Digital Commons Network^™

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

Genetic Newborn Screening For Retinoblastoma: A Belgian Initiative Baby Detect, Christina Y Weng

Faculty, Staff and Students Publications

Baby Detect Project, started in September 2022, aimed to create a newborn screening test using targeted next-generation sequencing for all early-onset, treatable, and serious conditions. The elaborated gene panel covers 405 genes, associated with 165 genetic conditions, and includes RB1, linked to retinoblastoma, the only oncological disease tested for. Germline RB1 mutations concern around 50% of all retinoblastoma cases and 100% of the most severe, bilateral cases. Ninety percent of them occur de novo, which delays the diagnosis by about a year with subsequent loss of vision and sometimes the eye itself. Detecting children with germline RB1 mutation at …

Comment On “Effectiveness And Safety Of Oral Vancomycin For The Treatment Of Inflammatory Bowel Disease Associated With Primary Sclerosing Cholangitis: A Systematic Review And Pooled Analysis”, James Tabibian, Kevin Johnson, Shamita Shah, Parambir Dulai, Ahmad H Ali, Ayesha Shah, Gerald Holtmann, Harland S Winter

Faculty, Staff and Students Publications

No abstract provided.

Examining Parents’ Perceptions Of Their Children’S Autism And Completion Of Genetic Testing, Chaya N Murali, Susan X Day

Faculty, Staff and Students Publications

Though genetic testing is recommended for children diagnosed with autism spectrum disorder (ASD), both internal (e.g. parents’ and providers’ valuation of genetic testing) and external (e.g. insurance coverage) barriers exist, and exploration of these factors is required to close the gap between provider recommendations and parent follow-through. In a sample of 290 parents, we explored (a) how parents’ ASD-related etiological beliefs and symptom attributions, as well as income, affected genetic testing completion; and (b) whether these factors influence parents’ hopes or concerns about genetic testing. Principal component analysis (PCA) was used to investigate the factor structure of the ASD attribution …

Leveraging Human Microbiomes For Disease Prediction And Treatment

Faculty, Staff and Students Publications

The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice. This challenge is partially due to demographic and technological biases that impede the development of reliable disease classifiers. Here, we examine recent advances in 16S rRNA and shotgun-metagenomics sequencing, along with bioinformatics tools designed to enhance microbiome data integration for precision …

Correction: Health-Related Quality Of Life After Neonatal Treatment Of Symptomatic Tetralogy Of Fallot: Insights From The Congenital Cardiac Research Collaborative, Bryan H Goldstein, Christopher J Petit, Yun Zhang, Courtney E Mccracken, Athar M Qureshi, Caren S Goldberg, Jennifer C Romano, Mark A Law, Jeffery J Meadows, Shabana Shahanavaz, Sarosh P Batlivala, Shiraz A Maskatia, Asaad Beshish, Michael L O'Byrne, R Allen Ligon, Kathryn O Stack, Hala Q Khan, Shalin Parekh, Dawn L Ilardi

Faculty, Staff and Students Publications

No abstract provided.

Phenotypic Variation In Disease Severity Among Hospitalized Pediatric Patients With Covid-19: Assessing The Impact Of Covid-19 In The Epico Study, María Camila David, Pablo Vásquez-Hoyos, María Lucía Mesa-Rubio, Luis Miguel Navarro-Ramirez, Sergio Moreno-Lopez, Olga Lucía Baquero, Luz Marina Mejía, Juan Gabriel Piñeros, Sonia Restrepo-Gualteros, Carlos Álvarez-Moreno, Alejandro Díaz-Díaz, Iván Gutierrez-Tobar, Andrés Camilo Mesa, William Ricardo Bachiller Tuta, Clara Esperanza Galvis Diaz, Martha Africano, José Manuel Nieto, Paola Marsela Pérez Camacho, Rosalba Vivas Trochez, Irati Gastesi, Cinta Moraleda, Alfredo Tagarro García, Blanca Herrero, Lourdes Calleja, Carlos Grasa, Paula Rodriguez, Susana Melendo, Antoni Soriano-Arandes, Irene Gómez Pastrana, Sonsoles García García, Victoria Fumado, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Objective: To characterize the clinical phenotypes of SARS-CoV-2 infection in hospitalized children as part of the EPICO multicenter cohort study.

Methods: We included hospitalized children with confirmed SARS-CoV-2 infection from Colombian and Spanish institutions to assess disease evolution and outcomes. Cluster analysis was performed to identify clinical phenotypes.

