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Articles 5521 - 5550 of 29653
Full-Text Articles in Entire DC Network
Impulsivity Facets And Substance Use Involvement: Insights From Genomic Structural Equation Modeling, Laura Vilar-Ribó, Alexander S Hatoum, Andrew D Grotzinger, Travis T Mallard, 23andme Research Team, Sarah Elson, Pierre Fontanillas, Abraham A Palmer, Daniel E Gustavson, Sandra Sanchez-Roige
Impulsivity Facets And Substance Use Involvement: Insights From Genomic Structural Equation Modeling, Laura Vilar-Ribó, Alexander S Hatoum, Andrew D Grotzinger, Travis T Mallard, 23andme Research Team, Sarah Elson, Pierre Fontanillas, Abraham A Palmer, Daniel E Gustavson, Sandra Sanchez-Roige
2020-Current year OA Pubs
BACKGROUND: Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear.
METHODS: We used genomic structural equation modeling and genome-wide association studies (
RESULTS: We found that the SU and SUD factors were strongly genetically inter-correlated (
CONCLUSIONS: Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.
Antisense Oligonucleotide-Mediated Tra2Β Poison Exon Inclusion Induces The Expression Of A Lncrna With Anti-Tumor Effects., Nathan Leclair, Mattia Brugiolo, Sunghee Park, Maeva Devoucoux, Laura M Urbanski, Brittany Lynn Angarola, Marina Yurieva, Olga Anczuków
Antisense Oligonucleotide-Mediated Tra2Β Poison Exon Inclusion Induces The Expression Of A Lncrna With Anti-Tumor Effects., Nathan Leclair, Mattia Brugiolo, Sunghee Park, Maeva Devoucoux, Laura M Urbanski, Brittany Lynn Angarola, Marina Yurieva, Olga Anczuków
Faculty Research 2025
Upregulated expression of the oncogenic splicing factor TRA2β occurs in human tumors partly through decreased inclusion of its autoregulatory non-coding poison exon (PE). Here, we reveal that low TRA2β-PE inclusion negatively impacts patient survival across several tumor types. We demonstrate the ability of splice-switching antisense oligonucleotides (ASOs) to promote TRA2β-PE inclusion and lower TRA2β protein levels in pre-clinical cancer models. TRA2β-PE-targeting ASOs induce anti-cancer phenotypes and widespread transcriptomic alterations with functional impact on RNA processing, mTOR, and p53 signaling pathways. Surprisingly, the effect of TRA2β-PE-targeting ASOs on cell viability are not phenocopied by TRA2β knockdown. Mechanistically, we find that the …
Framework, Design, And Baseline Data Of A Collective Impact Initiative To Strengthen The Community Health Worker Workforce Ecosystem In Texas, Shreela V Sharma, Heidi Hagen Mcpherson, Jemima John, Rosalia Guerrero, Sisan B Tennyson, Deborah Banerjee, Nadia Siddiqui, Sheila Savannah, Peter Durand, Amanda Gao, Sean A Haley, Elisa Garcia, Jennifer Cofer, Adrick Harris
Framework, Design, And Baseline Data Of A Collective Impact Initiative To Strengthen The Community Health Worker Workforce Ecosystem In Texas, Shreela V Sharma, Heidi Hagen Mcpherson, Jemima John, Rosalia Guerrero, Sisan B Tennyson, Deborah Banerjee, Nadia Siddiqui, Sheila Savannah, Peter Durand, Amanda Gao, Sean A Haley, Elisa Garcia, Jennifer Cofer, Adrick Harris
Faculty, Staff and Student Publications
BACKGROUND: The Health Equity Collective (HEC), a multi-sector systems-level collective impact coalition in the Greater Houston region, partnered with the City of Houston Health Department (HHD) to launch a 2-year effort to implement a comprehensive approach towards strengthening the regional Community Health Workers (CHW) workforce infrastructure as a pathway to advancing health equity. Our paper presents the logic model, methods, and baseline qualitative and quantitative data from this initiative.
