Digital Commons Network^™

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Cone Beam Ct Dose Optimisation: A Review And Expert Consensus By The 2022 Estro Physics Workshop Igrt Working Group, Lydia J. Wilson, Andria Hadjipanteli, Daniella E. Østergaard, Evelien Bogaert, Kirstie F. Brown, Rianne Dejong, James Earley, Magali Edouard, Marina Khan, Josh Lindsay, Jessica Van Der Himst, George X. Ding, Tim Wood, Marianne C. Aznar, Nuria Jornet, Georgios Ntentas

Department of Radiation Oncology Faculty Papers

Image guided radiotherapy (IGRT) using kilovoltage cone-beam CT (CBCT) has become an indispensable tool to ensure the geometric accuracy of radiotherapy treatment delivery. Although significant technical advances have been made in reducing imaging dose, the repeated imaging procedures can still accumulate significant dose to healthy tissues. Despite the widespread use, we still lack clear guidance for optimisation and widely accepted frameworks for evaluating the quality and suitability of CBCT imaging protocols. To address this gap, the 2022 European Society for Radiotherapy and Oncology (ESTRO) Physics Workshop focused on image-quality and imaging-dose optimisation for IGRT using CBCT. This publication represents a …

Steps Toward Clinical Validation Of Exhaled Volatile Organic Compound Biomarkers For Hypoglycemia In Persons With Type 1 Diabetes., Mark Woollam, Paula Angarita-Rivera, Sanskar Thakur, Ali Daneshkhah, Amanda P Siegel, Dana S Hardin, Mangilal Agarwal

Ambulatory and Primary Care Articles

Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG <  70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.

The Cgas/Sting Pathway: Friend Or Foe In Regulating Cardiomyopathy, Weiyue Wang, Yuanxu Gao, Hyun Kyoung Lee, Albert Cheung-Hoi Yu, Markus Kipp, Hannes Kaddatz, Jiangshan Zhan

Duncan NRI Faculty and Staff Publications

Inflammation is a central hallmark of cardiomyopathy, where misdirected immune responses contribute to chronic myocardial dysfunction. Among the emerging molecular mechanisms implicated in this process, the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has garnered increasing attention. Acting as a key cytosolic DNA sensor, the cGAS/STING pathway orchestrates inflammatory responses triggered by microbial infections or endogenous cellular stressors such as autophagy and apoptosis. Despite its pivotal role, the precise molecular mechanisms regulating this pathway and its role in cardiomyopathy-associated inflammation remain poorly understood and subject to ongoing debate. To address this scientific gap, we first reviewed key …

“Non-Markovian” And “Directional” Errors Inhibit Scientific Self-Correction And Can Lead Fields Of Study Astray: An Illustration Using Gardening And Obesity-Related Outcomes, Jon Agley, Sarah E Deemer, David B Allison

Children’s Nutrition Research Center Staff Publications

Herein we coin the terms non-Markovian error and biased Markovian error to describe categories of scientific errors for which general progress within a field of study may be unlikely to result in scientific self-correction. We provide examples of such errors and show their impact on studies about gardening and obesity.

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Prevalence, Experience, And Awareness Of Substandard And Falsified Medicines Among The Public And Healthcare Professionals In Jordan., Maysa Falah, Eman Daar, Daniel Zahra, Michael Dillon

Peninsula Medical School

INTRODUCTION: This study aimed to assess the awareness, experiences and perspectives on substandard and falsified (SF) medicines among the general public and healthcare professionals in Jordan. SF medicines pose a global public health concern, yet data on their prevalence and associated risks in Jordan remain limited.

METHODS: A cross-sectional study was conducted between January and June 2023 using a convergent mixed-methods approach. Quantitative data were collected through structured surveys administered to 209 members of the public and 136 healthcare professionals (pharmacists and clinicians) recruited via convenience sampling across Jordan's 12 governorates. Surveys were conducted in English and Arabic. Qualitative data …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

Personalizing Neoadjuvant Chemotherapy Regimens For Triple-Negative Breast Cancer Using A Biology-Based Digital Twin, Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens …

A Hierarchy Of Pdz Domain Scaffolding Proteins Clusters The Kv1 K+ Channel Protein Complex At The Axon Initial Segment, Wei Zhang, Victoria L Palfini, Yu Wu, Xiaoyun Ding, Allison J Melton, Yudong Gao, Yuki Ogawa, Matthew N Rasband