Results: A total of 2318 patients were included (55% male, 36% infants). Five phenotype clusters emerged: Cluster 1 (26.5%): infants without comorbidities, low PICU admissions and mortality; Cluster 2 (18.5%): respiratory comorbidities, high microorganism co-detection and mortality; Cluster 3 (11.5%): fever, gastrointestinal symptoms, high PICU admissions; Cluster 4 (32%): mild unspecific symptoms, …

Gene Expression Changes In Human Cerebral Arteries Following Hemoglobin Exposure: Implications For Vascular Responses In Sah, Devin W Mcbride, Kumar T Peeyush, Spiros L Blackburn

Faculty, Staff and Student Publications

Subarachnoid hemorrhage (SAH), characterized by the presence of hemoglobin (Hb) in the subarachnoid space, significantly impacts cerebral vessels, leading to various pathological outcomes. The toxicity of cell-free Hb released from erythrocytes and its metabolites after SAH causes vasoconstriction and neuronal damage, and correlates with delayed ischemic neurological deficits (DIND). While animal models have provided substantial and invaluable data in the research of aneurysmal SAH, the specific effects of subarachnoid blood on cerebral arteries remain greatly understudied. Here, we describe the changes in the genetic profile of human cerebral arteries exposed to free Hb for 48 h. We performed an ex …

A Bayesian Deep Segmentation Framework For Glioblastoma Tumor Segmentation Using Follow-Up Mris, Juan C Rodriguez Quintero, Octavio Arevalo, Kangyi Zhao, Jay-Jiguang Zhu, Roy F Riascos, Mahboubeh Madadi, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) is the most common malignant brain tumor with an abysmal prognosis. Since complete tumor cell removal is impossible due to the infiltrative nature of GBM, accurate measurement is paramount for GBM assessment. Preoperative magnetic resonance images (MRIs) are crucial for initial diagnosis and surgical planning, while follow-up MRIs are vital for evaluating treatment response. The structural changes in the brain caused by surgical and therapeutic measures create significant differences between preoperative and follow-up MRIs. In clinical research, advanced deep learning models trained on preoperative MRIs are often applied to assess follow-up scans, but their effectiveness in this …

Recovery Of Verbal Working Memory Depends On Left Hemisphere White Matter Tracts, Randi C Martin, Junhua Ding, Ali I Alwani, Steve H Fung, Tatiana T Schnur

Faculty, Staff and Student Publications

Researchers propose that the recovery of language function following stroke depends on the recruitment of perilesional regions in the left hemisphere and/or homologous regions in the right hemisphere. Many investigations of recovery focus on changes in gray matter regions, whereas relatively few examine white matter tracts and none address the role of these tracts in the recovery of verbal working memory. The present study addressed these gaps, examining the role of left versus right hemisphere tracts in the longitudinal recovery of phonological and semantic working memory. For 24 individuals with left hemisphere stroke, we assessed working memory performance within 1 …

Effects Of Perinatal Exposure To Lipopolysaccharide And Acetaminophen On Learning In Adult Long-Evans Rats, Lucy A. Sivils

College of Graduate Studies: Theses & Dissertations

The present study investigated the individual and combined effects of elevated perinatal inflammation, oxidative stress caused by acetaminophen (APAP) exposure, or elevated inflammation and oxidative stress on adult learning behaviors in Long-Evans rats. While prior studies have examined these factors independently, the combined effects of inflammation and oxidative stress via APAP exposure during early development on learning-related behaviors remain unexplored. The present research aimed to address this gap by the analysis of potential long-term neurodevelopmental consequences of lipopolysaccharide (LPS)-induced inflammation and APAP-induced oxidative stress. LPS, APAP, or LPS + APAP was administered during the perinatal period: postnatal days (PD) 9, …

Astrocyte Specific Enhancers In The Cortex And Striatum Of Mice, Mikaela Kottelich

Williams Honors College, Honors Research Projects

Among glial cells, astrocytes have a prevalent influence on supporting neuronal function and overall brain health. Specifically targeting this cell type for disease treatment is an existing issue. Other cell types tend to express the desired treatment, which is not always wanted and can lead to unintended, negative consequences. Astrocytes contribute largely to maintaining the blood brain barrier, which is disrupted in Parkinson’s disease. Certain genes are thought to be the reason for this disruption, so if they can be specifically targeted in astrocytes with a specific enhancer, the disruption of the disease could be reversed. In our experiment, we …