METHODS: In the fall of 2022, the Health Equity Collective brought together a Network of CHW-employing or training organizations in the Greater Houston region. This Network was the working group of …
Reassessing Estrogen Receptor Expression Thresholds For Breast Cancer Prognosis In Her2-Negative Patients Using Shape Restricted Modeling, Wenli Dong, Takeo Fujii, Jing Ning, Toshiaki Iwase, Jing Qin, Naoto T Ueno, Yu Shen
Reassessing Estrogen Receptor Expression Thresholds For Breast Cancer Prognosis In Her2-Negative Patients Using Shape Restricted Modeling, Wenli Dong, Takeo Fujii, Jing Ning, Toshiaki Iwase, Jing Qin, Naoto T Ueno, Yu Shen
Faculty, Staff and Student Publications
We used a novel shape-restricted Cox model to determine the desirable ER expression cutoff to predict breast cancer prognoses. Our model treats ER as a continuous variable using a flexible monotone-shaped Cox regression to assess its association with survival outcomes holistically. The study included 3055 patients with stage II/III HER2-negative breast cancer. The primary outcomes were time to recurrence or death (TTR) and overall survival (OS). The shape-restricted Cox model identified 10% ER as the preferred cutoff to predict TTR. The finding was confirmed by the log-rank test and standard Cox model that patients with ER ≥ 10% had TTR …
Perceived Hbv-Related Stigma Is Associated With Lower Antiviral Medication Adherence In Patients With Chronic Hepatitis B, Hee-Soon Juon, Daniel Yang, Cindy Xin Fang, Hie-Won Hann, Ho Bae, Mimi Chang, Ann C. Klassen
Perceived Hbv-Related Stigma Is Associated With Lower Antiviral Medication Adherence In Patients With Chronic Hepatitis B, Hee-Soon Juon, Daniel Yang, Cindy Xin Fang, Hie-Won Hann, Ho Bae, Mimi Chang, Ann C. Klassen
Department of Medical Oncology Faculty Papers
Medication nonadherence among patients with chronic hepatitis B (CHB) can lead to severe liver disease progression, including liver cirrhosis and hepatocellular carcinoma (HCC). Yet the factors that influence adherence in high-risk groups, like Korean Americans, remain unclear. Thus, this study explored the psychosocial and clinical factors affecting medication adherence in CHB patients. A cohort of 365 Korean American patients with CHB from two clinics in Philadelphia and Los Angeles was studied. The 8-item Morisky Medication Adherence Scale (MMAS-8) gauged their adherence to antiviral medication. Using descriptive and multivariable logistic regression analyses, we identified factors associated with MMAS-8 scores. Of the …
Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi
Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi
Faculty, Staff and Student Publications
Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers.
Methods: Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, …
9-Aminominocycline Potentiates The Efficacy Of Eidd-1931 And Pf-332 By Targeting The Papain Like Protease Enzyme Of Sars-Cov-2., Kabita Pandey, Devin Shane M Lewis, Kyeongin Heo, Arpan Acharya, Travis Fields, Kritika Gowda, George Dean, Srujana Rayalam, Siddappa N Byrareddy, Vicky Mody, Shashidharamurthy Taval
9-Aminominocycline Potentiates The Efficacy Of Eidd-1931 And Pf-332 By Targeting The Papain Like Protease Enzyme Of Sars-Cov-2., Kabita Pandey, Devin Shane M Lewis, Kyeongin Heo, Arpan Acharya, Travis Fields, Kritika Gowda, George Dean, Srujana Rayalam, Siddappa N Byrareddy, Vicky Mody, Shashidharamurthy Taval
PCOM Scholarly Works
The 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) are key enzymes in SARS-CoV-2 replication and serve as critical targets for an antiviral drug. Currently, Paxlovid® and Lagevrio™ specifically target 3CLpro and RdRp, respectively, for COVID-19 treatment. However, no antivirals target for the SARS-CoV-2 PLpro enzyme, essential for viral replication and suppression of the host antiviral immune response. This study identified 9-aminominocycline (9-AMN) as a potent inhibitor of SARS-CoV-2 PLpro. Unlike the parent compound minocycline, 9-AMN inhibits PLpro's proteolytic and deubiquitinase activities by approximately 90%, with IC
Patient Partner Engagement In The Publication Process: Challenges And Possible Solutions, Krista E Cooksey, Mark Neuman, Mara Bollini, Bethany Pennington, Hugo De O Campos, Kathleen Oberst, Melissa Wurst, Mary C Politi
Patient Partner Engagement In The Publication Process: Challenges And Possible Solutions, Krista E Cooksey, Mark Neuman, Mara Bollini, Bethany Pennington, Hugo De O Campos, Kathleen Oberst, Melissa Wurst, Mary C Politi
2020-Current year OA Pubs
Patient engagement in research is gaining traction as an international standard, and often requirement, of many health research funding agencies. Drivers of this increase include patient interest, increased attention to and recognition of the value of patients' voices in research, and more patients leading or partnering in the conduct research. Patient engagement includes collaborating and providing insights into research question and study design, and may extend to the publication process. When patients contribute to publications, they can bring unique perspectives that may enhance the impact, reach, and utility of the research in real-world contexts. Currently, there is limited systematic guidance …
Inadequate Intensification Of Ldl-Cholesterol Lowering Therapy After Coronary Revascularization: Insights From The Gould Registry, Benjamin E Peterson, Deepak L Bhatt, Christie M Ballantyne, James A De Lemos, Robert S Rosenson, Mikhail N Kosiborod, Christopher P Cannon
Inadequate Intensification Of Ldl-Cholesterol Lowering Therapy After Coronary Revascularization: Insights From The Gould Registry, Benjamin E Peterson, Deepak L Bhatt, Christie M Ballantyne, James A De Lemos, Robert S Rosenson, Mikhail N Kosiborod, Christopher P Cannon
Faculty, Staff and Students Publications
Background: Patients with a history of coronary revascularization are at a higher risk for subsequent cardiovascular events and all-cause mortality. Lowering LDL-cholesterol (LDL-C) levels post-revascularization significantly reduces these risks.
Methods: This analysis compared LDL-C-lowering therapies at baseline and over time among patients with and without prior coronary revascularization in the GOULD registry (a prospective multicenter cohort study). Baseline- and 24-month follow-up characteristics-including LDL-C levels and strategies for lipid-lowering therapy (LLT)-were evaluated.
Results: Out of 5006 patients, 2195 (43.8%) had prior coronary revascularization. At baseline, these patients had lower LDL-C (99.2 mg/dL vs. 102.5 mg/dL; p < 0.001) and were more likely to be on intensive LLT (52.8% vs. 42.7%; p < 0.001). At 24 months, they had small reductions in LDL-C (-15.6% vs. -13.7%; p = 0.145) and were more likely to be on intensive LLT (61.9% vs. 51.5%; p < 0.001). Similar LDL-C reductions were observed in the PCSK9i group regardless of revascularization status.
Conclusions: Despite slightly better baseline …
Rideshare Services For Transportation Assistance In Gynecologic Oncology: A Quality Improvement Study, Anna Jo Smith, Sam Pancoe, Mary Pat Lynch, Megan Wachlin, Kristina Powell, Stefanie N. Hinkle, Nathanael C. Koelper, Meredith Doherty, Justin E. Bekelman, Fiona Simpkins, Emily M. Ko
Rideshare Services For Transportation Assistance In Gynecologic Oncology: A Quality Improvement Study, Anna Jo Smith, Sam Pancoe, Mary Pat Lynch, Megan Wachlin, Kristina Powell, Stefanie N. Hinkle, Nathanael C. Koelper, Meredith Doherty, Justin E. Bekelman, Fiona Simpkins, Emily M. Ko
SKMC Student Presentations and Publications
OBJECTIVE: Transportation barriers can lead to delays in care and suboptimal treatment. Our objective was to assess the utilization of a novel transportation pilot intervention in gynecologic oncology.
METHODS: Since May 2022, we have provided donor-funded transportation to patients receiving gynecologic cancer treatment at 5 University of Pennsylvania practices. Patients are screened for transportation barriers at first visit and re-screened during care. Patients who screen positive are referred to the intervention, a HIPAA-compliant ride-sharing service. There are no income or insurance restrictions; distance was limited to 25 miles. We report descriptive statistics on ride completion, distance traveled, and cost.
