine-Induced Neurovascular Breakdown Alike, In An, Srijayaprakash Uppada, Dianxiong Zou, Erin M Scott, Gladys Ko, Stephen Pflugfelder, M N V Ravi Kumar, Raghu Ganugula

Faculty, Staff and Students Publications

Neurovascular eye problems are better prevented than managed or treated. Despite growing concern of occurrence in aging populations and development secondary to diseases such as diabetes and hypertension, we currently have very few options to tackle this global problem. Creating effective and high-throughput screening strategies is as important as the intervention itself. Here, we present for the first time a robust ex vivo rat eye model of histamine-induced vascular damage for investigating the therapeutic potential of paclitaxel (PTX) and urolithin A (UA) as alternatives to dexamethasone for preventing vascular damage in the retina. Extensive loss of vascularization and apoptosis were …

Magnetically Recoverable Silica-Decorated Ferromagnetic-Nanoceria Nanocatalysts And Their Use With O- And N-Butyloxycarbonylation Reaction Via Solvent-Free Condition, Shripad M Patil, Runjhun Tandon, Nitin Tandon

Faculty, Staff and Student Publications

Silica-decorated ferrite nanoparticles, a new kind, coated with ceric ammonium nitrate (CAN), have been prepared successfully by simple coprecipitation techniques. Powder X-ray diffraction spectroscopy (PXRD), Fourier transform-infrared spectroscopy (FT-IR), field emission-scanning electron microscope (FE-SEM), wavelength-dispersive X-ray spectroscopy (WDX), energy-dispersive spectroscopy (EDS), inductive coupled plasma-optical emission spectroscopy (ICP-OES), and thermogravimetric analysis (TGA) techniques were used to characterize these nanoparticles. The catalysts are further studied for catalytic activity in solvent-free conditions. Importantly, these nanoparticles have been collected from the reaction mixture using an external magnet and recycled up to minimum of 15 cycles with no substantial loss of catalytic characteristics.

Cardiovascular Adverse Events In Oncology Trials: Understanding And Appreciating The Differences Between Clinical Trial Data And Real-World Reports, Michael S Ewer, Jay Herson

Duncan NRI Faculty and Staff Publications

Reports of cardiac adverse events from oncology clinical trials often are at variance with reports derived from clinical observations or data-base reviews. These differences may lead to confusion, as different levels of risks abound in the literature, and the true cardiac risk of using some agents is uncertain. Additionally, such discrepancies may lead to the creation of over-cautious surveillance algorithms. Reasons for these reported differences are complex and often reflect subtleties in the criteria for individual patient evaluation. Both clinical trial data and real-world data have potential flaws that make reconciliation problematic. Importantly, however, both provide crucial information regarding the …

Sox9 Directs Divergent Epigenomic States In Brain Tumor Subtypes, Debosmita Sardar, Hsiao-Chi Chen, Amanda Reyes, Srinidhi Varadharajan, Antrix Jain, Carrie Mohila, Rachel Curry, Brittney Lozzi, Kavitha Rajendran, Alexis Cervantes, Kwanha Yu, Ali Jalali, Ganesh Rao, Stephen C Mack, Benjamin Deneen

Duncan NRI Faculty and Staff Publications

Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations; however, the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here, we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). Using our autochthonous mouse models, we found that Sox9 suppresses HGG growth and expands associated H3K27ac states, while promoting ZFTA-RELA (ZR

Hippo-Taz Signaling Is The Master Regulator Of The Onset Of Triple-Negative Basal-Like Breast Cancers, Hirotoshi Soyama, Miki Nishio, Junji Otani, Toshiko Sakuma, Shintaro Takao, Shigeo Hara, Takaaki Masuda, Koshi Mimori, Shinya Toyokuni, John P Lydon, Kazuwa Nakao, Hiroshi Nishina, Takumi Fukumoto, Tomohiko Maehama, Akira Suzuki

Faculty, Staff and Students Publications

A universal oncogenic driver of basal-like breast cancer (BLBC) has resisted identification. We show that continuous transcriptional coactivator with PDZ-binding motif (TAZ) activation in precancerous murine luminal cells generates luminal cancers that later become BLBCs. Subsequent TP53 alteration, a feature of invasive human BLBCs, accelerates tumor progression. Because BLBC development is inhibited by TAZ inactivation in vivo, our work provides a sound rationale for targeting Hippo-TAZ signaling as therapy for human BLBC. Our mouse model of BLBC represents a powerful tool for evaluating such drugs.

