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Articles 8461 - 8490 of 79082

Full-Text Articles in Medical Specialties

Lipoprotein(A) And Heart Failure Among Black And White Participants In Atherosclerosis Risk In Communities Study, Framingham Offspring Study, And Multi-Ethnic Study Of Atherosclerosis: The Pooling Project, Geoffrey H Tison, Hiroaki Ikezaki, Margaret R Diffenderfer, Ching-Ti Liu, Ron C Hoogeveen, Christie M Ballantyne, Ernst J Schaefer, Michael Y Tsai Jun 2025

Lipoprotein(A) And Heart Failure Among Black And White Participants In Atherosclerosis Risk In Communities Study, Framingham Offspring Study, And Multi-Ethnic Study Of Atherosclerosis: The Pooling Project, Geoffrey H Tison, Hiroaki Ikezaki, Margaret R Diffenderfer, Ching-Ti Liu, Ron C Hoogeveen, Christie M Ballantyne, Ernst J Schaefer, Michael Y Tsai

Faculty, Staff and Students Publications

Background: This study investigated Lp(a) (lipoprotein(a)) levels with heart failure (HF) incidence overall and ejection fraction (EF) subtypes among Black and White participants in a pooled analysis of MESA (Multi-Ethnic Study of Atherosclerosis), FOS (Framingham Offspring Study), and ARIC (Atherosclerosis Risk in Communities Study).

Methods: This study was conducted among 16 771 White and Black participants in ARIC (N=10 347), MESA (N=4150), and FOS (N=2274). Baseline was time of Lp(a) measurement (ARIC Visit 4: 1996-1998; MESA Visit 1: 2000-2002; FOS Cycle 6: 1995-1998). HF with reduced EF (HFrEF) was defined as EF < 50% and ≥50% as HF with preserved EF (HFpEF). Cox proportional hazards regression was used to evaluate associations between Lp(a) (log-transformed continuous, dichotomized at ≥30 mg/dL and ≥50 mg/dL, and quartiles) and HF (overall, HFpEF, HFrEF) in the overall population and stratified by race. Analyses were replicated excluding prior history of myocardial infarction.

Results: There were 2759 HF cases (HFpEF N=859; …


Verifiable Summarization Of Electronic Health Records Using Large Language Models To Support Chart Review, Leslie Chang, Kirollos Roman, Esteban Gershanik, Camellia Hernandez, Miguel Linares, Jorge Rodriguez, Durga Thakral, Ozan Unlu, Jacqueline You, Li Zhou, David Bates Jun 2025

Verifiable Summarization Of Electronic Health Records Using Large Language Models To Support Chart Review, Leslie Chang, Kirollos Roman, Esteban Gershanik, Camellia Hernandez, Miguel Linares, Jorge Rodriguez, Durga Thakral, Ozan Unlu, Jacqueline You, Li Zhou, David Bates

Faculty, Staff and Students Publications

Information overload in electronic health records (EHRs) hampers clinicians' ability to efficiently extract and synthesize critical information from a patient's longitudinal health record, leading to increased cognitive burden and delays in care. This study explores the potential of large language models (LLMs) to address this challenge by generating problem-based admission summaries for patients admitted with heart failure, a leading cause of hospitalization worldwide. We developed an extract-then-abstract approach guided by disease-specific "summary bundles" to generate summaries of longitudinal clinical notes that prioritize clinically relevant information. Through a mixed-methods evaluation using real-world clinical notes, we compared physicians' ability to answer patient-specific …


Phage-Induced Protection Against Lethal Bacterial Reinfection, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso Jun 2025

Phage-Induced Protection Against Lethal Bacterial Reinfection, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …


Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus Jun 2025

Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus

Dissertations

MLL-rearranged (MLL-r) leukemia is an aggressive subset of acute leukemia, accounting for up to 10% of adult and 70% of infant AML and ALL cases. These leukemias are driven by MLL fusion proteins, which recruit epigenetic cofactors to dysregulate gene expression, leading to poor prognosis and resistance to conventional chemotherapy. Previous lab work identified EYA1’s role in leukemogenesis, establishing it as a therapeutic target in MLL-r leukemia. EYA1, is a transcriptional coactivator and protein tyrosine phosphatase (PTP). Originally a gout medication, benzbromarone (BBR), was identified in an NCI Diversity Set screen as an EYA1-specific PTP inhibitor. BBR provides a tool …