RESULTS: …
Proxy Panels Enable Privacy-Aware Outsourcing Of Genotype Imputation, Degui Zhi, Xiaoqian Jiang, Arif Harmanci
Proxy Panels Enable Privacy-Aware Outsourcing Of Genotype Imputation, Degui Zhi, Xiaoqian Jiang, Arif Harmanci
Faculty, Staff and Student Publications
One of the major challenges in genomic data sharing is protecting participants' privacy in collaborative studies and in cases when genomic data are outsourced to perform analysis tasks, for example, genotype imputation services and federated collaborations genomic analysis. Although numerous cryptographic methods have been developed, these methods may not yet be practical for population-scale tasks in terms of computational requirements, rely on high-level expertise in security, and require each algorithm to be implemented from scratch. In this study, we focus on outsourcing of genotype imputation, a fundamental task that utilizes population-level reference panels, and develop protocols that rely on using …
Single-Cell Analysis Identifies Ifi27l2a As A Gene Regulator Of Microglial Inflammation In The Context Of Aging And Stroke In Mice, Gab Seok Kim, Elisabeth Harmon, Manuel C Gutierrez, Sodam Kim, Lauren Vance, Haven Burrous, Jessica M Stephenson, Anjali Chauhan, Anik Banerjee, Zachary Wise, Andrea Doan, John Ahn, Ting Wu, Jesus Bautista-Garrido, Juneyoung Lee, Chunfeng Tan, Joo Eun Jung, Louise D Mccullough, Joshua D Wythe, Sean P Marrelli
Single-Cell Analysis Identifies Ifi27l2a As A Gene Regulator Of Microglial Inflammation In The Context Of Aging And Stroke In Mice, Gab Seok Kim, Elisabeth Harmon, Manuel C Gutierrez, Sodam Kim, Lauren Vance, Haven Burrous, Jessica M Stephenson, Anjali Chauhan, Anik Banerjee, Zachary Wise, Andrea Doan, John Ahn, Ting Wu, Jesus Bautista-Garrido, Juneyoung Lee, Chunfeng Tan, Joo Eun Jung, Louise D Mccullough, Joshua D Wythe, Sean P Marrelli
Faculty, Staff and Student Publications
Inflammation is a significant driver of ischemic stroke pathology in the brain. To identify potential regulators of inflammation, we performed single-cell RNA sequencing (scRNA-seq) of young and aged mouse brains following stroke and found that interferon alpha-inducible protein 27 like 2 A (Ifi27l2a) was significantly up-regulated, particularly in microglia of aged brain. Ifi27l2a is induced by interferons for viral host defense and has been linked with pro-inflammatory cellular mechanisms. However, its potential role in neurodegeneration is unknown. Using a combination of cell culture, experimental stroke models in mice, and human autopsy brain samples, we demonstrated that induction of Ifi27l2a occurs …
Identification Of Distinct Stool Metabolites In Women With Endometriosis For Non-Invasive Diagnosis And Potential For Microbiota-Based Therapies, Chandni Talwar, Goutham Venkata Naga Davuluri, Abu Hena Mostafa Kamal, Cristian Coarfa, Sang Jun Han, Surabi Veeraragavan, Krishna Parsawar, Nagireddy Putluri, Kristi Hoffman, Patricia Jimenez, Scott Biest, Ramakrishna Kommagani
Identification Of Distinct Stool Metabolites In Women With Endometriosis For Non-Invasive Diagnosis And Potential For Microbiota-Based Therapies, Chandni Talwar, Goutham Venkata Naga Davuluri, Abu Hena Mostafa Kamal, Cristian Coarfa, Sang Jun Han, Surabi Veeraragavan, Krishna Parsawar, Nagireddy Putluri, Kristi Hoffman, Patricia Jimenez, Scott Biest, Ramakrishna Kommagani
Faculty, Staff and Students Publications
Background: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.
Methods: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.
