Life Sciences Commons^™

Cobimetinib Plus Vemurafenib In Patients With Solid Tumors With Braf Mutations: Results From The Targeted Agent And Profiling Utilization Registry Study, Funda Meric-Bernstam, Michael Rothe, Pam K Mangat, Elizabeth Garrett-Mayer, Rodolfo Gutierrez, Eugene R Ahn, Timothy L Cannon, Steven Powell, John C Krauss, Christopher M Reynolds, Margaret Von Mehren, Deepti Behl, Carmen J Calfa, Herbert L Duvivier, Henry G Kaplan, Michael B Livingston, Manish R Sharma, Walter J Urba, Gina N Grantham, Dominique C Hinshaw, Abigail Gregory, Susan Halabi, Richard L Schilsky

Faculty, Staff and Student Publications

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported.

Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of …

Correction: “The 5th Edition Of The World Health Organization Classification Of Haematolymphoid Tumours: Lymphoid Neoplasms” Leukemia 2022 Jul; 36(7):1720–1748, Rita Alaggio, Catalina Amador, Ioannis Anagnostopoulos, Ayoma D Attygalle, Iguaracyra Barreto De Oliveira Araujo, Emilio Berti, Govind Bhagat, Anita Maria Borges, Daniel Boyer, Mariarita Calaminici, Amy Chadburn, John K C Chan, Wah Cheuk, Wee-Joo Chng, John K Choi, Shih-Sung Chuang, Sarah E Coupland, Magdalena Czader, Sandeep S Dave, Daphne De Jong, Arianna Di Napoli, Ming-Qing Du, Kojo S Elenitoba-Johnson, Judith Ferry, Julia Geyer, Dita Gratzinger, Joan Guitart, Sumeet Gujral, Marian Harris, Christine J Harrison, Sylvia Hartmann, Andreas Hochhaus, Patty M Jansen, Kennosuke Karube, Werner Kempf, Joseph Khoury, Hiroshi Kimura, Wolfram Klapper, Alexandra E Kovach, Shaji Kumar, Alexander J Lazar, Stefano Lazzi, Lorenzo Leoncini, Nelson Leung, Vasiliki Leventaki, Xiao-Qiu Li, Megan S Lim, Wei-Ping Liu, Abner Louissaint, Andrea Marcogliese, L Jeffrey Medeiros, Michael Michal, Roberto N Miranda, Christina Mitteldorf, Santiago Montes-Moreno, William Morice, Valentina Nardi, Kikkeri N Naresh, Yasodha Natkunam, Siok-Bian Ng, Ilske Oschlies, German Ott, Marie Parrens, Melissa Pulitzer, S Vincent Rajkumar, Andrew C Rawstron, Karen Rech, Andreas Rosenwald, Jonathan Said, Clémentine Sarkozy, Shahin Sayed, Caner Saygin, Anna Schuh, William Sewell, Reiner Siebert, Aliyah R Sohani, Ritsuro Suzuki, Reuben Tooze, Alexandra Traverse-Glehen, Francisco Vega, Beatrice Vergier, Ashutosh D Wechalekar, Brent Wood, Luc Xerri, Wenbin Xiao

Faculty, Staff and Student Publications

No abstract provided.

Exploring Stakeholders' Perspectives On Implementing Universal Germline Testing For Colorectal Cancer: Findings From A Clinical Practice Survey, Linda Rodgers-Fouche, Sanjeevani Arora, Charité Ricker, Dan Li, Maheen Farooqi, Francesc Balaguer, Mev Dominguez-Valentin, Jose G Guillem, Priyanka Kanth, David Liska, Joshua Melson, Kathryn A Mraz, Brian H Shirts, Eduardo Vilar, Bryson W Katona, Rachel Hodan

Faculty, Staff and Student Publications

Purpose: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers.