Faculty, Staff and Students Publications

Action potentials are initiated and modulated at the axon initial segment (AIS) by highly clustered ion channels. Voltage-gated Kv1 potassium channels underlie most outward AIS K+ current. AIS Kv1 channels exist in a large protein complex including ADAM22, Caspr2, and LGI1. However, their clustering mechanisms remain unknown. Because Kv1 channels have a highly conserved PDZ-binding motif, we used CRISPR-based genome editing to screen 18 PDZ domain-containing proteins identified in our previous AIS proximity proteome for their AIS localization. Among these, we found that the scaffolding proteins SCRIB and PSD93 are highly enriched at the AIS. Using CRISPR-mediated knockout, cell surface …

Decoding Resistance To Immune Checkpoint Inhibitors In Non-Small Cell Lung Cancer: A Comprehensive Analysis Of Plasma Proteomics And Therapeutic Implications, Michal Harel, Nili Dahan, Coren Lahav, Eyal Jacob, Yehonatan Elon, Igor Puzanov, Ronan J. Kelly, Yuval Shaked, Raya Leibowitz, David P. Carbone, David R. Gandara, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown substantial benefit for patients with advanced non-small cell lung cancer (NSCLC). However, resistance to ICIs remains a major clinical challenge. Here, we perform a comprehensive bioinformatic analysis of plasma proteomic profiles to explore the underlying biology of treatment resistance in NSCLC.

METHODS: The analysis was performed on 388 "resistance-associated proteins" (RAPs) that were previously described as pretreatment plasma proteomic predictors within the PROphet computational model designed to predict ICI clinical benefit in NSCLC. Putative tissue origins of the RAPs were explored using publicly available datasets. Enrichment analyses were performed to investigate RAP-related biological …

Increasing Advance Directive Completion: A Future Initiative For All, Hilda A. Lince

Doctor of Nursing Practice Final Manuscripts

Abstract

Problem Statement: Healthcare providers focus on delivering quality and patient-centered care. Yet, without any direction, healthcare providers treat patients as a full code until someone can speak on the patient’s behalf. Therefore, it is crucial that patients make their wishes known.

Description of Innovation: On a cardiac step-down unit, registered nurses were educated on the PREPARE advance directive. Upon admission to the unit, patients were asked if they had an advance directive. If the patient did not have an advance directive, they were educated on the importance of having an advance directive. Then they were given the PREPARE …

A Review Of Medical Ethics In Orthopaedic Surgery: Current Foci And Future Considerations, Ryan X Lam, Zhi Mei Sonia He, Ruhi Thapar, Maggie Wang, Dion G Birhiray, Matthew Milad, Lara Ouellette, Umar Ghilzai, Tucker J Cushing, M Brent Price, Brenden B Ronna, Omar H Atassi, Christopher H Perkins, John R Dawson, William M Granberry, Melvyn A Harrington, Douglas R Dirschl, Lorenzo R Deveza

Library Staff Publications

Medical ethics education is a required component of orthopaedic surgery resident training per the Accreditation Council for Graduate Medical Education (ACGME) guidelines, although no standardized curriculum currently exists.

Beyond the 4 principles of bioethics (autonomy, beneficence, nonmaleficence, justice), additional ethical concepts relevant to orthopaedic care include utilitarianism, deontology, virtue ethics, moral intuitionism, microethics, and narrative ethics.

Ethical themes identified in the literature relevant to orthopaedic surgery include the ethics involved in medical decision-making, use of new technologies, caring for vulnerable patients, performing high-stakes procedures, the impacts of trainee status on patient care, and patient attitude regarding conflict of interest.

Ethical …

Comprehensive Evaluation Of Phosphoproteomic-Based Kinase Activity Inference, Sophia Müller-Dott, Eric J Jaehnig, Khoi Pham Munchic, Wen Jiang, Tomer M Yaron-Barir, Sara R Savage, Martin Garrido-Rodriguez, Jared L Johnson, Alessandro Lussana, Evangelia Petsalaki, Jonathan T Lei, Aurelien Dugourd, Karsten Krug, Lewis C Cantley, D R Mani, Bing Zhang, Julio Saez-Rodriguez

Faculty, Staff and Students Publications

Kinases regulate cellular processes and are essential for understanding cellular function and disease. To investigate the regulatory state of a kinase, numerous methods have been developed to infer kinase activities from phosphoproteomics data using kinase-substrate libraries. However, few phosphorylation sites can be attributed to an upstream kinase in these libraries, limiting the scope of kinase activity inference. Moreover, inferred activities vary across methods, necessitating evaluation for accurate interpretation. Here, we present benchmarKIN, an R package enabling comprehensive evaluation of kinase activity inference methods. Alongside classical perturbation experiments, benchmarKIN introduces a tumor-based benchmarking approach utilizing multi-omics data to identify highly active …