Findings: We discovered a unique bacteria-derived …
Aberrant Homeodomain-Dna Cooperative Dimerization Underlies Distinct Developmental Defects In Two Dominant Crx Retinopathy Models, Yiqiao Zheng, Gary D Stormo, Shiming Chen
Aberrant Homeodomain-Dna Cooperative Dimerization Underlies Distinct Developmental Defects In Two Dominant Crx Retinopathy Models, Yiqiao Zheng, Gary D Stormo, Shiming Chen
2020-Current year OA Pubs
Paired-class homeodomain (HD) transcription factors (TFs) play essential roles in vertebrate development, and their mutations are linked to human diseases. One unique feature of a paired-class HD is cooperative dimerization on specific palindrome DNA sequences. Yet, the functional significance of HD cooperative dimerization in animal development and its dysregulation in diseases remains elusive. Using the retinal TF cone-rod homeobox (CRX) as a model, we have studied how blindness-causing mutations in the paired HD, p.E80A and p.K88N, alter CRX's cooperative dimerization, leading to gene misexpression and photoreceptor developmental deficits in dominant manners. CRX
Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand
Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand
Faculty, Staff and Students Publications
Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …
Divergence In Cellular Markers Observed In Single-Cell Transcriptomics Datasets Between Cultured Primary Trabecular Meshwork Cells And Tissues, Alice Tian, Sangbae Kim, Hasna Baidouri, Jin Li, Xuesen Cheng, Janice Vranka, Yumei Li, Rui Chen, Vijaykrishna Raghunathan
Divergence In Cellular Markers Observed In Single-Cell Transcriptomics Datasets Between Cultured Primary Trabecular Meshwork Cells And Tissues, Alice Tian, Sangbae Kim, Hasna Baidouri, Jin Li, Xuesen Cheng, Janice Vranka, Yumei Li, Rui Chen, Vijaykrishna Raghunathan
Faculty, Staff and Students Publications
The trabecular meshwork within the outflow apparatus is critical in maintaining intraocular pressure homeostasis. In vitro studies employing primary cell cultures of the human trabecular meshwork (hTM) have conventionally served as surrogates for investigating the pathobiology of TM dysfunction. Despite its abundant use, translation of outcomes from in vitro studies to ex vivo and/or in vivo studies remains a challenge. Given the cell heterogeneity, performing single-cell RNA sequencing comparing primary hTM cell cultures to hTM tissue may provide important insights on cellular identity and translatability, as such an approach has not been reported before. In this study, we assembled a …
Treatment Of Small Intracranial Aneurysms Using The Smallss Scoring System: A Novel System For Decision Making, Mira Salih, Michael Young, Thomas B. Fodor, Alexander Andreev, Samuel D. Pettersson, Joanna M. Roy, Basel Musmar, Max Shutran, Phillip Taussky, Christopher S. Ogilvy
Treatment Of Small Intracranial Aneurysms Using The Smallss Scoring System: A Novel System For Decision Making, Mira Salih, Michael Young, Thomas B. Fodor, Alexander Andreev, Samuel D. Pettersson, Joanna M. Roy, Basel Musmar, Max Shutran, Phillip Taussky, Christopher S. Ogilvy
Department of Neurosurgery Faculty Papers
BACKGROUND: Treatment of unruptured intracranial aneurysms (UIA) less than 7 mm is controversial. We created a scoring system to guide decision making and validated the system utilizing over 700 cases treated with microsurgery or endovascular procedures.
METHODS: The scoring system SMALLSS included Size, (4-7 mm: 1 point, < 3.9 mm: 0 point), Multiple aneurysms (yes: 1, no: 0), Anatomic location (posterior: 1, anterior: 0), Lineage- family history of aneurysm (yes:1, no: 0), Lifetime risk (age < 65: 1, age > 65: 0), Smoking history (yes: 1, no: 0 ), Shape (irregular:1, smooth:0 ). Validation of this system was performed through retrospective review of prospectively maintained data for UIA patients treated between 2014 and 2021. We then performed an external validation of a cohort of 200 small aneurysms < 7 mm treated at a high volume cerebrovascular center.
