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Glucagon-Like Peptide-1 Receptor Agonists And Risk Of Substance Use Disorders Among Us Veterans With Type 2 Diabetes: Cohort Study, Miao Cai, Taeyoung Choi, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVES: To investigate whether initiation of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with both reduced risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders (SUDs) in people with no history of SUDs (protocol 1) and with reduced risk of SUD related adverse clinical outcomes among people with a pre-existing SUD (protocol 2).

DESIGN: Emulation of eight parallel, new user, active comparator target trials using electronic health records: seven trials for each incident SUD outcome (protocol 1) and one trial for adverse outcomes in people with pre-existing SUD (protocol 2).

SETTING: US Department of Veterans Affairs. …

Association Between Functional Status And Cardiac Function In Chronic Heart Failure: Insights From The C-Mic Ii Trial., Marat Fudim, Tamara Kovacevic-Preradovic, Marija Zdravkovic, Sasko Jovev, Nermir Granov, Tanja Popov, Igor Rudez, Petar Vukovic, Velibor Ristic, Annette Holtdirk, Muhammad Shahzeb Khan, Faouzi Kallel, Miodrag Peric, Javed Butler, Stefan D. Anker, Dragana Kosevic, J. Eduardo Rame

Department of Medicine Faculty Papers

INTRODUCTION: Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response.

METHODS: This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischaemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25-35%. Correlations between changes in Kansas …

Clinical Validation Of Perfusion Imaging With Pulmonary Function Test Data Using Voronoi-Based Discretization, Jorge Cisneros, Caleb J. Herrera, Yi-Kuan Liu, Lisa V. Du, Yevgeniy Vinogradskiy, Richard Castillo, Girish Nair, Edward Castillo

Department of Medicine Faculty Papers

Objective.Accurate lung function assessment is essential for diagnosing and managing diseases like chronic obstructive pulmonary disorder, pulmonary emboli, and lung cancer. Single-photon emission computed tomography (SPECT) provides valuable 3D functional imaging of ventilation and perfusion, but is limited by low spatial resolution, availability, additional radiation, and cost. Alternative methods, including CT-based perfusion (CT-P) and deep learning models, require large datasets to validate results that are often scarce. Pulmonary function tests (PFTs) offer rapid and noninvasive global lung function measures and are clinically widely used. While ventilation correlates well with PFTs, perfusion imaging presents challenges due to complex blood flow and …

Post-Traumatic Stress Disorder And Risk Of All-Cause And Cause-Specific Mortality: A Nationwide Population And Sibling-Controlled Cohort Study In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aims: Post-traumatic stress disorder (PTSD) may shorten life expectancy, but evidence for Asian populations and cause-specific mortality remains limited. The aim of this study is to investigate the association between PTSD and mortality risk in an Asian population.

Methods: We used Taiwan's National Health Insurance Research Database (2000-2022) to assemble a cohort of 28,777 individuals with incident PTSD and 115,108 age- and sex-matched unexposed individuals, plus a sibling cohort of 13,305 affected patients and 22,030 unaffected siblings. Cox models estimated adjusted hazard ratios (AHRs) for all-cause, unnatural-cause (suicide and accidents) and natural-cause mortality, with progressive adjustment for sociodemographic factors, comorbidity …

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

Ten Years Real-World Experience With Sacubitril/Valsartan In Patients With Heart Failure With Reduced Ejection Fraction, Gianluigi Savarese, Christian Basile, Alexandre Mebazaa, Antoni Bayes-Genis, Seok Min Kang, Byung-Su Yoo, Carlos Eid, Biykem Bozkurt, Javed Butler

Faculty, Staff and Students Publications

Introduction: Sacubitril/valsartan (Sac/Val) represents a cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. This systematic review provides a comprehensive overview of real-world evidence (RWE) regarding the implementation, clinical effectiveness, and safety of Sac/Val in patients with HFrEF.

Methods: A systematic literature search of PubMed was conducted through March 2024 following PRISMA guidelines.

Results: The review included 45 manuscripts from 30 different studies, primarily from Europe (44%) and the US (30%). RWE confirmed that Sac/Val was associated with a lower risk of cardiovascular mortality (10%-16%), HF hospitalization (10%-38%), and all-cause mortality (10%-25%). Sac/Val was significantly associated with cardiac …

Pregnancy, Cancer, And Radiation-A Modern Refresher, Kelly Kisling, Sandra M Meyers, Rebecca Milman, Susan Richardson, Christina Chapman, Justine Dupere, Grace Eliason, Suzanne Evans, Titania Juang, Young Lee, Jeffrey Masten, Julia Maues, Rachel Newman, Mike Silosky, Catherine Song, Catheryn Yashar, Sara Thrower

Faculty, Staff and Student Publications

Cancer occurs in ∼1 per 1000 pregnancies; thousands of patients may require radiation procedures for diagnosis and treatment each year in the United States alone. This rare but high-risk scenario, coupled with fear of radiation, has created ambiguity in the ideal management of pregnant patients. Without a comprehensive guide for the use of radiation in imaging and treatment for pregnant cancer patients, it is difficult for providers to offer optimal patient-centered care without introducing disparities. The goal of this paper is to provide guidance on the use of radiation for screening, diagnosis, staging, and treatment of cancer, while highlighting gaps …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

Sex-Related Differences In Clinical Profile, Management, And Outcomes Of Patients With Type A And B Acute Aortic Dissection: Observations From Irad, Elizabeth Jackson, Andreina Carbone, Sherene Shalhub, Chih-Wen Pai, Marek Ehrlich, Toru Suzuki, G Chad Hughes, Anil Bhan, Rumi Faizer, Antonio Cittadini, Alan Braverman, Eric Isselbacher, Kim Eagle, Christoph Nienaber, Eduardo Bossone

2020-Current year OA Pubs

BACKGROUND: Available data about sex differences in patients with acute aortic dissection (AAD) are scant and conflicting. The aim of this study is to assess sex-related differences in clinical characteristics, presentation, diagnostic findings, management, and outcomes among patients with type A (TA-AAD) and type B AAD (TB-AAD).

METHODS: Data about 11 586 patients enrolled in the IRAD (International Registry of Acute Aortic Dissection) from 1996 to 2022, were analyzed; 7819 (67.5%) experienced TA-AAD and 3867 (33.0%) TB-AAD. Men and women were compared with regard to diagnosis, treatment, and in-hospital and long-term survival.

RESULTS: One third of patients were women (TA-AAD, …

The Development Of Ace-Iii Performance Validity Tests For Dementia Screening, Donnchadh Murphy, Rupert Noad

Peninsula Medical School

Objective: Performance validity tests (PVTs) are an essential component of a neuropsychological evaluation. There is a lack of brief validated PVTs for use alongside cognitive screening assessments for dementia. The current study sought to develop and evaluate a series of brief PVTs, which could be embedded into the Addenbrooke’s Cognitive Examination (ACE-III) and used in a dementia clinic. Method: This study used a diagnostic accuracy design to compare the performance of 31 individuals with Alzheimer’s disease dementia and 26 healthy older adults who simulated having Alzheimer’s disease. Participants were asked to complete ACE-III, the Test of Memory Malingering (TOMM), and …

Ifn Signaling Is Associated With Radiotherapy Response In Malignant Peripheral Nerve Sheath Tumors., Iowis Zhu, Julian Chien, Gabriel E Rech, Kanish Mirchia, Sixuan Pan, Kaeli Miller, Joanna Pak, Rosanna Wustrack, Varun Monga, Steve E Braunstein, Mark D Adams, Line Jacques, Melike Pekmezci, S John Liu, Harish N Vasudevan

Faculty Research 2026

Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of …

Ifn Signaling Is Associated With Radiotherapy Response In Malignant Peripheral Nerve Sheath Tumors., Iowis Zhu, Julian Chien, Gabriel E Rech, Kanish Mirchia, Sixuan Pan, Kaeli Miller, Joanna Pak, Rosanna Wustrack, Varun Monga, Steve E Braunstein, Mark D Adams, Line Jacques, Melike Pekmezci, S John Liu, Harish N Vasudevan

Faculty Research 2026

Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani

Department of Medical Oncology Faculty Papers

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life …

Population Analysis And Immunologic Landscape Of Melanoma In People Living With Hiv, Lindsay Barger, Derek Wang, Ashley Saravia, Valeria Mezzano, Gyles Ward, Cynthia Loomis, Carly Feldman, Madalina Tuluc, Rino Seedor, Peter Gaskill, Anna Coghill, Gita Suneja, Iman Dehzangi, Jennifer Hope, George Jour, Gabriele Romano

Department of Medical Oncology Faculty Papers

PURPOSE: To dissect the clinical and immunologic features of people living with human immunodeficiency virus (HIV; PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer.

EXPERIMENTAL DESIGN: We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n = 11), with downstream validation using multiplex immunofluorescence (mIF; n = 15 PLWH, n = 14 PLw/oH).

RESULTS: PLWH were diagnosed at a younger age, had a greater representation of Hispanic and …

Shifts In Antipsychotic Prescribing By Clinician Type For Medicare Part D Beneficiaries, 2013-2023, Youngran Kim, Xuan Zhou, Shilei Du, Trudy M Krause, Rafael Samper-Ternent, Antonio L Teixeira

Faculty, Staff and Student Publications

Importance: Despite safety warnings, antipsychotics remain commonly prescribed to older adults, particularly those with dementia, and for off-label indications. However, little is known about how prescribing patterns vary by clinician type over time.

Objective: To examine trends in antipsychotic prescribing by clinician type among Medicare beneficiaries from 2013 to 2023.

Design, setting, and participants: This repeated cross-sectional study used the Medicare Part D Prescribers by Provider and Drug dataset from 2013 to 2023. Participants included Medicare beneficiaries enrolled in Medicare Part D. Analyses were performed between November 2024 and June 2025.

Exposure: Prescribing clinician type, categorized as psychiatrist, primary care …

Surface Morphometrics Reveals Local Membrane Thickness Variation In Organellar Subcompartments, Michaela Medina, Ya-Ting Chang, Hamidreza Rahmani, Mark Frank, Zidan Khan, Daniel Fuentes, Frederick A Heberle, M Neal Waxham, Benjamin A Barad, Danielle A Grotjahn

Faculty, Staff and Student Publications

Lipid bilayers form the basis of organellar architecture, structure, and compartmentalization in the cell. Decades of biophysical, biochemical, and imaging studies on purified or in vitro-reconstituted liposomes have shown that variations in lipid composition influence the physical properties of membranes, such as thickness and curvature. However, similar studies characterizing these membrane properties within the native cellular context have remained technically challenging. Recent advancements in cellular cryo-electron tomography (cryo-ET) imaging enable high-resolution, three-dimensional views of native organellar membrane architecture preserved in near-native conditions. We previously developed a "Surface Morphometrics" pipeline that generates surface mesh reconstructions to model and quantify cellular membrane …

Continuous Vs Intermittent Postoperative Vital Sign Monitoring: A Cluster Randomized Crossover Trial, Ashish K Khanna, Nathaniel Sean O'Connell, Amit K Saha, Megan Henley Hicks, Robert S Weller, Lynnette Harris, Bruce D Cusson, Ann Faris, Carolyn S Huffman, Scott Segal, Brian J Wells, Eric S Kirkendall, Daniel I Sessler

Faculty, Staff and Student Publications

Importance: Continuous postoperative monitoring on general nursing units detects vital sign abnormalities that are missed with conventional intermittent monitoring. Early recognition may prompt interventions to limit potentially harmful blood pressure, heart rate, and oxygen saturation perturbations.

Objective: To test the hypothesis that continuous unblinded monitoring of vital signs would decrease blood pressure, heart rate, and oxygen saturation abnormalities compared with intermittent monitoring in patients recovering from noncardiac surgery.

Design, setting, and participants: This multiple crossover randomized cluster trial in 2 postoperative hospital wards included patients recovering from noncardiac surgery and was conducted from October 7, 2020, to October 7, 2021. …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

The Relationship Between Apparent Potentiation And The Magnitude Of The Control Response, Joe Henry Steinbach, Gustav Akk

2020-Current year OA Pubs

The effect of a potentiating drug on ion channel function is typically evaluated by comparing current responses to the control agonist in the presence and absence of the potentiator. Differences in ratios of responses are then taken as proof of distinct potentiation properties when comparing modulation by different compounds. In these experiments, the concentration of the agonist is typically kept low to generate a small fractional control response. The precise relative magnitude of the control response is, however, not standardized among labs and can range from a concentration producing a response equal to just 2% of maximal (EC2) to over …

Shiga Toxin-Producing Escherichia Coli Outbreak In Canadian Daycare Centers, Mohamed Eltorki, Oluwatimilehin O Ajayi, Jina Seok, Jianling Xie, Francesco A Rizzuti, Byron M Berenger, Phillip I Tarr, Andrew T Pavia, Kate Snedeker, Silviu Grisaru, Otto G Vanderkooi, Linda Chui, Gillian A M Tarr, Gemma Vomiero, Stephen B Freedman

2020-Current year OA Pubs

IMPORTANCE: Shiga toxin-producing Escherichia coli (STEC) infections have significant morbidity, with 15% to 20% of children developing hemolytic uremic syndrome (HUS), more than half of whom require kidney replacement therapy (KRT).

OBJECTIVE: To describe health care resource utilization, clinical outcomes, and outcomes associated with daily laboratory monitoring for thrombotic microangiopathy (TMA) in a large point-source STEC outbreak.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted among a population-based cohort of individuals exposed to a contaminated food item served in 11 childcare centers in Calgary, Alberta, Canada, on August 29, 2023. Children and adults with confirmed STEC infection linked …

Trends In Mammography Use Among Women Aged 40 To 74 Years In The Us, 2002-2022, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Understanding how prior policies, systemic factors, and public health events have shaped mammography use among US women is essential for interpreting the 2024 US Preventive Services Task Force (USPSTF) recommendation update and identifying gaps to inform equitable public health strategies.

OBJECTIVE: To analyze mammography use trends in US women aged 40 to 49 and 50 to 74 years from 2002 to 2022 and assess variation by sociodemographic, health care access, behavioral, and geographic factors, including associations with the 2009 USPSTF recommendation and the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Behavioral Risk Factor …

Pharmacokinetic Profiles Of Sertraline In Pregnancy As A Predictor Of Postpartum Depressive Symptoms, Sílvia M. Illamola, Zachary N. Stowe, Marc L. Kalin, Michael D. Evans, Catherine M.T. Sherwin, Maged M. Costantine, D. Jeffrey Newport, James C. Ritchie, Angela K. Birnbaum

Pediatrics Faculty Publications

Aim: To characterize pharmacokinetic changes of sertraline and its metabolite during pregnancy and postpartum, and their relationship to maternal postpartum depressive symptoms. Methods: This was a prospective observational, longitudinal study of pregnant women with a major depressive disorder treated with sertraline (N = 185 women, 205 pregnancies). Women were enrolled at <16 weeks' gestation and followed at 4-8 week intervals throughout pregnancy and the first postpartum year. Baseline measures included structured clinical interviews and demographic information. Drug and metabolite concentrations and psychometric measures (study outcomes) (ie, Hamilton Rating Scale for depression - 17 item, Beck Depression Inventory, Edinburgh Postnatal Depression Scale [EPDS], Clinical Global Impression [CGI]) were measured at follow-up visits. Serum sertraline and N-desmethylsertraline exposure were reported asstandardized 24-h concentration-to-dose (C/D) and parent to metabolite (P/M) ratios. Linear mixed-effects and latent trajectory models were used to characterize longitudinal patterns in concentration measures across pregnancy and postpartum, and their association with study outcomes. Results: Mean 24-h C/D ratios showed high variability throughout pregnancy and postpartuM.T.hat were characterized by three trajectories for sertraline and five for N-desmethylsertraline and P/M ratio corresponding to different sertraline pharmacokinetic profiles. At postpartum, sertraline drug exposure was inversely associated with higher EPDS score (P < .05), while N-desmethylsertraline exposure was associated with higher scores for all measured depression scales (P < .001). Higher P/M ratios had higher CGI scores (P < .05) postpartum. Conclusion: Sertraline pharmacokinetic profiles varied across pregnant women and were associated with postpartum depressive symptoms. The use of therapeutic monitoring may provide clinical insight that can be useful for identifying patients with a potential toward depressive symptoms.

Single-Nucleus Transcriptomics, Pharmacokinetics, And Pharmacodynamics Of Cdk4/6 And Mtor Inhibition In A Phase 0/1 Trial Of Recurrent High-Grade Glioma., Kevin C Johnson, An-Chi Tien, Jun Jiang, James Mcnamara, Yu-Wei Chang, Chelsea Montgomery, Anita Desantis, Leonel Elena-Sanchez, Yoko Fujita, Seongho Kim, Avishay Spitzer, Paul Gabriel, William F Flynn, Elise T Courtois, Amy Hong, Jocelyn Harmon, Yoshie Umemura, Artak Tovmasyan, Jing Li, Shwetal Mehta, Roel G W Verhaak, Nader Sanai

Faculty Research 2026

BACKGROUND: Outcomes for adult patients with high-grade glioma (HGG) remain poor, necessitating new treatment strategies. Key challenges include poor drug penetration in the brain and malignant cell state plasticity. Phase 0 studies identify agents that achieve target modulation through pharmacologically relevant brain concentrations.

METHODS: A Phase 0/1 clinical trial combined the 2 targeted inhibitors ribociclib (CDK4/6 inhibitor) and everolimus (mTOR inhibitor) in recurrent HGG patients, aiming to identify brain-penetrant combinations and assess their impact on malignant cell states. We enrolled 24 patients with recurrent HGG, characterized by CDKN2A/B deletion or CDK4/6 amplification, PTEN loss or PIK3CA mutations, and wildtype retinoblastoma …

Prevalence Of, Edison Liu, Margaret Antonio, Tracy Nance, Francesca Menghi

Faculty Research 2026

Purpose

Methods

Improving Gene Isoform Quantification With Miniquant., Haoran Li, Dingjie Wang, Qi Gao, Puwen Tan, Yunhao Wang, Xiaoyu Cai, Aifu Li, Yue Zhao, Andrew L Thurman, Seyed Amir Malekpour, Ying Zhang, Roberta Sala, Andrea Cipriano, Chia-Lin Wei, Vittorio Sebastiano, Chi Song, Nancy R Zhang, Kin Fai Au

Faculty Research 2026

RNA sequencing has been widely applied for gene isoform quantification, but limitations exist in quantifying isoforms of complex genes accurately, especially for short reads. Here we identify genes that are difficult to quantify accurately with short reads and illustrate the information benefit of using long reads to quantify these regions. We present miniQuant, which ranks genes with quantification errors caused by the ambiguity of read alignments and integrates the complementary strengths of long reads and short reads with optimal combination in a gene- and data-specific manner to achieve more accurate quantification. These results are supported by rigorous mathematical proofs, validated …

Meta-Analysis Of Genetic Mapping Studies In Mice Reveals Candidate Epilepsy Modifier Genes That Are Outside The Current Drug Development Landscape., Giovanna L Durante, Anna L. Tyler, Rod C Scott, Amanda E Hernan, J Matthew Mahoney

Faculty Research 2026

OBJECTIVE: Despite decades of development in anti-seizure medications, ~30% of individuals remain refractory to all treatments, and none of the existing therapies are disease modifying. Identifying targets outside the current preclinical paradigm is critically important. This study aimed to characterize the landscape of current epilepsy treatments at the level of gene interaction networks and identify novel genetic modifiers of epilepsy as potential novel therapeutic targets.

METHODS: We performed a functional network analysis to score genes based on their interactions with known epilepsy genes, and we integrated these functional scores with population genetics data and drug tractability information. In parallel, we …