Digital Commons Network^™

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of …

The Proteasome: A Key Modulator Of Nervous System Function, Brain Aging, And Neurodegenerative Disease, Kanisa Davidson, Andrew M Pickering

Faculty, Staff and Student Publications

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of …

Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Ekere James Essien

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic constitutes a global health threat and poses a major burden on the African continent. We assessed the real-world burden of COVID-19 infection in African Union (AU) member states to determine the distributional patterns of epidemiological measures during the first 1 year of the pandemic.

METHODS: This retrospective cross-sectional study utilized COVID-19 data from publicly available data repositories of the African Center for Disease Control and Prevention and

RESULTS: A total of 3.21 million cases were reported during the 1-year period, with 2.6 million recoveries, 536,784 cases remaining active, and 77,486 deaths. Most countries (49.1%,

CONCLUSION: Understanding …

Radiotherapy Reimagined: Integrating Nanomedicines Into Radiotherapy Clinical Trials, Allison N Duross, Jack Phan, Alexander J Lazar, Joshua M Walker, Alexander R Guimaraes, Sunil Krishnan, Conroy Sun, Alexander F Bagley

Faculty, Staff and Student Publications

Radioenhancing nanoparticles (NPs) are being evaluated in ongoing clinical trials for various cancers including head and neck, lung, esophagus, pancreas, prostate, and soft tissue sarcoma. Supported by decades of preclinical investigation and recent randomized trial data establishing clinical activity, these agents are poised to influence future multimodality treatment paradigms involving radiotherapy. Although the physical interactions between NPs and ionizing radiation are well characterized, less is known about how these agents modify the tumor microenvironment, particularly regarding tumor immunogenicity. In this review, we describe the key multidisciplinary considerations related to radiation, surgery, immunology, and pathology for designing radioenhancing NP clinical trials. …

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …

Fostering A High-Functioning Team In Cancer Care Using The 4r Oncology Model: Assessment In A Large Health System And A Blueprint For Other Institutions, Raymond Liu, Christine B Weldon, Elizabeth Linehan, Nancy Gordon, Thea Abbe, Henie James, Chun Ng, Megumi Tomita, Jeffrey B Velotta, Stephanie Ossowski, Lori C Sakoda, Sharon Likely Sprague, Anna Dowling, Kimberly Beringer, Arliene Ravelo, Elaine Yu, Julia R Trosman

Faculty, Staff and Student Publications

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system.

METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. …

Computed Tomography: State-Of-The-Art Advancements In Musculoskeletal Imaging, Hamza Ahmed Ibad, Cesar De Cesar Netto, Delaram Shakoor, Alejandro Sisniega, Stephen Z Liu, John A Carrino, Shadpour Demehri

Faculty, Staff and Student Publications

Although musculoskeletal magnetic resonance imaging (MRI) plays a dominant role in characterizing abnormalities, novel computed tomography (CT) techniques have found an emerging niche in several scenarios such as trauma, gout, and the characterization of pathologic biomechanical states during motion and weight-bearing. Recent developments and advancements in the field of musculoskeletal CT include 4-dimensional, cone-beam (CB), and dual-energy (DE) CT. Four-dimensional CT has the potential to quantify biomechanical derangements of peripheral joints in different joint positions to diagnose and characterize patellofemoral instability, scapholunate ligamentous injuries, and syndesmotic injuries. Cone-beam CT provides an opportunity to image peripheral joints during weight-bearing, augmenting the …

Association Of Immune-Related Adverse Events With The Outcomes Of Immune Checkpoint Inhibitors In Patients With Dmmr/Msi-H Metastatic Colorectal Cancer, Vincenzo Nasca, Francesco Barretta, Francesca Corti, Sara Lonardi, Monica Niger, Marwan Fakih, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Chiara Cremolini, Javier Ros, Margherita Ambrosini, Giacomo Mazzoli, Rossana Intini, Michael J Overman, Rosalba Miceli, Filippo Pietrantonio

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

METHODS: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by …

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Ziwei Liu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

The Mediating Effect Of Resilience On The Relationship Between Symptom Burden And Anxiety/Depression Among Chinese Patients With Primary Liver Cancer After Liver Resection, Xue Zhang, Haoran Zhang, Zonghao Zhang, Hua Fan, Shuwen Li

Faculty, Staff and Student Publications

Purpose: Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression.

Patients and methods: A total of 223 postoperative PLC patients …

Effects Of Heterozygous Deletion Of Autism-Related Gene Cullin-3 In Mice, Qiang-Qiang Xia, Angela K Walker, Chenghui Song, Jing Wang, Anju Singh, Zhong X Xuan, Craig M Powell

Faculty, Staff and Student Publications

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area …

Accommodating Time-Varying Heterogeneity In Risk Estimation Under The Cox Model: A Transfer Learning Approach, Ziyi Li, Yu Shen, Jing Ning

Faculty, Staff and Student Publications

Transfer learning has attracted increasing attention in recent years for adaptively borrowing information across different data cohorts in various settings. Cancer registries have been widely used in clinical research because of their easy accessibility and large sample size. Our method is motivated by the question of how to utilize cancer registry data as a complement to improve the estimation precision of individual risks of death for inflammatory breast cancer (IBC) patients at The University of Texas MD Anderson Cancer Center. When transferring information for risk estimation based on the cancer registries (i.e., source cohort) to a single cancer center (i.e., …

Financial Toxicity In Cancer Patients And Subsequent Risk Of Repeat Acute Care Utilization, Julia J Shi, J Alberto Maldonado, Chi-Fang Wu, Susan K Peterson, Ying-Shiuan Chen, Robert J Volk, Ya-Chen T Shih, Kelsey Kaiser, Grace L Smith

Faculty, Staff and Student Publications

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization.

Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, …

Editorial: Advances In Mathematical And Computational Oncology, Volume Iii, George Bebis, Mamoru Kato, Mohammad Kohandel, Kathleen Wilkie, Dinler A Antunes, Jinzhuang Dou

Faculty, Staff and Student Publications

No abstract provided.

Plasma Enzymatic Activity, Proteomics And Peptidomics In Covid-19-Induced Sepsis: A Novel Approach For The Analysis Of Hemostasis, Fernando Dos Santos, Joyce B Li, Nathalia Juocys, Rafi Mazor, Laura Beretta, Michael T Y Lam, Maria Claudia Irigoyen, Anthony J O'Donoghue, Federico Aletti, Erik B Kistler

Faculty, Staff and Student Publications

Introduction: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation). Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained …

Complex I Inhibitor Of Oxidative Phosphorylation In Advanced Solid Tumors And Acute Myeloid Leukemia: Phase I Trials, Timothy A Yap, Naval Daver, Mikhila Mahendra, Jixiang Zhang, Carlos Kamiya-Matsuoka, Hagop M Kantarjian, Meghan E Collins, Maria Emilia Di Francesco, Ecaterina E Dumbrava, Siqing Fu, Sisi Gao, Jason P Gay, Sonal Gera, Jing Han, David S Hong, Elias J Jabbour, Zhenlin Ju, Daniel D Karp, Alessia Lodi, Jennifer R Molina, Natalia Baran, Aung Naing, Maro Ohanian, Shubham Pant, Naveen Pemmaraju, Prithviraj Bose, Sarina A Piha-Paul, Jordi Rodon, Carolina Salguero, Koji Sasaki, Anand K Singh, Vivek Subbiah, Apostolia M Tsimberidou, Quanyun A Xu, Musa Yilmaz, Qi Zhang, Yuan Li, Christopher A Bristow, Meenakshi B Bhattacharjee, Stefano Tiziani, Timothy P Heffernan, Christopher P Vellano, Philip Jones, Cobi J Heijnen, Annemieke Kavelaars, Joseph R Marszalek, Marina Konopleva

Faculty, Staff and Student Publications

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759. The PK, PD, and preliminary antitumor activities of IACS-010759 in patients were also evaluated as secondary endpoints in both clinical trials. IACS-010759 had a narrow …

Benchmarking Outcomes For Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveal, Brian De, Ahsan S Farooqi, Kyle G Mitchell, Ethan B Ludmir, Jeff Lewis, Vadeerat Rinsurongkawong, Stephen G Swisher, Don L Gibbons, Jianjun Zhang, Xiuning Le, Yasir Y Elamin, Daniel R Gomez, Matthew S Ning, Steven H Lin, Zhongxing Liao, Joe Y Chang, Ara A Vaporciyan, John V Heymach, Mara B Antonoff, Saumil J Gandhi

Faculty, Staff and Student Publications

Purpose: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients.

Methods: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis.

Results: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with …

Effectiveness Without Efficacy: Cautionary Tale From A Landmark Breast Cancer Randomized Controlled Trial, Yu Shen, Jing Ning, Heather Y Lin, Simona F Shaitelman, Henry M Kuerer

Faculty, Staff and Student Publications

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data.

Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment …

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Xuebo Chen, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …

Receptor-Interacting Protein 1 And 3 Kinase Activity Are Required For High-Fat Diet Induced Liver Injury In Mice, Xiaoqin Wu, Rakesh K Arya, Emily Huang, Megan R Mcmullen, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

METHODS:Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate …

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Christopher R Kelsey, Ricardo Otazo, Jing Cai

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …

Risk Prediction Of Pancreatic Cancer In Patients With Recent-Onset Hyperglycemia: A Machine-Learning Approach, Wansu Chen, Rebecca K Butler, Eva Lustigova, Suresh T Chari, Anirban Maitra, Bechien U Wu

Faculty, Staff and Student Publications

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia.

Materials and methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets …

Self-Administered Meditation Application Intervention For Cancer Patients With Psychosocial Distress: A Pilot Study, Gabriel Lopez, Alejandro Chaoul, Carla L Warneke, Aimee J Christie, Catherine Powers-James, Santhosshi Narayanan, Yisheng Li, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

BACKGROUND: We explored the use of a novel smart phone-based application (APP) for delivery and monitoring of meditation to treat mood symptoms experienced by cancer patients.

METHODS: We assessed the feasibility of using a meditation delivery and tracking APP over 2-weeks and its impact on cancer patients' self-reported anxiety and depression. Outpatients reporting depression and/or anxiety were recruited and randomized to the APP or waitlist control group. Assessments included an expectancy scale, exit survey, mood rating before and after each meditation, and the Edmonton Symptom Assessment Scale (ESAS-FS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) …

Powerful, Scalable And Resource-Efficient Meta-Analysis Of Rare Variant Associations In Large Whole Genome Sequencing Studies, Xihao Li, Corbin Quick, Hufeng Zhou, Sheila M Gaynor, Yaowu Liu, Margaret Sunitha Selvaraj, Rounak Dey, Donna K Arnett, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Paul S De Vries, Ravindranath Duggirala, Barry I Freedman, Harald H H Göring, Xiuqing Guo, Jeffrey Haessler, Rita R Kalyani, Charles Kooperberg, Brian G Kral, Leslie A Lange, Ani Manichaikul, Lisa W Martin, Stephen T Mcgarvey, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Susan Redline, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Ramachandran S Vasan, Cristen J Willer, James G Wilson, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Lipids Working Group, Jerome I Rotter, Pradeep Natarajan, Gina M Peloso, Zilin Li, Xihong Lin

Faculty, Staff and Student Publications

Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of …

Estimating Causal Effects With Hidden Confounding Using Instrumental Variables And Environments, James P Long, Hongxu Zhu, Kim-Anh Do, Min Jin Ha

Faculty, Staff and Student Publications

Recent works have proposed regression models which are invariant across data collection environments [24, 20, 11, 16, 8]. These estimators often have a causal interpretation under conditions on the environments and type of invariance imposed. One recent example, the Causal Dantzig (CD), is consistent under hidden confounding and represents an alternative to classical instrumental variable estimators such as Two Stage Least Squares (TSLS). In this work we derive the CD as a generalized method of moments (GMM) estimator. The GMM representation leads to several practical results, including 1) creation of the Generalized Causal Dantzig (GCD) estimator which can be applied …

A Scientific Communication Mentoring Intervention Benefits Diverse Mentees With Language Variety Related Discomfort, Carrie A Cameron, Hwa Young Lee, Cheryl B Anderson, Erin K Dahlstrom, Shine Chang

Faculty, Staff and Student Publications

We studied social-psychological effects over time of a faculty-mentor workshop intervention that addressed attitudes associated with language variety and their impact on scientific communication (SC) skill development of PhD and postdoctoral STEM research trainees (N = 274). Six months after their mentors attended the workshop, all mentees had significant gains in productivity in speaking tasks. In particular, mentees with high language discomfort rated their quality of communication with their mentor and their enthusiasm about communicating more highly (p < .05 for both measures), compared to mentees with low language discomfort. In addition, mentees raised speaking nonstandardized varieties of English reported significant reductions in discomfort related to language use (p = .003), compared to mentees raised speaking standardized English. We conclude that training mentors to understand and respond to …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

Risk Factors Associated With Severe Clostridioides Difficile Infection In Patients With Cancer, Denise Marie A Francisco, Liangliang Zhang, Ying Jiang, Adilene Olvera, Javier Adachi, Samuel L Aitken, Christine B Peterson, Kim-Anh Do, Ryan Dillon, Engels N Obi, Robert Jenq, Pablo C Okhuysen

Faculty, Staff and Student Publications

INTRODUCTION: Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer.

METHODS: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome …

Associative Learning Contributes To The Persistence Of Fatigue-Like Behavior In Male Mice In A Model Of Cancer Survivorship, Elisabeth G Vichaya, Josephine K Darpolor, Phillip S Gross, Jessica M Molkentine, Daniel W Vermeer, John H Lee, Robert Dantzer

Faculty, Staff and Student Publications

Persistent fatigue is a debilitating side effect that impacts a significant proportion of cancer survivors for which there is not yet an FDA-approved treatment. While certainly a multi-factorial problem, persistent fatigue could be due, in part, to associations learned during treatment. Therefore, we sought to investigate the role of associative learning in the persistence of fatigue using a preclinical model of cancer survivorship. For this purpose, we used a murine model of human papilloma virus-related head and neck cancer paired with a curative regimen of cisplatin-based chemoradiation in male C57BL/6J mice. Fatigue-like behavior was assessed by measuring variations in voluntary …

Treatment De-Escalation In Philadelphia Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia: The Emerging Role Of Chemotherapy-Free Regimens, Fadi G Haddad, Jacki Sawyers, Nicholas J Short

Faculty, Staff and Student Publications

The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many …