Digital Commons Network^™

Integrated Screens Uncover A Cell Surface Tumor Suppressor Gene Kirrel Involved In Hippo Pathway, Chao Wang, Xu Feng, Dan Su, Zhen Chen, Shimin Wang, Mengfan Tang, Min Huang, Litong Nie, Huimin Zhang, Siting Li, Ling Yin, Randy L Johnson, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Cell surface proteins play essential roles in various biological processes and are highly related to cancer development. They also serve as important markers for cell identity and targets for pharmacological intervention. Despite their great potentials in biomedical research, comprehensive functional analysis of cell surface proteins remains scarce. Here, with a de novo designed library targeting cell surface proteins, we performed in vivo CRISPR screens to evaluate the effects of cell surface proteins on tumor survival and proliferation. We found that

Promoting Cancer Health Equity: A Qualitative Study Of Mentee And Mentor Perspectives Of A Training Program For Underrepresented Scholars In Cancer Health Disparities, Anastasia Rogova, Isabel Martinez Leal, Maggie Britton, Shine Chang, Kamisha H Escoto, Kayce D Solari Williams, Crystal Roberson, Lorna H Mcneill, Lorraine R Reitzel

Faculty, Staff and Student Publications

Racial and ethnic minorities, and women, experience stark disparities in cancer risk behaviors and mortality rates, yet often remain underrepresented in scientific research positions. We conducted an exploratory, qualitative study to examine the value of mentored research experience as part of an NCI-funded research training program designed to increase the representation of minority and women scientists in cancer disparities research. Using individual interviews, we explored 16 mentees' and 7 mentors' program experiences and perspectives to identify the most effective strategies to build strong mentoring relationships that could ultimately contribute to increased representation in health disparities research. Two expert analysts employed …

Lilrb2-Mediated Trem2 Signaling Inhibition Suppresses Microglia Functions, Peng Zhao, Yuanzhong Xu, Lu-Lin Jiang, Xuejun Fan, Zhiqiang Ku, Leike Li, Xiaoye Liu, Mi Deng, Hisashi Arase, Jay-Jiguang Zhu, Timothy Y Huang, Yingjun Zhao, Chengcheng Zhang, Huaxi Xu, Qingchun Tong, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

Background: Microglia plays crucial roles in Alzheimer's disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs.

Methods: To specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)-derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammatory …

Directed Evolution Of Pd-L1-Targeted Affibodies By Mrna Display, Brian J Grindel, Brian J Engel, Justin N Ong, Anupallavi Srinivasamani, Xiaowen Liang, Niki M Zacharias, Robert C Bast, Michael A Curran, Terry T Takahashi, Richard W Roberts, Steven W Millward

Faculty, Staff and Student Publications

Therapeutic monoclonal antibodies directed against PD-L1 (e.g., atezolizumab) disrupt PD-L1:PD-1 signaling and reactivate exhausted cytotoxic T-cells in the tumor compartment. Although anti-PD-L1 antibodies are successful as immune checkpoint inhibitor (ICI) therapeutics, there is still a pressing need to develop high-affinity, low-molecular-weight ligands for molecular imaging and diagnostic applications. Affibodies are small polypeptides (∼60 amino acids) that provide a stable molecular scaffold from which to evolve high-affinity ligands. Despite its proven utility in the development of imaging probes, this scaffold has never been optimized for use in mRNA display, a powerful

Inflammatory Breast Cancer: The Cytokinome Of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, And Stem Cell Markers, Alshaimaa Tarek, Shrouk Khalaf El-Sayed, Wendy A Woodward, Mohamed El-Shinawi, Jon Mark Hirshon, Mona Mostafa Mohamed

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed …

Anxiety Symptoms And Suicidal Thoughts And Behaviors Among Patients With Mood Disorders, Marsal Sanches, Linh K Nguyen, Tong Han Chung, Paul Nestadt, Holly C Wilcox, William H Coryell, Jair C Soares, Sudhakar Selvaraj

Faculty, Staff and Student Publications

Background: Though the association between anxiety disorders and suicidal behavior is well-described, the impact of anxiety symptoms on suicidal thoughts and behaviors (STB) across different mood disorders is still unclear.