Untargeted Proteomics Enables Ultra-Rapid Variant Prioritisation In Mitochondrial And Other Rare Diseases, Daniella H Hock, Nikeisha J Caruana, Liana N Semcesen, Nicole J Lake, Luke E Formosa, Sumudu S C Amarasekera, Tegan Stait, Simone Tregoning, Leah E Frajman, Adam M Bournazos, David R L Robinson, Megan Ball, Boris Reljic, Bryony Ryder, Mathew J Wallis, Anand Vasudevan, Cara Beck, Heidi Peters, Joy Lee, Natalie B Tan, Mary-Louise Freckmann, Mitomdt Diagnostic Network For Genomics And Omics, Vasiliki Karlaftis, Chantal Attard, Paul Monagle, Amanda Samarasinghe, Rosie Brown, Weimin Bi, Monkol Lek, Robert Mcfarland, Robert W Taylor, Michael T Ryan, Sandra T Cooper, Zornitza Stark, John Christodoulou, Alison G Compton, David R Thorburn, David A Stroud

Faculty, Staff and Students Publications

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Methods: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Subcortical Correlates Of Consciousness With Human Single Neuron Recordings, Michael Pereira, Nathan Faivre, Fosco Bernasconi, Nicholas Brandmeir, Jacob E Suffridge, Kaylee Tran, Shuo Wang, Victor Finomore, Peter Konrad, Ali Rezai, Olaf Blanke

2020-Current year OA Pubs

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness remains unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing …

A Cross-Sectional Study Of The Role Of Epithelial Cell Injury In Kidney Transplant Outcomes, Philip F. Halloran, Tarek Alhamad, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.

METHODS: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.

RESULTS: In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. …

Identification Of Surrogate Biomarkers For Mucopolysaccharidosis Type Iva, Yasuhiko Ago, Shaukat Khan, Kimberly Klipner, Allison Bradford, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 …

In Vivo Crispr Activation Screen Identifies Acyl-Coa-Binding Protein As A Driver Of Bone Metastasis, Hongqi Teng, Qinglei Hang, Caishang Zheng, Yuelong Yan, Shaomin Liu, Yang Zhao, Yalan Deng, Litong Nie, Weiche Wu, Marisela Sheldon, Zachary Yu, Wei Shi, Jianxuan Gao, Chenling Meng, Consuelo Martinez, Jie Zhang, Fan Yao, Yutong Sun, Di Zhao, Boyi Gan, Tong Meng, Li Ma

Faculty, Staff and Student Publications

One of the most common sites of cancer metastasis is to the bone. Bone metastasis is associated with substantial morbidity and mortality, and current therapeutic interventions remain largely palliative. Metastasizing tumor cells need to reprogram their metabolic states to adapt to the nutrient environment of distant organs; however, the role and translational relevance of lipid metabolism in bone metastasis remain unclear. Here, we used an in vivo CRISPR activation screening system coupled with positive selection to identify acyl-coenzyme A (CoA) binding protein (ACBP) as a bone metastasis driver. In nonmetastatic and weakly metastatic cancer cells, overexpression of wild-type ACBP, but …

Simultaneous Targeting Of Tumor Cells And Tumor-Associated Macrophages To Reprogram Glioblastoma Using Trypsinized Extracellular Vesicles Carrying Tumor Suppressive Microrna, Grace H Nguyen, Minhye Noh, Jin Muk Kang, Alexandra A Miller, Minxin Huang, Jiyeon Kim, Jeong-Yeon Lee, Sangwoon Chung, Hongyu Wang, George A Calin, Cynthia Ju, Holger K Eltzschig, Yeshavanth Banasavadi-Siddegowda, Zhongming Zhao, Ji Young Yoo, Tae Jin Lee

Faculty, Staff and Student Publications

Glioblastoma (GBM) remains difficult to treat due to poor drug delivery across the blood-brain barrier and an immunosuppressive tumor microenvironment (TME). Tumor-suppressive microRNAs (miRNAs) offer a promising strategy to reprogram both tumor cells and the TME, but inefficient delivery systems limit their clinical application. We previously reported that tumor-suppressive miR-138 regresses tumor growth in preclinical GBM models. Here, we demonstrate that trypsin digestion of extracellular vesicles (EVs) enhances labeling efficiency with folate (FA), enhancing selective targeting of folate receptor (FR)-positive GBM cells and enabling simultaneous targeting of tumor-associated macrophages (TAMs). FA-labeled trypsinized EVs (tEVs) loaded with miR-138 inhibit tumor growth, …

A Review Of Mirvetuximab Soravtansine-Gynx In Folate Receptor Alpha-Expressing Platinum-Resistant Ovarian Cancer, Judith A Smith, Patrick Medina, Mary Miao, Kathleen N Moore

Faculty, Staff and Student Publications

Purpose: To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).