Methods: A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

Trans-Pacific Multicenter Collaborative Study Of Minimally Invasive Proximal Versus Total Gastrectomy For Proximal Gastric And Gastroesophageal Junction Cancers, Naruhiko Ikoma, Travis Grotz, Hirofumi Kawakubo, Hyoung-Il Kim, Satoru Matsuda, Yuki Hirata, Atsushi Nakao, Loretta A Williams, Xin Shelley Wang, Tito Mendoza, Xuemei Wang, Brian D Badgwell, Paul F Mansfield, Woo-Jin Hyung, Vivian E Strong, Yuko Kitagawa

Faculty, Staff and Student Publications

Background: The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts …

Important Considerations For Real-World Analysis Of Neurotrophic Tyrosine Receptor Kinase Fusion Cancer And Tropomyosin Receptor Kinase Inhibitors, Marcia S Brose, David S Hong, Alexander Drilon

Faculty, Staff and Student Publications

No abstract provided.

Not Getting Laid: Consumer Acceptance Of Precision Fermentation Made Egg, Oscar Z. Thomas, Mark Chong, Angela K. Y. Leung, Tricia M. Fernandex, Shu Tian Ng

Research Collection Lee Kong Chian School Of Business

Mounting concern over the negative externalities of industrialized animal agriculture, coupled with falling cost curves of novel food technologies have birthed the field of cellular agriculture: a new category of food technology seeking to reproduce the sensory experiences of animal protein, and promising a cleaner, more ethical way of enjoying animal proteins. This research examines consumer acceptance of precision fermentation (PF) made egg products in Germany, Singapore, and the USA. Using an online survey of 3,006 participants, the study examines demographic and dietary traits that predict willingness to try such products and identifies the reasons why consumers are most attracted …

Population Genomics, Ecology And Conservation Of Asterias Sea Stars In The North Atlantic, Melenia I. Giakoumis

Dissertations, Theses, and Capstone Projects

Uncovering how species respond to environmental change is a central question in biology (Ehrlén & Morris 2015; Habibullah et al. 2022). It is the key to elucidating the past, understanding the present and predicting the future of species’ population dynamics. This dissertation investigates the influence of environmental change on intertidal species’ distributions and genomics at several timescales, with implications for conservation.

Environmental changes have occurred throughout history, on a geological scale, and have shaped the global patterns of species’ distributions and population sizes. Biologists have long studied how geological history has shaped species distributions (Sanmartín 2012) in both terrestrial (Liu …

Drug Repurposing Using Gene Expression Data Mining, Yue Qiu

Dissertations, Theses, and Capstone Projects

The conventional drug discovery process that employs the "one disease, one target, one drug'' paradigm is expensive, time-consuming, and has a high rate of failure for multi-genic complex diseases. An alternative approach to drug discovery is to repurpose an existing drug that has been used to treat some medical conditions. Drug repurposing is considered a promising method due to its accelerated the process of drug discovery and lower overall cost and risk.

Drug-perturbed gene expression profiles are powerful phenotype readouts of biological systems, and they have been widely used in drug repurposing studies. However, the existing drug-perturbed gene expression datasets …

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Characterization And Modulation Of The Emergent Material Properties Of Biomolecular Condensates, Alfredo Vidal Ceballos

Dissertations, Theses, and Capstone Projects

The discovery of membraneless organelles has revolutionized the field of cell biology and our understanding of cell compartmentalization. These organelles lack a distinct phospholipid bilayer and interact with the cytoplasm mediated by a liquid-liquid interface. The emergent properties and characterization of these organelles are essential for decoding the mechanisms underlying their function and dysfunction. In this thesis, we focus on two reconstituted in-vitro model systems of protein condensates and advance current methodology in order to address these fundamental questions. The first model system examined is the neuronal granule protein Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein, that aids …

Remote Sensing Characterization Of Ecosystem Structure And Functional Types To Inform On Biodiversity Conservation In The Lowland Chocó Rainforest, Derek Tesser