Methods: We performed a registry-based retrospective study utilizing outcome measure data collected by the National Network of Depression Centers (NNDC), a nationwide nonprofit consortium of 26 leading clinical and academic member centers in the United States. The sample consisted of 2607 outpatients with mood disorders (major depressive disorder or bipolar disorders). Demographic and clinical variables were compared based on the presence or absence of STB and severity of anxiety symptoms …

Gut Dysbiosis And Age-Related Neurological Diseases In Females, Janelle M Korf, Bhanu P Ganesh, Louise D Mccullough

Faculty, Staff and Student Publications

Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand …

Stat3 Activates The Pentraxin 3 Gene In Chronic Lymphocytic Leukemia Cells, Uri Rozovski, Ivo Veletic, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Taghi Manshouri, Alessandra Ferrajoli, Jan A Burger, Prithviraj Bose, Phillip A Thompson, Nitin Jain, William G Wierda, Srdan Verstovsek, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells. …

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …

Real-World Use Of Palbociclib Monotherapy In Retroperitoneal Liposarcomas At A Large Volume Sarcoma Center, Elise F Nassif, Brandon Cope, Raymond Traweek, Russell G Witt, Derek J Erstad, Christopher P Scally, Prapassorn Thirasastr, Maria Alejandra Zarzour, Joseph Ludwig, Robert Benjamin, Andrew J Bishop, B Ashleigh Guadagnolo, Davis Ingram, Khalida Wani, Wei-Lien Wang, Alexander J Lazar, Keila E Torres, Kelly K Hunt, Barry W Feig, Christina L Roland, Neeta Somaiah, Emily Z Keung

Faculty, Staff and Student Publications

Palbociclib has been evaluated in early phase trials for well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) patients, with reported median progression-free survival (PFS) of 18 weeks. Here, we report on real-world use and surgical outcomes associated with palbociclib treatment. We retrospectively reviewed 61 consecutive patients with retroperitoneal WDLPS (n = 14) or DDLPS (n = 47) treated with palbociclib monotherapy between 1 March 2016 and 28 February 2021 at The University of Texas MD Anderson Cancer Center. At palbociclib initiation, median age was 64 (interquartile range [IQR] 56-72). In WDLPS and DDLPS cohorts, the median number of prior systemic treatments …

Challenges And Opportunities For Advancing Patient-Centered Clinical Decision Support: Findings From A Horizon Scan, Prashila Dullabh, Shana F Sandberg, Krysta Heaney-Huls, Lauren S Hovey, David F Lobach, Aziz Boxwala, Priyanka J Desai, Elise Berliner, Chris Dymek, Michael I Harrison, James Swiger, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: We conducted a horizon scan to (1) identify challenges in patient-centered clinical decision support (PC CDS) and (2) identify future directions for PC CDS.

MATERIALS AND METHODS: We engaged a technical expert panel, conducted a scoping literature review, and interviewed key informants. We qualitatively analyzed literature and interview transcripts, mapping findings to the 4 phases for translating evidence into PC CDS interventions (Prioritizing, Authoring, Implementing, and Measuring) and to external factors.

RESULTS: We identified 12 challenges for PC CDS development. Lack of patient input was identified as a critical challenge. The key informants noted that patient input is critical …

Up To 8-Year Follow-Up From Resonate-2: First-Line Ibrutinib Treatment For Patients With Chronic Lymphocytic Leukemia, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Steve E Coutre, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian-Yong Li, Fritz Offner, Carol Moreno, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg ≤12 cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs chlorambucil (hazard ratio …

Sirpα+ Macrophages Are Increased In Patients With Fl Who Progress Or Relapse After Frontline Lenalidomide And Rituximab, Mario L Marques-Piubelli, Edwin R Parra, Lei Feng, Luisa Solis Soto, Mariana Gallardo, Sushanth Gouni, Felipe Samaniego, Mansoor Noorani, Fredrick B Hagemeister, Jason R Westin, Hun Ju Lee, Maria A Rodriguez, Sattva S Neelapu, Jillian R Gunther, Nathan H Fowler, Christopher R Flowers, Ignacio I Wistuba, Loretta J Nastoupil, Francisco Vega, Paolo Strati

Faculty, Staff and Student Publications

Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2 in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2. A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein α [SIRPα]), and CD274 (also known as …

Case Report: Successful Treatment Of A Child With Covid-19 Reinfection-Induced Fulminant Myocarditis By Cytokine-Adsorbing Oxiris® Hemofilter Continuous Veno-Venous Hemofiltration And Extracorporeal Membrane Oxygenation, Phuc H Phan, Dung T Nguyen, Nam H Dao, Ha T T Nguyen, An V Vu, Son T Hoang, Lam V Nguyen, Tung V Cao, Dien M Tran

Faculty, Staff and Student Publications

BACKGROUND: Indirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities.

