Digital Commons Network^™

Defining The Value Of Elective Lumbar Fusion: A Systematic Review Of Existing Methodologies And Framework For The Operative Value Index, Advith Sarikonda, Anthony Chen, Theo S. Biddle, Danyal A. Quraishi, Preston Carey, Arbaz A. Momin, Matthews Lan, Dwight Mitchell Self, Ashmal S. Kabani, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: Despite wide variation in the outcomes and costs of lumbar fusion, few studies have integrated these domains together within a single metric to assess "value" (outcomes achieved per dollar spent). In this review, we sought to 1) characterize existing metrics of cost-effectiveness for lumbar fusion, 2) evaluate all applications of time-driven activity-based costing (TDABC) in spine surgery, and 3) outline the conceptual foundation for a standardized Operative Value Index (OVI).

METHODS: Two PRISMA-concordant systematic reviews were performed on PubMed and Scopus databases. The first review examined all studies which reported a cost-effectiveness metric for lumbar fusion. The second review …

Cracking The Code: The Systematic Development Of A Coding Matrix For Qualitative Data Analysis, Greta Gray, Marie-Christine Potvin

Department of Occupational Therapy Faculty Papers

A systematic approach was used to develop a coding matrix for a qualitative study with the intent to strengthen the credibility and dependability of the findings. Coding matrixes are commonly used in qualitative studies to organize data into meaningful units of text to be interpreted by the researchers. Current methods of coding matrix development can be problematic as they may introduce biases in the results and have limited reproducibility. A novel approach was employed to address this need with the “a priori” development of a coding matrix using a multi-step deductive and inductive process with multi-coders (n=5).  The coders who …

Intermembrane Coupling Between Bcl-Xl And The Ip3 Receptor Supports Local Ca2+ Transfer At Er-Mitochondrial Contacts, Arijita Ghosh, David Weaver, Chi Li, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Bcl-xL, an anti-apoptotic Bcl-2 family protein, engages laterally with Bak/Bax in the outer mitochondrial membrane (OMM) to inhibit apoptosis and interacts with the IP₃ receptor Ca²⁺ channels (IP3Rs) in the endoplasmic reticulum (ER) membrane to control Ca²⁺ release. It is unknown if OMM-localized Bcl-xL can also interact in trans with IP3Rs at ER-mitochondrial contacts to form a tethering complex that supports IP3R-mediated local Ca²⁺ transfer from ER to mitochondria. We establish that IP3R-mitochondria Ca²⁺ signal propagation depends on Bcl-xL. By targeting Bcl-xL specifically to different subcellular compartments, we find that OMM-localized Bcl-xL increases the efficacy …

Comment On: Managing Sickle Cell Disease And Related Complications In Pregnancy: Results Of An International Delphi Panel, Deva Sharma, Ilknur Pamuk, Kenneth I. Ataga, Alexandra Benachi, Selim Büyükkurt, Sophie Lanzkron, Hakan Ozdogu, Shivan Pancham, Lydia H. Pecker, Susan E. Robinson, Safak Yilmaz Baran

Cardeza Foundation for Hematologic Research

Consensus-based recommendations on managing sickle cell disease in pregnancy were recently published in a hematology journal. As this topic is also of great interest to obstetricians and gynecologists, we summarize some of these recommendations, while highlighting the challenges of providing evidence-based medical care to pregnant individuals with sickle cell disease.

"It's Probably Like A Web": Complex Relationships Between Pain And Mental Health Among Bisexual+ Women With Chronic Pain, Aster Harrison, Mansha Mirza

Department of Occupational Therapy Faculty Papers

INTRODUCTION: Bisexual+ women experience higher rates of both mental illness and chronic pain when compared to either straight or lesbian women. Their experiences of the relationship between their mental health and chronic pain remain underexplored. This article presents an intersectional Interpretive Phenomenological Analysis of the experiences of six bisexual+ women with chronic pain.

METHODS: Each woman completed two semi-structured interviews. Interviews were analyzed with Interpretive Phenomenological Analysis, beginning with in-depth case study analysis of each person's interviews before moving to comparison across cases.

RESULTS: Results indicated a complex web of multidirectional relationships between mental health and chronic pain. These relationships …

Metastatic Large Cell Neuroendocrine Carcinoma: A Rare Cause Of Hypopituitarism, Smriti Nair, Taskeen Ahmed, Jessica Watari

Division of Internal Medicine Faculty Papers & Presentations

Pituitary metastases from pulmonary large cell neuroendocrine carcinoma (LCNEC) are exceedingly rare but should be considered in patients presenting with arginine vasopressin deficiency and panhypopituitarism in the context of known or suspected metastatic lung cancer. Early recognition and prompt initiation of hormonal replacement therapy are essential to prevent life-threatening endocrine crises and to improve symptom burden. We describe a case of a 43-year-old male who presented with dyspnea, weight loss, and weakness who was found to have metastatic LCNEC involving the liver. Endocrine evaluation revealed central hypothyroidism, central adrenal insufficiency, and later arginine vasopressin deficiency manifested by polyuria and hypernatremia. …

Ophthoevidence Report: Comparative Effects Of Prophylactic Strategies For Post-Intravitreal Injection Endophthalmitis: Protocol For A Systematic Review And Network Meta-Analysis, Maryam Ghadimi, Dena Zeraatkar, João Pedro Lima, Jinhui Ma, Sunir J. Garg, Peter Kaiser, David Steel, Tien Yin Wong, Sobha Sivaprasad, Charles Wykoff, Varun Chaudhary

Wills Eye Hospital Papers

BACKGROUND: Endophthalmitis is a rare but serious complication of intravitreal injections (IVI). To mitigate the risk of post-injection endophthalmitis (PIE), retinal specialists use different strategies, combining various prophylactic measures. However, existing systematic reviews have evaluated the effects of these measures in isolation, which does not consider their concurrent use in practice. A trustworthy systematic review with network meta-analysis (NMA) by providing a framework for simultaneous comparisons of different prophylactic combinations is essential to guide decision-making.

OBJECTIVES: To present a protocol for addressing the comparative effects of different strategies for the prevention of PIE.

METHODS: We will search Medline, EMBASE, Cochrane …

De Novo Pyrimidine Synthesis Controls Germinal Center B Cell And Plasma Cell Fates And Systemic Autoimmunity, Julia L. Weber, Tien Bui, Keomonyroth Nuon, Adam J. Fike, Sophia M. Crocker, Kristen N. Bricker, Anju Maharjan, Wujuan Zhang, Aaron R. Goldman, Sathi Babu Chodisetti, Ziaur S. M. Rahman

Department of Microbiology and Immunology Faculty Papers

Whether and how pyrimidine metabolites promote systemic autoimmunity is unknown. Here, metabolomics and 15N-amide glutamine tracing show enhanced flux through de novo pyrimidine synthesis in systemic lupus erythematosus (SLE)-prone B cells. Temporal inhibition of pyrimidine synthesis dampens SLE-prone but not foreign antigen-specific germinal center (GC), plasma cell (PC), and antibody responses. Uridine monophosphate synthase (UMPS) conditional deletion, however, reveals a B cell-intrinsic requirement of de novo pyrimidine synthesis in foreign antigen-driven and SLE-prone GC, PC, and antibody responses and kidney immune complex deposition. Metabolomics, mitochondrial stress test, metabolic flow cytometry, glycolytic rate assay, and RNA sequencing highlight the importance of …

Under Pressure: Negative Urgency And Disordered Eating In The Context Of Parental Differential Support, Hamide Gozu, Jenna K. Rieder

College of Humanities and Sciences Faculty Papers

Disordered eating behaviors are prevalent in emerging adulthood and may be shaped by family dynamics. This study examined associations among maternal and paternal differential support, weight-shape concerns, and binge eating and compensatory behaviors in emerging adulthood, while testing the moderating role of negative urgency. Participants were 517 emerging adults from across the United States (ages 18-29; M = 22.60, SD = 3.81; 76% female). Participants reported on parental differential support, weight-shape concerns, eating behaviors, and negative urgency. Using moderated-mediation analyses, we found that weight-shape concerns mediated associations between differential support and eating behaviors. Unequal maternal support and paternal favoritism showed …

From Chromosomes To Precision Therapy: Clinical Cytogenetics And Cytogenomics In The Era Of Genomic Medicine, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Correction To: A Double‑Edged Sword: Ethical And Psychological Implications Of Apoe Genotype Disclosure Across The Lifespan, Diego Iacono

Department of Neurology Faculty Papers

No abstract provided.

