Medicine and Health Sciences Commons^™

Targeted Neurostimulation Reverses A Spatiotemporal Biomarker Of Treatment-Resistant Depression, Anish Mitra, Marcus E Raichle, Andrew D Geoly, Ian H Kratter, Nolan R Williams

2020-Current year OA Pubs

Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT). We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the …

Tau Polarizes An Aging Transcriptional Signature To Excitatory Neurons And Glia, Timothy Wu, Jennifer M Deger, Hui Ye, Caiwei Guo, Justin Dhindsa, Brandon T Pekarek, Rami Al-Ouran, Zhandong Liu, Ismael Al-Ramahi, Juan Botas, Joshua M Shulman

Faculty, Staff and Students Publications

Aging is a major risk factor for Alzheimer’s disease (AD), and cell-type vulnerability underlies its characteristic clinical manifestations. We have performed longitudinal, single-cell RNA-sequencing in Drosophila with pan-neuronal expression of human tau, which forms AD neurofibrillary tangle pathology. Whereas tau- and aging-induced gene expression strongly overlap (93%), they differ in the affected cell types. In contrast to the broad impact of aging, tau-triggered changes are strongly polarized to excitatory neurons and glia. Further, tau can either activate or suppress innate immune gene expression signatures in a cell-type-specific manner. Integration of cellular abundance and gene expression pinpoints nuclear factor kappa B …

Upregulation Of The Oct3/4 Network In Basal Breast Cancer Is Associated With Its Metastatic Potential And Shows Tissue Dependent Variability, Robin G Rajan, Raisa I Krutilina, Tatyana N Ignatova, Zoran S Pavicevich, Galina M Dulatova, Maria A Lane, Arindam R Chatterjee, Robert J Rooney, Mymoon Antony, Vivian R Hagerty, Nickolay V Kukekov, Khalid A Hanafy, Frank D Vrionis

2020-Current year OA Pubs

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the

Smarcb1 Regulates The Hypoxic Stress Response In Sickle Cell Trait, Melinda Soeung, Luigi Perelli, Ziheng Chen, Eleonora Dondossola, I-Lin Ho, Federica Carbone, Li Zhang, Hania Khan, Courtney N Le, Cihui Zhu, Michael D Peoples, Ningping Feng, Shan Jiang, Niki Millward Zacharias, Rosalba Minelli, Daniel D Shapiro, Angela K Deem, Sisi Gao, Emily H Cheng, Donatella Lucchetti, Cheryl L Walker, Alessandro Carugo, Virginia Giuliani, Timothy P Heffernan, Andrea Viale, Nizar M Tannir, Giulio F Draetta, Pavlos Msaouel, Giannicola Genovese

Faculty, Staff and Student Publications

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels …

The Deleted In Oral Cancer (Doc1 Aka Cdk2ap1) Tumor Suppressor Gene Is Downregulated In Oral Squamous Cell Carcinoma By Multiple Micrornas, Roberto Stabile, Mario Román Cabezas, Mathijs P Verhagen, Francesco A Tucci, Thierry P P Van Den Bosch, Maria J De Herdt, Berdine Van Der Steen, Alex L Nigg, Meng Chen, Cristina Ivan, Masayoshi Shimizu, Senada Koljenović, Jose A Hardillo, C Peter Verrijzer, Robert J Baatenburg De Jong, George A Calin, Riccardo Fodde

Faculty, Staff and Student Publications

Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1; also known as deleted in oral cancer or DOC1) is a tumor suppressor gene known to play functional roles in both cell cycle regulation and in the epigenetic control of embryonic stem cell differentiation, the latter as a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex. In the vast majority of oral squamous cell carcinomas (OSCC), expression of the CDK2AP1 protein is reduced or lost. Notwithstanding the latter (and the DOC1 acronym), mutations or deletions in its coding sequence are extremely rare. Accordingly, CDK2AP1 protein-deficient oral cancer cell lines express as …

Smoking Status, Nicotine Medication, Vaccination, And Covid-19 Hospital Outcomes: Findings From The Covid Ehr Cohort At The University Of Wisconsin (Cec-Uw) Study, Thomas M Piasecki, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown.

METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission.

RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass …

Connecting Circuits With Networks In Addiction Neuroscience: A Salience Network Perspective, Adriana K Cushnie, Wei Tang, Sarah R Heilbronner

Faculty, Staff and Students Publications

Human neuroimaging has demonstrated the existence of large-scale functional networks in the cerebral cortex consisting of topographically distant brain regions with functionally correlated activity. The salience network (SN), which is involved in detecting salient stimuli and mediating inter-network communication, is a crucial functional network that is disrupted in addiction. Individuals with addiction display dysfunctional structural and functional connectivity of the SN. Furthermore, while there is a growing body of evidence regarding the SN, addiction, and the relationship between the two, there are still many unknowns, and there are fundamental limitations to human neuroimaging studies. At the same time, advances in …

Beclin-1-Dependent Autophagy, But Not Apoptosis, Is Critical For Stem-Cell-Mediated Endometrial Programming And The Establishment Of Pregnancy, Pooja Popli, Suni Tang, Sangappa B Chadchan, Chandni Talwar, Edmund B Rucker, Xiaoming Guan, Diana Monsivais, John P Lydon, Christina L Stallings, Kelle H Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

The human endometrium shows a remarkable regenerative capacity that enables cyclical regeneration and remodeling throughout a woman's reproductive life. Although early postnatal uterine developmental cues direct this regeneration, the vital factors that govern early endometrial programming are largely unknown. We report that Beclin-1, an essential autophagy-associated protein, plays an integral role in uterine morphogenesis during the early postnatal period. We show that conditional depletion of Beclin-1 in the uterus triggers apoptosis and causes progressive loss of Lgr5+/Aldh1a1+ endometrial progenitor stem cells, with concomitant loss of Wnt signaling, which is crucial for stem cell renewal and epithelial gland development. Beclin-1 knockin …

Machine Learning-Based Aggression Detection In Children With Adhd Using Sensor-Based Physical Activity Monitoring, Catherine Park, Mohammad Dehghan Rouzi, Md Moin Uddin Atique, M G Finco, Ram Kinker Mishra, Griselda Barba-Villalobos, Emily Crossman, Chima Amushie, Jacqueline Nguyen, Chadi Calarge, Bijan Najafi

Center on Aging Staff Publications

Aggression in children is highly prevalent and can have devastating consequences, yet there is currently no objective method to track its frequency in daily life. This study aims to investigate the use of wearable-sensor-derived physical activity data and machine learning to objectively identify physical-aggressive incidents in children. Participants (n = 39) aged 7 to 16 years, with and without ADHD, wore a waist-worn activity monitor (ActiGraph, GT3X+) for up to one week, three times over 12 months, while demographic, anthropometric, and clinical data were collected. Machine learning techniques, specifically random forest, were used to analyze patterns that identify physical-aggressive incident …

Hiv-1 Transmission Among Injecting Drug Users Is Principally Derived From Local Circulating Strains In Guangxi, China, Ping Cen, Hua Yue Liang, Yuan Yang, Fei Zhang, Shi Xiong Yang, Ju Cong Mo, Yi Feng, Jie Gang Huang, Chuan Yi Ning, Chun Yuan Huang, Yao Yang, Na Liang, Bing Yu Liang, Li Ye, Hao Liang

Faculty, Staff and Student Publications

OBJECTIVE: The mode of human immunodeficiency virus (HIV) transmission

METHODS: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.