CASE PRESENTATION: We reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of

CONCLUSION: We conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced …

Atr-Mediated Cd47 And Pd-L1 Up-Regulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A Depinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley, Spencer T Lea, Rishika Prasad, Brittany Morrow, Coline Agnes Couillault, Madeline Steiner, Chun-Chieh Wang, Bhanu Prasad Venkatesulu, Cullen Taniguchi, Yon Son Betty Kim, Junjie Chen, Nils-Petter Rudqvist, Michael A Curran

Faculty, Staff and Student Publications

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. This postirradiation CD47 and PD-L1 up-regulation was observed across various human solid tumor cells. Concordantly, rectal cancer patients with poor responses to neoadjuvant RT exhibited …

Exploring School Staff Perceptions Relating To Animals And Their Involvement In Interventions To Support Mental Health, Rhoda A Leos, Paula M Cuccaro, John R Herbold, Belinda F Hernandez

Faculty, Staff and Student Publications

Given the growing awareness of the health benefits of human-animal interactions, the use of animal-assisted interventions (AAIs) in educational settings has increased over the years. While many school districts are now considering or utilizing AAIs, the literature investigating AAI-related perceptions among school stakeholders is limited with previous studies focusing on evaluating specific programs. to address this gap, a qualitative exploratory study was conducted using semi-structured interviews with school staff in the San Antonio, TX community. A total of 11 interviews were completed with staff serving preschool and elementary school age children. Data collected from interviews were analyzed using thematic analysis. …

Genome-Wide Crispr Screens Using Isogenic Cells Reveal Vulnerabilities Conferred By Loss Of Tumor Suppressors, Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A Depinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley, Spencer T Lea, Rishika Prasad, Brittany Morrow, Coline Agnes Couillault, Madeline Steiner, Chun-Chieh Wang, Bhanu Prasad Venkatesulu, Cullen Taniguchi, Yon Son Betty Kim, Junjie Chen, Nils-Petter Rudqvist, Michael A Curran

Faculty, Staff and Student Publications

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. This postirradiation CD47 and PD-L1 up-regulation was observed across various human solid tumor cells. Concordantly, rectal cancer patients with poor responses to neoadjuvant RT exhibited …

Risk Of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review And Individual Patient Data Meta-Analysis, Miranda P Steenbeek, Majke H D Van Bommel, Johan Bulten, Julia A Hulsmann, Joep Bogaerts, Christine Garcia, Han T Cun, Karen H Lu, Heleen J Van Beekhuizen, Lucas Minig, Katja N Gaarenstroom, Marielle Nobbenhuis, Mateja Krajc, Vilius Rudaitis, Barbara M Norquist, Elizabeth M Swisher, Marian J E Mourits, Leon F A G Massuger, Nicoline Hoogerbrugge, Rosella P M G Hermens, Joanna Inthout, Joanne A De Hullu

Faculty, Staff and Student Publications

Purpose: After risk-reducing salpingo-oophorectomy (RRSO), BRCA1/2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO.

Methods: Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without …

Atr-Mediated Cd47 And Pd-L1 Up-Regulation Restricts Radiotherapy-Induced Immune Prming And Abscopal Responses In Colorectal Cancer, Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A Depinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley, Spencer T Lea, Rishika Prasad, Brittany Morrow, Coline Agnes Couillault, Madeline Steiner, Chun-Chieh Wang, Bhanu Prasad Venkatesulu, Cullen Taniguchi, Yon Son Betty Kim, Junjie Chen, Nils-Petter Rudqvist, Michael A Curran

Faculty, Staff and Student Publications

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. This postirradiation CD47 and PD-L1 up-regulation was observed across various human solid tumor cells. Concordantly, rectal cancer patients with poor responses to neoadjuvant RT exhibited …

Resistance To Targeted Therapies: Delving Into Flt3 And Idh, Sai Prasad Desikan, Naval Daver, Courtney Dinardo, Tapan Kadia, Marina Konopleva, Farhad Ravandi

Faculty, Staff and Student Publications

Recent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance.