Serum And Plasma Levels Of Brain-Derived Neurotrophic Factor In Individuals With Eating Disorders (Eds): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Sara Bagherieh, Parsa Mirzayi, Amirali Kalantari, Omid Mirmosayyeb, Antônio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

Background: Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, development, and plasticity. Evidence suggests that fluctuations in peripheral levels (i.e., plasma or serum) of BDNF are associated with eating behaviors. Nevertheless, the findings are inconsistent. The purpose of this study is to determine if serum or plasma levels of BDNF are altered in individuals with eating disorders (EDs) compared to controls.

Methods: We conducted a systematic search of the core electronic medical databases from inception to March 2022 and identified observational studies that compared individuals with EDs to controls without EDs on serum or plasma levels of BDNF. …

A Narrative Review On Yoga: A Potential Intervention For Augmenting Immunomodulation And Mental Health In Covid-19, Indranill Basu-Ray, Kashinath Metri, Dibbendhu Khanra, Rishab Revankar, Kavitha M Chinnaiyan, Nagaratna Raghuram, Mahesh Chandra Mishra, Bhushan Patwardhan, Manjunath Sharma, Ishwar V Basavaraddi, Akshay Anand, Shrinath Reddy, K K Deepak, Marian Levy, Sue Theus, Glenn N Levine, Holger Cramer, Gregory L Fricchione, Nagendra R Hongasandra

Faculty, Staff and Students Publications

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as …

Therapeutic Targeting Of Macrophage Plasticity Remodels The Tumor-Immune Microenvironment, Hee-Jin Jang, Hyun-Sung Lee, Wendong Yu, Maheshwari Ramineni, Cynthia Y Truong, Daniela Ramos, Taylor Splawn, Jong Min Choi, Sung Yun Jung, Ju-Seog Lee, Daniel Y Wang, Joel M Sederstrom, Massimo Pietropaolo, Farrah Kheradmand, Christopher I Amos, Thomas M Wheeler, R Taylor Ripley, Bryan M Burt

Center for Medical Ethics and Health Policy Staff Publications

Although the majority of patients with advanced lung adenocarcinoma (LUAD) are eligible to receive immune checkpoint blockade, approximately 80% of these tumors are resistant to this therapeutic approach. Insights at the single-cell level into mechanisms that drive LUAD tumorigenesis and the relationship of LUAD histologic heterogeneity to response to immune checkpoint blockade could help identify biomarkers and potential combinational approaches to improve immunotherapy efficacy. Here we used a genetically engineered mouse model that replicates the development of human LUAD through a spectrum of pre-invasive to invasive adenocarcinoma histologic subtypes. A systems onco-immunology approach of integrating the analytical power and unique, …

Limited Benefit From The Addition Of Immunotherapy To Chemotherapy In Tki-Refractory Egfr-Mutant Lung Adenocarcinoma, Lingzhi Hong, Whitney E Lewis, Monique Nilsson, Sonia Patel, Susan Varghese, Melvin J Rivera, Robyn R Du, Pingjun Chen, Haley N Kemp, Waree Rinsurongkawong, Simon Heeke, Amy R Spelman, Yasir Y Elamin, Marcelo V Negrao, Boris Sepesi, Don L Gibbons, J Jack Lee, Jia Wu, Natalie I Vokes, John V Heymach, Jianjun Zhang, Xiuning Le

Faculty, Staff and Student Publications

Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting.

Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n …

Scintillation Light Detection In The 6-M Drift-Length Protodune Dual Phase Liquid Argon Tpc, A Abed Abud, B Abi, R Acciarri, M A Acero, M R Adames, G Adamov, M Adamowski, D Adams, M Adinolfi, A Aduszkiewicz, J Aguilar, Z Ahmad, J Ahmed, B Aimard, B Ali-Mohammadzadeh, T Alion, K Allison, S Alonso Monsalve, M Alrashed, C Alt, A Alton, R Alvarez, P Amedo, J Anderson, C Andreopoulos, M Andreotti, M Andrews, F Andrianala, S Andringa, N Anfimov, A Ankowski, M Antoniassi, M Antonova, A Antoshkin, S Antusch, A Aranda-Fernandez, L Arellano, L O Arnold, M A Arroyave, J Asaadi, L Asquith, A Aurisano, V Aushev, D Autiero, V Ayala Lara, M Ayala-Torres, F Azfar, A Back, H Back, J J Back, C Backhouse, I Bagaturia, L Bagby, N Balashov, S Balasubramanian, P Baldi, B Baller, B Bambah, F Barao, G Barenboim, P Barham Alzas, G Barker, W Barkhouse, C Barnes, G Barr, J Barranco Monarca, A Barros, N Barros, J L Barrow, A Basharina-Freshville, A Bashyal, V Basque, C Batchelor, E Batista Das Chagas, J B R Battat, F Battisti, F Bay, M C Q Bazetto, J L L Bazo Alba, J F Beacom, E Bechetoille, B Behera, C Beigbeder, L Bellantoni, G Bellettini, V Bellini, O Beltramello, N Benekos, C Benitez Montiel, F Bento Neves, J Berger, S Berkman, P Bernardini, R M Berner, A Bersani, S Bertolucci, M Betancourt, A Betancur Rodríguez, A Bevan, Y Bezawada, T J C Bezerra, A Bhardwaj, V Bhatnagar, M Bhattacharjee, D Bhattarai, S Bhuller, B Bhuyan, S Biagi, J Bian, M Biassoni, K Biery, B Bilki, M Bishai, A Bitadze, A Blake, F Blaszczyk, G C Blazey, E Blucher, J Boissevain, S Bolognesi, T Bolton, L Bomben, M Bonesini, M Bongrand, C Bonilla-Diaz, F Bonini, A Booth, F Boran, S Bordoni, A Borkum, N Bostan, P Bour, C Bourgeois, D Boyden, J Bracinik, D Braga, D Brailsford, A Branca, A Brandt, J Bremer, D Breton, C Brew, S J Brice, C Brizzolari, C Bromberg, J Brooke, A Bross, G Brunetti, M Brunetti, N Buchanan, H Budd, I Butorov, I Cagnoli, T Cai, D Caiulo, R Calabrese, P Calafiura, J Calcutt, M Calin, S Calvez, E Calvo, A Caminata, M Campanelli, D Caratelli, D Carber, J C Carceller, G Carini, B Carlus, M F Carneiro, P Carniti, I Caro Terrazas, H Carranza, T Carroll, J F Castaño Forero, A Castillo, C Castromonte, E Catano-Mur, C Cattadori, F Cavalier, G Cavallaro, F Cavanna, S Centro, G Cerati, A Cervelli, A Cervera Villanueva, M Chalifour, A Chappell, E Chardonnet, N Charitonidis, A Chatterjee, S Chattopadhyay, M S S Chavarry Neyra, H Chen, M Chen, Y Chen, Z Chen, Z Chen-Wishart, Y Cheon, D Cherdack, C Chi, S Childress, R Chirco, A Chiriacescu, G Chisnall, K Cho, S Choate, D Chokheli, P S Chong, A Christensen, D Christian, G Christodoulou, A Chukanov, M Chung, E Church, V Cicero, P Clarke, G Cline, T E Coan, A G Cocco, J A B Coelho, N Colton, E Conley, R Conley, J Conrad, M Convery, S Copello, P Cova, L Cremaldi, L Cremonesi, J I Crespo-Anadón, M Crisler, E Cristaldo, J Crnkovic, R Cross, A Cudd, C Cuesta, Y Cui, D Cussans, O Dalager, H Da Motta, L Da Silva Peres, C David, Q David, G S Davies, S Davini, J Dawson, K De, S De, P Debbins, I De Bonis, M P Decowski, A De Gouvêa, P C De Holanda, I L De Icaza Astiz, A Deisting, P De Jong, A Delbart, D Delepine, M Delgado, A Dell'acqua, N Delmonte, P De Lurgio, J R T De Mello Neto, D M Demuth, S Dennis, C Densham, G W Deptuch, A De Roeck, V De Romeri, G De Souza, R Devi, R Dharmapalan, M Dias, F Diaz, J S Díaz, S Di Domizio, L Di Giulio, P Ding, L Di Noto, G Dirkx, C Distefano, R Diurba, M Diwan, Z Djurcic, D Doering, S