RESULTS: Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission …

Toll-Like Receptors 2, 4, And 9 Modulate Promoting Effect Of Copd-Like Airway Inflammation On K-Ras-Driven Lung Cancer Through Activation Of The Myd88/Nf-ĸb Pathway In The Airway Epithelium, Walter V Velasco, Nasim Khosravi, Susana Castro-Pando, Nelly Torres-Garza, Maria T Grimaldo, Avantika Krishna, Michael J Clowers, Misha Umer, Sabah Tariq Amir, Diana Del Bosque, Soudabeh Daliri, Maria Miguelina De La Garza, Marco Ramos-Castaneda, Scott E Evans, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

INTRODUCTION: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable

METHODS: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on …

Phase Ii Clinical Trial Of Axitinib And Avelumab In Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma, Renata Ferrarotto, Luana G Sousa, Lei Feng, Frank Mott, George Blumenschein, Mehmet Altan, Diana Bell, Flavia Bonini, Kaiyi Li, Mario L Marques-Piubelli, Eduardo A Dal Lago, Jason J Johnson, Yoshitsugu Mitani, Myrna Godoy, Anna Lee, Michael Kupferman, Ehab Hanna, Bonnie S Glisson, Yasir Elamin, Adel El-Naggar

Faculty, Staff and Student Publications

Purpose: We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).

Patients and methods: Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis.

Results: …

Efficacy Of A Smoking Cessation Intervention For Survivors Of Cervical Intraepithelial Neoplasia Or Cervical Cancer: A Randomized Controlled Trial, Jennifer I Vidrine, Steven K Sutton, David W Wetter, Ya-Chen Tina Shih, Lois M Ramondetta, Linda S Elting, Joan L Walker, Katie M Smith, Summer G Frank-Pearce, Yisheng Li, Sarah R Jones, Darla E Kendzor, Vani N Simmons, Damon J Vidrine

Faculty, Staff and Student Publications

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population.

METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) …

Magrolimab In Combination With Azacitidine In Patients With Higher-Risk Myelodysplastic Syndromes: Final Results Of A Phase Ib Study, David A Sallman, Monzr M Al Malki, Adam S Asch, Eunice S Wang, Joseph G Jurcic, Terrence J Bradley, Ian W Flinn, Daniel A Pollyea, Suman Kambhampati, Tiffany N Tanaka, Joshua F Zeidner, Guillermo Garcia-Manero, Deepa Jeyakumar, Rami Komrokji, Jeffrey Lancet, Hagop M Kantarjian, Lin Gu, Yajia Zhang, Anderson Tan, Mark Chao, Carol O'Hear, Giridharan Ramsingh, Indu Lal, Paresh Vyas, Naval G Daver

Faculty, Staff and Student Publications

Purpose: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479).

Patients and methods: Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once-weekly or once-every-2-week …

Parent Perspectives Of School/Daycare Experiences In Young Children Newly Diagnosed With Diabetes, Alexa Stern, Brenda Duran, Randi Streisand, Christine H Wang, Carrie Tully, Lauren Clary, Katherine Gallagher, Fran Cogen, Lefkothea Karaviti, Maureen Monaghan, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis.

METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 >months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods …

Integrating Tobacco Treatment Into Oncology Care: Reach And Effectiveness Of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers, Sarah D Hohl, Alex T Ramsey, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

PURPOSE: Quitting smoking improves patients' clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness.

METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified …

Serum Metabolomic Signatures Of Fatty Acid Oxidation Defects Differentiate Host-Response Subphenotypes Of Acute Respiratory Distress Syndrome, Tomeka L Suber, Stacy G Wendell, Steven J Mullett, Benjamin Zuchelkowski, William Bain, Georgios D Kitsios, Bryan J Mcverry, Prabir Ray, Anuradha Ray, Rama K Mallampalli, Yingze Zhang, Faraaz Shah, Seyed Mehdi Nouraie, Janet S Lee

2020-Current year OA Pubs

BACKGROUND: Fatty acid oxidation (FAO) defects have been implicated in experimental models of acute lung injury and associated with poor outcomes in critical illness. In this study, we examined acylcarnitine profiles and 3-methylhistidine as markers of FAO defects and skeletal muscle catabolism, respectively, in patients with acute respiratory failure. We determined whether these metabolites were associated with host-response ARDS subphenotypes, inflammatory biomarkers, and clinical outcomes in acute respiratory failure.

METHODS: In a nested case-control cohort study, we performed targeted analysis of serum metabolites of patients intubated for airway protection (airway controls), Class 1 (hypoinflammatory), and Class 2 (hyperinflammatory) ARDS patients …

Multi-Stakeholder Perspectives Regarding Preferred Modalities For Mental Health Intervention Delivered In The Orthopedic Clinic: A Qualitative Analysis, Abby L Cheng, Ashwin J Leo, Ryan P Calfee, Christopher J Dy, Melissa A Armbrecht, Joanna Abraham

2020-Current year OA Pubs

BACKGROUND: Although depressive and anxious symptoms negatively impact musculoskeletal health and orthopedic outcomes, a gap remains in identifying modalities through which mental health intervention can realistically be delivered during orthopedic care. The purpose of this study was to understand orthopedic stakeholders' perceptions regarding the feasibility, acceptability, and usability of digital, printed, and in-person intervention modalities to address mental health as part of orthopedic care.

METHODS: This single-center, qualitative study was conducted within a tertiary care orthopedic department. Semi-structured interviews were conducted between January and May 2022. Two stakeholder groups were interviewed using a purposive sampling approach until thematic saturation was …

Blockchain-Enabled Immutable, Distributed, And Highly Available Clinical Research Activity Logging System For Federated Covid-19 Data Analysis From Multiple Institutions, Tsung-Ting Kuo, Anh Pham, Maxim E Edelson, Jihoon Kim, Jason Chan, Yash Gupta, Lucila Ohno-Machado

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.

MATERIALS AND METHODS: We preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain …

Deepmicetl: A Deep Transfer Learning Based Prediction Of Mice Cardiac Conduction Diseases Using Early Electrocardiograms, Ying Liao, Yisha Xiang, Mingjie Zheng, Jun Wang

Faculty, Staff and Student Publications

Cardiac conduction disease is a major cause of morbidity and mortality worldwide. There is considerable clinical significance and an emerging need of early detection of these diseases for preventive treatment success before more severe arrhythmias occur. However, developing such early screening tools is challenging due to the lack of early electrocardiograms (ECGs) before symptoms occur in patients. Mouse models are widely used in cardiac arrhythmia research. The goal of this paper is to develop deep learning models to predict cardiac conduction diseases in mice using their early ECGs. We hypothesize that mutant mice present subtle abnormalities in their early ECGs …

Joint Effect Of Human Papillomavirus Exposure, Smoking And Alcohol On Risk Of Oral Squamous Cell Carcinoma, Zheng Yang, Peng Sun, Kristina R Dahlstrom, Neil Gross, Guojun Li

Faculty, Staff and Students Publications

BACKGROUND: Smoking, alcohol consumption, and human papillomavirus (HPV) infection are known risk factors for oral squamous cell carcinoma (OSCC) including SCC of oropharynx (SCCOP) and SCC of oral cavity (SCCOC). Researchers have examined each of these risk factors independently, but few have observed the potential risk of their interaction. This study investigated the interactions among these risk factors and risk of OSCC.

METHODS: Totally 377 patients with newly diagnosed SCCOP and SCCOC and 433 frequency-matched cancer-free controls by age and sex were included. Multivariable logistic regression was performed to calculate ORs and 95% CIs.