Mapping Epidermal And Dermal Cellular Senescence In Human Skin Aging, Grace T Yu, Clarisse Ganier, David B Allison, Tamara Tchkonia, Sundeep Khosla, James L Kirkland, Magnus D Lynch, Saranya P Wyles

Children’s Nutrition Research Center Staff Publications

Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts. Photoaging due to ultraviolet light exposure was associated with higher burdens of senescent cells, a sign of biological aging, compared to chronological aging. A skin-specific cellular senescence gene set, termed …

Delayed Tooth Eruption As An Early Clinical Indicator Of Genetical Tooth Agenesis: A Family-Based Study Of Cases With Whole-Exome Sequencing, Yu-Chen Jeng, I-Ting Chen, Hui-Ching Cheng, Hsin-Yu Huang, Chao-Kai Hsu, Yu-Fen Yen

Journal of Dental Sciences

Delayed tooth eruption is frequently considered a benign developmental variation but may represent an early sign of genetically driven tooth agenesis. We evaluated a 22-month-old female presenting with markedly delayed eruption (only eight primary teeth) and a positive family history of ectodermal features. Given the inconclusive early radiographic findings, whole-exome sequencing (WES) was utilized. WES revealed the proband carried a heterozygous EDARADD variant (NM_080738:c.328G>T; p.Asp110Tyr). Subsequent familial segregation analysis identified an additional heterozygous WNT10A variant (NM_025216:c.637G>A; p.Gly213Ser) within the broader family. The EDARADD variant alone was associated with varying presentations from normal dentition to delayed eruption. Furthermore, the …

Characterization Of The Overexpression Of Reca Homologs Rad51 And Dmc1 In Tetrahymena Thermophila, Jianna M. Cox

Graduate Theses/Dissertations

RecA homologs, Dmc1 and Rad51, work to repair DNA double-strand breaks (DSBs) within the cell through the recombination of homologous sections of DNA. Dmc1 works to repair programmed DSBs through meiotic recombination, while Rad51 functions to repair both meiotic and non-meiotic DSBs, the latter repaired through the process of homologous recombination repair (HHR). Chemotherapeutics, exogenous agents, work to form DSBs in cancer cells, attempting to inhibit the cell’s growth. A hyper recombinant phenotype is often seen in cancer cells due to the overexpression of RAD51, leading to drug resistance, the persistence of cancers, and an overall poor patient outcome. …

Cardiac Timing Effects On Response Speed Are Modulated By Blood Pressure But Not Heart Rate Variability In Healthy Young Adults, Xiao Yang, Catalina Roldan, Michael Gazzanigo, Yasmine Nabulsi, Fang Fang

Research and Infrastructure Service Enterprise (RISE) Faculty Publications

Cardiac timing effects reflect the dynamic interplay between interoceptive and exteroceptive processes. Human information processing tends to be facilitated during cardiac diastole and inhibited during systole, reflecting autonomic regulation and the neuromodulation by baroreceptor afferents. Thus, blood pressure (BP) and vagally-mediated heart rate variability (vmHRV) are potential modulators of those effects. Additionally, cognitive control appears to play a critical role in the processes. However, whether cardiac timing effects are influenced by those factors remains unclear. The present study aimed to clarify these relationships. Fifty-one healthy young adults completed three experimental sessions to assess BP, short-term HRV, and cardiac timing effects. …

The Impact Of State-Mandated Certification Of Surgical Technologists On Surgical Site Infection Rates: Evaluating Policy, Practice, And Patient Outcomes, Katherine E. Geiger

Graduate Student Theses, Dissertations, & Professional Papers

Abstract

Chairperson: Matthew Schertz, Ph.D.

Committee Member: Morgen J Alwell, Ph.D.

Committee Member: Jill Davis, M.Ed.