Dolan, F Dolek, M Dolinski, L Domine, Y Donon, D Douglas, D Douillet, A Dragone, G Drake, F Drielsma, L Duarte, D Duchesneau, K Duffy, P Dunne, B Dutta, H Duyang, O Dvornikov, D Dwyer, A Dyshkant, M Eads, A Earle, D Edmunds, J Eisch, L Emberger, S Emery, P Englezos, A Ereditato, T Erjavec, C Escobar, G Eurin, J J Evans, E Ewart, A C Ezeribe, K Fahey, A Falcone, M Fani', C Farnese, Y Farzan, D Fedoseev, J Felix, Y Feng, E Fernandez-Martinez, P Fernandez Menendez, M Fernandez Morales, F Ferraro, L Fields, P Filip, F Filthaut, M Fiorini, V Fischer, R S Fitzpatrick, W Flanagan, B Fleming, R Flight, S Fogarty, W Foreman, J Fowler, W Fox, J Franc, K Francis, D Franco, J Freeman, J Freestone, J Fried, A Friedland, F Fuentes Robayo, S Fuess, I K Furic, K Furman, A P Furmanski, A Gabrielli, A Gago, H Gallagher, A Gallas, A Gallego-Ros, N Gallice, V Galymov, E Gamberini, T Gamble, F Ganacim, R Gandhi, R Gandrajula, F Gao, S Gao, D Garcia-Gamez, M Á García-Peris, S Gardiner, D Gastler, J Gauvreau, G Ge, N Geffroy, B Gelli, A Gendotti, S Gent, Z Ghorbani-Moghaddam, P Giammaria, T Giammaria, N Giangiacomi, D Gibin, I Gil-Botella, S Gilligan, C Girerd, A K Giri, D Gnani, O Gogota, M Gold, S Gollapinni, K Gollwitzer, R A Gomes, L V Gomez Bermeo, L S Gomez Fajardo, F Gonnella, D Gonzalez-Diaz, M Gonzalez-Lopez, M C Goodman, O Goodwin, S Goswami, C Gotti, E Goudzovski, C Grace, R Gran, E Granados, P Granger, A Grant, C Grant, D Gratieri, P Green, L Greenler, J Greer, J Grenard, W C Griffith, M Groh, J Grudzinski, K Grzelak, W Gu, E Guardincerri, V Guarino, M Guarise, R Guenette, E Guerard, M Guerzoni, D Guffanti, A Guglielmi, B Guo, A Gupta, V Gupta, K K Guthikonda, R Gutierrez, P Guzowski, M M Guzzo, S Gwon, C Ha, K Haaf, A Habig, H Hadavand, R Haenni, A Hahn, J Haiston, P Hamacher-Baumann, T Hamernik, P Hamilton, J Han, D A Harris, J Hartnell, T Hartnett, J Harton, T Hasegawa, C Hasnip, R Hatcher, K W Hatfield, A Hatzikoutelis, C Hayes, K Hayrapetyan, J Hays, E Hazen, M He, A Heavey, K M Heeger, J Heise, S Henry, M A Hernandez Morquecho, K Herner, J Hewes, C Hilgenberg, T Hill, S J Hillier, A Himmel, E Hinkle, L R Hirsch, J Ho, J Hoff, A Holin, E Hoppe, G A Horton-Smith, M Hostert, A Hourlier, B Howard, R Howell, J Hoyos, I Hristova, M S Hronek, J Huang, Z Hulcher, G Iles, N Ilic, A M Iliescu, R Illingworth, G Ingratta, A Ioannisian, B Irwin, L Isenhower, R Itay, C M Jackson, V Jain, E James, W Jang, B Jargowsky, F Jediny, D Jena, Y S Jeong, C Jesús-Valls, X Ji, L Jiang, S Jiménez, A Jipa, R Johnson, W Johnson, N Johnston, B Jones, S Jones, M Judah, C K Jung, T Junk, Y Jwa, M Kabirnezhad, A Kaboth, I Kadenko, I Kakorin, A Kalitkina, D Kalra, F Kamiya, N Kaneshige, D M Kaplan, G Karagiorgi, G Karaman, A Karcher, M Karolak, Y Karyotakis, S Kasai, S P Kasetti, L Kashur, N Kazaryan, E Kearns, P Keener, K J Kelly, E Kemp, O Kemularia, W Ketchum, S H Kettell, M Khabibullin, A Khotjantsev, A Khvedelidze, D Kim, B King, B Kirby, M Kirby, J Klein, A Klustova, T Kobilarcik, K Koehler, L W Koerner, D H Koh, S Kohn, P P Koller, L Kolupaeva, D Korablev, M Kordosky, T Kosc, U Kose, V A Kostelecký, K Kothekar, R Kralik, L Kreczko, F Krennrich, I Kreslo, W Kropp, T Kroupova, S Kubota, Y Kudenko, V A Kudryavtsev, S Kulagin, J Kumar, P Kumar, P Kunze, N Kurita, C Kuruppu, V Kus, T Kutter, J Kvasnicka, D Kwak, A Lambert, B Land, C E Lane, K Lang, T Langford, M Langstaff, J Larkin, P Lasorak, D Last, A Laundrie, G Laurenti, A Lawrence, I Lazanu, R Lazur, M Lazzaroni, T Le, S Leardini, J Learned, P