The Biological Response Of Human Np Cells To Soluble Collagen Vi, Jonathan Dalton, Srikanth N. Divi, Yasmine Eichbaum, Panya Luksanapruksa, Mitchell K. Ng, Rachel Huang, Alan S. Hilibrand, Alex R. Vaccaro, Dessislava Z. Markova, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

Extracellular matrix (ECM) dysregulation plays a significant role in the development of intervertebral disc disease (IVDD). The ECM around the chondrocytes in the nucleus pulposus (NP) is unique in that it contains ColVI. While linked to chondrocyte proliferation in cartilage, ColVI's specific role in IVD degeneration is less clear. Our aim was to determine the expression of ColVI in NP cells from degenerative IVDs, along with the effects of soluble ColVI on NP cells. Thus, we compared the expression levels of ColVI in human degenerated IVD samples, along with the effect of soluble ColVI on primary human NP cells. A …

Depression And Psychotic Disorders Elevate Inpatient Burden After Posterior Cervical Decompression And Fusion: Prioritizing Screening And Targeted Discharge Planning, Leonidas E. Mastrokostas, Paul G. Mastrokostas, Daniel Yusupov, Abigail Razi, Aaron B. Lavi, Luke B. Schwartz, Sean Inzerillo, Mohamed Said, Alexander Kucherina, Pemla Jagtiani, Arie Monas, John K. Houten, Christopher K Kepler, Jad Bou Bou Monsef, Afshin E. Razi, Mitchell K. Ng

Rothman Institute Papers

CONTEXT: Psychiatric comorbidity has been associated with worse perioperative outcomes and greater healthcare utilization after spine surgery.

AIMS: This study compared complications and healthcare utilization among posterior cervical decompression and fusion (PCDF) patients with depression, psychotic disorders, or no mental-health diagnosis.

SETTINGS AND DESIGN: Retrospective cohort analysis of the National Inpatient Sample from 2016 to 2022.

MATERIALS AND METHODS: The database was queried for elective adult PCDF encounters. Mental-health exposures were defined using Elixhauser indicators for depression and psychoses. Outcomes included medical complications, non-routine discharge, inpatient mortality, length of stay (LOS), and costs.

STATISTICAL ANALYSIS USED: Chi-square and multivariate logistic …

Higher Mortality And Distinct Complications After Anterior Cervical Discectomy And Fusion In Dialysis Patients, Despite Improvements Over Prior Decade: A National Inpatient Study, Mitchell K. Ng, Leonidas E. Mastrokostas, Paul G. Mastrokostas, William A. Green, Joshua Mathew, Gregorio Baek, Yasmine Eichbaum, Yulia Lee, Morgan Hitchner, Jonathan Dalton, Adam Fano, Alec Giakas, Rajendra Singh, Brendan Reitman, Afshin E. Razi, Daniel R. Fassett, Alan S. Hilibrand, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder, Andrew P. Alvarez

Rothman Institute Papers

Introduction: Dialysis patients undergoing anterior cervical discectomy and fusion (ACDF) face elevated perioperative risk due to complex comorbidities. This study aimed to (1) identify associations between dialysis status and perioperative complications after ACDF, (2) quantify differences in length of stay (LOS), hospitalization costs, and discharge disposition, and (3) provide a contemporary national benchmark for outcomes in this high-risk population. Materials and Methods: The 2016–2022 National Inpatient Sample was queried for adult elective ACDF cases. Dialysis dependence was identified through International Classification of Diseases-10 codes for end-stage renal disease with hemodialysis or peritoneal dialysis. Demographics, comorbidities, complications, LOS, costs, and discharge …

Locoregional Therapy Pressure-Enabled Drug Delivery For Liver Cancers, Thomas Eggleston, Bassem Fayek, Jacqueline Kowalke, Mina Makary