RESULTS: We found that overall OSCC …

Breaking Down Grit: Persistency And Flexibility In The Career Plans Of Military Medical Students., Ryan R Landoll, Krista Highland, Kameha Bell, Anthony R. Artino, Col Lisa K Moores, Michael Soh, Sebastian Uijtdehaage, Steven J Durning, Neil E Grunberg, Ting Dong

Health Sciences Education Research

INTRODUCTION: The field of medicine is experiencing a crisis as high levels of physician and trainee burnout threaten the pipeline of future physicians. Grit, or passion and perseverance for long-term goals, has been studied in high-performing and elite military units and found to be predictive of successful completion of training in adverse conditions. The Uniformed Services University of the Health Sciences (USU) graduates military medical leaders who make up a significant portion of the Military Health System physician workforce. Taken together, an improved understanding of the relationships between burnout, well-being, grit, and retention among USU graduates is critical to the …

Well-Being At A Military Medical School And Implications For Military Retention., Michael Soh, Jessica Bunin, Sebastian Uijtdehaage, Anthony R. Artino, Erin S Barry, Steven J Durning, Neil E Grunberg, Ryan R Landoll, Ashley Maranich, Lisa K Moores, Jessica Servey, Dario Torre, Pamela M Williams, Ting Dong

Health Sciences Education Research

INTRODUCTION: Physical and psychological well-being play a critical role in the academic and professional development of medical students and can alter the trajectory of a student's quality of personal and professional life. Military medical students, given their dual role as officer and student, experience unique stressors and issues that may play a role in their future intentions to continue military service, as well as practice medicine. As such, this study explores well-being across the 4 years of medical school at Uniformed Services University (USU) and how well-being relates to a student's likelihood to continue serving in the military and practicing …

Treatment Of Angular Deformity And Limb Length Discrepancy With A Retrograde Femur Magnetic Intramedullary Nail: A Fixator-Assisted, Blocking Screw Technique, Erik J. Geiger, Adam D Geffner, S Robert Rozbruch, Austin T Fragomen

Rothman Institute Papers

Background: Fixator-assisted nailing techniques that incorporate magnetic internal lengthening nails (MILNs) permit acute deformity correction and then gradual limb lengthening without needing postoperative external fixators.

Purposes: We sought to investigate the safety and accuracy of a fixator-assisted, blocking screw technique using retrograde MILNs for the correction of LLD and limb malalignment.

Methods: Forty-one patients (13 patients with genu varum and 28 patients with genu valgum) with LLD treated with fixator-assisted, blocking screw retrograde MILN reconstruction were included. Preoperative LLD, mechanical axis deviation, and joint orientation angles were compared with values at the end of treatment, and bone healing indices were …

Cxcl8/Cxcr2 Signaling Mediates Bone Marrow Fibrosis And Is A Therapeutic Target In Myelofibrosis, Andrew J Dunbar, Dongjoo Kim, Min Lu, Mirko Farina, Robert L Bowman, Julie L Yang, Young Park, Abdul Karzai, Wenbin Xiao, Zach Zaroogian, Kavi O'Connor, Shoron Mowla, Francesca Gobbo, Paola Verachi, Fabrizio Martelli, Giuseppe Sarli, Lijuan Xia, Nada Elmansy, Maria Kleppe, Zhuo Chen, Yang Xiao, Erin Mcgovern, Jenna Snyder, Aishwarya Krishnan, Corrine Hill, Keith Cordner, Anouar Zouak, Mohamed E Salama, Jayden Yohai, Eric Tucker, Jonathan Chen, Jing Zhou, Timothy Mcconnell, Anna R Migliaccio, Richard Koche, Raajit Rampal, Rong Fan, Ross L Levine, Ronald Hoffman

Faculty, Staff and Student Publications

Proinflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution are yet to be fully elucidated. Previously, we identified a critical role for combined constitutive JAK/STAT and aberrant NF-κB proinflammatory signaling in MF development. Using single-cell transcriptional and cytokine-secretion studies of primary cells from patients with MF and the human MPLW515L (hMPLW515L) murine model of MF, we extend our previous work and delineate the role of …

Dual Targeting Of Cd19 And Cd22 With Bicistronic Car-T Cells In Patients With Relapsed/Refractory Large B-Cell Lymphoma, Claire Roddie, Nancy Bartlett, Et Al.