Lebrun, T Lecompte, C Lee, S Y Lee, G Lehmann Miotto, R Lehnert, M A Leigui De Oliveira, M Leitner, L M Lepin, S W Li, Y Li, H Liao, C S Lin, Q Lin, S Lin, R A Lineros, J Ling, A Lister, B R Littlejohn, J Liu, Y Liu, S Lockwitz, T Loew, M Lokajicek, I Lomidze, K Long, T Lord, J M Losecco, W C Louis, X-G Lu, K B Luk, B Lunday, X Luo, E Luppi, T Lux, V P Luzio, J Maalmi, D Macfarlane, A A Machado, P Machado, C T Macias, J R Macier, A Maddalena, A Madera, P Madigan, S Magill, K Mahn, A Maio, A Major, J A Maloney, G Mandrioli, R C Mandujano, J Maneira, L Manenti, S Manly, A Mann, K Manolopoulos, M Manrique Plata, V N Manyam, L Manzanillas, M Marchan, A Marchionni, W Marciano, D Marfatia, C Mariani, J Maricic, R Marie, F Marinho, A D Marino, D Marsden, M Marshak, C Marshall, J Marshall, J Marteau, J Martín-Albo, N Martinez, D A Martinez Caicedo, P Martínez Miravé, S Martynenko, V Mascagna, K Mason, A Mastbaum, F Matichard, S Matsuno, J Matthews, C Mauger, N Mauri, K Mavrokoridis, I Mawby, R Mazza, A Mazzacane, E Mazzucato, T Mcaskill, E Mccluskey, N Mcconkey, K S Mcfarland, C Mcgrew, A Mcnab, A Mefodiev, P Mehta, P Melas, O Mena, H Mendez, P Mendez, D P Méndez, A Menegolli, G Meng, M D Messier, W Metcalf, T Mettler, M Mewes, H Meyer, T Miao, G Michna, T Miedema, V Mikola, R Milincic, G Miller, W Miller, J Mills, O Mineev, A Minotti, O G Miranda, S Miryala, C S Mishra, S R Mishra, A Mislivec, M Mitchell, D Mladenov, I Mocioiu, K Moffat, N Moggi, R Mohanta, T A Mohayai, N Mokhov, J Molina, L Molina Bueno, E Montagna, A Montanari, C Montanari, D Montanari, L M Montañno Zetina, S H Moon, M Mooney, A F Moor, D Moreno, D Moretti, C Morris, C Mossey, M Mote, E Motuk, C A Moura, J Mousseau, G Mouster, W Mu, L Mualem, J Mueller, M Muether, S Mufson, F Muheim, A Muir, M Mulhearn, D Munford, H Muramatsu, S Murphy, J Musser, J Nachtman, S Nagu, M Nalbandyan, R Nandakumar, D Naples, S Narita, A Nath, A Navrer-Agasson, N Nayak, M Nebot-Guinot, K Negishi, J K Nelson, J Nesbit, M Nessi, D Newbold, M Newcomer, H Newton, R Nichol, F Nicolas-Arnaldos, A Nikolica, E Niner, K Nishimura, A Norman, A Norrick, R Northrop, P Novella, J A Nowak, M Oberling, J Ochoa-Ricoux, A Olivier, A Olshevskiy, Y Onel, Y Onishchuk, J Ott, L Pagani, G Palacio, O Palamara, S Palestini, J M Paley, M Pallavicini, C Palomares, W Panduro Vazquez, E Pantic, V Paolone, V Papadimitriou, R Papaleo, A Papanestis, S Paramesvaran, S Parke, E Parozzi, Z Parsa, M Parvu, S Pascoli, L Pasqualini, J Pasternak, J Pater, C Patrick, L Patrizii, R B Patterson, S J Patton, T Patzak, A Paudel, B Paulos, L Paulucci, Z Pavlovic, G Pawloski, D Payne, V Pec, S J M Peeters, A Pena Perez, E Pennacchio, A Penzo, O L G Peres, J Perry, D Pershey, G Pessina, G Petrillo, C Petta, R Petti, V Pia, F Piastra, L Pickering, F Pietropaolo, V L Pimentel, G Pinaroli, K Plows, R Plunkett, R Poling, F Pompa, X Pons, N Poonthottathil, F Poppi, S Pordes, J Porter, M Potekhin, R Potenza, B V K S Potukuchi, J Pozimski, M Pozzato, S Prakash, T Prakash, M Prest, S Prince, F Psihas, D Pugnere, X Qian, J L Raaf, V Radeka, J Rademacker, B Radics, A Rafique, E Raguzin, M Rai, M Rajaoalisoa, I Rakhno, A Rakotonandrasana, L Rakotondravohitra, R Rameika, M A Ramirez Delgado, B Ramson, A Rappoldi, G Raselli, P Ratoff, S Raut, R F Razakamiandra, E M Rea, J S Real, B Rebel, R Rechenmacher, M Reggiani-Guzzo, J Reichenbacher, S D Reitzner, H Rejeb Sfar, A Renshaw, S Rescia, F Resnati, M Ribas, S Riboldi, C Riccio, G Riccobene, L C J Rice, J S Ricol, A Rigamonti, Y