Dissertations, Theses, and Capstone Projects

This dissertation focuses on the utilization of remote sensing techniques to characterize ecosystem structure and functional types to inform on biodiversity conservation. This work is motivated by a guiding hypothesis that increased degradation of tropical forest biodiversity due to human activity results in in measurable changes in ecosystem processes that can be detected using remote sensing technologies. Throughout this dissertation, testing of aspects of this hypothesis involve comparing areas with varying degrees of human-induced degradation in a biodiverse tropical ecoregion, the lowland Chocó rainforest of Ecuador. Remote sensing data is used to evaluate changes in vegetation structure, thermal regimes, and …

Magnetically-Driven Therapeutic Agents Delivery System Using Iron Oxide Nanocages And Enhancement Of Exosome Secretion, A Potential Biological Drug Delivery Carrier, Min A Kang

Dissertations, Theses, and Capstone Projects

Nano-scale particles have attracted research attention due to their differences in properties such as penetration, circulation, and toxicity compared to bulk materials. This thesis mainly focused on using 20 nm iron oxide nanoparticles as siRNA delivery carriers under the alternating magnetic field and the development of a method to amplify the secretion of 150 nm exosomes from the cells, which could potentially use as a biological drug carrier.

Chapter 2 discusses a magnetically driven nanoparticle therapeutic agent delivery system, which efficiently modified the gene expression post-transcriptionally. In this work, we examined whether the caged-shaped 20nm iron oxide nanoparticles (IO-nanocages) can …

Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma

Dissertations, Theses, and Capstone Projects

Oligodendrocytes (OLs) are specialized cells whose membrane extension, called myelin, wraps the axons providing insulation, trophic and metabolic support, and is essential for proper functioning of the central nervous system. Inappropriate myelin formation, damage or dysfunction of oligodendrocytes has been identified in several neurological disorders and often precedes the loss of neuronal cells. OLs derive from proliferating oligodendrocyte progenitor cells (OPCs), which exit from the cell cycle and undergo a series of transcriptional and epigenetic events, including histone post-translational modifications, resulting in morphological and functional changes. Our lab previously identified elevated levels of histone acetylation in proliferating OPCs during the …

Pre-Clinical Evaluation Of A Potential Ruthenium-Based Chemotherapeutic Agent For The Treatment Of Triple Negative Breast Cancer, Nazia Nayeem

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that represents roughly 15% of all diagnosed breast cancers. TNBC is defined by the absence of expression of progesterone, estrogen, and human epidermal growth factor 2 receptors, and has a higher incidence rate in pre-menopausal women and women of African and of Hispanic ancestry. Due to the inability to target a receptor, treatment is limited to nonspecific chemotherapy or immunotherapy. Only one FDA approved therapy is available specifically to treat TNBC, which is antibody drug conjugate Sacitzumab-govitecan, given to patients who have already gone through two rounds of …

Expanding The Role Of The Temporal Dimension In Ecological Niche Models: A Study On Mexican Montane Small Mammals, Gonzalo E. Pinilla Buitrago

Dissertations, Theses, and Capstone Projects

Ecological niche models (ENMs) are commonly used to estimate the potential geographic distributions of species and have various uses, such as predicting invasive species' potential distribution, assessing vulnerability to climate change, or estimating paleodistributions. However, ENM developments have primarily focused on solving spatially related issues, underemphasizing the temporal dimensionality of occurrence and environmental data collected over the last century. One limitation of ENMs is the common practice of using recent environmental averages that fail to capture the gradual environmental change over the time span of the occurrence records and can hide trends in environmental variables, a critical piece of information …

Determining The Influence Of Abiotic And Biotic Predictors On Ecological Niche Models, Erica Johnson

Dissertations, Theses, and Capstone Projects

Biotic variables, including those reflecting interactions such as competition and parasitism, are generally assumed to have negligible effects on broadscale species distributions and are typically excluded from ecological niche models (ENMs). However, the role such interactions play in shaping species distributions is increasingly recognized, sparking the development of methods for their integration into ENMs.

Among the most common approaches are those that limit the ENM output of the focal species by the distribution of biotic interactors (post-processing) and those that incorporate biotic interactors as predictor variables. These endeavors hold widespread and critical usages, such as predicting the impacts of climate …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

Out-Of-Distribution Generalization Of Deep Learning To Illuminate Dark Protein Functional Space, Tian Cai

Dissertations, Theses, and Capstone Projects

Dark protein illumination is a fundamental challenge in drug discovery where majority human proteins are understudied, i.e. with only known protein sequence but no known small molecule binder. It's a major road block to enable drug discovery paradigm shift from single-targeted which looks to identify a single target and design drug to regulate the single target to multi-targeted in a Systems Pharmacology perspective. Diseases such as Alzheimer's and Opioid-Use-Disorder plaguing millions of patients call for effective multi-targeted approach involving dark proteins. Using limited protein data to predict dark protein property requires deep learning systems with OOD generalization capacity. Out-of-Distribution (OOD) …

A Novel Therapeutic Strategy For Alzheimer’S Disease: Sex-Dependent Mechanisms Altered By The Hdac Inhibitor Rg2833 In A Transgenic Rat Model, Kelechi Ndukwe

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, AD affects about 6.2 million Americans and is projected to reach 13.8 million by 2050. Currently, there are no effective therapies for AD and therapies targeting epigenetic mechanisms have shown to be effective in improving cognitive performance in animal models of AD. However, until now no study has reported sex-dependent mechanisms leading to differential expression of genes that contribute to changes in AD pathology. From our in silico studies, we identified an FDA-approved drug, RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) that penetrates the blood brain barrier and can potentially ameliorate …

Sex In The Noisy City: Changes In Vocal Behavior Patterns And Dopamine Neurochemistry In The Auditory System Of Oyster Toadfish (Opsanus Tau), Kelsey N. Hom

Dissertations, Theses, and Capstone Projects

Intense anthropogenic noise can induce stress, behavioral changes, and even hearing loss in aquatic animals. However, there are few studies that have demonstrated how ecologically relevant noise affects aquatic life, and even fewer studies on the effect of noise on animals that require sound for reproduction. The oyster toadfish (Opsanus tau) is an excellent animal model to examine the effects of anthropogenic noise on behavior and neurochemistry since they use a reproductive call to find mates and live near urban areas like New York City. Despite living alongside the most populous city in the United States, these vocal …

Electrophysiological Signatures Of Stress Adaptability In The Bnst-Vta Pathway, Yuka Miura

Dissertations, Theses, and Capstone Projects

Chronic stress has detrimental effects on psychological and physiological health. Incapability to adapt to chronic stress can lead to depression, anxiety disorders, and addiction. The brain regions critical for reward processing share diverse physiological and molecular changes linked to depressive-like behaviors as a result of chronic stress. Cumulative evidence shows that counteraction or prevention of these alterations in neurons, occasionally in a projection-specific manner, can enhance stress adaptation or resilience.

Chronic stress induces various changes in the brain, including in the bed nucleus of the stria terminalis (BNST) and the ventral tegmental area (VTA). The neural projections from the BNST …

Brainwaves, Memory, And Reward, Rebecca Mccune

Dissertations, Theses, and Capstone Projects

The development of effective educational curricula for enhancing learning involves the crucial consideration of effort and rewards. In the realm of education, teachers commonly employ rewards as motivational tools. Traditionally, these rewards are given to students as a recognition of their successful performance. However, a thought-provoking idea emerges: What if we were to extend rewards to students not solely based on accurate answers, but also on the effort they invest, even in cases where their actual response might be incorrect? Our study explores the potential impact of this approach on the way information is absorbed and subsequently retained, specifically focusing …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Characterization Of The Conformational Binding Of N-Methyl Mesoporphyrin Ix With Dna Model Telomeric G-Quadruplex Forming Sequences, Jessica Desamero