RESULTS: A total of 1152 cases …
Structure-Activity Relationship Studies Of Dna Methyltransferase 1 Monovalent Degraders, Chao Qian, Youngeun Lee, Yulin Han, Yue Zhong, Jujun Zhou, Joel Hrit, Ling Xie, Qin Chen, H Ümit Kaniskan, Xian Chen, Scott Rothbart, Xiaodong Cheng, Yan Xiong, Jian Jin
Structure-Activity Relationship Studies Of Dna Methyltransferase 1 Monovalent Degraders, Chao Qian, Youngeun Lee, Yulin Han, Yue Zhong, Jujun Zhou, Joel Hrit, Ling Xie, Qin Chen, H Ümit Kaniskan, Xian Chen, Scott Rothbart, Xiaodong Cheng, Yan Xiong, Jian Jin
Faculty, Staff and Student Publications
DNA methyltransferase 1 (DNMT1), which catalyzes maintenance methylation of hemimethylated DNA during DNA replication, is overexpressed in cancer. Recently, the first-in-class DNMT1-selective noncovalent small-molecule inhibitors, GSK3484862 and GSK3685032, were discovered. These inhibitors were also reported to degrade DNMT1. However, structure–activity relationship (SAR) studies of these monovalent DNMT1 degraders are lacking. Here, we report our SAR studies of this scaffold on degrading DNMT1, which led to the discovery of multiple lead degraders, including compound 4 (MS9024). Compound 4 potently and selectively degraded DNMT1 in multiple cancer cell lines in a concentration-, time-, and proteasome-dependent manner without altering DNMT1 transcription. Further mechanism-of-action …
Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar
Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar
Faculty, Staff and Student Publications
Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …
Successful Posthospitalisation Oncology Workflow Implementing Lace+ Score To Stratify And Reduce Readmissions Within A Safety-Net Hospital, Cindy M Pabon, Janine Wong, Marcela Perez, Jessica Jimenez-Abarca, Lianchun Xiao, Lymesia Jackson, Anne Park, Anjali Lankford, Vinita Akula, Saumil Datar, Taylor Hopper, Yaser Alkhatib, Terri Earles, Tejal Patel
Successful Posthospitalisation Oncology Workflow Implementing Lace+ Score To Stratify And Reduce Readmissions Within A Safety-Net Hospital, Cindy M Pabon, Janine Wong, Marcela Perez, Jessica Jimenez-Abarca, Lianchun Xiao, Lymesia Jackson, Anne Park, Anjali Lankford, Vinita Akula, Saumil Datar, Taylor Hopper, Yaser Alkhatib, Terri Earles, Tejal Patel
Faculty, Staff and Student Publications
Background: Patients with advanced cancers visit the emergency room and get hospitalised frequently, with potentially half of these visits being avoidable. Our institution provides comprehensive, low-cost cancer treatment to a safety-net population in Texas. We performed a retrospective review of hospital readmission patterns amongst our oncology patients and developed a posthospitalisation workflow to reduce readmissions.
Method: Following discharge, oncology patients were risk stratified based on their Length of stay, Acuity of admission, Charlson comorbidity index score and Emergency department visits+index in the past 6 months. The higher the score, the quicker the outpatient oncology follow-up. In addition to addressing acute …
Feasibility Of An Undergraduate Academic Fellowship In Global Health System Development, Haleigh Pine, Brody R Mayoras, Maxwell C Klapow, Nathanael J Smith, Peter G Delaney, Zachary J Eisner
Feasibility Of An Undergraduate Academic Fellowship In Global Health System Development, Haleigh Pine, Brody R Mayoras, Maxwell C Klapow, Nathanael J Smith, Peter G Delaney, Zachary J Eisner
2020-Current year OA Pubs
BACKGROUND: Despite increasing student interest in global health, undergraduate opportunities remain limited and often lack practical, multidisciplinary experiences. To address professional gaps for future healthcare professionals and global health workers, it is crucial to incorporate resource management, business practices, and leadership into undergraduate volunteer service-learning programs.
METHODS: Lay First Responders (LFR) International's Fellowship Program in Emergency Medical Care and Innovation (ECMI) trains undergraduates to develop community-based emergency medical services in low- and middle-income countries, focusing on global capacity building, service leadership, and cultural competency. The year-long program guides fellows through a three-stage process of skill-development, design, and project implementation. The …
Phase 3 Trial Of Cabozantinib To Treat Advanced Neuroendocrine Tumors, Jennifer A Chan, Nikolaos A Trikalinos, Et Al.
Phase 3 Trial Of Cabozantinib To Treat Advanced Neuroendocrine Tumors, Jennifer A Chan, Nikolaos A Trikalinos, Et Al.
2020-Current year OA Pubs
BACKGROUND: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.
METHODS: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points …
Long-Term 3-Year Follow-Up Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma After ≥2 Prior Therapies, Laurie H Sehn, Nancy L Bartlett, Et Al.
Long-Term 3-Year Follow-Up Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma After ≥2 Prior Therapies, Laurie H Sehn, Nancy L Bartlett, Et Al.
2020-Current year OA Pubs
Mosunetuzumab, a CD20×CD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7 to not estimable [NE]). Among 54 patients who achieved CR, 49 …
Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu
Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu
Faculty, Staff and Students Publications
Background: Early diagnosis and accurate prognosis of cognitive decline in Alzheimer's disease (AD) is important to timely assignment to optimal treatment modes. We aimed to develop a deep learning model to predict cognitive conversion to guide re-assignment decisions to more intensive therapies where needed.
Methods: Longitudinal data including five variable sets, i.e. demographics, medical history, neuropsychological outcomes, laboratory and neuroimaging results, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. We first developed a deep learning model to predicted cognitive conversion using all five variable sets. We then gradually removed variable sets to obtained parsimonious models for four different …
Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul
Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul
Faculty, Staff and Students Publications
Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …
Contribution Of Rare Chromosome 22q112 Copy Number Variants To Non-Syndromic Bicuspid Aortic Valve, Helene Digregorio, Sara Mansoorshahi, Steven G Carlisle, Catherina Tovar Pensa, Abi Watts, Courtney Mcneely, Anna Sabate-Rotes, Anji Yetman, Hector I Michelena, Julie F A De Backer, Laura Muiño Mosquera, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Simon C Body, Dianna M Milewicz, Siddharth K Prakash, Ebav Investigators
Contribution Of Rare Chromosome 22q112 Copy Number Variants To Non-Syndromic Bicuspid Aortic Valve, Helene Digregorio, Sara Mansoorshahi, Steven G Carlisle, Catherina Tovar Pensa, Abi Watts, Courtney Mcneely, Anna Sabate-Rotes, Anji Yetman, Hector I Michelena, Julie F A De Backer, Laura Muiño Mosquera, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Simon C Body, Dianna M Milewicz, Siddharth K Prakash, Ebav Investigators
Faculty, Staff and Student Publications
Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications.
Methods: Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset …
Efficacy And Safety Of Nivolumab Plus Ipilimumab In Patients With Metastatic Variant Histology (Non-Clear Cell) Renal Cell Carcinoma, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Kiran L Malikayil, Devaki Shilpa Surasi, Tharakeswara K Bathala, Yiyun Lin, Priya Rao, Pheroze Tamboli, Kanishka Sircar, Helen Ajufo, Khaled M Elsayes, Amishi Shah, Andrew C Johns, Sangeeta Goswami, Elshad Hasanov, Eric Jonasch, Pavlos Msaouel, Matthew T Campbell, Omar Alhalabi, Nizar M Tannir
Efficacy And Safety Of Nivolumab Plus Ipilimumab In Patients With Metastatic Variant Histology (Non-Clear Cell) Renal Cell Carcinoma, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Kiran L Malikayil, Devaki Shilpa Surasi, Tharakeswara K Bathala, Yiyun Lin, Priya Rao, Pheroze Tamboli, Kanishka Sircar, Helen Ajufo, Khaled M Elsayes, Amishi Shah, Andrew C Johns, Sangeeta Goswami, Elshad Hasanov, Eric Jonasch, Pavlos Msaouel, Matthew T Campbell, Omar Alhalabi, Nizar M Tannir
Faculty, Staff and Student Publications
Background: Nivolumab plus ipilimumab (nivo/ipi) is a standard of care first-line (1 L) therapy for patients with metastatic clear-cell renal cell carcinoma (ccRCC), but its role in patients with metastatic, non-ccRCC has not been fully defined. We report a single-institution experience with nivo/ipi in non-ccRCC.
Methods: Between November 2017 and February 2024, 55 patients with metastatic non-ccRCC received nivo/ipi at MD Anderson Cancer Center. The tumor response was assessed by blinded radiologists using RECIST v1.1. The overall response rate (ORR), progression-free survival (PFS), PFS milestone, duration of response (DoR), and overall survival (OS) were determined. Next-generation sequencing (NGS) was performed …
Mapping The Numbers Of Dementia In Brazil: A Delphi Consensus Study, Márlon Juliano Romero Aliberti, Claudia Kimie Suemoto, Jerson Laks, Paulo Caramelli, Sonia Maria Dozzi Brucki, Nicolas Farina, Daniel Apolinario, Einstein Francisco Camargos, Eleonora D'Orsi, Gilberto Sousa Alves, Karolina Gouveia César-Freitas, Luís Fernando Rangel, Márcia Lorena Fagundes Chaves, Marcos Antonio Lopes, Marcus Vinicius Della Coletta, Matheus Ghossain Barbosa, Norberto Anizio Ferreira Frota, Ricardo Nitrini, Cleusa Pinheiro Ferri
Mapping The Numbers Of Dementia In Brazil: A Delphi Consensus Study, Márlon Juliano Romero Aliberti, Claudia Kimie Suemoto, Jerson Laks, Paulo Caramelli, Sonia Maria Dozzi Brucki, Nicolas Farina, Daniel Apolinario, Einstein Francisco Camargos, Eleonora D'Orsi, Gilberto Sousa Alves, Karolina Gouveia César-Freitas, Luís Fernando Rangel, Márcia Lorena Fagundes Chaves, Marcos Antonio Lopes, Marcus Vinicius Della Coletta, Matheus Ghossain Barbosa, Norberto Anizio Ferreira Frota, Ricardo Nitrini, Cleusa Pinheiro Ferri
Peninsula Medical School
OBJECTIVES: As the global dementia crisis intensifies, especially in low-and middle-income countries (LMICs), there is a pressing need for comprehensive prevalence data across diverse regions, including Brazil, where studies have been predominantly limited to affluent urban centers. This study aimed to conduct an expert consensus to determine the prevalence of all-cause dementia in Brazil, considering various age groups, sexes, and geographical areas.
METHODS: A Delphi consensus process with clinical and academic experts from across Brazil was conducted to provide dementia prevalence estimates in people aged ≥ 60 years living throughout Brazil for 2019. Each round consisted of answering structured questionnaires …
Fiber- And Acetate-Mediated Modulation Of Mhc-Ii Expression On Intestinal Epithelium Protects From Clostridioides Difficile Infection, José L Fachi, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Krzysztof L Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Marco Colonna, Et Al.
Fiber- And Acetate-Mediated Modulation Of Mhc-Ii Expression On Intestinal Epithelium Protects From Clostridioides Difficile Infection, José L Fachi, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Krzysztof L Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Marco Colonna, Et Al.
2020-Current year OA Pubs
Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4
Assessment Of Environmental, Sociocultural, And Physiological Influences On Women's Toileting Decisions And Behaviors Using "Where I Go": Pilot Study Of A Mobile App, Abigail R Smith, Elizabeth R Mueller, Cora E Lewis, Alayne Markland, Caroline Smerdon, Ariana L Smith, Siobhan Sutcliffe, Jean F Wyman, Lisa Kane Low, Janis M Miller
Assessment Of Environmental, Sociocultural, And Physiological Influences On Women's Toileting Decisions And Behaviors Using "Where I Go": Pilot Study Of A Mobile App, Abigail R Smith, Elizabeth R Mueller, Cora E Lewis, Alayne Markland, Caroline Smerdon, Ariana L Smith, Siobhan Sutcliffe, Jean F Wyman, Lisa Kane Low, Janis M Miller
2020-Current year OA Pubs
BACKGROUND: Little is known about women's decisions around toileting for urination and how those decisions influence moment-to-moment behaviors to manage bladder needs. The new smartphone app "Where I Go" captures such nuanced and granular data in real-world environments.
OBJECTIVE: This study aims to describe participant engagement with "Where I Go", variation in novel parameters collected, and readiness for the data collection tool's use in population-based studies.
METHODS: "Where I Go" has three components: (1) real-time data, (2) short look-back periods (3-4 h), and (3) event location (GPS recorded at each interaction). The sample size was 44 women. Recording of real-time …