Tumor Microenvironment Governs The Prognostic Landscape Of Immunotherapy For Head And Neck Squamous Cell Carcinoma: A Computational Model-Guided Analysis, Priyan Bhattacharya, Alban J Linnenbach, Andrew P. South, Ubaldo E. Martinez-Outshoorn, Joseph M. Curry, Jennifer M. Johnson, Larry A. Harshyne, Mỹ G. Mahoney, Adam J. Luginbuhl, Rajanikanth Vadigepalli Jun 2025

Tumor Microenvironment Governs The Prognostic Landscape Of Immunotherapy For Head And Neck Squamous Cell Carcinoma: A Computational Model-Guided Analysis, Priyan Bhattacharya, Alban J Linnenbach, Andrew P. South, Ubaldo E. Martinez-Outshoorn, Joseph M. Curry, Jennifer M. Johnson, Larry A. Harshyne, Mỹ G. Mahoney, Adam J. Luginbuhl, Rajanikanth Vadigepalli

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Immune checkpoint inhibition (ICI) has emerged as a critical treatment strategy for squamous cell carcinoma of the head and neck (HNSCC) that halts the immune escape of the tumor cells. Increasing evidence suggests that the onset, progression, and lack of/no response of HNSCC to ICI are emergent properties arising from the interactions within the tumor microenvironment (TME). Deciphering how the diversity of cellular and molecular interactions leads to distinct HNSCC TME subtypes subsequently governing the ICI response remains largely unexplored. We developed a cellular-molecular model of the HNSCC TME that incorporates multiple cell types, cellular states, and transitions, and molecularly …


Racial And Ethnic Representation And Study Engagement In A Siteless Digital Clinical Trial Using A Smartwatch: Findings From The Apple Heart Study., Kaylin T. Nguyen, Jingzhi Yu, Haley Hedlin, Adam T. Phillips, Sumbul Desai, Lauren Cheung, Peter R Kowey, Sneha S. Jain, John S. Rumsfeld, Andrea M. Russo, Christopher B. Granger, Mellanie True Hills, Manisha Desai, Kenneth W. Mahaffey, Mintu P. Turakhia, Marco V. Perez Jun 2025

Racial And Ethnic Representation And Study Engagement In A Siteless Digital Clinical Trial Using A Smartwatch: Findings From The Apple Heart Study., Kaylin T. Nguyen, Jingzhi Yu, Haley Hedlin, Adam T. Phillips, Sumbul Desai, Lauren Cheung, Peter R Kowey, Sneha S. Jain, John S. Rumsfeld, Andrea M. Russo, Christopher B. Granger, Mellanie True Hills, Manisha Desai, Kenneth W. Mahaffey, Mintu P. Turakhia, Marco V. Perez

Department of Medicine Faculty Papers

OBJECTIVE: To evaluate differences in study engagement in diverse racial/ethnic groups that have been significantly underrepresented in atrial fibrillation and digital clinical trials.

PATIENTS AND METHODS: This was a secondary analysis of participants from the Apple Heart Study, a prospective, siteless, single-arm pragmatic clinical trial from November 29, 2017, to January 31, 2019. Black, Hispanic, Asian, and White participants were monitored using an irregular rhythm notification algorithm designed to detect atrial fibrillation on a smartwatch. Logistic regression was performed to evaluate the relationship between race/ethnicity and completion of the first study visit after an irregular rhythm notification, adjusting for demographic …


Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy Jun 2025

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.


