Digital Commons Network^™

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …

Part I Antimicrobial Resistance: Bacterial Pathogens Of Dermatologic Significance And Implications Of Rising Resistance, Saira George, Fiorinda F Muhaj, Celine D Nguyen, Stephen K Tyring

Faculty, Staff and Student Publications

Although the COVID-19 pandemic has been the defining global health crisis of our time, public health officials have been sounding the alarm of another ominous threat for years: an impending antimicrobial resistance crisis. In dermatology, antibiotics are often used for prolonged courses in the treatment of skin and soft tissue infections and common inflammatory skin conditions, increasing the risk of microbiome alteration and antibiotic-related adverse effects, all while exerting consequential selective pressures on both pathogenic and bystander bacteria. In this review, we hope to raise awareness of the crisis of antimicrobial resistance and review resistance concerns related to dermatology-relevant bacterial …

Anal Cytology Screening In Men Who Have Sex With Men With Hiv At A University Hospital In Bogotá, Colombia, I Tatiana Ordoñez-Blanco, Samuel Martínez-Vernaza, Kevin J Blair, Camilo Quiroga, Ellen Lowenstein, Luis J Lombana Amaya, Jesse Clark, Jordan E Lake, Sandra Liliana Valderrama-Beltrán

Faculty, Staff and Student Publications

Background: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV.

Methods: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology.

Results: A total of 211 patients were included. Mean age was 35.6 years. …

Role Of The Chemokine System In Liver Fibrosis: A Narrative Review, Kyle L Poulsen, Christina K Cajigas-Du Ross, Jarod K Chaney, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Liver fibrosis is a disease with characteristics of an aberrant wound healing response. Fibrosis is commonly the end-stage for chronic liver diseases like alcohol-associated liver disease (ALD), metabolic-associated liver disease, viral hepatitis, and hepatic autoimmune disease. Innate immunity contributes to the progression of many diseases through multiple mechanisms including production of pro-inflammatory mediators, leukocyte infiltration and tissue injury. Chemokines and their receptors orchestrate accumulation and activation of immune cells in tissues and are associated with multiple liver diseases; however, much less is known about their potential roles in liver fibrosis. This is a narrative review of current …

Noninvasive Testing And Surrogate Markers In Invasive Fungal Diseases, George R Thompson, David R Boulware, Nathan C Bahr, Cornelius J Clancy, Thomas S Harrison, Carol A Kauffman, Thuy Le, Marisa H Miceli, Eleftherios Mylonakis, M Hong Nguyen, Luis Ostrosky-Zeichner, Thomas F Patterson, John R Perfect, Andrej Spec, Dimitrios P Kontoyiannis, Peter G Pappas

Faculty, Staff and Student Publications

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these …

A Nickase Cas9 Gene-Drive System Promotes Super-Mendelian Inheritance In Drosophila, Víctor López Del Amo, Sara Sanz Juste, Valentino M Gantz

Faculty, Staff and Student Publications

CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (>50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a gene-drive that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that …

Tissue-Specific Variations In Transcription Factors Elucidate Complex Immune System Regulation, Hengwei Lu, Yi-Ching Tang, Assaf Gottlieb

Faculty, Staff and Student Publications

Gene expression plays a key role in health and disease. Estimating the genetic components underlying gene expression can thus help understand disease etiology. Polygenic models termed "transcriptome imputation" are used to estimate the genetic component of gene expression, but these models typically consider only the cis regions of the gene. However, these cis-based models miss large variability in expression for multiple genes. Transcription factors (TFs) that regulate gene expression are natural candidates for looking for additional sources of the missing variability. We developed a hypothesis-driven approach to identify second-tier regulation by variability in TFs. Our approach tested two models …

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Faculty, Staff and Student Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …

Vikela Ekhaya: A Novel, Community-Based, Tuberculosis Contact Management Program In A High Burden Setting, Alexander W Kay, Micaela Sandoval, Godwin Mtetwa, Musa Mkhabela, Banele Ndlovu, Tara Devezin, Welile Sikhondze, Debrah Vambe, Joyce Sibanda, Gloria S Dube, Robert H Stevens, Bhekumusa Lukhele, Anna M Mandalakas

Faculty, Staff and Student Publications

BACKGROUND: The prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.

METHODS: Vikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants' homes.

RESULTS: In total, 945 contacts from …

Novel And Extendable Genotyping System For Human Respiratory Syncytial Virus Based On Whole-Genome Sequence Analysis, Jiani Chen, Xueting Qiu, Vasanthi Avadhanula, Samuel S Shepard, Do-Kyun Kim, James Hixson, Pedro A Piedra, Justin Bahl

Faculty, Staff and Student Publications

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes, and there is no consensus on RSV genotype definition.