Dissertations, Theses, and Capstone Projects

DNA G-quadruplexes are alternative secondary structures formed from guanine rich DNA sequences. G-quadruplexes are found most abundantly at the ends of chromosomes called telomeres, where they can ultimately prevent further tumor growth and progression. Thus, quadruplex interactive agents, or ligands that can bind to and stabilize DNA G-quadruplex structures, are of high interest for their potential chemotherapeutic abilities. One quadruplex interactive agent is the porphyrin N-methyl mesoporphyrin IX (NMM), which has high binding selectivity for quadruplex structures. While the NMM-quadruplex complex in crystallized form has been greatly studied, this complex in solution form is not as well studied. Through circular …

Automatic Analysis Of The Frequency, Vigor, And Complexity Of Spontaneous Locomotion Bouts Of Mice With Loss And Gain Of Function Of The G Protein-Coupled Receptor Smoothened In Cholinergic Neurons, Aleksandra Feshchenko

Dissertations, Theses, and Capstone Projects

Locomotion, a fundamental behavior, is classically assessed using simple metrics of velocity and total distance moved in an open field. This behavior however offers rich data about the organization and breadth of actions an animal can take while only facing limitations due to the bio-mechanical constraints of the organism. Importantly, these actions are not biased towards a particular task-solution space imposed by many behavioral paradigms. Here, to analyze motor complexity in freely ambulating mice, we developed a method for the automatic and unbiased identification of locomotor bouts which we call Bout Finder (BF). This analysis utilizes Open Feld data to …

Optimization And Application Of Graph Neural Networks, Shuo Zhang

Dissertations, Theses, and Capstone Projects

Graph Neural Networks (GNNs) are widely recognized for their potential in learning from graph-structured data and solving complex problems. However, optimal performance and applicability of GNNs have been an open-ended challenge. This dissertation presents a series of substantial advances addressing this problem. First, we investigate attention-based GNNs, revealing a critical shortcoming: their ignorance of cardinality information that impacts their discriminative power. To rectify this, we propose Cardinality Preserved Attention (CPA) models that can be applied to any attention-based GNNs, which exhibit a marked improvement in performance. Next, we introduce the Directional Node Pair (DNP) descriptor and the Robust Molecular Graph …

You Hurt My Feelings: Autonomic And Behavioral Responses To Social Exclusion And The Moderating Effect Of Psychopathic Traits, Liat Kofler

Dissertations, Theses, and Capstone Projects

Humans have a fundamental need to form and maintain social connections, and thus experiencing social exclusion is extremely distressing as it threatens this basic human need. Individuals who are socially excluded often respond aggressively, not only towards their ostracizers but also towards innocent bystanders, with ostracism being implicated in extreme acts of violence such as school shootings. However, individual differences in behavior exist within the context of social exclusion as not everyone responds aggressively after being ostracized. Identifying risk factors for retaliatory aggressive behavior following experiences of social exclusion may facilitate the development of targeted interventions aimed at mitigating such …

Attenuated Typicality Effect In Category-Based Inferences: Implications For Autism Spectrum Disorder, Janani Rajagopalan

Dissertations, Theses, and Capstone Projects

Individuals diagnosed with Autism Spectrum Disorder (ASD) often encounter challenges in assimilating atypical exemplars into their categorical prototypes, a cognitive hurdle that can impact their interpretative and integrative capacities. Addressing this problem, the present research sought to develop a robust methodological approach to reduce the effect of this disparity. We examined the elements embedded within the category's internal structure, with the intention of experimentally attenuating the pronounced typicality effect, which is often exaggerated in ASD.

Across four experiments, the thesis investigated the cognitive and neural underpinnings that shape the access to the typicality gradient intrinsic to a category's structure. The …

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Faculty, Staff and Student Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …