Digital Commons Network^™

An Observational Study Of The Effect Of Concomitant Levetiracetam On Apixaban Concentrations In A Hospital Cohort, Chazmyn Riley, Kevin Lam, Cristina Micale, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the lack of evidence of a mechanism-based drug interaction, some professional organizations have advised caution coadministering apixaban and levetiracetam. Eligible patients taking apixaban with or without levetiracetam for any indication for at least 72 h were screened from the electronic medical records. Plasma samples from 77 patients were retrieved from salvaged clinical blood collections. Apixaban minimum and maximum concentrations (Cmin and Cmax) were compared using descriptive statistics in R. While the median Cmin and Cmax appear to be marginally elevated, there were no apparent differences relative to apixaban alone. These findings suggest no apparent interaction of levetiracetam and support …

Postoperative Complications In Patients With Sickle Cell Disease After Total Shoulder Arthroplasty, Katie Zehner, Gwyneth C. Maloy, John Slevin, Wesley Day, Mitchell K. Ng, Xuan Luo, Jonathan N. Grauer, Arya G. Varthi

Rothman Institute Papers

BACKGROUND: Sickle cell disease (SCD) encompasses a spectrum of genetic hematologic disorders characterized by erythrocyte sickling. Patients may experience musculoskeletal manifestations, such as osteonecrosis, which may warrant consideration for total shoulder arthroplasty (TSA). While prior literature suggests patients with SCD more frequently suffer complications after orthopaedic procedures, this is not well characterized for TSA.

METHODS: Adult TSA patients (older than 18 years) were identified in the 2010 to 2023 PearlDiver M170 database. Patients with SCD were matched 1:4 to patients without SCD based on age, sex, and Elixhauser Comorbidity Index (ECI). Ninety-day postoperative complications, emergency department (ED) visits, and readmissions …

Timing Of Isotretinoin Exposure And Early Postoperative Complications After Anterior Cruciate Ligament Reconstruction, Areeb Ahmad, Ronald J. Shamus, Kassem Ghayyad, Daryl C. Osbahr, Adam J. Money, Michael G. Ciccotti, George J. Richard

Rothman Institute Papers

INTRODUCTION: Isotretinoin (ITN) is widely prescribed for severe acne in adolescents and young adults, a population where anterior cruciate ligament reconstruction (ACLR) is commonly performed. Long-standing concerns about impaired wound healing have prompted many surgeons to delay procedures, despite limited orthopaedic-specific evidence. This retrospective case series evaluates early postoperative clinical complications in patients with documented ITN exposure undergoing ACLR.

METHODS: We retrospectively reviewed primary ACLR cases from 2015 to 2025 at a multisite orthopaedic practice with documented ITN exposure within 12 months of surgery and at least 3 months of follow-up. ITN exposure was categorized as perioperative (≤10 days), recent …

The Who Classification Of Genetic Tumour Syndromes: Considerations For Genetics, Ian A Cree, Mark J Arends, Joseph D Khoury, Erika R E Denton, Anthony J Gill, Alexander J Lazar, Ian M Frayling, Stefan M Pfister, Mark A Rubin, Katia R M Leite, Raymond Dalgleish, Elspeth A Bruford, Sharon E Plon, Ada Hamosh, Michael Francis Walsh, Gabrielle Goldman-Lévy, Harshima Wijesinghe, William D Foulkes, Dilani Lokuhetty

Faculty, Staff and Students Publications

The WHO Classification of Tumours is used widely by histopathologists and other disciplines as it provides an internationally agreed taxonomy of neoplastic disorders. Now published online and in print, it has often included genetic tumour syndromes (GTS) relevant to particular organs, as suggested by the editorial board. This highlighted the lack of a systematic classification of GTS, providing international standards for their diagnosis and a basis for research. The need for this was established by a series of meetings, leading to the adoption of a hierarchical classification of GTS based on the cellular mechanism affected, the molecular pathway involved, the …

Bivip: A Competitive Neural Network For Bilateral Visuo-Haptic Processing, Eleonore Federica Di Rosa, Aaisha Sheth, Jeffrey Min-In Yau, Laura Astolfi, Cristiano Cuppini

Faculty, Staff and Students Publications

Visuo-haptic interactions are gaining interest in perception research because of their relevance to robotics and rehabilitation. While the benefits of integrating concurrent visuo-tactile cues are well-documented, the temporal dynamics of competitive interactions between vision and touch remain less understood. Building on extant empirical evidence of unilateral intersensory switching, we ask whether bilateral detection of visual and tactile stimuli can be explained by cross-sensory competition and explore the underlying sensorineural dynamics via a multi-level neural network model. Tested against results from a speeded reaction time task to unilateral and bilateral visual, tactile, and visuo-tactile targets, the network successfully predicts higher switch …

Lidocaine Combined With Low-Dose Esketamine For Movement-Evoked Pain After Hepatectomy: A Double-Blind Randomised Controlled Trial, Yan Xu, Li Zhou, Qianqian Tang, Feng Yu, Jingwen Wu, Siyu Yan, Min Cai, Jialu Wan, Yi Kang, Lajing Luowu, Mengmeng Zhou, Lulong Bo, Daniel I Sessler, Chunling Jiang

Faculty, Staff and Student Publications

Introduction: Pain following hepatectomy may delay recovery and increase opioid use. We tested the primary hypothesis that combining lidocaine and low-dose esketamine would reduce movement-evoked pain 24 h after hepatic resection. We also evaluated whether this approach reduced opioid consumption and improved quality of recovery.

Methods: Patients having elective hepatic resections were allocated randomly to receive lidocaine-esketamine or placebo from induction of anaesthesia until the end of surgery. After surgery, patients allocated to lidocaine-esketamine were given a continuous infusion of lidocaine with esketamine for 72 h. All patients received transversus abdominis plane blocks with ropivacaine 2 mg.kg-1 after induction of …

Hydroxyethyl Starch And Perioperative Complications: A Systematic Review And Meta-Analysis, Daniel I Sessler, Lorenzo Pradelli, Massimiliano Povero, Daniel Chappell, E Wang

Faculty, Staff and Student Publications

Background: Based on renal injury reported in critically ill and septic patients, the U.S. Food and Drug Administration issued a black box warning regarding hydroxyethyl starch (HES 130/0.4) use in 2013 and expanded the warning to surgical and trauma patients in 2021. Similarly, the European Medicines Agency initiated withdrawal of hydroxyethyl starch in 2022. This study was a new meta-analysis focused on renal injury designed to complement a 2021 meta-analysis of perioperative hydroxyethyl starch use, adding 45 trials and 6,895 patients. The focus was acute kidney injury and preoperative-to-postoperative change in creatinine concentration in surgical patients.

Methods: This study searched …

The American Society Of Extracorporeal Technology Standards And Guidelines For Pediatric And Congenital Perfusion Practice: 2025 Update☆., Molly Elisabeth Oldeen, Carrie Whittaker Striker, Ronald Angona, Dafne Andrea Chianella, Chelsea Capone, Ashley B Walczak, Thomas Klein

Heart and Vascular Articles

Background: In 2019, the American Society of ExtraCorporeal Technology (AmSECT) approved the inaugural Standards and Guidelines for Pediatric and Congenital Perfusion Practice. These standards and guidelines were created with the intent of periodic revision to ensure continued alignment with evolving best practices. In 2023, an AmSECT subcommittee initiated this review in consideration of current literature and contemporary clinical practices.

Methods: The subcommittee, consisting of pediatric and congenital perfusionists, conducted a systematic literature review assessing each standard and guideline to determine if current evidence supports elevation of guidelines to standards, incorporation of new guidelines or standards, or whether existing standards and …

International Migration And Sex Trafficking: A Scoping Review., Higinio Fernández-Sánchez, Mutaz T Abdulrazag Gamra, Luis E Caso Vega, Julio Rodriguez-Araujo, Jennifer Stockton, Tahilin Sanchez Karver, Carlos Rodriguez-Diaz, Diane Santa Maria

Library Staff Publications

Introduction: Sex trafficking is a pervasive threat that disproportionately affects migrant populations. These groups are often targeted due to socioeconomic status, legal insecurity, and limited access to appropriate protections. The intersection between migration status and current structural inequalities further intensifies risks to migrant health and general well-being, making them highly susceptible to coercion and abuse. Despite growing research around these issues, evidence on sex trafficking among migrants remains an area for further exploration.

Objective: To examine the scope, nature, and thematic trends in the literature on international migration and sex trafficking.

Methods: This scoping review was guided by the population-Concept-Context …

Best Practices For Supporting Occupational Therapy Students With Disabilities During Clinical Education: Results From A Three-Round Delphi Study, Courtney Gohean, Katie Mclaughlin, Aster Harrison

Department of Occupational Therapy Faculty Papers

INTRODUCTION: Disabled occupational therapy students face systemic barriers in clinical education. Although legal mandates require reasonable accommodations, implementation is often inconsistent, and few standardized guidelines exist for fieldwork education. This study is aimed at establishing best practices for supporting occupational therapy and occupational therapy assistant students with disabilities during fieldwork.

MATERIALS AND METHODS: A three-round Delphi study was conducted with a panel of 30 experts, including disabled occupational therapy students, disabled occupational therapy practitioners, academic fieldwork coordinators (AFWCs), fieldwork educators (FWEs), disability services staff, and researchers. In Round 1, participants answered open-ended questions about challenges, accommodations, and environmental supports. Responses …

Non-Vigorous Physical Activity Associated With Reduced Hospitalization Risk With Or Without Diabetes Or Peripheral Artery Disease: Study Of Latinos., Sarah K. Alver, Carmen C. Cuthbertson, Kelly R. Evenson, Jennifer A. Schrack, Daniela Sotres-Alvarez, Natasha Z. Anita, Yasmin Mossavar-Rahmani, Linda C. Gallo, Jordan A. Carlson, Matthew Allison, Martha L. Daviglus, Olga Garcia-Bedoya, Christina Cordero, Xiaonan Xue, Jianwen Cai, Kunihiro Matsushita, Robert C. Kaplan

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study assessed whether greater physical activity (PA) and lesser sedentary behavior (SB) reduce hospitalization risk equally among those with and without prediabetes, diabetes, or peripheral artery disease (PAD).

METHODS: We studied PA, SB and hospitalizations in 12,734 adults from the Hispanic Community Health Study/Study of Latinos, who were 52.2% female with mean (standard deviation) age 41.1 (14.9) yr at baseline. Participants reported 10,025 nonpregnancy-related hospitalizations (excluding emergency room only) over 13 yr. We modeled the association between accelerometer-measured activity (SB; light intensity physical activity [LPA]; moderate physical activity [MPA]; vigorous physical activity [VPA]) and hospitalization, using Andersen-Gill proportional …

Ovarian Cancer Tumor Immune Profiles Associated With Intrauterine Device And Oral Contraceptive Use., Jennifer M. Mongiovi, Ana Babic, Naoko Sasamoto, Mary K. Townsend, Allison F. Vitonis, Mollie Barnard, Jonathan Hecht, T Rinda Soong, Jose R. Conejo-Garcia, Lauren C. Peres, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Francesmary Modugno, Brooke L. Fridley, Shelley S. Tworoger, Kathryn L. Terry

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Non-hormonal intrauterine devices (IUDs) create an inflammatory uterine environment while oral contraceptives (OC) suppress ovulation and have different associations with ovarian cancer risk. We have evaluated the associations of these two contraceptive exposures with ovarian tumor immune infiltration.

METHODS: This study assessed associations of IUD and OC use with tumor immune features via multiplex immunofluorescence in 24 ovarian tumor tissue microarrays from four case-control and two cohort studies. Multivariable-adjusted beta-binomial models estimated the odds of tumor T cell positivity by contraceptive history.

RESULTS: High-grade serous tumors had the highest percentage of tumor cells positive for total T cells (CD3+ …

The Rise And Fall Of Lateral Electrical Surface Stimulation (Less) Through The Lens Of Srs Archives., Ali Rezazadeh Shirazi, Jay I. Kumar, Katie Dold, George H. Thompson, Andrew G. King, Richard M. Schwend, John P. Lubicky, Jay Shapiro, Behrooz A. Akbarnia, History Committee Of The Scoliosis Research Society

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Lateral electrical surface stimulation (LESS), commercially known as the ScoliTron™, emerged in the late 1970s as a noninvasive alternative to bracing for adolescent idiopathic scoliosis. Early clinical reports generated considerable enthusiasm and adoption, but the technique was ultimately abandoned. This study examined the rise and fall of LESS through a combined analysis of the Scoliosis Research Society (SRS) archives and published literature, with the goal of understanding factors that influence the adoption, evaluation, and abandonment of innovation in scoliosis care.

METHODS: A structured historical review was conducted using archival materials from the Scoliosis Research Society (SRS), including meeting abstracts, …

Outcomes For Congenitally Corrected Transposition Of Great Arteries Using Various Surgical Techniques: A Systematic Review And Network Meta-Analysis., S U Hasan, Sur Usmani, S H Ahmed, A Pervez, M A Kamalia, A D Shah, Mujeeb Zubair

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disorder. Here, we evaluated the effectiveness of physiological, anatomical and Fontan repair techniques for ccTGA.

METHODS: A systematic database search in PubMed, Embase and Cochrane Central Register of Controlled Trials was conducted from inception to 5 June 2023. Random-effects network meta-analysis was performed, comparing mortality, postoperative arrhythmias, reintervention after definitive surgery and transplant-free survival in patients undergoing physiological, anatomical and Fontan repair.

FINDINGS: A total of 1,209 patients were included from nine studies. Fontan repair was associated with a higher rate of transplant-free survival (absolute risk [AR] 0.999 …

Patient-Specific Computational Fluid Dynamics Modeling Of Airway Collapse In Infants With Robin Sequence., Gautam Jalori, Michael Barbour, Michael Bindschadler, Kelly Evans, John P. Dahl, Alberto Aliseda

Manuscripts, Articles, Book Chapters and Other Papers

Robin Sequence (RS) is a congenital condition in which patients experience dynamic, periodic obstruction or collapse of the upper airway due to an underdeveloped jaw and a posteriorly displaced tongue. Current clinical techniques for evaluating airway obstruction do not provide quantifiable data and fail to account for the dynamic nature of obstruction or collapse. There is no standardized criterion to characterize obstruction or collapse severity. This study presents the first method that extracts airway motion from 4-dimensional computed tomography and performs a patient-specific, moving-mesh computational fluid dynamics (CFD) analysis of RS patients with complete airway collapse or obstruction. To quantify …

Inosine-Triphosphate-Pyrophosphatase Activity As A Potential Predictor Of Methotrexate Remission In Juvenile Idiopathic Arthritis., Sofia Sindici Forgiarini, Marianna Lucafò, Debora Curci, Davide Selvestrel, Valentina Moressa, Sofia Pagarin, Barbara Bellich, Martina Franzin, Alberto Tommasini, Mara L. Becker, Laura Ramsey, Susan D. Thompson, Carl D. Langefeld, Federica Corba, Edoardo Marrani, Gabriele Simonini, Gabriele Stocco, Giuliana Decorti, Andrea Taddio, Serena Pastore

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Methotrexate (MTX) is the first-line therapy for juvenile idiopathic arthritis (JIA), but up to 40% of patients do not respond to it. Low inosine triphosphate pyrophosphatase (ITPA) activity has been associated with reduced clinical remission. We investigated the role and underlying mechanisms of ITPA in vitro.

METHODS: ITPA enzymatic activity was measured by high-performance liquid chromatography with ultraviolet detection in erythrocyte lysates from patients with JIA (enrolled in Trieste, Italy; Florence, Italy; and Kansas City, Missouri) receiving weekly MTX (10-15 mg/m²) for at least 12 months. Remission was evaluated by Wallace et al criteria. ITPA rs1127354, which …

Posaconazole Target Attainment In Critically Ill Children: A 15-Year Single-Center Retrospective Analysis., Kathryn Pavia, Addison M. Pritchett Ms, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Posaconazole is a triazole antifungal agent used for prophylaxis and treatment of invasive fungal diseases. Posaconazole has high inter-individual variability in dose-exposure relationship and benefits from therapeutic drug monitoring (TDM). Adult studies report particularly high rates of subtherapeutic exposure among intensive care unit (ICU) patients related to changes in physiology during critical illness. The rates of subtherapeutic posaconazole exposure among critically ill children in ICU's are unknown. This single-center retrospective analysis at a large freestanding children's hospital used TDM results from 2010 to 2025 obtained while patients were undergoing care in a pediatric ICU. Therapeutic targets were ≥ 1.0 mg/L …

Single Immunoglobulin Interleukin1-Related Receptor-Twist1 Axis Regulates Barrier Function In Neonatal Intestine., Aparna Venkatraman, Wei Yu, Heather Menden, Sherry M. Mabry, Joshua Wheatley, Shahid Umar, Susana Chavez-Bueno, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: The genetic basis of impaired intestinal barrier function in preterm infants is poorly understood. Variants in single immunoglobulin interleukin1-related receptor, a negative regulator of Toll-like receptor signaling, have been identified in preterm infants with necrotizing enterocolitis. We hypothesized that single immunoglobulin interleukin1-related receptor variants associated with necrotizing enterocolitis impair gut barrier function to pathobionts. The aim of this study was to determine how single immunoglobulin interleukin1-related receptor genetic variants disrupt neonatal intestinal barrier integrity and promote susceptibility to Gram-negative bacteria implicated in sepsis and necrotizing enterocolitis pathogenesis.

METHODS: Transgenic mice and preterm infant-derived enteroids expressing SIGIRR variants …

Nf1 Loss In Estrogen Receptor-Positive Breast Cancer Induces Osteoclast Formation And Immunosuppression To Promote Bone Metastasis, Zifan Zhao, Ze-Yi Zheng, Jonathan T Lei, Matthew J Baik, Yi-Hsuan Wu, Lauren K Somes, Andres F Mosquera Paternina, Omar A Harb, Owen A Chang, Fengshuo Liu, Matthew V Holt, Junkai Wang, Igor Bado, Hai Wang, George Miles, Zbigniew Gugala, Meenakshi Anurag, Ahmed Elkhanany, Yi Li, Valentina Hoyos, Xiang H-F Zhang, Eric C Chang

Faculty, Staff and Students Publications

Estrogen receptor-positive (ER+) breast cancer exhibits a marked propensity for skeletal metastasis; however, the molecular drivers of bone colonization remain incompletely defined. We investigated the tumor suppressor neurofibromin (NF1), a dual repressor for RAS and ER signaling, whose inactivation promotes endocrine therapy (ET) resistance and is associated with inferior relapse-free survival. NF1 copy number loss was detected in 62% of ER+ patients who subsequently developed metastases and was associated with an increased likelihood of bone metastases at initial diagnosis. In mouse xenograft models, NF1-depleted ER+ breast cancer cells demonstrated enhanced dissemination to skeletal sites following surgical resection of primary tumors. …

A Small Molecule Inhibits Ebola Virus Entry Through Glycoprotein Stabilization, Fan Bu, Gang Ye, Kiran L Sharma, Bruno La Rosa, Murugesan Palaniappan, Martin M Matzuk, Damian W Young, Hailey Turner-Hubbard, Kimberly Morsheimer, Callum Owen, Katalin Toth, Michael Cameron, Robert Davey, Srinivas Chamakuri, Peter Dosa, Fang Li

Faculty, Staff and Students Publications

Ebola virus (EBOV) causes outbreaks with high fatality rates, yet potent small-molecule inhibitors targeting EBOV glycoprotein (GP) remain limited. Here, using DNA-encoded chemical libraries, we screen 4.73 billion compounds against EBOV GP and, through stereochemical optimization, identify MWAC-3634. This compound binds GP with high affinity (Kd=40.7 nM), potently neutralizes infection (IC₅₀ = 0.65 nM), shows no detectable cytotoxicity, and exhibits favorable pharmacokinetics in mice. This potency substantially exceeds that of known small-molecule inhibitors targeting EBOV GP. Cryo-EM at 2.54 Å resolution reveals that MWAC-3634 occupies a hydrophobic cavity at the GP subunit interface and stabilizes GP, supporting an entry-blocking mechanism …

Population Pharmacokinetics Of Bosutinib In Children With Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia Based On A Phase I Dose-Finding Trial (Itcc-054/Cog Aaml1921) And Pediatric Recommended Phase Ii Dosage Evaluation, Jen-Hao Wu, Francisco Bautista, Erica Brivio, Marieke Willemse, Karey Kowalski, Brian Jermain, May Garrett, Andrew Bukowinski, Carmelo Rizzari, Jessica Pollard, Laura Murillo-Sanjuán, Matthew Kutny, Sara Zarnegar-Lumley, Michele Redell, Stacy Cooper, Yves Bertrand, Arnaud Petit, Julie Krystal, Markus Metzler, Donna Lancaster, Jean-Pierre Bourquin, Jayashree Motwani, Inge M Van Der Sluis, Franco Locatelli, Michael E Roth, Nobuko Hijiya, C Michel Zwaan, Alwin D R Huitema

Faculty, Staff and Students Publications

Background and objectives: Bosutinib, an orally administered dual Src and Bcr-Abl tyrosine kinase inhibitor (TKI), is approved for the treatment of chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia, newly diagnosed or resistant/intolerant to previous treatment of one or more TKIs in adults and children ≥ 1 years (by the US Food and Drug Administration) and ≥ 6 years (by the European Medicines Agency). Owing to the limitations of non-compartmental analysis in pharmacokinetic (PK) characterization, this study applies a prior population PK modeling approach to describe the pediatric PK of bosutinib on the basis of its phase I dose-finding trial and …

Cerebellar Atrophy In Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study, Rebecca Macrae, Kierstin Hederstedt, Christopher Cortina, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman

Faculty, Staff and Students Publications

Background and objectives: Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.

Methods: This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.

Results: Of participants with follow-up imaging, cerebellar atrophy …

Inaccurate Interpretation Of Hypoxia Signatures From Transcriptomic Analyses In Neuro-Oncology, Rebecca K Simmons, Pratima Raut, Subhi Talal Younes, Marco Gallo

Faculty, Staff and Students Publications

We aim to highlight problems with the biological interpretation of computationally-derived hypoxia signatures for neuro-oncology research. By reviewing important experimental work in the field, we discuss common misinterpretations of the concepts of normoxia and hypoxia. In fact, the concentration of oxygen in the adult brain is in the range of 1-7%. Unfortunately, this oxygen concentration range is often mistakenly considered hypoxic in neuro-oncology experiments, although it should be considered physioxic. Further, given the lack of a universal hypoxic signature, we stress the importance of deriving cell type-specific hypoxic signatures using carefully-executed experiments.

Loss Of Function Dnmt3a Mutation Leads To Aberrant Neutrophil Migration, Frieda Zimmer, Daniel E Kennedy, Spencer L Redding, Ruoqiong Cao, Sarah M Waldvogel, Apoorva Thatavarty, Bryan Bahoua, Brandon T Tran, Arushana A Maknojia, Margaret A Goodell, Antony Rodriguez, Katie A Matatall, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis (CH), an age-related expansion of somatically mutated hematopoietic clones, is associated with increased risk of severe infections including coronavirus disease (COVID)-19, yet the underlying mechanisms remain unclear. Here, we investigated the impact of Dnmt3a deficiency in a murine model of influenza A virus (IAV) pneumonia. Dnmt3a-deficient mice exhibited increased pulmonary viral burden and reduced neutrophil accumulation in IAV-infected lungs despite comparable circulating neutrophil numbers. Functional analyses of neutrophils showed impaired chemotactic migration in vitro, whereas maturation, antimicrobial enzyme content, and metabolic capacity were unchanged. Transcriptomic profiling revealed downregulation of pathways involved in chemotaxis, cytokine signaling, and cellular activation, …

Rhino: An Integrative Multi-Omics Framework Linking Circadian Physiology To Precision Medicine, Ying Chen, Chengxuan Chen, Dishu Zhou, Panpan Liu, Roberto E López-Valiente, Yuan Liu, Cam Mong La, Isabella Beraldo Xavier, Sean M Hartig, Pradip Saha, Zheng Sun, Leng Han, Dongyin Guan

Faculty, Staff and Students Publications

Circadian rhythms are involved in nearly all physiological processes, and their disruption increases disease risk. Aligning drug administration timing with the body's internal clock, known as circadian medicine, holds promise for improving treatment efficacy and safety. However, systematic strategies to identify circadian‐regulated therapeutic targets remain limited. Here, we develop RHINO (RHythmic Interacting Network for multi‐Omics), an integrative multi‐omics framework for exploring circadian regulation across diverse genetic and disease contexts, and prioritizing druggable circadian targets. Applying RHINO reveals that human genetic variation broadly shapes rhythmic gene expression, with approximately 80% of FDA‐approved drug targets exhibiting genotype‐dependent rhythmicity, thereby substantially expanding the …

Language-Serving Hospitals And Seven-Day Readmission Among Patients With A Non-English Primary Language, Alyssa N Jones, Brittany M Dacier, Jesus Mejia, Benjamin G Allar, Rachel E Murphy, Regan W Bergmark, Esteban F Gershanik, Alicia Fernandez, Andrea L Pusic, Gregory L Peck, David W Bates, Gezzer Ortega

Faculty, Staff and Students Publications

Objectives. To compare 7-day readmission among patients with a non-English primary language in language-serving versus non-language-serving hospitals.

Methods. We conducted a retrospective cohort study using the New Jersey State Inpatient Database (2010-2022). We identified 578 030 inpatient discharges home among patients with a non-English primary language. We used generalized linear mixed models to compare 7-day readmission between language-serving hospitals-defined as those with a higher proportion of patients with a non-English primary language-and non-language-serving hospitals.

Results. Patients with a non-English primary language were less likely to be readmitted within 7 days at language-serving versus non-language-serving hospitals (4.8% vs 9.8%; adjusted odds …

Towards Human-Centered Digital Health Interventions, Kristin M Kostick-Quenet, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

This article discusses the potential of digital health interventions (DHIs) in mental health care, emphasizing the importance of designing them to foster genuine humanistic care. It highlights current challenges in measuring engagement and outcomes, advocating for integrating human-centered endpoints such as dignity, autonomy, and therapeutic alliance into evaluation frameworks. The authors call for mechanistic research to identify effective engagement strategies and context-specific implementation approaches. Ultimately, successful DHIs should demonstrate both clinical efficacy and the preservation of humane, person-centered care, ensuring ethical and meaningful mental health support through technology.

Cracking The Code: Genotype-Phenotype Correlation Models In Sarcoglycanopathies, Leonela Luce, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sarcoglycanopathies are among the most severe limb-girdle muscular dystrophies (LGMD), though milder presentations have been described. These diseases are primarily caused by missense variants, but the limited predictability of their effect on protein maturation, complex formation, and transport has hindered reliable genotype-phenotype correlations. This study aimed to establish accurate genotype-phenotype correlations for LGMDR3, LGMDR4, and LGMDR5.

METHODS: We analyzed the largest sarcoglycanopathy cohort to date (n = 541). Clinical data, including age at symptom onset and loss of ambulation, were collected and used to define phenotype severity. Predictive models were developed considering the impact of non-truncating variants on secondary …

Opioid Dispensing Volume And Per-Patient Intensity In Sickle Cell Disease, Kevin Y Xu, Brandon K Attell, Joanna L Buss, Tashalee R Brown, Charles R Jonassaint, Richard A Grucza, Allison A King, Max Jordan Nguemeni Tiako

2020-Current year OA Pubs

IMPORTANCE: Opioids remain central to management of acute and chronic pain in sickle cell disease (SCD). Opioid dispensing declined over the 2010s amid opioid stewardship efforts, but patterns since 2020 are less clear. Analyses aggregating opioids into morphine milligram equivalents (MME) may obscure agent-specific patterns.

OBJECTIVE: To characterize opioid dispensing volume and per-recipient frequency, duration, and dose among individuals with SCD.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of commercially insured and Medicaid-enrolled patients with SCD using the Merative MarketScan databases across 3 periods from January 2011 to February 2016, March 2016 to December 2020, and January 2021 to …

Spinal Cord Imaging For Multiple Sclerosis: Advances, Priorities, And Opportunities, Cornelia Laule, Matthew R Brier, Et Al.

2020-Current year OA Pubs

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of …