As a surgical technology instructor, I have witnessed firsthand the impact that certified surgical technologists (CSTs) have on patient safety, particularly in the prevention of surgical site infections (SSIs). This professional paper investigates the relationship between state-mandated certification of surgical technologists and SSI rates, with a focus on how standardized education and credentialing influence clinical outcomes. SSIs remain a significant concern in surgical environments, contributing to increased morbidity, longer hospital stays, and greater healthcare costs. The research presented here examines certification requirements across various …

One And Half Versus Bi-Ventricular Repair In Pediatric E Bstein Anomaly, Short-Term Outcomes Retrospective Analysis, Rania Abushokka, Hanan Mohammed Hassan, Ahmed Meawad, Ahmed Algebaly

Journal of Medicine in Scientific Research

-Background: The application of one and half-ventricular repair in Ebstein anomaly(EA) should be considered, in association with effective cone repair, to reduce the volume preload on a dysfunctional right ventricle, and to take the benefit of obtaining ante-grade pulmonary blood flow. The one and half-ventricular repair that applied in patients with hypoplastic sub pulmonic ventricle can alternate effectively the Fontan pathway. This provides pulsatility in pulmonary circulation. However, pressure elevation in superior vena cava (SVC) and right atrial hypertension can occur in patient’s undergone one and half ventricular repair. Aim The aim of this study to evaluate the short-term outcomes …

Immunophenotype In Major Depressive Disorder Patient, Muanpetch Rachayon

Chulalongkorn University Theses and Dissertations (Chula ETD)

Major Depressive Disorder (MDD) is associated with immune dysregulation, yet the combined effects of T-cell activation, T regulatory (Treg) cell deficits, and the failure of immune checkpoint mechanisms on illness severity remain unclear. This research investigated these factors in patients with acute MDD compared with healthy participants. Using multi-parameter flow cytometry, we analyzed T-cell markers of activation (CD40L, CD71), regulation (CD152, GARP), apoptosis (CD95), and exhaustion (TIM3) under unstimulated and stimulated conditions; cytokine levels were also measured. Patients showed increased activated T helper and cytotoxic T-cells (CD4+CD40L+, CD8+CD40L+) and reduced Tregs, with this imbalance strongly predicting depression severity. Lower CD95 …

Recommendations For The Novel Assessment System In The Doctor Of Medicine Program From The Medical Students’ And The Educators’ Perspectives, Tanat Tabtieang

Chulalongkorn University Theses and Dissertations (Chula ETD)

The 2024 Doctor of Medicine curriculum at Chulalongkorn University introduced a new assessment system comprising outcome-based assessment system with milestones, a non-tiered grading model with recognition of excellence, a professional development dashboard (PDD), remediation with re-examination, and a faculty-level student profile (FLSP). This study employed a quantitative cross-sectional survey design, complemented by a sequential exploratory element, to compare student and faculty perspectives using a questionnaire across five themes, analyzed with descriptive statistics, Mann-Whitney U tests, and effect sizes (ES). A total of 490 students and 285 faculty responded. When analyzed by theme, students showed greater confidence than faculty in the …

Evaluation Of Leptospirosis Vaccine Efficacy After Modifications Of N-Linked Glycosylation In Liga Mrna Vaccines., Rampapat Phaetthayanan

Chulalongkorn University Theses and Dissertations (Chula ETD)

Leptospirosis, caused by pathogenic Leptospira species, is a widespread zoonotic disease, particularly prevalent in developing countries in tropical areas. Commercially available bacterins have several limitations. A previous study developed a messenger RNA (mRNA) vaccine encoding the carboxy-terminal domain 7-13 of LigA (LigAc) that was expressed with glycosylation in mammalian cells and elicited high humoral immune response in a hamster model but failed to provide protection against lethal challenge. To improve the protective efficacy, this study aimed to develop LigAc-mRNA vaccines with minimal glycosylation. Three mRNA constructs were developed based on two strategies: modifying the potential N-glycosylation sites (from asparagine to …

Fiber Photometry Analysis Of Spontaneous Dopamine Signals: The Z-Scored Data Are Not The Data, Conner W. Wallace, Clare Y. Slinkard, Rachael Shaughnessy, Katherine M. Holleran, Samuel W. Centanni, Christopher C. Lapish, Sara R. Jones

Department of Medicine Faculty Publications

Fluorescent sensors have revolutionized the measurement of molecules in the brain, and the dLight dopamine sensor has been used extensively to examine reward- and cue-evoked dopamine release, but only recently has the field turned its attention to spontaneous release events. Analysis of spontaneous events typically requires evaluation of hundreds of events over minutes to hours, and the most common method of analysis, z-scoring, was not designed for this purpose. Here, we compare the accuracy and reliability of three different analysis methods to identify pharmacologically induced changes in dopamine release and uptake in freely moving C57BL/6J mice. The D1-like receptor antagonist …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

Key Brain Region Identification In Obesity Prediction With Structural Mri And Probabilistic Uncertainty Aware Model, Walia Farzana, Megan A. Witherow, Ahmed Temtam, Liangsuo Ma, Melanie Bean, F. Gerry Moeller, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Objectives/Goals: Predictive performance alone may not determine a model’s clinical utility. Neurobiological changes in obesity alter brain structures, but traditional voxel-based morphometry is limited to group-level analysis. We propose a probabilistic model with uncertainty heatmaps to improve interpretability and personalized prediction. Methods/Study Population: The data for this study are sourced from the Human Connectome Project (HCP), with approval from the Washington University in St. Louis Institutional Review Board. We preprocessed raw T1-weighted structural MRI scans from 525 patients using an automated pipeline. The dataset is divided into training (357 cases), calibration (63 cases), and testing (105 cases). Our probabilistic model …

Eeg Spectral Analysis Of Nighttime Sleep And Daytime Mslts And Neurocognitive Evaluations In Subjects With Co-Morbid Insomnia And Osa, Yuan Shi, Yuru Nie, Fengyi Hao, Xujun Feng, Ye Zhang, Larry D. Sanford, Rong Ren, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

Background

Chronic insomnia and obstructive sleep apnea commonly co-occur. Few studies have explored the neurophysiological and neurocognitive characteristics of COMISA, which could help guide improving treatment diagnostic tools and determining novel therapeutic targets. This study aims to explore the neurophysiological and neurocognitive characteristics of COMISA using electroencephalographic (EEG) spectral analysis and subjective and objective neurocognitive measurements.

Methods

Participants were from our community recruited OSA-insomnia-COMISA cohort with 206 included for our current analysis including 74 chronic insomniacs (CIs), 55 OSA patients and 77 COMISA patients. Standard polysomnography (PSG) and multiple sleep latency tests (MSLTs) were recorded and used to obtain relative …

Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased …

Microbial Remodeling Of Gut Tryptophan Metabolism And Indole-3-Lactate Production Regulate Epithelial Barrier Repair And Viral Suppression In Human And Simian Immunodeficiency Virus Infections, Clarissa Santos Rocha, Katie L. Alexander, Carolina Herrera, Mariana G. Weber, Irina Grishina, Lauren A. Hirao, Dylan J. Kramer, Juan Arredondo, Abigail Mende, Katti R. Crakes, Anne N. Fenton, Maria L. Marco, David A. Mills, John C. Kappes, Lesley E. Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D. Smith, Satya Dandekar

Department of Obstetrics & Gynecology Faculty Publications

Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are …

Methadone For Critically Ill Patients Under Mechanical Ventilation In The Intensive Care Unit: A Systematic Review, Sérgio Martins Pereira, Megan Abbott, João Francisco Figueiredo Marcondes Ferraz, Akash Goel, Andrea Rigamonti, Charmaine De Castro, Lisa Burry, Airton Leonardo De Oliveira Manoel, Michael Chaim Sklar

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Pain may pose significant challenges in the intensive care unit, especially in mechanically ventilated patients. Methadone has recently emerged as an alternative option for eliciting acute analgesia. In this systematic review, we evaluated the use of methadone in mechanically ventilated patients in the intensive care unit.

Source: We searched MEDLINE, EMBASE, Wiley's Cochrane Library, CINAHL, PubMed (non-MEDLINE), Scopus, and LILACS databases from inception to January 24th, 2025. Eligible studies included randomized controlled trials and observational studies that compared the use of methadone to the standard of care or to other analgosedation strategies in mechanically ventilated patients in the intensive …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Dylan Jochum, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Quantile Regression Based Method For Characterizing Risk-Specific Behavioral Patterns In Relation To Longitudinal Left-Censored Biomarker Data Collected From Heterogeneous Populations, Minjae Lee, Belinda M Reininger, Kelley Pettee Gabriel, Nalini Ranjit, Larkin L Strong

Faculty, Staff and Student Publications

There are many studies aimed at promoting positive lifestyle behaviors to reduce lifetime risk of cancer and related diseases. However, assessing these modifiable behaviors through statistical modeling is challenging because of the multidimensionality of interrelated measurements that may dramatically differ between at-risk individuals. Taking into account this heterogeneity while considering the multidimensionality of behavior changes is fundamental to tailoring interventions to their needs. Biomarkers that identify high-risk individuals may help validate proximal measures, but the number of validated methods that link biomarkers to multiple behavioral measurements by determining their dynamic relations with disease risks is limited to just a few, …