A Peptide Blocking The Adora1-Neurabin Interaction Is Anticonvulsant And Inhibits Epilepsy In An Alzheimer's Model, Shalini Saggu, Yunjia Chen, Liping Chen, Diana Pizarro, Sandipan Pati, Wen Jing Law, Lori Mcmahon, Kai Jiao, Qin Wang

Faculty, Staff and Student Publications

Epileptic seizures are common sequelae of stroke, acute brain injury, and chronic neurodegenerative diseases, including Alzheimer's disease (AD), and cannot be effectively controlled in approximately 40% of patients, necessitating the development of novel therapeutic agents. Activation of the A1 receptor (A1R) by endogenous adenosine is an intrinsic mechanism to self-terminate seizures and protect neurons from excitotoxicity. However, targeting A1R for neurological disorders has been hindered by side effects associated with its broad expression outside the nervous system. Here we aim to target the neural-specific A1R/neurabin/regulator of G protein signaling 4 (A1R/neurabin/RGS4) complex that dictates A1R signaling strength and response outcome …

Signal Detection Of Adverse Events Associated With Trastuzumab In A Cohort Of Elderly Patients With Breast Cancer, Efstathia Polychronopoulou, Sharon H Giordano, Lin-Na Chou, Xiaoying Yu, Yong-Fang Kuo

Faculty, Staff and Student Publications

AIM: Utilization of signal detection methods in longitudinal claims data can improve post-marketing drug surveillance, but to date there has been limited application. The aim of this study is to use 3 approaches, the proportional reporting ratio, Gamma Poisson Shrinker, and tree-based scan statistic in detecting adverse drug events (ADEs) attributed to trastuzumab using an administrative claims dataset.

METHODS: Using data from the Texas Cancer Registry and SEER linked to Medicare from 2010 to 2013, we conducted 1:2 propensity score matching. Breast cancer HER2+ patients treated with trastuzumab in addition to standard chemotherapy were matched to HER2- patients treated with …

Targeting Il-1Β As An Immunopreventive And Therapeutic Modality For K-Ras-Mutant Lung Cancer, Bo Yuan, Michael J Clowers, Walter V Velasco, Stephen Peng, Qian Peng, Yewen Shi, Marco Ramos-Castaneda, Melody Zarghooni, Shuanying Yang, Rachel L Babcock, Seon Hee Chang, John V Heymach, Jianjun Zhang, Edwin J Ostrin, Stephanie S Watowich, Humam Kadara, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

K-ras-mutant lung adenocarcinoma (KM-LUAD) is associated with abysmal prognosis and is tightly linked to tumor-promoting inflammation. A human mAb, canakinumab, targeting the proinflammatory cytokine IL-1β, significantly decreased the risk of lung cancer in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study. Interestingly, we found high levels of IL-1β in the lungs of mice with K-rasG12D-mutant tumors (CC-LR mice). Here, we blocked IL-1β using an anti-IL-1β mAb in cohorts of 6- or 14-week-old CC-LR mice to explore its preventive and therapeutic effect, respectively. IL-1β blockade significantly reduced lung tumor burden, which was associated with reprogramming of the lung microenvironment toward an antitumor phenotype …

Host Gut Resistome In Gulf War Chronic Multisymptom Illness Correlates With Persistent Inflammation, Dipro Bose, Somdatta Chatterjee, Ethan Older, Ratanesh Seth, Patricia Janulewicz, Punnag Saha, Ayan Mondal, Jeffrey M Carlson, Alan W Decho, Kimberly Sullivan, Nancy Klimas, Stephen Lasley, Jie Li, Saurabh Chatterjee