METHODS: We conducted maximum likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were determined by using phylogenetic analysis and pair-wise node distances.

RESULTS: …

Accessory Genomes Drive Independent Spread Of Carbapenem-Resistant Klebsiella Pneumoniae Clonal Groups 258 And 307 In Houston, Tx, William C Shropshire, An Q Dinh, Michelle Earley, Lauren Komarow, Diana Panesso, Kirsten Rydell, Sara I Gómez-Villegas, Hongyu Miao, Carol Hill, Liang Chen, Robin Patel, Bettina C Fries, Lilian Abbo, Eric Cober, Sara Revolinski, Courtney L Luterbach, Henry Chambers, Vance G Fowler, Robert A Bonomo, Samuel A Shelburne, Barry N Kreiswirth, David Van Duin, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 …

Meal Timing, Meal Frequency And Metabolic Syndrome, Fatema Alkhulaifi, Charles Darkoh

Faculty, Staff and Student Publications

Individuals with metabolic syndrome have increased risk for developing health conditions, including cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary patterns and habits are extremely successful in controlling more than one of the metabolic syndrome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardiovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

Exploring Preventive Healthcare In A High-Risk Vulnerable Population, Trisha L Amboree, Jane R Montealegre, Kayo Fujimoto, Osaro Mgbere, Charles Darkoh, Paige Padgett Wermuth

Faculty, Staff and Student Publications

This study describes preventive care behaviors and explores opportunities to deliver preventive sexual healthcare to a high-risk vulnerable population. Data from the National HIV Behavioral Surveillance (NHBS) system high-risk heterosexuals (HET) cycle (2019) in Houston, Texas, was used to describe preventive care utilization and assess the relationship between healthcare utilization and sociodemographic characteristics. More than 47% reported having no usual source of healthcare, and 94.6% reported receiving no non-HIV STI testing in the past 12 months. Additionally, many sociodemographic factors were associated with healthcare utilization and having a usual source of healthcare. Future efforts should be targeted at increasing preventive …

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Host Diversity And Behavior Determine Patterns Of Interspecies Transmission And Geographic Diffusion Of Avian Influenza A Subtypes Among North American Wild Reservoir Species, Joseph T Hicks, Kimberly Edwards, Xueting Qiu, Do-Kyun Kim, James E Hixson, Scott Krauss, Richard J Webby, Robert G Webster, Justin Bahl

Faculty, Staff and Student Publications

Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic sequences from North American wild birds, including 303 newly sequenced isolates, to estimate interspecies and geographic viral transition patterns among multiple co-circulating subtypes. Our results show high transition rates within Anseriformes and Charadriiformes, but limited transitions between these orders. Patterns of transition between species were positively associated with breeding habitat range overlap, and negatively associated with host genetic distance. Distance between …

Comparative Molecular Genomic Analyses Of A Spontaneous Rhesus Macaque Model Of Mismatch Repair-Deficient Colorectal Cancer, Nejla Ozirmak Lermi, Stanton B Gray, Charles M Bowen, Laura Reyes-Uribe, Beth K Dray, Nan Deng, R Alan Harris, Muthuswamy Raveendran, Fernando Benavides, Carolyn L Hodo, Melissa W Taggart, Karen Colbert Maresso, Krishna M Sinha, Jeffrey Rogers, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

Notch-Induced Mdsc Recruitment After Ohsv Virotherapy In Cns Cancer Models Modulates Antitumor Immunotherapy, Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanth Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caligiuri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur

Faculty, Staff and Student Publications

PURPOSE: Oncolytic herpes simplex virus-1 (oHSV) infection of brain tumors activates NOTCH, however the consequences of NOTCH on oHSV-induced immunotherapy is largely unknown. Here we evaluated the impact of NOTCH blockade on virus-induced immunotherapy.

EXPERIMENTAL DESIGN: RNA sequencing (RNA-seq), TCGA data analysis, flow cytometry, Luminex- and ELISA-based assays, brain tumor animal models, and serum analysis of patients with recurrent glioblastoma (GBM) treated with oHSV was used to evaluate the effect of NOTCH signaling on virus-induced immunotherapy.

RESULTS: TCGA data analysis of patients with grade IV glioma and oHSV treatment of experimental brain tumors in mice showed that NOTCH signaling significantly …

Predictive Radiation Oncology - A New Nci-Doe Scientific Space And Community, Jeffrey C Buchsbaum, David A Jaffray, Demba Ba, Lynn L Borkon, Christine Chalk, Caroline Chung, Matthew A Coleman, C Norman Coleman, Maximilian Diehn, Kelvin K Droegemeier, Heiko Enderling, Michael G Espey, Emily J Greenspan, Christopher M Hartshorn, Thuc Hoang, H Timothy Hsiao, Cynthia Keppel, Nathan W Moore, Fred Prior, Eric A Stahlberg, Georgia Tourassi, Karen E Willcox

Faculty, Staff and Student Publications

With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops-and a final concluding "World Café" on March 29, 2021-focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, …

Durable Reduction Of Clostridioides Difficile Infection Recurrence And Microbiome Restoration After Treatment With Rbx2660: Results From An Open-Label Phase 2 Clinical Trial, Robert Orenstein, Erik R Dubberke, Sahil Khanna, Christine H Lee, David Yoho, Stuart Johnson, Gail Hecht, Herbert L Dupont, Dale N Gerding, Ken F Blount, Sarah Mische, Adam Harvey

Faculty, Staff and Student Publications

BACKGROUND: Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort.

METHODS: This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered …

Clinical Outcomes And Bacterial Characteristics Of Carbapenem-Resistant Klebsiella Pneumoniae Complex Among Patients From Different Global Regions (Crackle-2): A Prospective, Multicentre, Cohort Study, Minggui Wang, Michelle Earley, Liang Chen, Blake M Hanson, Yunsong Yu, Zhengyin Liu, Soraya Salcedo, Eric Cober, Lanjuan Li, Souha S Kanj, Hainv Gao, Jose M Munita, Karen Ordoñez, Greg Weston, Michael J Satlin, Sandra L Valderrama-Beltrán, Kalisvar Marimuthu, Martin E Stryjewski, Lauren Komarow, Courtney Luterbach, Steve H Marshall, Susan D Rudin, Claudia Manca, David L Paterson, Jinnethe Reyes, Maria V Villegas, Scott Evans, Carol Hill, Rebekka Arias, Keri Baum, Bettina C Fries, Yohei Doi, Robin Patel, Barry N Kreiswirth, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Cesar A Arias, David Van Duin, Multi-Drug Resistant Organism Network Investigators

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.

METHODS: In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability …

Community-Clinic Linkages For Promoting Hiv Prevention: Organizational Networks For Prep Client Referrals And Collaborations, Rebecca L Mauldin, Tamara Al Rawwad, Muhammad Amith, Lisa M Kuhns, John A Schneider, Kayo Fujimoto

Faculty, Staff and Student Publications

Community-clinic linkages may help communities increase HIV pre-exposure prophylaxis (PrEP) uptake. Referrals from community-based organizations may be particularly important for linking Black men who have sex with men (MSM) to PrEP. This study describes PrEP referral and HIV/STI prevention networks among organizations that serve MSM in Houston, TX (N = 40), and Chicago, IL (N = 28), and compares network positions of organizations based on percentage of Black/African American clients. A majority of organizations conducted PrEP awareness/promotion activities, but fewer made PrEP referrals, with little overlap between the collaboration and referral networks. The networks tended to have a …

Cancer Incidence, Mortality, Years Of Life Lost, Years Lived With Disability, And Disability-Adjusted Life Years For 29 Cancer Groups From 2010 To 2019: A Systematic Analysis For The Global Burden Of Disease Study 2019, Jonathan M Kocarnik, Kelly Compton, Frances E Dean, Weijia Fu, Brian L Gaw, James D Harvey, Hannah Jacqueline Henrikson, Dan Lu, Alyssa Pennini, Rixing Xu, Emad Ababneh, Mohsen Abbasi-Kangevari, Hedayat Abbastabar, Sherief M Abd-Elsalam, Amir Abdoli, Aidin Abedi, Hassan Abidi, Hassan Abolhassani, Isaac Akinkunmi Adedeji, Qorinah Estiningtyas Sakilah Adnani, Shailesh M Advani, Muhammad Sohail Afzal, Mohammad Aghaali, Bright Opoku Ahinkorah, Sajjad Ahmad, Tauseef Ahmad, Ali Ahmadi, Sepideh Ahmadi, Tarik Ahmed Rashid, Yusra Ahmed Salih, Gizachew Taddesse Akalu, Addis Aklilu, Tayyaba Akram, Chisom Joyqueenet Akunna, Hanadi Al Hamad, Fares Alahdab, Ziyad Al-Aly, Saqib Ali, Yousef Alimohamadi, Vahid Alipour, Syed Mohamed Aljunid, Motasem Alkhayyat, Amir Almasi-Hashiani, Nihad A Almasri, Sadeq Ali Ali Al-Maweri, Sami Almustanyir, Nivaldo Alonso, Nelson Alvis-Guzman, Hubert Amu, Etsay Woldu Anbesu, Robert Ancuceanu, Fereshteh Ansari, Alireza Ansari-Moghaddam, Maxwell Hubert Antwi, Davood Anvari, Anayochukwu Edward Anyasodor, Muhammad Aqeel, Jalal Arabloo, Morteza Arab-Zozani, Olatunde Aremu, Hany Ariffin, Timur Aripov, Muhammad Arshad, Al Artaman, Judie Arulappan, Zatollah Asemi, Mohammad Asghari Jafarabadi, Tahira Ashraf, Prince Atorkey, Avinash Aujayeb, Marcel Ausloos, Atalel Fentahun Awedew, Beatriz Paulina Ayala Quintanilla, Temesgen Ayenew, Mohammed A Azab, Sina Azadnajafabad, Amirhossein Azari Jafari, Ghasem Azarian, Ahmed Y Azzam, Ashish D Badiye, Saeed Bahadory, Atif Amin Baig, Jennifer L Baker, Senthilkumar Balakrishnan, Maciej Banach, Till Winfried Bärnighausen, Francesco Barone-Adesi, Fabio Barra, Amadou Barrow, Masoud Behzadifar, Uzma Iqbal Belgaumi, Woldesellassie M Mequanint Bezabhe, Yihienew Mequanint Bezabih, Devidas S Bhagat, Akshaya Srikanth Bhagavathula, Nikha Bhardwaj, Pankaj Bhardwaj, Sonu Bhaskar, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Sadia Bibi, Ali Bijani, Antonio Biondi, Catherine Bisignano, Tone Bjørge, Archie Bleyer, Oleg Blyuss, Obasanjo Afolabi Bolarinwa, Srinivasa Rao Bolla, Dejana Braithwaite, Amanpreet Brar, Hermann Brenner, Maria Teresa Bustamante-Teixeira, Nadeem Shafique Butt, Zahid A Butt, Florentino Luciano Caetano Dos Santos, Yin Cao, Giulia Carreras, Ferrán Catalá-López, Francieli Cembranel, Ester Cerin, Achille Cernigliaro, Raja Chandra Chakinala, Soosanna Kumary Chattu, Vijay Kumar Chattu, Pankaj Chaturvedi, Odgerel Chimed-Ochir, Daniel Youngwhan Cho, Devasahayam J Christopher, Dinh-Toi Chu, Michael T Chung, Joao Conde, Sanda Cortés, Paolo Angelo Cortesi, Vera Marisa Costa, Amanda Ramos Cunha, Omid Dadras, Amare Belachew Dagnew, Saad M A Dahlawi, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Aso Mohammad Darwesh, José Das Neves, Fernando Pio De La Hoz, Asmamaw Bizuneh Demis, Edgar Denova-Gutiérrez, Deepak Dhamnetiya, Mandira Lamichhane Dhimal, Meghnath Dhimal, Mostafa Dianatinasab, Daniel Diaz, Shirin Djalalinia, Huyen Phuc Do, Saeid Doaei, Fariba Dorostkar, Francisco Winter Dos Santos Figueiredo, Tim Robert Driscoll, Hedyeh Ebrahimi, Sahar Eftekharzadeh, Maha El Tantawi, Hassan El-Abid, Iffat Elbarazi, Hala Rashad Elhabashy, Muhammed Elhadi, Shaimaa I El-Jaafary, Babak Eshrati, Sharareh Eskandarieh, Firooz Esmaeilzadeh, Arash Etemadi, Sayeh Ezzikouri, Mohammed Faisaluddin, Emerito Jose A Faraon, Jawad Fares, Farshad Farzadfar, Abdullah Hamid Feroze, Simone Ferrero, Lorenzo Ferro Desideri, Irina Filip, Florian Fischer, James L Fisher, Masoud Foroutan, Takeshi Fukumoto, Peter Andras Gaal, Mohamed M Gad, Muktar A Gadanya, Silvano Gallus, Mariana Gaspar Fonseca, Abera Getachew Obsa, Mansour Ghafourifard, Ahmad Ghashghaee, Nermin Ghith, Maryam Gholamalizadeh, Syed Amir Gilani, Themba G Ginindza, Abraham Tamirat T Gizaw, James C Glasbey, Mahaveer Golechha, Pouya Goleij, Ricardo Santiago Gomez, Sameer Vali Gopalani, Giuseppe Gorini, Houman Goudarzi, Giuseppe Grosso, Mohammed Ibrahim Mohialdeen Gubari, Maximiliano Ribeiro Guerra, Avirup Guha, D Sanjeeva Gunasekera, Bhawna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Reyna Alma Gutiérrez, Nima Hafezi-Nejad, Mohammad Rifat Haider, Arvin Haj-Mirzaian, Rabih Halwani, Randah R Hamadeh, Sajid Hameed, Samer Hamidi, Asif Hanif, Shafiul Haque, Netanja I Harlianto, Josep Maria Haro, Ahmed I Hasaballah, Soheil Hassanipour, Roderick J Hay, Simon I Hay, Khezar Hayat, Golnaz Heidari, Mohammad Heidari, Brenda Yuliana Herrera-Serna, Claudiu Herteliu, Kamal Hezam, Ramesh Holla, Md Mahbub Hossain, Mohammad Bellal Hossain Hossain, Mohammad-Salar Hosseini, Mostafa Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Mowafa Househ, Mohamed Hsairi, Junjie Huang, Fernando N Hugo, Rabia Hussain, Nawfal R Hussein, Bing-Fang Hwang, Ivo Iavicoli, Segun Emmanuel Ibitoye, Fidelia Ida, Kevin S Ikuta, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Lalu Muhammad Irham, Jessica Y Islam, Rakibul M Islam, Sheikh Mohammed Shariful Islam, Nahlah Elkudssiah Ismail, Gaetano Isola, Masao Iwagami, Louis Jacob, Vardhmaan Jain, Mihajlo B Jakovljevic, Tahereh Javaheri, Shubha Jayaram, Seyed Behzad Jazayeri, Ravi Prakash Jha, Jost B Jonas, Tamas Joo, Nitin Joseph, Farahnaz Joukar, Mikk Jürisson, Ali Kabir, Danial Kahrizi, Leila R Kalankesh, Rohollah Kalhor, Feroze Kaliyadan, Yogeshwar Kalkonde, Ashwin Kamath, Nawzad Kameran Al-Salihi, Himal Kandel, Neeti Kapoor, André Karch, Ayele Semachew Kasa, Srinivasa Vittal Katikireddi, Joonas H Kauppila, Taras Kavetskyy, Sewnet Adem Kebede, Pedram Keshavarz, Mohammad Keykhaei, Yousef Saleh Khader, Rovshan Khalilov, Gulfaraz Khan, Maseer Khan, Md Nuruzzaman Khan, Moien A B Khan, Young-Ho Khang, Amir M Khater, Maryam Khayamzadeh, Gyu Ri Kim, Yun Jin Kim, Adnan Kisa, Sezer Kisa, Katarzyna Kissimova-Skarbek, Jacek A Kopec, Rajasekaran Koteeswaran, Parvaiz A Koul, Sindhura Lakshmi Koulmane Laxminarayana, Ai Koyanagi, Burcu Kucuk Bicer, Nuworza Kugbey, G Anil Kumar, Narinder Kumar, Nithin Kumar, Om P Kurmi, Tezer Kutluk, Carlo La Vecchia, Faris Hasan Lami, Iván Landires, Paolo Lauriola, Sang-Woong Lee, Shaun Wen Huey Lee, Wei-Chen Lee, Yo Han Lee, James Leigh, Elvynna Leong, Jiarui Li, Ming-Chieh Li, Xuefeng Liu, Joana A Loureiro, Raimundas Lunevicius, Muhammed Magdy Abd El Razek, Azeem Majeed, Alaa Makki, Shilpa Male, Ahmad Azam Malik, Mohammad Ali Mansournia, Santi Martini, Seyedeh Zahra Masoumi, Prashant Mathur, Martin Mckee, Ravi Mehrotra, Walter Mendoza, Ritesh G Menezes, Endalkachew Worku Mengesha, Mohamed Kamal Mesregah, Tomislav Mestrovic, Junmei Miao Jonasson, Bartosz Miazgowski, Tomasz Miazgowski, Irmina Maria Michalek, Ted R Miller, Hamed Mirzaei, Hamid Reza Mirzaei, Sanjeev Misra, Prasanna Mithra, Masoud Moghadaszadeh, Karzan Abdulmuhsin Mohammad, Yousef Mohammad, Mokhtar Mohammadi, Seyyede Momeneh Mohammadi, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Nagabhishek Moka, Ali H Mokdad, Mariam Molokhia, Lorenzo Monasta, Mohammad Ali Moni, Mohammad Amin Moosavi, Yousef Moradi, Paula Moraga, Joana Morgado-Da-Costa, Shane Douglas Morrison, Abbas Mosapour, Sumaira Mubarik, Lillian Mwanri, Ahamarshan Jayaraman Nagarajan, Shankar Prasad Nagaraju, Chie Nagata, Mukhammad David Naimzada, Vinay Nangia, Atta Abbas Naqvi, Sreenivas Narasimha Swamy, Rawlance Ndejjo, Sabina O Nduaguba, Ionut Negoi, Serban Mircea Negru, Sandhya Neupane Kandel, Cuong Tat Nguyen, Huong Lan Thi Nguyen, Robina Khan Niazi, Chukwudi A Nnaji, Nurulamin M Noor, Virginia Nuñez-Samudio, Chimezie Igwegbe Nzoputam, Bogdan Oancea, Chimedsuren Ochir, Oluwakemi Ololade Odukoya, Felix Akpojene Ogbo, Andrew T Olagunju, Babayemi Oluwaseun Olakunde, Emad Omar, Ahmed Omar Bali, Abidemi E Emmanuel Omonisi, Sokking Ong, Obinna E Onwujekwe, Hans Orru, Doris V Ortega-Altamirano, Nikita Otstavnov, Stanislav S Otstavnov, Mayowa O Owolabi, Mahesh P A, Jagadish Rao Padubidri, Keyvan Pakshir, Adrian Pana, Demosthenes Panagiotakos, Songhomitra Panda-Jonas, Shahina Pardhan, Eun-Cheol Park, Eun-Kee Park, Fatemeh Pashazadeh Kan, Harsh K Patel, Jenil R Patel, Siddhartha Pati, Sanjay M Pattanshetty, Uttam Paudel, David M Pereira, Renato B Pereira, Arokiasamy Perianayagam, Julian David Pillay, Saeed Pirouzpanah, Farhad Pishgar, Indrashis Podder, Maarten J Postma, Hadi Pourjafar, Akila Prashant, Liliana Preotescu, Mohammad Rabiee, Navid Rabiee, Amir Radfar, Raghu Anekal Radhakrishnan, Venkatraman Radhakrishnan, Ata Rafiee, Fakher Rahim, Shadi Rahimzadeh, Mosiur Rahman, Muhammad Aziz Rahman, Amir Masoud Rahmani, Nazanin Rajai, Aashish Rajesh, Ivo Rakovac, Pradhum Ram, Kiana Ramezanzadeh, Kamal Ranabhat, Priyanga Ranasinghe, Chythra R Rao, Sowmya J Rao, Reza Rawassizadeh, Mohammad Sadegh Razeghinia, Andre M N Renzaho, Negar Rezaei, Nima Rezaei, Aziz Rezapour, Thomas J Roberts, Jefferson Antonio Buendia Rodriguez, Peter Rohloff, Michele Romoli, Luca Ronfani, Gholamreza Roshandel, Godfrey M Rwegerera, Manjula S, Siamak Sabour, Basema Saddik, Umar Saeed, Amirhossein Sahebkar, Harihar Sahoo, Sana Salehi, Marwa Rashad Salem, Hamideh Salimzadeh, Mehrnoosh Samaei, Abdallah M Samy, Juan Sanabria, Senthilkumar Sankararaman, Milena M Santric-Milicevic, Yaeesh Sardiwalla, Arash Sarveazad, Brijesh Sathian, Monika Sawhney, Mete Saylan, Ione Jayce Ceola Schneider, Mario Sekerija, Allen Seylani, Omid Shafaat, Zahra Shaghaghi, Masood Ali Shaikh, Erfan Shamsoddin, Mohammed Shannawaz, Rajesh Sharma, Aziz Sheikh, Sara Sheikhbahaei, Adithi Shetty, Jeevan K Shetty, Pavanchand H Shetty, Kenji Shibuya, Reza Shirkoohi, K M Shivakumar, Velizar Shivarov, Soraya Siabani, Sudeep K Siddappa Malleshappa, Diego Augusto Santos Silva, Jasvinder A Singh, Yitagesu Sintayehu, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Matthew J Soeberg, Ahmad Sofi-Mahmudi, Houman Sotoudeh, Paschalis Steiropoulos, Kurt Straif, Ranjeeta Subedi, Mu'awiyyah Babale Sufiyan, Iyad Sultan, Saima Sultana, Daniel Sur, Viktória Szerencsés, Miklós Szócska, Rafael Tabarés-Seisdedos, Takahiro Tabuchi, Hooman Tadbiri, Amir Taherkhani, Ken Takahashi, Iman M Talaat, Ker-Kan Tan, Vivian Y Tat, Bemnet Amare A Tedla, Yonas Getaye Tefera, Arash Tehrani-Banihashemi, Mohamad-Hani Temsah, Fisaha Haile Tesfay, Gizachew Assefa Tessema, Rekha Thapar, Aravind Thavamani, Viveksandeep Thoguluva Chandrasekar, Nihal Thomas, Hamid Reza Tohidinik, Mathilde Touvier, Marcos Roberto Tovani-Palone, Eugenio Traini, Bach Xuan Tran, Khanh Bao Tran, Mai Thi Ngoc Tran, Jaya Prasad Tripathy, Biruk Shalmeno Tusa, Irfan Ullah, Saif Ullah, Krishna Kishore Umapathi, Bhaskaran Unnikrishnan, Era Upadhyay, Marco Vacante, Maryam Vaezi, Sahel Valadan Tahbaz, Diana Zuleika Velazquez, Massimiliano Veroux, Francesco S Violante, Vasily Vlassov, Bay Vo, Victor Volovici, Giang Thu Vu, Yasir Waheed, Richard G Wamai, Paul Ward, Yi Feng Wen, Ronny Westerman, Andrea Sylvia Winkler, Lalit Yadav, Seyed Hossein Yahyazadeh Jabbari, Lin Yang, Sanni Yaya, Taklo Simeneh Yazie Yazie, Yigizie Yeshaw, Naohiro Yonemoto, Mustafa Z Younis, Zabihollah Yousefi, Chuanhua Yu, Deniz Yuce, Ismaeel Yunusa, Vesna Zadnik, Fariba Zare, Mikhail Sergeevich Zastrozhin, Anasthasia Zastrozhina, Jianrong Zhang, Chenwen Zhong, Linghui Zhou, Cong Zhu, Arash Ziapour, Ivan R Zimmermann, Christina Fitzmaurice, Christopher J L Murray, Lisa M Force

Faculty, Staff and Student Publications

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite …

Kaposiform Lymphangiomatosis Presenting With A Group A Streptococcus Pericardial Effusion, Taylor Koerner, Mehul D Patel, Vinay Pai, Gitanjali Indramohan

Faculty, Staff and Student Publications

A 4-year-old child was transferred to the paediatric intensive care unit with acute respiratory failure following 4 days of fever, nausea and vomiting. Chest X-ray on admission had an enlarged cardiac silhouette and transthoracic echo confirmed a large pericardial effusion. An emergent pericardiocentesis was performed at bedside which drained nearly 1000 mL of purulent fluid. Postdrainage course was complicated by acute systolic and diastolic heart failure, thrombocytopenia and acute renal failure. A chest CT and MRI were concerning for a diffuse mediastinal soft-tissue density, so the patient underwent interventional radiology-guided biopsy complicated by haemorrhage requiring mediastinal exploration and subtotal thymectomy. …

Fully Resolved Assembly Of Cryptosporidium Parvum, Vipin K Menon, Pablo C Okhuysen, Cynthia L Chappell, Medhat Mahmoud, Medhat Mahmoud, Qingchang Meng, Harsha Doddapaneni, Vanesa Vee, Yi Han, Sejal Salvi, Sravya Bhamidipati, Kavya Kottapalli, George Weissenberger, Hua Shen, Matthew C Ross, Kristi L Hoffman, Sara Javornik Cregeen, Donna M Muzny, Ginger A Metcalf, Richard A Gibbs, Joseph F Petrosino, Fritz J Sedlazeck

Faculty, Staff and Student Publications

BACKGROUND: Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies.

FINDINGS: Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from …

Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation Of Acceptability And Usability, Ajay Sheshadri, Sukh Makhnoon, Amin M Alousi, Lara Bashoura, Rene Andrade, Christopher J Miller, Karen R Stolar, Muhammad Hasan Arain, Laila Noor, Amulya Balagani, Akash Jain, David Blanco, Abel Ortiz, Michael S Taylor, Alex Stenzler, Rohtesh Mehta, Uday R Popat, Chitra Hosing, David E Ost, Richard E Champlin, Burton F Dickey, Susan K Peterson

Faculty, Staff and Student Publications

Background: Home-based spirometry (HS) allows for the early detection of lung complications in recipients of an allogeneic hematopoietic cell transplant (AHCT). Although the usability and acceptability of HS are critical for adherence, patient-reported outcomes of HS use remain poorly understood in this setting.

Objective: The aim of this study is to design a longitudinal, mixed methods study to understand the usability and acceptability of HS among recipients of AHCT.

Methods: Study participants performed HS using a Bluetooth-capable spirometer that transmitted spirometry data to the study team in real time. In addition, participants completed usability questionnaires and in-depth interviews and reported …

Artificial Intelligence In Clinical And Translational Science: Successes, Challenges And Opportunities, Elmer V Bernstam, Paula K Shireman, Funda Meric-Bernstam, Meredith N Zozus, Xiaoqian Jiang, Bradley B Brimhall, Ashley K Windham, Susanne Schmidt, Shyam Visweswaran, Ye Ye, Heath Goodrum, Yaobin Ling, Seemran Barapatre, Michael J Becich

Faculty, Staff and Student Publications

Artificial intelligence (AI) is transforming many domains, including finance, agriculture, defense, and biomedicine. In this paper, we focus on the role of AI in clinical and translational research (CTR), including preclinical research (T1), clinical research (T2), clinical implementation (T3), and public (or population) health (T4). Given the rapid evolution of AI in CTR, we present three complementary perspectives: (1) scoping literature review, (2) survey, and (3) analysis of federally funded projects. For each CTR phase, we addressed challenges, successes, failures, and opportunities for AI. We surveyed Clinical and Translational Science Award (CTSA) hubs regarding AI projects at their institutions. Nineteen …

Spatial Epidemiology: An Empirical Framework For Syndemics Research, Shikhar Shrestha, Cici X C Bauer, Brian Hendricks, Thomas J Stopka

Faculty, Staff and Student Publications

Syndemics framework describes two or more co-occurring epidemics that synergistically interact with each other and the complex structural social forces that sustain them leading to excess disease burden. The term syndemic was first used to describe the interaction between substance abuse, violence, and AIDS by Merrill Singer. A broader range of syndemic studies has since emerged describing the framework's applicability to other public health scenarios. With syndemic theory garnering significant attention, the focus is shifting towards developing robust empirical analytical approaches. Unfortunately, the complex nature of the disease-disease interactions nested within several social contexts complicates empirical analyses. In answering the …

Combined Il-2, Agonistic Cd3 And 4–1bb Stimulation Preserve Clonotype Hierarchy In Propagated Non-Small Cell Lung Cancer Tumor-Infiltrating Lymphocytes, Parin Shah, Marie-Andrée Forget, Meredith L Frank, Peixin Jiang, Donastas Sakellariou-Thompson, Lorenzo Federico, Roohussaba Khairullah, Chantal Alexia Neutzler, Ignacio Wistuba, Chi-Wan B Chow, Yan Long, Junya Fujimoto, Shiaw-Yih Lin, Anirban Maitra, Marcelo V Negrao, Kyle Gregory Mitchell, Annikka Weissferdt, Ara A Vaporciyan, Tina Cascone, Jack A Roth, Jianjun Zhang, Boris Sepesi, Don L Gibbons, John V Heymach, Cara L Haymaker, Daniel J Mcgrail, Alexandre Reuben, Chantale Bernatchez

Faculty, Staff and Student Publications

Background: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion …

Corticosteroid-Refractory Myositis After Dual Braf And Mek Inhibition In A Patient With Braf V600e-Mutant Metastatic Intrahepatic Cholangiocarcinoma, Timothy P Diperi, Mehmet Demirhan, Daniel D Karp, Siqing Fu, David S Hong, Vivek Subbiah, Joann Lim, Leomar Y Ballester, Jean H Tayar, Maria E Suarez-Almazor, Milind Javle, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Intrahepatic cholangiocarcinoma is a rare malignancy, which is rich in actionable alterations. Genomic aberrations in the mitogen-activated protein kinase (MAPK) pathway are common, and

The Impact Of Age And Sex On Aortic Dissection Outcomes: A True Controversy Or Lack Of Standardization?, Erin F Mccaffrey, Michele Donato, Leeat Keren, Zhenghao Chen, Alea Delmastro, Megan B Fitzpatrick, Sanjana Gupta, Noah F Greenwald, Alex Baranski, William Graf, Rashmi Kumar, Marc Bosse, Christine Camacho Fullaway, Pratista K Ramdial, Erna Forgó, Vladimir Jojic, David Van Valen, Smriti Mehra, Shabaana A Khader, Sean C Bendall, Matt Van De Rijn, Daniel Kalman, Deepak Kaushal, Robert L Hunter, Niaz Banaei, Adrie J C Steyn, Purvesh Khatri, Michael Angelo

Faculty, Staff and Student Publications

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1