A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker Jun 2025

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …


Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn Jun 2025

Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn

Department of Surgery Faculty Papers

INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …


Time-Driven Activity-Based Costing For Cervical Myelopathy Surgery: A Step Towards Total Episode Costs, Kavantissa M. Keppetipola, Adam Leibold, Jay Trivedi, Ashmal Sami, Advith Sarikonda, D. Mitchell Self, Emily L. Isch, Steven R. Glener, Srinivas Prasad, Jack Jallo, Joshua E. Pelta-Heller, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan Jun 2025

Time-Driven Activity-Based Costing For Cervical Myelopathy Surgery: A Step Towards Total Episode Costs, Kavantissa M. Keppetipola, Adam Leibold, Jay Trivedi, Ashmal Sami, Advith Sarikonda, D. Mitchell Self, Emily L. Isch, Steven R. Glener, Srinivas Prasad, Jack Jallo, Joshua E. Pelta-Heller, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

INTRODUCTION: Time-driven activity-based costing (TDABC) is a highly accurate method for determining the true cost of delivering a healthcare service. However, TDABC is most often applied to a singular phase of care such as an outpatient visit or a surgical event. Here we broaden the scope by using TDABC to estimate the costs of surgically treating cervical myelopathy - from the moment of surgical scheduling until post-operative hospital discharge.

METHODS: In a single-center retrospective study at a large tertiary academic institution, TDABC was employed to measure pre-operative, intra-operative, and post-operative (inpatient) costs for 63 patients undergoing elective surgery for cervical …


Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Alyssa M Brown, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky Jun 2025

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Alyssa M Brown, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …


Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting Jun 2025

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …


Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee Jun 2025

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …


Mitral Valve Surgery After Failed Transcatheter Intervention For Mitral Regurgitation: Surgical Techniques, Challenges And Outcomes, Michael A Borger, Serdar Akansel, Thilo Noack, David Holzhey, Tsuyoshi Kaneko, Isaac George, Gorav Ailawadi, Robert L Smith, Arnar Geirrson, Ahmed El-Eshmawi, Dimosthenis Pandis, Suzanne De Waha, Nikolaos Bonaros, Fabien Praz, Maurizio Taramasso, Michele De Bonis, Lenard Conradi, Christian Hagl, Nicolas Doll, Mahmoud Wehbe, Alexey Dashkevich, Manuela De La Cuesta, Jagdip Kang, Zara Dietze, Philipp Kiefer, Gilbert H L Tang Jun 2025

Mitral Valve Surgery After Failed Transcatheter Intervention For Mitral Regurgitation: Surgical Techniques, Challenges And Outcomes, Michael A Borger, Serdar Akansel, Thilo Noack, David Holzhey, Tsuyoshi Kaneko, Isaac George, Gorav Ailawadi, Robert L Smith, Arnar Geirrson, Ahmed El-Eshmawi, Dimosthenis Pandis, Suzanne De Waha, Nikolaos Bonaros, Fabien Praz, Maurizio Taramasso, Michele De Bonis, Lenard Conradi, Christian Hagl, Nicolas Doll, Mahmoud Wehbe, Alexey Dashkevich, Manuela De La Cuesta, Jagdip Kang, Zara Dietze, Philipp Kiefer, Gilbert H L Tang

Faculty, Staff and Students Publications

Objectives: This review article aims to examine the surgical approach to patients with failed mitral transcatheter edge-to-edge repair (M-TEER), focusing on operative challenges, decision-making and contemporary outcome data. Technical considerations, including device removal and the management of complex mitral valve (MV) anatomy, are discussed.

Methods: We performed a comprehensive literature review and gathered the experience from high-volume centres in the surgical management of failed M-TEER.

Results: MV surgery after failed M-TEER is a complex but increasingly necessary procedure as the use of M-TEER grows. It occurs in up to 6% of patients, with a median age of 70-76 years at …


A Meta-Analysis And Systematic Review Of Cardiac Troponin I Vs T In Community Dwelling Adults: Is Specificity At Risk?, Brian Claggett, Saman Asad Siddiqui, Ajari Winifred Ogheneochuko, Christie M Ballantyne, Christopher Defilippi Jun 2025

A Meta-Analysis And Systematic Review Of Cardiac Troponin I Vs T In Community Dwelling Adults: Is Specificity At Risk?, Brian Claggett, Saman Asad Siddiqui, Ajari Winifred Ogheneochuko, Christie M Ballantyne, Christopher Defilippi

Faculty, Staff and Students Publications

Background: Cardiac troponin I and T measured by high-sensitivity assays (hs-cTn) are detectable in most ambulatory adults. Hs-cTnI and T may perform differently for prediction of cardiovascular (CV) events. In adults with myopathies and advanced age, hs-cTnT can lose CV specificity. We undertook a meta-analysis of ambulatory studies measuring hs-cTn to determine whether hs-cTnI is a superior predictor of CV outcomes.

Methods: Articles evaluating hs-cTnI or T for incident heart failure (HF), myocardial infarction (MI), CV, and all-cause death in ambulatory adults were screened. Adjusted HRs were extracted standardized as hs-cTn tertile 3 vs 1. Pooled effects were calculated, and …


Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu Jun 2025

Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Center for Medical Ethics and Health Policy Staff Publications

Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.

Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …


Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone Jun 2025

Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone

Faculty, Staff and Students Publications

Background: Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods: We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …


Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh Jun 2025

Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh

Faculty, Staff and Students Publications

Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.

Methods: Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins.

Results: SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of …


Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management? Jun 2025

Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?

Faculty, Staff and Students Publications

No abstract provided.


In Situ Structure And Assembly Of The Abc-Type Tripartite Pump Macab-Tolc, Wei Zheng, Yaoming Wu, Qiuyu Ren, Zekai Wan, Junli Cao, Zhao Wang, Xiaodong Shi Jun 2025

In Situ Structure And Assembly Of The Abc-Type Tripartite Pump Macab-Tolc, Wei Zheng, Yaoming Wu, Qiuyu Ren, Zekai Wan, Junli Cao, Zhao Wang, Xiaodong Shi

Faculty, Staff and Students Publications

The MacAB-TolC tripartite efflux pump is widely distributed in Gram-negative bacteria, extruding antibiotics and virulence factors that lead to multidrug resistance and pathogenicity. However, the in situ structure and assembly mechanism of MacAB-TolC remain unclear. Here, we resolve the in situ structures of the MacAB-TolC efflux pump in Escherichia coli by electron cryo-tomography and subtomogram averaging. In the cells without antibiotic treatment, we observe a fully assembled MacAB-TolC pump. When Escherichia coli cells are treated with erythromycin, in addition to the tripartite pumps, we also discover the emergence of MacA-TolC subcomplexes without MacB, indicating flexible binding of MacB in the …


Beyond The Surface: Mapping Dde's Metabolic Footprint On Adolescent Obesity, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S Mcconnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi Jun 2025

Beyond The Surface: Mapping Dde's Metabolic Footprint On Adolescent Obesity, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S Mcconnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Background: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored.

Objectives: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.

Methods: We conducted a longitudinal study involving 60 adolescents with severe obesity …


Education In Advance Care Planning: A Novel Equity-Based, Interprofessional Service-Learning Approach, Dorothy Yam, Sriya Kudaravalli, Elizabeth A. Mulvaney, Leslie Scheunemann, Grace W. Orsatti Jun 2025

Education In Advance Care Planning: A Novel Equity-Based, Interprofessional Service-Learning Approach, Dorothy Yam, Sriya Kudaravalli, Elizabeth A. Mulvaney, Leslie Scheunemann, Grace W. Orsatti

Journal of Innovation in Health Sciences Education

Introduction: Despite health sciences graduate schools emphasizing service-learning and interprofessionalism, they often struggle to integrate these values into the curricula effectively. Advance care planning is inherently interdisciplinary and presents an opportunity to address equity gaps through service-learning. This report describes a novel interdisciplinary service-learning initiative for graduate student trainees, focused on advance care planning in underserved communities.

Methods: After targeted training, teams of medical, law, and social work students, and professionals from their respective fields, took part in two Life Planning Fairs in historically underserved neighborhoods in Pittsburgh, Pennsylvania. Using a form developed by the Allegheny County Bar Association …


Early Versus Late Vasopressor Initiation In Septic Shock – Elviss Study, Nathan Crawford, Brittanii Prahl, Jordan Amaro, Barbara Branneman, Jack Huber Jun 2025

Early Versus Late Vasopressor Initiation In Septic Shock – Elviss Study, Nathan Crawford, Brittanii Prahl, Jordan Amaro, Barbara Branneman, Jack Huber

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.


Once-Daily Versus Twice-Daily Oral Vancomycin For Secondary Prevention Of Clostridioides Difficile Infection In Patients Treated With Systemic Antibiotics, Catherine Palmer Jun 2025

Once-Daily Versus Twice-Daily Oral Vancomycin For Secondary Prevention Of Clostridioides Difficile Infection In Patients Treated With Systemic Antibiotics, Catherine Palmer

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.


Impact Of A Multidisciplinary Pulmonary Embolism Response Team (Pert) At A Quaternary Referral Center, Sabrina Mangal, Kristina Pratt, Jennifer Nagel, Juan N Pulido, Jun Vic L. Obaob, Tabitha Weinbrenner, George P Pappas, Paul P Huang, Eric J Lehr Jun 2025

Impact Of A Multidisciplinary Pulmonary Embolism Response Team (Pert) At A Quaternary Referral Center, Sabrina Mangal, Kristina Pratt, Jennifer Nagel, Juan N Pulido, Jun Vic L. Obaob, Tabitha Weinbrenner, George P Pappas, Paul P Huang, Eric J Lehr

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.


Cefdinir Use For Adults With Urinary Tract Infections In The Emergency Department, Emily Vo, Brittanii Prahl, William Barany, Barbara Branneman, Jack Huber Jun 2025

Cefdinir Use For Adults With Urinary Tract Infections In The Emergency Department, Emily Vo, Brittanii Prahl, William Barany, Barbara Branneman, Jack Huber

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.


Impact Of Gum Chewing On Postoperative Ileus Following Open Heart Surgery, Jacinta Smith, Mary Jo Kelly Jun 2025

Impact Of Gum Chewing On Postoperative Ileus Following Open Heart Surgery, Jacinta Smith, Mary Jo Kelly

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.


Modifying Electronic Medical Record Workflows To Improve Protein Provision To Enterally Fed Icu Patients, Catherine Karlak Jun 2025

Modifying Electronic Medical Record Workflows To Improve Protein Provision To Enterally Fed Icu Patients, Catherine Karlak

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.


Whole-Genome Bisulfite Sequencing Of Cell-Free Dnas Identified Molecular Contributors To Racial Survival Difference In Advanced-Stage Triple-Negative Breast Cancer Patients, Chun Wang, Steven Manobianco, Maria Hafez, Mouadh Barbirou, Grace Qiu, Ashley Wetzel, David Baek, Hushan Yang, Maysa Abu-Khalaf Jun 2025

Whole-Genome Bisulfite Sequencing Of Cell-Free Dnas Identified Molecular Contributors To Racial Survival Difference In Advanced-Stage Triple-Negative Breast Cancer Patients, Chun Wang, Steven Manobianco, Maria Hafez, Mouadh Barbirou, Grace Qiu, Ashley Wetzel, David Baek, Hushan Yang, Maysa Abu-Khalaf

Department of Medical Oncology Posters

Background

  • Black women are twice as likely to be diagnosed with triple-negative breast cancer (TNBC) as compared to White women.
  • The impact of genomic and molecular factors on the racial disparity in TNBC survival remains understudied.
  • Liquid biopsy has yet to be explored in the context of racial survival disparities in TNBC.


Antibiotic Lock Therapy Fpr Dialysis Catheters: Implementation At An Urban Hospital, Erik Enquist, Hilary Klastae, Mary Jo Kelly Jun 2025

Antibiotic Lock Therapy Fpr Dialysis Catheters: Implementation At An Urban Hospital, Erik Enquist, Hilary Klastae, Mary Jo Kelly

2025 Swedish FISH (Fostering Interdisciplinary Solutions in Healthcare) Conference

No abstract provided.