Faculty, Staff and Student Publications

Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal …

Effect Of Awake Prone Positioning On Endotracheal Intubation In Patients With Covid-19 And Acute Respiratory Failure: A Randomized Clinical Trial, Waleed Alhazzani, Ken Kuljit S Parhar, Jason Weatherald, Zainab Al Duhailib, Mohammed Alshahrani, Abdulrahman Al-Fares, Sarah Buabbas, Sujith V Cherian, Laveena Munshi, Eddy Fan, Fahad Al-Hameed, Jamal Chalabi, Amera A Rahmatullah, Erick Duan, Jennifer L Y Tsang, Kimberley Lewis, François Lauzier, John Centofanti, Bram Rochwerg, Sarah Culgin, Katlynne Nelson, Sheryl Ann Abdukahil, Kirsten M Fiest, Henry T Stelfox, Haytham Tlayjeh, Maureen O Meade, Dan Perri, Kevin Solverson, Daniel J Niven, Rachel Lim, Morten Hylander Møller, Emilie Belley-Cote, Lehana Thabane, Hani Tamim, Deborah J Cook, Yaseen M Arabi, Covi-Prone Trial Investigators And The Saudi Critical Care Trials Group

Faculty, Staff and Student Publications

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.

Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.

Design, setting, and participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.

Intervention: Patients were …

Malinc1 An Immune-Related Long Non-Coding Rna Associated With Early-Stage Breast Cancer Progression, María Laura Fabre, Romina Canzoneri, Agustina Gurruchaga, Jaeho Lee, Pradeep Tatineni, Hyunsuk Kil, Ezequiel Lacunza, C Marcelo Aldaz, Martín Carlos Abba

Faculty, Staff and Student Publications

Simple Summary

Here we characterize the phenotypic and molecular effects of MALINC1, a long non-coding RNA (lncRNA) that we found significantly upregulated in premalignant ductal carcinoma in-situ lesions. We provide evidence that MALINC1 behaves as an oncogenic and immune-related lncRNA involved with early-stage breast cancer progression, showing prognostic and predictive value to immunotherapy in invasive breast carcinomas.

Abstract

Long non-coding RNAs are increasingly being recognized as cancer biomarkers in various malignancies, acting as either tumor suppressors or oncogenes. The long non-coding MALINC1 intergenic RNA was identified as significantly upregulated in breast ductal carcinoma in situ. The aim of this …

Mobile Health Applications For Postpartum Depression Management: A Theory-Informed Analysis Of Change-Use-Engagement (Cue) Criteria In The Digital Environment, Alexandra Zingg, Laura Carter, Deevakar Rogith, Sudhakar Selvaraj, Amy Franklin, Sahiti Myneni

Faculty, Staff and Student Publications

Postpartum Depression (PPD) is the most common childbirth complication, with approximately 15% of postpartum women experiencing depression symptoms. Mobile applications have potential to expand delivery of mental health interventions. However, our understanding of how these tools engage women with PPD and facilitate positive behavioral changes is limited. In our paper, we analyze 15 commercial PPD applications to understand their role as facilitators of change, engagement, and sustained use. Applications reviewed contained an average of four theory-based behavioral change techniques, and highest patient engagement level reached was to empower patients through patient-generated data. Heuristic violations were identified in areas including user …

Unpacking Misinfodemic During A Global Health Crisis: A Qualitative Inquiry Of Psychosocial Characteristics In Social Media Interactions, Sofia M Olivares, Sahiti Myneni

Faculty, Staff and Student Publications

The pervasiveness of health information in social media has led to a modern misinformation crisis, also known as a misinfodemic. Misinfodemics have upended public health activities as clearly evident during the COVID-19 pandemic. The objective of this study is to characterize social media content and information sources using theory-driven health behavior and psychology constructs to better understand the motifs of misinformation and their role in the dissemination of health (mis)information in Twitter posts. We analyzed 1,400 randomly selected tweets related to COVID-19 to ascertain four important variables, what is the tweet about (content), how is it structured (linguistic features), who …

Latent Linguistic Motifs In Social Media Postings Resisting Covid-19 Misinformation, Tavleen Singh, Sofia Olivares, Sahiti Myneni

Faculty, Staff and Student Publications

Social media has become a predominant source of information for many health care consumers. However, false and misleading information is a pervasive problem in this context. Specifically, health-related misinformation has become a significant public health challenge, impeding the effectiveness of public health awareness campaigns and resulting in suboptimal responsiveness to the communication of legitimate risk-related information. Little is known about the mechanisms driving the seeding and spreading of such information. In this paper, we specifically examine COVID-19 tweets which attempt to correct misinformation. We employ a mixed-methods approach comprising qualitative coding, deep learning classification, and computerized text analysis to understand …

Phosphorylation And Stabilization Of Pd-L1 By Ck2 Suppresses Dendritic Cell Function, Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

UNLABELLED: Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor …