Digital Commons Network^™

Nf1-Depleted Er+ Breast Cancers Are Differentially Sensitive To Cdk4/6 Inhibitors, Ze-Yi Zheng, Anran Chen, Eric J Jaehnig, Meenakshi Anurag, Jonathan T Lei, Long Feng, Chenwei Wang, Diana Fandino, Purba Singh, Hilda Kennedy, Ghazal Yadav, Craig T Vollert, Jill Tsai, Xi Chen, Yi Li, Bora Lim, Alastair Thompson, Shunqiang Li, Charles E Foulds, Bing Zhang, Matthew J Ellis, Eric C Chang

Faculty, Staff and Students Publications

Neurofibromin/NF1 is a RAS (rat sarcoma virus) GTPase activating protein and estrogen receptor (ER) transcriptional corepressor. NF1low status, identified by copy number loss or low mRNA/protein expression is associated with endocrine therapy resistance in approximately 20% of ER+/HER2− (human epidermal growth factor receptor 2) early-stage breast cancers. The identification of targeted treatments for NF1low ER+/HER2− breast cancer is therefore a priority. In this study proteogenomic analysis of ER+/HER2− breast cancer demonstrated that NF1low tumors exhibited elevated cyclin-dependent kinase 4/6 (CDK4/6) activity. In cell lines, NF1-deletion had a dual effect on CDK4 activity. First, by promoting ER recruitment to CCND1 …

The Role Of Recruited Adipose Stromal Cells And Their Fibroblastic Differentiation In Cancer, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Faculty, Staff and Student Publications

Adipose stromal cells (ASCs) are perivascular mesenchymal progenitors of adipose tissue. In cancer patients, ASCs can mobilize and migrate to the tumor, where they subsequently play an important role in cancer progression. This biological process involves the conversion of recruited ASCs into cancer-associated fibroblasts (CAFs). ASC-derived CAFs influence the tumor microenvironment through extracellular matrix remodeling, vascularization, and immunomodulation. These and other processes mediated by secreted paracrine factors also affect gene expression in carcinoma cells to promote the epithelial-mesenchymal transition (EMT), metabolic adaptation, survival, and invasiveness of cancer cells. ASC-derived CAFs can enhance tumor aggressiveness, accounting in part for the link …

Reproducibility Of Statistically Significant Phase Iii Oncology Trials: An In Silico Meta-Epidemiological Analysis, Alexander D Sherry, Pavlos Msaouel, Avital M Miller, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Adina H Passy, Tomer Meirson, Nikolaos Ignatiadis, Zachary R Mccaw, Erik Van Zwet, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: The conventional assumption that P values ≤ 0.05 imply reproducible effects has come under recent criticism. This concern is particularly relevant in oncology, as phase III oncology trials, which directly inform practice, are usually not repeated. Using advanced modeling techniques, we investigated the relationship between P values and reproducibility in oncology.

Methods: We obtained the signal-to-noise ratio distribution in phase III oncology using outcomes from 632 two-arm superiority trials enrolling 496,219 patients. With this distribution, we estimated successful replication probability as the probability that a replicate trial, having the same design, effect size, and standard error, would have a …

Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations And Macrophage-Driven Metastasis In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Weiguo Wu, Brooks Scull, Angela M Major, Weidong Jin, Justin M M Cates, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a type of bone cancer that mostly affects kids and teens. The biggest danger is when the cancer spreads to the lungs, and current treatments do not work well for those cases. Immunotherapy, which helps the body’s immune system fight cancer, has worked for other cancers but is limited for osteosarcoma because we do not fully understand the environment around the tumor. Our research looked at various cells around the tumor to study why patients have worse outcomes. We found that certain cells, called M2 macrophages (M2) and myeloid-derived suppressor cells (MDSC), which weaken the immune system, are …