Student Papers, Posters & Projects

Hepatic malignancies account for a substantial portion of global cancer mortality, with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC), and metastatic liver disease representing the most common diagnoses. While surgical resection and liver transplantation remain curative options for eligible patients, most patients are diagnosed at stages unsuitable for surgery. This has shifted medical management towards locoregional therapies (LRTs) which are often catheter-directed. Of these interventions, the use of conventional end-hole catheters for therapeutic infusion has been a mainstay of treatment, but this method is constrained by retrograde particle escape and elevated tumoral interstitial fluid pressure. Together, these factors limit drug penetration …

Safety Of Early Discharge And Abbreviated Nimodipine Course In Patients With Good-Grade Aneurysmal Subarachnoid Hemorrhage, Patrick R. Toyota, Alexander D. Rebchuk, Michael A. Rizzuto, Hugh Mchugh, Kelsey Cruz, Charles S. Haw, Gary J. Redekop, Peter Gooderham

Department of Neurosurgery Faculty Papers

Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular emergency associated with substantial morbidity and mortality. Current guidelines recommend 14-21 days of inpatient monitoring and a 21-day course of nimodipine following aSAH. This retrospective study evaluates early outcomes early discharge (≤14 days post-ictus) and an abbreviated nimodipine course in highly selected patients with good-grade aSAH managed under a standardized institutional protocol. Consecutive patients enrolled in the Vancouver Ruptured Aneurysm Database (VRAD) at Vancouver General Hospital between 2022 and 2025 were included. Inclusion criteria were good-grade aSAH (WFNS Grade I-III) and discharge home within 14 days of ictus. The primary outcome was …

Neural-Immune-Cardiovascular Axis: From Mechanistic Crosstalk To Therapeutic Targets In Cardiovascular Disease, Junkang Cheng, Shuang Gao, Haowei Zhang, Wei Gao, Zeyuan Mei, Xiaoling Liu, Jocelyn Gao, Chenghu Guo, Guipeng An

Student Papers, Posters & Projects

The neural-immune-cardiovascular axis represents an emerging and highly integrated physiological and pathophysiological concept, describing a complex bidirectional communication network between the nervous, immune, and vascular systems. This review systematically examines the pivotal role of this axis in maintaining cardiovascular homeostasis and in the pathogenesis of cardiovascular diseases. We first provide an overview of the fundamental signaling pathways between the components of this axis. Subsequently, we delve into the specific crosstalk mechanisms within the axis in the context of major cardiovascular conditions, including atherosclerosis, hypertension, and heart failure. A central focus is placed on critically evaluating the potential therapeutic targets and …

Barriers To Recommendation Of Integrative Oncology Modalities In Supportive Care: A Mascc/Sio Survey, Alexandre Chan, Dalia Kagramanov, Reem Nasr, Chioma Asuzu, Ting Bao, Yin Ting Cheung, Jung Hye Kwon, Judith Lacey, Richard T. Lee, Maryam Lustberg, Beatrice M. Ohaeri, Santosh Rao, Enrique Soto-Perez-De-Celis, Claudia M. Witt, Ana M. Lopez

Kimmel Cancer Center Faculty Papers

PURPOSE: Integrative oncology (IO) modalities aim to improve the quality of life of persons with cancer, including strategies to manage treatment and disease-related symptoms. As evidence increases to include IO in supportive care, interest grows globally. Understanding barriers to IO recommendation is key to facilitating its uptake.

METHODS: Members of the Multinational Association of Supportive Care in Cancer (MASCC) and the Society for Integrative Oncology (SIO) were invited to complete an online survey in Fall 2023 assessing barriers to IO recommendation on a 5-point scale. Descriptive statistics assessed demographic data and general counts of scaled agreement, while logistic regression analysis …

Cervical Cancer Screening Coverage And Associated Factors Among Women Aged 25-59 In Eswatini: Insights From The 2021 Population-Based Hiv Impact Assessment (Phia), Abenezer Melaku Tafese, Bikiltu Dirbaba, Meseker Fentie, Charnita Zeigler-Johnson

College of Population Health Faculty Papers

BACKGROUND: Cervical cancer is the most common cancer and the leading cause of cancer mortality among women in Eswatini, which reported the highest cervical cancer incidence and mortality rates globally in 2022. However, recent nationally representative published data on cervical cancer screening coverage in Eswatini remain limited. This study aimed to estimate cervical cancer screening coverage and identify factors associated with screening uptake among women aged 25-59 years in Eswatini.

METHOD: Data were drawn from the 2021 Eswatini Population-based HIV Impact Assessment (PHIA), a nationally representative cross-sectional household survey. Survey-weighted bivariable and multivariable logistic regression analyses were conducted to identify …

Exploring Academic–Practice Partnerships In Community Settings: A Narrative Review, Laura C. Sarver

College of Nursing Faculty Papers & Presentations

Purpose: This narrative review explored the literature on academic–practice partnerships in community settings within prelicensure nursing education. Methods: A search of three databases—MEDLINE, CINAHL, and Scopus—led to the review of 12 articles exploring academic–practice partnerships in community settings within prelicensure nursing education. Results: Emergent themes encompassed components for planning, implementing, and evaluating academic–practice partnerships. Planning themes included completing community assessments, considering financial resources, and identifying guiding frameworks or models. Implementation themes included diverse nursing education and community partners and settings, academic–practice partnership initiatives, and integration of partnerships in prelicensure nursing education curricula. Lastly, evaluation themes included the exploration of a …

Sexual Orientation And Burnout Among Emergency Medicine Residents, David Rudolph, Kirlos Haroun, Michael Gottlieb, Susan Farrell, Yvette Calderon, Kayla Iuliucci, Lea Moujaes, Blake Denley, P. Logan Weygandt

Department of Emergency Medicine Faculty Papers

IMPORTANCE: Burnout is highly prevalent among emergency medicine (EM) residents and is associated with negative outcomes for physician well-being and patient care. Emerging evidence suggests sexual minority trainees may be at increased risk, but differences within EM residency are not well characterized.

OBJECTIVE: To determine if burnout prevalence among EM residents differs by sexual orientation after adjustment for key confounders.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included US resident physicians who took the 2024 American Board of Emergency Medicine In-Training Exam (ITE) postexamination survey and answered the question on sexual orientation.

EXPOSURE: Sexual minority status (heterosexual or straight and …

Intravenous Versus Oral Tranexamic Acid In Shoulder Arthroplasty, Tarishi Parmar, Akin Adio, Mohammad Daher, Adam Khan, John Horneff, Joseph A. Abboud

Rothman Institute Papers

PURPOSE: Tranexamic acid (TXA) is used in shoulder arthroplasty to reduce blood loss. While intravenous (IV) TXA is standard, oral TXA offers advantages in cost and administration. This study compares 90-day complications and postoperative laboratory values between IV and oral TXA in total shoulder arthroplasty (TSA).

METHODS: A retrospective cohort study using TriNetX identified adults undergoing primary TSA (2005-2025) receiving TXA on the day of surgery, stratified by route (IV vs. oral). One-to-one propensity score matching was performed. Ninety-day outcomes included transfusion, thromboembolic events, cardiac and renal complications, neurologic events, infection, wound dehiscence, readmissions, emergency department visits, opioid utilization, and …

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …

Interstitial Fluid N-Glycans Serve As A Proxy For Serum Biomarker Discovery In A Pilot Study, Radka Saldova, Talus K. Gaymore, Caitriona Walsh, Eder Zavala, Paula M. Mendes

Student Papers, Posters & Projects

Protein glycosylation is the most prevalent post-translational modification and is known to undergo profound alterations in disease. While serum N-glycosylation has been extensively studied, interstitial fluid is gaining prominence as a minimally invasive biomarker source, underscored by the widespread clinical adoption of wearable glucose monitors in diabetic patients. However, the glycomic landscape of interstitial fluid remains largely unexplored. Here, we have performed a comparative analysis of the N-glycome from interstitial fluid and matched plasma from five healthy volunteers using liquid chromatography, mass spectrometry and exoglycosidase digestions. Strikingly, the interstitial fluid N-glycome closely shows overlapping profiles with the plasma of each …

Less Frequent Versus More Frequent Cervical Examinations In Labor: A Systematic Review And Meta-Analysis, Alessandro Petrecca, Benedetta Bina, Chiara Tersigni, Tullio Ghi, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Digital cervical examinations are central to intrapartum care, yet their optimal frequency remains uncertain and is largely based on consensus rather than high-quality evidence.