2020-Current year OA Pubs

Relapse after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multiantigen targeting and programmed cell death protein-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in relapsed/refractory LBCL (NCT03289455). End points include toxicity (primary) and response rates (secondary). Fifty-two patients received AUTO3 and 48/52 received pembrolizumab. Median age was 59 years (range, 27-83), 46/52 had stage III/ IV disease and median follow-up was 21.6 months. AUTO3 was safe; grade 1-2 and grade 3 cytokine release syndrome affected 18/52 (34.6%) …

Post-Resettlement Food Insecurity: Afghan Refugees And Challenges Of The New Environment, Zahra Goliaei, Mariaelena Gonzalez, Karina Diaz Rios, Mamata Pokhrel, Nancy J Burke

Faculty Publications & Research of the TUC Public Health Program

BACKGROUND: Lack of access to adequate, safe, and nutritious food is a major concern for the Afghan population due to ongoing war and humanitarian crises. Recently resettled Afghan refugees in the US continue to face challenges securing adequate, nutritious food resources in new environments. This study examined Afghan refugees' food access and insecurity in the San Joaquin Valley, California.

METHODS: Semi-structured, in-depth interviews were conducted to collect the perspectives and experiences of key informants and newly arrived Afghan refugees.

RESULTS: This study highlights environmental and structural factors (availability and accessibility of grocery stores; availability of religious-appropriate items in the stores; …

The Child Healthcare At Mater Pediatric Study (Champs): A 2-Arm Cluster Randomized Control Trial Of Group Well Child Care For Mothers In Treatment For Opioid Use Disorder And Their Children, Vanessa L. Short, Diane J. Abatemarco, Erica Sood, Dennis J. Hand, Meghan Gannon, Jobayer Hossain, Neera K. Goyal

Department of Pediatrics Faculty Papers

BACKGROUND: Studies suggest that group-based well child care-a shared medical appointment where families come together as a group to receive pediatric primary care-increases patient-reported satisfaction and adherence to recommended care. Evidence supporting the use of group well child care for mothers with opioid use disorder, however, is lacking. The overall objective of the Child Healthcare at MATER Pediatric Study (CHAMPS) trial is to evaluate a group model of well child care for mothers with opioid use disorder and their children.

METHODS: CHAMPS is a single-site 2-arm cluster randomized controlled trial. A total of 108 mother-child dyads will be enrolled into …

Deciphering Tumor Ecosystems At Super Resolution From Spatial Transcriptomics With Tesla, Jian Hu, Kyle Coleman, Daiwei Zhang, Edward B Lee, Humam Kadara, Linghua Wang, Mingyao Li

Faculty, Staff and Student Publications

Cell populations in the tumor microenvironment (TME), including their abundance, composition, and spatial location, are critical determinants of patient response to therapy. Recent advances in spatial transcriptomics (ST) have enabled the comprehensive characterization of gene expression in the TME. However, popular ST platforms, such as Visium, only measure expression in low-resolution spots and have large tissue areas that are not covered by any spots, which limits their usefulness in studying the detailed structure of TME. Here, we present TESLA, a machine learning framework for tissue annotation with pixel-level resolution in ST. TESLA integrates histological information with gene expression to annotate …

The Evolution Of Primary Care Telehealth Disparities During Covid-19: Retrospective Cohort Study, Rachel D'Amico, Patrick M Schnell, Randi Foraker, J Nwando Olayiwola, Daniel E Jonas, Seuli Bose Brill

2020-Current year OA Pubs

BACKGROUND: Telehealth has become widely used as a novel way to provide outpatient care during the COVID-19 pandemic, but data about telehealth use in primary care remain limited. Studies in other specialties raise concerns that telehealth may be widening existing health care disparities, requiring further scrutiny of trends in telehealth use.

OBJECTIVE: Our study aims to further characterize sociodemographic differences in primary care via telehealth compared to in-person office visits before and during the COVID-19 pandemic and determine if these disparities changed throughout 2020.

METHODS: We conducted a retrospective cohort study in a large US academic center with 46 primary …