An Ehealth Delivery Alternative For Cancer Genetic Testing For Hereditary Predisposition In Patients With Metastatic Cancers: Protocol For A Randomized Trial, Kimberley T. Lee, Briana Mcleod, Brian Egleston, Sarah Brown, Sarah Howe, Dominique Fetzer, Lauren Gutstein, Cara Cacioppo, Dana Clark, Susan M. Domchek, Jessica Ebrahimzadeh, Dana Falcone, Demetrios Ofidis, Hannah Griffin, Rajia Mim, Santina Hernandez, Linda Fleisher, Kelsey Karpink, Enida Selmani, Aysha Tahsin, Lynne Wagner, Michelle Weinberg, Kuang-Yi Wen, Elisabeth Wood, Angela R. Bradbury

Department of Medical Oncology Faculty Papers

Background: Germline BRCA1 and BRCA2 testing is a standard evidence-based practice, with established risk reduction and cancer screening guidelines for genetic carriers. With Food and Drug Administration approval for poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors in patients with metastatic breast, ovarian, pancreatic, and prostate cancer, there is an additional therapeutic rationale for testing all patients with these cancers for germline BRCA1 and BRCA2 mutations. However, many at-risk patients do not have access to genetic services, leaving many genetic carriers unidentified.

Objective: The eREACH (A Randomized Study of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in …

Mri-Guided Focused Ultrasound Thalamotomy For Neuropathic Pain In An Adolescent With Cranial Metastases: Illustrative Case, Sarah G Van Winkle, Danika L Paulo, Ashwin Viswanathan, Daniel Curry, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Neuropathic cancer pain (NCP) is a debilitating condition that is often refractory to conventional medical management. MRI-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) is an incisionless neurosurgical option for neuropathic pain palliation, but its use in pediatric patients and those with cranial metastases, a relative contraindication to MRgFUS, remains largely unexamined.

Observations: A 16-year-old male with metastatic rhabdomyosarcoma (RMS) with numerous cranial metastases experienced severe, diffuse, refractory NCP. The patient underwent bilateral CLT with MRgFUS. After the procedure, the patient experienced complete and durable resolution of his neuropathic pain. He only reported occasional somatic pain at sites of …

Bridging Diagnostic Safety And Mental Health: A Systematic Review Highlighting Inequities In Autism Spectrum Disorder Diagnosis, Abirami Srivarathan, Andrea Bradford, Sara Shearkhani, Layla Heimlich, Sheryl Jefferson, Kristen E Miller, Kelly Smith, Helen Haskell, Traber D Giardina

Faculty, Staff and Students Publications

Introduction: There is increased recognition that diagnostic errors disproportionately affect marginalised and underserved patient populations in the USA. However, evidence on diagnostic inequities in mental disorders is sparse and not well integrated into the overall diagnostic safety literature.

Objective: We systematically reviewed and narratively synthesised evidence on inequities in diagnosis of mental disorders, guided by the Diagnostic Process Framework developed by The National Academies of Sciences, Engineering, and Medicine.

Methods: We conducted a systematic review and a narrative synthesis. Medline, Embase, PsycInfo and CINAHL were searched for studies published between 2015 and 2024. Studies were eligible if they reported on …

Conservative Management Of An Iatrogenic Left Ventricular Pseudo Aneurysm After Type A Aortic Dissection Surgery, Wiem Feki, Amal Kchaou, Rania Gargouri, Hichem Denguir

Journal of the Saudi Heart Association

Left ventricular pseudo aneurysm a rare but potentially fatal complication after surgery for type A aortic dissection, due to the fragile nature of the pseudo aneurysm wall. We present the case of a 69-year-old man who developed a pseudo aneurysm at the apex of the left ventricle following surgical repair of a type A aortic dissection. Initially under diagnosed on trans thoracic echocardiography , the lesion was clearly characterized by CMR . Given the patient’s stable clinical status and morbidities , a conservative approach was adopted. The patient showed favorable evolution over time.

A Phenomenological Study Of Caregivers For Sexual Minority Hospice Patients, Catherine H. Bianchi

Electronic Theses and Dissertations

Lesbian, gay, and bisexual (LGB) individuals face disproportionate barriers in healthcare across the lifespan that persist and often intensify at the end of life. Despite hospice’s mission to provide comfort, dignity, and patient-centered support, it remains unclear whether these services equitably meet the needs of sexual minority patients. Seeking hospice care presents a unique conundrum for many LGB individuals: it necessitates inviting representatives of a historically exclusionary healthcare system into the privacy of their homes - spaces that often serve as sanctuaries of identity, safety, and autonomy. The already vulnerable experience of seeking care in one’s final days can be …

Developing Deep Learning Methods For Cognitive Impairment Detection Based On Non-Invasive Data, Muath Alsuhaibani

Electronic Theses and Dissertations

Cognitive impairment detection is on the rise to help reduce the burden of healthcare costs on institutions and individuals. Mild Cognitive Impairment (MCI) is an early stage of cognitive decline progressing to Alzheimer’s disease (AD) or AD-related Dementia (ADRD). Detecting the early stages of AD/ADRD is crucial for early interventions among older adults to mitigate cognitive decline over time. However, the current diagnostic methods are often costly and/or invasive, such as MRI and PET scans. Thus, the search for non-invasive and cost-effective screening tools for the early detection of cognitive impairment using speech, language, visual, and motor data is growing. …

Supporting Healthy Siblings In Pediatric Cancer: Advancing Relational Interventions To Heal Invisible Wounds, Kristen K. Wederski

Graduate School of Professional Psychology: Doctoral Papers and Masters Projects

Healthy siblings of children diagnosed with cancer occupy a uniquely vulnerable position within the pediatric oncology landscape. Individuals within this population often demonstrate significant emotional distress and can experience long-term psychological challenges. Despite their risk, healthy siblings remain under-researched and under-supported compared to pediatric patients and caregivers. Existing interventions tend to prioritize individual coping skills and psychoeducation and often overlook the critical relational dynamics that shape healthy siblings' psychological adjustment. Grounded in systematic and relational theories, this paper proposes a paradigm shift toward relationally focused interventions that strengthen the caregiver-sibling bond as a core mechanism of change to foster resilience …

Review Of Human Papillomavirus Vaccination Programs In United States Schools, Cassandra Duran, Aditi Gupta, Lynda Aririguzo, Norma Castillo, Sanghamitra M Misra

Faculty, Staff and Students Publications

Background: School vaccination programs (school-based and school-located) that include the human papillomavirus (HPV) vaccine have been implemented throughout the United States since 2009.

Methods: We conducted a review of school HPV vaccination programs in PUBMED, Google Scholar, Web of Science, Ovid, Medline, and Embase and included peer-reviewed studies originating in the United States that focused on any aspect of HPV school vaccination programs.

Results: Our review yielded 47 articles that fell into several categories: (1) parent and child perceptions, (2) school nurse perceptions, (3) development, (4) implementation, (5) outcomes, and (6) barriers and facilitators of HPV vaccination programs in schools. …

Targeting Sting To Disrupt Macrophage-Mediated Adhesion In Encapsulating Peritoneal Sclerosis, Juan Sun, Yuxiang Sun, Dandan Guo, Huolin Ye, Qiang Huang, Hu Zhou, Canming Li, Mei Liao, Yujia You, Hongli Shang, Pan Zhou, Dongxuan Wu, Janusz Witowski, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Encapsulating peritoneal sclerosis (EPS) is a life-threatening fibrotic condition characterized by severe abdominal adhesions, chronic inflammation, and significant morbidity. The lack of effective treatments for EPS stems from a limited understanding of its underlying mechanisms. In this study, we developed a modified mouse model of PD-induced EPS and investigated the role of the STING signaling pathway in disease progression. Our findings reveal that STING activation in peritoneal mesothelial cells significantly increases the secretion of the macrophage chemokine CCL2, leading to enhanced macrophage infiltration and the formation of pathological adhesions. Notably, pharmacological inhibition of STING using the inhibitor H151 effectively reduced …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Prolonging Lung Cancer Response To Egfr Inhibition By Targeting The Selective Advantage Of Resistant Cells, Lisa Brunet, David Alexandre, Jiyoung Lee, Maria Del Mar Blanquer-Rosselló, David Bracquemond, Alexis Guernet, Houssein Chhouri, Mathilde Goupil, Zoulika Kherrouche, Arnaud Arabo, Maicol Mancini, Dorthe Cartier, Shen Yao, David Godefroy, Julie Dehedin, Jian-Rong Li, Céline Duparc, Philippe Jamme, Audrey Vinchent, Caroline Bérard, David Tulasne, Sabrina Arena, Alberto Bardelli, Chao Cheng, Byoung Chul Cho, Olivier Wurtz, Cédric Coulouarn, Antonio Maraver, Stuart A Aaronson, Alexis B Cortot, Youssef Anouar, Luca Grumolato

Faculty, Staff and Students Publications

Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Through a DNA barcoding approach, we show that the clinically approved drug sorafenib specifically abolishes the selective advantage of EGFR-TKI-resistant cells, while preserving the response of EGFR-TKI-sensitive cells. Sorafenib is active against multiple mechanisms of resistance/tolerance to EGFR-TKIs and its effects depend on early inhibition of MAPK-interacting kinase (MKNK) activity and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and later down-regulation of MCL1 and …

Prefrontal Cortex Astrocytes Modulate Distinct Neuronal Populations To Control Anxiety-Like Behavior, Eunyoung Kim, Hairuo Du, Yanqi Tan, Brandon L Brown, Yaowen Chang, Blanca Díaz-Castro, Jonathan V Sweedler, Xinzhu Yu

Faculty, Staff and Student Publications

Accumulating evidence has supported diverse regulatory functions of astrocytes in different neural circuits as well as various aspects of complex behaviors. However, little is known about how astrocytes regulate different neuronal subpopulations that are linked to specific behavioral aspects within a single brain region. Here, we show that astrocytes in the medial prefrontal cortex (mPFC) encode anxiogenic environmental cues in freely behaving mice. Silencing mPFC astrocyte Ca

Human Interpretable Grammar Encodes Multicellular Systems Biology Models To Democratize Virtual Cell Laboratories, Jeanette A I Johnson, Daniel R Bergman, Heber L Rocha, David L Zhou, Eric Cramer, Ian C Mclean, Yoseph W Dance, Max Booth, Zachary Nicholas, Tamara Lopez-Vidal, Atul Deshpande, Randy Heiland, Elmar Bucher, Fatemeh Shojaeian, Matthew Dunworth, André Forjaz, Michael Getz, Inês Godet, Furkan Kurtoglu, Melissa Lyman, John Metzcar, Jacob T Mitchell, Andrew Raddatz, Jacobo Solorzano, Aneequa Sundus, Yafei Wang, David G Denardo, Andrew J Ewald, Daniele M Gilkes, Luciane T Kagohara, Ashley L Kiemen, Elizabeth D Thompson, Denis Wirtz, Laura D Wood, Pei-Hsun Wu, Neeha Zaidi, Lei Zheng, Jacquelyn W Zimmerman, Jude M Phillip, Elizabeth M Jaffee, Joe W Gray, Lisa M Coussens, Young Hwan Chang, Laura M Heiser, Genevieve L Stein-O'Brien, Elana J Fertig, Paul Macklin

Faculty, Staff and Student Publications

Cells interact as dynamically evolving ecosystems. While recent single-cell and spatial multi-omics technologies quantify individual cell characteristics, predicting their evolution requires mathematical modeling. We propose a conceptual framework-a cell behavior hypothesis grammar-that uses natural language statements (cell rules) to create mathematical models. This enables systematic integration of biological knowledge and multi-omics data to generate in silico models, enabling virtual "thought experiments" that test and expand our understanding of multicellular systems and generate new testable hypotheses. This paper motivates and describes the grammar, offers a reference implementation, and demonstrates its use in developing both de novo mechanistic models and those informed …

Organizational Climate And Decision Aid Sustainability In Lupus Care: Mixed Methods Study, Aizhan Karabukayeva, Larry R Hearld, Nathan W Carroll, Reena Kelly, Jasvinder A Singh

Faculty, Staff and Students Publications

Background: Digital decision aids (DAs) are increasingly used in health care to support shared decision-making and promote patient engagement. In the context of systemic lupus erythematosus (SLE), a complex autoimmune disease characterized by diverse symptoms and uncertain prognoses, DAs offer guidance to patients in navigating treatment risks and benefits. Although numerous studies have examined the initial implementation of evidence-based tools, there is limited evidence on the organizational factors that influence their long-term sustainability in clinical practice. This gap is particularly salient for digital interventions, where integration into routine workflows and ongoing use require alignment with clinic readiness and culture. This …

A Religious Etiology Of Genito-Pelvic Pain And Pain With Penetration, Emily L. Carlson

Theses and Graduate Projects

Pelvic pain during penetration (PPDP) has been described using various diagnostic terms, including vaginismus, dyspareunia, and vulvodynia. The most recent and comprehensive classification is Genito-pelvic pain/penetration disorder (GPPPD) which is characterized by psychological distress associated with pain during or in anticipation of vaginal penetration (DSM-5-TR; American Psychiatric Association [APA], 2022). The etiology of PPDP is multifactorial, involving a complex interplay of biological, psychological, and relational factors. Religious and cultural influences may play a significant role in shaping individuals’ experiences of sexual pain. This study investigated the etiology of PPDP in relation to the religious influences among women raised in Judeo-Christian …

Targeted Proteomic Analysis Identifies Acvrl1 As A Marker Of Cerebral Edema In Aneurysmal Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Lena O'Keefe, Sarah Hinds, Hua Chen, Athziry Paz, Jude Savarraj, Han-Gil Jeong, Moon-Ku Han, Aaron Gusdon, Xuefang Sophie Ren, Spiros Blackburn, Huimahn Alex Choi

Faculty, Staff and Student Publications

Cerebral edema (CE) is a major component of early brain injury from aneurysmal subarachnoid hemorrhage (SAH). Despite the utility of blood-based protein markers, biomarkers targeting cerebral edema have yet to be developed. We performed a targeted proteomic search analyzing 141 proteins in plasma samples taken from 80 adult patients within 48 hours after aneurysmal rupture to identify plasma biomarkers of cerebral edema. The protein expression profiles were analyzed for associations with a higher level of the subarachnoid hemorrhage early brain edema score measured in admission computed tomography scans. Five differentially expressed proteins-brorin, ectodysplasin A2 receptor, layilin, scavenger receptor class A …

Clinical Validity Of Foundationone Liquid Cdx For Detection Of Braf V600e In Colorectal Cancer, Rona Yaeger, Jean-François Martini, Lincoln Pasquina, Brian Tunquist, Xiaosong Zhang, Fatima Khaiser, Norberto Panoja Galicia, Shibing Deng, Siliang Gong, Cui Guo, Jimmy Kiely, Ta-Chou Vincent Ng, Graham Ferrier, Josep Tabernero, Scott Kopetz

Faculty, Staff and Student Publications

Background: The BRAF inhibitor encorafenib plus the anti-EGFR antibody cetuximab improved overall survival, objective response rate, and progression-free survival in previously treated BRAF V600E-mutant metastatic colorectal cancer in BEACON, a phase 3 randomized trial, leading to regulatory approval for this indication. To support rapid, plasma-based testing for BRAF V600E identification, clinical validity of a circulating tumor DNA (ctDNA)-based assay, FoundationOne®Liquid CDx (F1LCDx) was assessed, versus the reference tumor-based clinical trial assay (CTA) in liquid biopsy-evaluable samples from BEACON and commercially-obtained tissue-matched plasma samples.