OBJECTIVES: To compare less frequent versus more frequent cervical examinations during labor in terms of obstetrical, maternal and neonatal outcomes.

SEARCH STRATEGY: We searched Medline, Cochrane Library, EMBASE, PubMed Central, Scopus and ClinicalTrials.gov from inception to August 2025, without language or geographic restrictions. The review was registered in PROSPERO (CRD420251033729).

SELECTION CRITERIA: Randomized controlled trials comparing different frequencies of cervical examinations in term singleton pregnancies during labor were included.

DATA COLLECTION AND ANALYSIS: Two reviewers …

Pharky, Phedro, Phractured, And Stagephright: Complete Genome Sequences Of Four Ek2 Cluster Microbacterium Phages, Susan M. R. Gurney, Medha Gupta, Deeksha Reddy, Gloria Zacharias, Aleda S. Jomy, Carly J. Smith, Matthew T. Mcdonald, Brett M. Condon

Student Papers, Posters & Projects

We report the complete genome sequence of four Microbacterium phages, Pharky, Phedro, Phractured, and StagePhright, isolated using the bacterial host Microbacterium foliorum from soil samples collected in Philadelphia. All four phages are genetically very similar and contain a gene of unknown function, which is uncommon in the EK2 cluster.

Assessing Current Non-Pharmacologic Pain Management Practices For Sickle Cell Disease In Adults, Shreya Kolipaka, Michelle Axe, Charmaine Wright, Stephanie Guarino

Student Papers, Posters & Projects

OBJECTIVES: Both acute and chronic pain caused by sickle cell disease (SCD) is often managed with opioid therapy despite limited evidence for long-term efficacy. Adequately managing SCD pain requires a comprehensive approach, incorporating both pharmacologic and non-pharmacologic interventions. In other conditions, peer-mentored group programs are effective in managing chronic pain; however, their role in SCD is not yet described. Our objective is to understand patients' current pharmacologic and non-pharmacologic SCD management practices as well as further exploring perspectives of pain related to SCD.

METHODS: Participants were interviewed using semi-structured format. Audio-recorded interviews were transcribed. Descriptive statistics and pain management modality …

Questionnaire-Based Identification And Participation In Lung Cancer Screening In Sweden, Julie Barta

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.

Targeting The Prmt5/Nur77 Methylation Axis Enhances Endometrial Decidualization Capacity And Female Fertility In Preclinical Models, Zhiwen Cao, Xinyu Cai, Jie Mei, Na Kong, Yang Liu, Xiaoyue Shen, Min Wu, Xin Zhen, Jianxin Sun, Rong Li, Ruiwei Jiang, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Defective endometrial decidualization is one major cause of female infertility, yet the underlying mechanisms remain elusive. Here, we identified that protein arginine methyltransferase 5 (PRMT5), which was upregulated during decidualization and by progesterone stimulation, was markedly downregulated in the endometria of patients with recurrent implantation failure (RIF), along with a global reduction of symmetric dimethylarginine (SDMA). Uterine stroma-specific ablation of Prmt5 in mice severely impaired decidualization, leading to infertility. A multiomics analysis in human endometrial stromal cells (EnSCs) revealed that PRMT5 promoted decidualization primarily by catalyzing SDMA at arginine 346 (R346) of the orphan nuclear receptor Nur77, which directs its …

Aberrant Stat Signaling And T Cell Dysregulation Define A Targetable Pediatric Sepsis Endotype, Robert B. Lindell, Samir U. Sayed, Jose S. Campos Duran, Sydney A. Sheetz, Apoorva Babu, Montana S. Knight, Andrea A. Mauracher, Ceire A. Hay, Peyton E. Conrey, Julie C. Fitzgerald, Nadir Yehya, Stephen T. Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M. Behrens, David T. Teachey, Lisa R. Forbes Satter, Alexandra F. Freeman, Jenna Re Bergerson, Steven M. Holland, Jennifer W. Leiding, Scott L. Weiss, Mark W. Hall, Deanne M. Taylor, Rui Feng, E. John Wherry, Nuala J. Meyer, Sarah E. Henrickson

Department of Pediatrics Faculty Papers

BACKGROUNDSepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.METHODSWe integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.RESULTSUnsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group ("Group C") characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a strong association between hyperinflammatory cytokine …