Rigaut, E V Rincón, H Ritchie-Yates, D Rivera, A Robert, L Rochester, M Roda, P Rodrigues, M J Rodriguez Alonso, E Rodriguez Bonilla, J Rodriguez Rondon, S Rosauro-Alcaraz, M Rosenberg, P Rosier, B Roskovec, M Rossella, M Rossi, J Rout, P Roy, A Rubbia, C Rubbia, B Russell, D Ruterbories, A Rybnikov, A Saa-Hernandez, R Saakyan, S Sacerdoti, T Safford, N Sahu, K Sakashita, P Sala, N Samios, O Samoylov, M C Sanchez, V Sandberg, D A Sanders, D Sankey, S Santana, M Santos-Maldonado, N Saoulidou, P Sapienza, C Sarasty, I Sarcevic, G Savage, V Savinov, A Scaramelli, A Scarff, A Scarpelli, T Schefke, H Schellman, S Schifano, P Schlabach, D Schmitz, A W Schneider, K Scholberg, A Schukraft, E Segreto, A Selyunin, C R Senise, J Sensenig, A Sergi, D Sgalaberna, M H Shaevitz, S Shafaq, F Shaker, M Shamma, R Sharankova, H R Sharma, R Sharma, R K Sharma, T Shaw, K Shchablo, C Shepherd-Themistocleous, A Sheshukov, S Shin, I Shoemaker, D Shooltz, R Shrock, H Siegel, L Simard, J Sinclair, G Sinev, J Singh, L Singh, P Singh, V Singh, R Sipos, F W Sippach, G Sirri, A Sitraka, K Siyeon, K Skarpaas, A Smith, E Smith, P Smith, J Smolik, M Smy, E Snider, P Snopok, D Snowden-Ifft, M Soares Nunes, H Sobel, M Soderberg, S Sokolov, C J Solano Salinas, S Söldner-Rembold, S R Soleti, N Solomey, V Solovov, W E Sondheim, M Sorel, A Sotnikov, J Soto-Oton, F A Soto Ugaldi, A Sousa, K Soustruznik, F Spagliardi, M Spanu, J Spitz, N J C Spooner, K Spurgeon, M Stancari, L Stanco, C Stanford, R Stein, H M Steiner, A F Steklain Lisbôa, J Stewart, B Stillwell, J Stock, F Stocker, T Stokes, M Strait, T Strauss, L Strigari, A Stuart, J G Suarez, J M Suárez Sunción, H Sullivan, D Summers, A Surdo, V Susic, L Suter, C M Sutera, R Svoboda, B Szczerbinska, A M Szelc, H Tanaka, S Tang, A Tapia, B Tapia Oregui, A Tapper, S Tariq, E Tarpara, N Tata, E Tatar, R Tayloe, A M Teklu, P Tennessen, M Tenti, K Terao, C A Ternes, F Terranova, G Testera, T Thakore, A Thea, J L Thompson, C Thorn, S C Timm, V Tishchenko, L Tomassetti, A Tonazzo, D Torbunov, M Torti, M Tortola, F Tortorici, N Tosi, D Totani, M Toups, C Touramanis, R Travaglini, J Trevor, S Trilov, W H Trzaska, Y Tsai, Y-T Tsai, Z Tsamalaidze, K V Tsang, N Tsverava, S Tufanli, C Tull, E Tyley, M Tzanov, L Uboldi, M A Uchida, J Urheim, T Usher, S Uzunyan, M R Vagins, P Vahle, S Valder, G D A Valdiviesso, E Valencia, R Valentim, Z Vallari, E Vallazza, J W F Valle, S Vallecorsa, R Van Berg, R G Van De Water, D Vanegas Forero, D Vannerom, F Varanini, D Vargas Oliva, G Varner, J Vasel, S Vasina, G Vasseur, N Vaughan, K Vaziri, S Ventura, A Verdugo, S Vergani, M A Vermeulen, M Verzocchi, M Vicenzi, H Vieira De Souza, C Vignoli, C Vilela, B Viren, T Vrba, T Wachala, A V Waldron, M Wallbank, C Wallis, H Wang, J Wang, L Wang, M H L S Wang, X Wang, Y Wang, K Warburton, D Warner, M O Wascko, D Waters, A Watson, K Wawrowska, P Weatherly, A Weber, M Weber, H Wei, A Weinstein, D Wenman, M Wetstein, A White, L H Whitehead, D Whittington, M J Wilking, A Wilkinson, C Wilkinson, Z Williams, F Wilson, R J Wilson, W Wisniewski, J Wolcott, T Wongjirad, A Wood, K Wood, E Worcester, M Worcester, K Wresilo, C Wret, W Wu, Y Xiao, F Xie, B Yaeggy, E Yandel, G Yang, K Yang, T Yang, A Yankelevich, N Yershov, K Yonehara, Y S Yoon, T Young, B Yu, H Yu, J Yu, Y Yu, W Yuan, R Zaki, J Zalesak, L Zambelli, B Zamorano, A Zani, L Zazueta, G P Zeller, J Zennamo, K Zeug, C Zhang, S Zhang, Y Zhang, M Zhao, E Zhivun, G Zhu, E D Zimmerman, S Zucchelli, J Zuklin, V Zutshi, R Zwaska, Dune Collaboration

Faculty, Staff and Students Publications

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6 × 6 × 6 m3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019–2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the …

Describing Characteristics Of Adults With And Without Congenital Heart Defects Hospitalized With Covid-19, Perla Diaz, Will Coughlin, Wilson Lam, Peter Ermis, David Aguilar, Cecilia M Ganduglia Cazaban, A J Agopian

Faculty, Staff and Student Publications

BACKGROUND: We sought to describe patient characteristics in adults with and without congenital heart defects (CHDs) during hospitalization for COVID-19.

METHODS: We analyzed data collected by Optum®, a nationally representative database of electronic medical records, for 369 adults with CHDs and 41,578 without CHDs hospitalized for COVID-19 between January 1, 2020, and December 10, 2020. We used Poisson regression to describe and compare epidemiologic characteristics, heart-related conditions, and severe outcomes between these two groups.

RESULTS: The distributions of many epidemiologic characteristics were similar between the two groups, but patients with CHDs were significantly more likely to be current or former …

Infiltration Of Peripheral Immune Cells Into The Olfactory Bulb In A Mouse Model Of Acute Nasal Inflammation, Hinami Asano, Sanae Hasegawa-Ishii, Ken Arae, Aki Obara, Geoffroy Laumet, Robert Dantzer, Atsuyoshi Shimada

Faculty, Staff and Student Publications

Chronic nasal inflammation induces robust olfactory bulb (OB) atrophy in mice. Here we examined initial events that occur in the OB after bilateral intranasal administration of lipopolysaccharide, focusing on the olfactory nerve fibers and meninges. We analyzed the time course of OB and meninges inflammation using histological and biochemical approaches. Within 12 h, we observed increased chemokine expression and transient infiltration of peripheral immune cells into the OB, resulting in the development of pro-inflammatory status in the OB. Meningeal immunity was activated. Resident microglia produced anti-inflammatory cytokines within 24 h. These could be the initial events that lead to OB …

The Origin Of Bladder Cancer From Mucosal Field Effects, Jolanta Bondaruk, Roman Jaksik, Ziqiao Wang, David Cogdell, Sangkyou Lee, Yujie Chen, Khanh Ngoc Dinh, Tadeusz Majewski, Li Zhang, Shaolong Cao, Feng Tian, Hui Yao, Paweł Kuś, Huiqin Chen, John N Weinstein, Neema Navai, Colin Dinney, Jianjun Gao, Dan Theodorescu, Christopher Logothetis, Charles C Guo, Wenyi Wang, David Mcconkey, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Student Publications

Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of the process. An aberrant methylation/expression of multiple HOX genes signified dysregulation of the differentiation program. We identified three types of mutations based on their geographic distribution. The most common were mutations restricted to individual mucosal samples that targeted uroprogenitor cells. Two types of mutations were associated with clonal expansion and involved large areas of …

Impairing Proliferation Of Glioblastoma Multiforme With Cd44+ Selective Conjugated Polymer Nanoparticles, Dorota Lubanska, Sami Alrashed, Gage T Mason, Fatima Nadeem, Angela Awada, Mitchell Dipasquale, Alexandra Sorge, Aleena Malik, Monika Kojic, Mohamed A R Soliman, Ana C Decarvalho, Abdalla Shamisa, Swati Kulkarni, Drew Marquardt, Lisa A Porter, Simon Rondeau-Gagné

Faculty, Staff and Student Publications

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood-brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood-brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake …

Alphafold2 And Cryoem: Revisiting Cryoem Modeling In Near-Atomic Resolution Density Maps, Corey F Hryc, Matthew L Baker

Faculty, Staff and Student Publications

With the advent of new artificial intelligence and machine learning algorithms, predictive modeling can, in some cases, produce structures on par with experimental methods. The combination of predictive modeling and experimental structure determination by electron cryomicroscopy (cryoEM) offers a tantalizing approach for producing robust atomic models of macromolecular assemblies. Here, we apply AlphaFold2 to a set of community standard data sets and compare the results with the corresponding reference maps and models. Moreover, we present three unique case studies from previously determined cryoEM density maps of viruses. Our results show that AlphaFold2 can not only produce reasonably accurate models for …

Kras Mutations As Essential Promoters Of Lymphangiogenesis Via Extracellular Vesicles In Pancreatic Cancer, Radu Pirlog, George A Calin

Faculty, Staff and Student Publications

Kirsten rat sarcoma virus (KRAS) gene mutations are present in more than 90% of pancreatic ductal adenocarcinomas (PDACs). KRASG12D is the most frequent alteration, promoting preneoplastic lesions and associating with a more aggressive phenotype. These tumors possess increased intratumoral lymphatic networks and frequent lymph node (LN) metastases. In this issue of the JCI, Luo, Li, et al. explored the relationship between the presence of the KRASG12D mutation and lymphangiogenesis in PDAC. The authors used in vitro and in vivo models and an elegant mechanistic approach to describe an alternative pathway for lymphangiogenesis promotion. KRASG12D induced SUMOylation of heterogenous nuclear ribonucleoprotein …

Cd11bhigh B Cells Increase After Stroke And Regulate Microglia: Cd11bhigh B Cells Increase After Stroke And Regulate Mg, Janelle M Korf, Pedram Honarpisheh, Eric C Mohan, Anik Banerjee, Maria P Blasco-Conesa, Parisa Honarpisheh, Gary U Guzman, Romeesa Khan, Bhanu P Ganesh, Amy L Hazen, Juneyoung Lee, Aditya Kumar, Louise D Mccullough, Anjali Chauhan

Faculty, Staff and Student Publications

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed based on expression levels of transcription factors (e.g. T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b^high subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b^{high …}

Pneumonitis After Immune Checkpoint Inhibitor Therapies In Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study, Ajay Sheshadri, Alberto A Goizueta, Vickie R Shannon, David London, Guillermo Garcia-Manero, Hagop M Kantarjian, Farhad Ravandi-Kashani, Tapan M Kadia, Marina Y Konopleva, Courtney D Dinardo, Sherry Pierce, Abdulrazzak Zarifa, Aya A Albittar, Linda L Zhong, Fechukwu O Akhmedzhanov, Muhammad H Arain, Mansour Alfayez, Ahmad Alotaibi, Mehmet Altan, Aung Naing, Tito R Mendoza, Myrna C B Godoy, Girish Shroff, Sang T Kim, Saadia A Faiz, Dimitrios P Kontoyiannis, Fareed Khawaja, Kristofer Jennings, Naval G Daver

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were …