Methods: Pre-treatment tissue samples were collected in BEACON to confirm BRAF mutational status using the central single …

The Impact Of Different Antidiabetic Drugs On Fracture Risk In Patients With Type 2 Diabetes Mellitus: A Systematic Review And Network Meta-Analysis Of Randomized Controlled Trials With A Focus On Sglt2 Inhibitors, Bushra Admani, Fizza Z. Raza, Fatima Siddiqui, Muhammad T. Ashraf, Muhammad K. Khan, Ifra Habib, Ayesha Usman, Bareeha Mansoor, Zaira Nadeem, Rana J. Ghaffer, Muhammad Riyyan, Sawaira Sajid, Muhammad H. A. Chania, Mahnoor Saleem, Saad Javaid, Nikhil Duseja, Hussam Al Hennawi, Sunita Lakhani

Abington Jefferson Health Papers

SGLT2 inhibitors are a new class of antidiabetic drugs that have shown cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, their effects on fracture risk are unclear and may depend on the type and duration of treatment. This meta-analysis compares the fracture risk of different antidiabetic drugs, including SGLT2 inhibitors, based on data from randomized controlled trials (RCTs). We searched 4 databases for RCTs that reported fracture events in patients with T2DM who received different antidiabetic drugs. We included 117 RCTs that compared 9 types of antidiabetic drugs: SGLT2 inhibitors, DPP-4 inhibitors, α-glucosidase inhibitors, …

Germline Structural Variations Involving The Pediatric Brain Tumor Transcriptome Include Disease-Relevant And Ancestry-Related Genes, Fengju Chen, Yiqun Zhang, Luis F Paulin, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Background: Germline Structural Variants (SVs) represent an important source of genetic diversity, in large part due to their influence on gene transcription. It is necessary to systematically catalog germline SVs and their associated impacted genes across different cohorts and tissue and cellular contexts, including pediatric brain or Central Nervous System (CNS) tumors.

Methods: We combined RNA with whole genome sequencing across 1430 pediatric brain or CNS tumor patients from the Children's Brain Tumor Network. We set out to systematically identify genes for which the proximity of germline SVs was recurrently and significantly associated with differential expression in the tumor sample …

Immunogenicity And Safety Of A Rabies-Based Highly Pathogenic Influenza A Virus H5 Vaccine In Cattle, Nir Paran, Christoph Wirblich, Catherine Olal, Alessandro Tarquinio, Kimberly H. Lohmeyer, Drishya Kurup, Stacey Schultz-Cherry, Ismaila Shittu, Gregory C. Gray, Dennis A. Bente, Pia U. Olafson, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The circulation of highly pathogenic H5 influenza A viruses in cattle, other mammals, and wildlife threatens animal and human health. To address this, we vaccinated heifer-calves with a deactivated rabies-virus-based H5 vaccine, which was well-tolerated and elicited neutralizing antibodies against both clade-1 and clade-2.3.4.4b H5N1 viruses, comparable to naturally H5-infected and convalescing cows. The immune responses to the vaccine platform were durable for at least 200 days and unaffected by preexisting RABV immunity.

Causes Of Symptoms And Symptom Persistence In Long Covid And Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Anthony L Komaroff, Robert Dantzer

Faculty, Staff and Student Publications

Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural …

Nurse-Initiated Improvement For Documentation Of Penicillin Adverse Drug Reactions In Pediatric Urgent Care Clinics., Elizabeth Monsees, Diane Petrie, Rana El Feghaly, Sarah Suppes, Brian R. Lee, Megan Whitt, Amanda Nedved

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objective: Penicillin allergy labels (PALs) contribute to broad-spectrum antibiotic use. Thorough documentation can help prescribers identify and remove unnecessary PALs. We aimed to improve documentation of PALs in three pediatric urgent care (PUC) clinics, using a nurse-initiated quality improvement (QI) approach. Methods: QI interventions included a survey to assess prescriber and nurse confidence, an online educational module, and an algorithm to aid in clarifying PALs. We measured the percentage of PALs with a clarified reaction severity as our primary outcome using annotated control charts. Descriptive and inferential statistics evaluated survey responses between nurses and prescribers. Results: Clarified PAL reaction severity …

Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma

Faculty, Staff and Students Publications

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular …

Changes In Self-Reported Excessive Daytime Sleepiness Are Associated With 5-Year All-Cause Mortality Risk Among Veterans, Katherine G Bay, Arash Maghsoudi, Amin Ramezani, Drew A Helmer, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

Excessive daytime sleepiness (EDS) is linked to adverse clinical outcomes. This study evaluated changes in a validated tool to assess EDS, the Epworth Sleepiness Scale (ESS) and mortality risk. This retrospective cohort study included Veterans receiving sleep-related services in the Department of Veterans Affairs (VA) from October 4, 1999 to August 18, 2018, with two qualifying ESS measures. ESS values were extracted from patient notes using a validated natural language processing (NLP) pipeline (96% accuracy). ESS scores were categorised as Normal (0-10) or Abnormal (11-24). Patients were grouped based on ESS changes: Normal-Normal, Normal-Abnormal, Abnormal-Abnormal and Abnormal-Normal. Cox proportional hazards …

Current Practices In The Study Of Biomolecular Acondensates: A Community Comment, Simon Alberti, Paolo Arosio, Robert B Best, Steven Boeynaems, Danfeng Cai, Rosana Collepardo-Guevara, Gregory L Dignon, Rumiana Dimova, Shana Elbaum-Garfinkle, Nicolas L Fawzi, Monika Fuxreiter, Amy S Gladfelter, Alf Honigmann, Ankur Jain, Jerelle A Joseph, Tuomas P J Knowles, Keren Lasker, Edward A Lemke, Kresten Lindorff-Larsen, Reinhard Lipowsky, Jeetain Mittal, Samrat Mukhopadhyay, Sua Myong, Rohit V Pappu, Karsten Rippe, Tatyana A Shelkovnikova, Anthony G Vecchiarelli, Susanne Wegmann, Huaiying Zhang, Mingjie Zhang, Chloe Zubieta, Markus Zweckstetter, Dorothee Dormann, Tanja Mittag

Duncan NRI Faculty and Staff Publications

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes, fundamentally changing the study of biology. The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics. As such, they are intimately related to aqueous two-phase systems and water-in-water emulsions. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials–. …

Anti-Inflammatory Diet And Probiotic Supplementation As Strategies To Modulate Immune Dysregulation In Autism Spectrum Disorder, Carlos Andrés Naranjo-Galvis, Diana María Trejos-Gallego, Cristina Correa-Salazar, Jessica Triviño-Valencia, Marysol Valencia-Buitrago, Andrés Felipe Ruiz-Pulecio, Luisa Fernanda Méndez-Ramírez, Jovanny Zabaleta, Miguel Andres Meñaca-Puentes, Carlos Alberto Ruiz-Villa, Marcela Orjuela-Rodriguez, Juan Carlos Carmona-Hernández, Luisa Matilde Salamanca-Duque

School of Medicine Faculty Publications

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with behavioral and cognitive impairments. Increasing evidence also links ASD with systemic immune dysregulation, including abnormal cytokine profiles and chronic low-grade inflammation. Emerging evidence suggests that targeted dietary strategies and probiotic supplementation may modulate immune responses and gut–brain interactions in patients with ASD. This study aimed to evaluate the immunomodulatory effects of a structured anti-inflammatory diet (NeuroGutPlus) compared to multi-strain probiotics in children with ASD. NeuroGutPlus is a nutritionally complete anti-inflammatory dietary protocol that targets gut integrity, inflammation, and mitochondrial function. It includes a diet low in gluten, FODMAPs, casein, …