Summary: A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed. Mirvetuximab soravtansine-gynx is dosed at 6 mg/kg AIBW every 3 weeks and comprises an FRα-binding antibody, a hydrophilic disulfide linker, and a maytansinoid DM4 payload. Mirvetuximab soravtansine-gynx binds to FRα, which induces …

Conveying The Need For Mental Healthcare – A Qualitative Study Of How Patients Communicate Mental Health Challenges’, Marit Nymoen, Marit Lomeland, Eva Biringer, Mirjam Extedt, Øystein Hetlevik, Rod Sheaff, Olav Thorsen, Miriam Hartveit

Peninsula Medical School

Background: Access to timely mental healthcare relies on patients’ descriptions of their mental health problems. We therefore sought to better understand, from the patients’ perspective, how they communicate their need for specialised mental healthcare to their GPs or mental health specialists and what factors affect communication when patients are referred from their GPs to specialised mental healthcare. Methods: This was an exploratory interview study. Ten adults who started treatment in specialised mental healthcare facilities were interviewed individually. The interviews were audiotaped and transcribed verbatim. A method based on thematic analysis was used to develop patterns and themes within the dataset …

Turning Analysis Into Action: Opportunities And Challenges In Implementing Wastewater Science For Public Health Decision-Making, Anna Gitter, Valeria Ruvalcaba, Katelyn Clark, Theresa Tran Carapucci, Fuqing Wu, Blake M Hanson, Jennifer Deegan, John Balliew, Eric Boerwinkle, Anthony W Maresso, Kristina D Mena

Faculty, Staff and Students Publications

In the 5 years since the emergence of the COVID-19 pandemic, the field of wastewater-based epidemiology (WBE) has dramatically expanded with programs implemented across the globe to monitor for SARS-CoV-2 and other viruses of public health concern. However, the best way to use wastewater surveillance data and inform local communities of the utility of wastewater science remains limited and sporadically discussed. Specifically, there is vague guidance regarding interpreting varying levels of viral loads in wastewater for public health significance. While collaborative efforts are key to implementing these community-specific wastewater surveillance programs, effectively using the data for public health decision-making still …

Global Dna Methylation Differences Involving Germline Structural Variation Impact Gene Expression In Pediatric Brain Tumors, Fengju Chen, Yiqun Zhang, Wei Li, Fritz J Sedlazeck, Lanlan Shen, Chad J Creighton

Children’s Nutrition Research Center Staff Publications

The extent of genetic variation and its influence on gene expression across multiple tissue and cellular contexts is still being characterized, with germline Structural Variants (SVs) being historically understudied. DNA methylation also represents a component of normal germline variation across individuals. Here, we combine germline SVs (by short-read sequencing) with tumor DNA methylation across 1292 pediatric brain tumor patients. For thousands of methylation probes for CpG Islands (CGIs) or enhancers, rare and common SV breakpoints upstream or downstream associate with differential methylation in tumors spanning various histologic types, a significant subset involving genes with SV-associated differential expression. Cancer predisposition genes …

Treatment Of Overactive Katp Channels With Glibenclamide In A Zebrafish Model And A Clinical Trial In Humans With Cantú Syndrome, Lotte Kleinendorst, Sarah E Siegelaar, Helen I Roessler, Lema Meiwand, Malou Van Den Boogaard, Rianne H A C M De Bruin-Bon, Kirsten F Van Duinen, R Nils Planken, Elisabeth H Jaspars, Patrick M J H Kemperman, Berto J Bouma, Colin G Nichols, Marcel W Bekkenk, Gijs W Van Haaften, Mieke M Van Haelst

2020-Current year OA Pubs

This study explores the efficacy of glibenclamide, a K

Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Because of their ubiquitous presence, ions interact with numerous macromolecules in the cell and affect critical biological processes. Here, we discuss how cations including Mg²⁺ alter the enzymatic activity of a DNA glycosylase by tuning its affinity for DNA. The response of uracil DNA glycosylase (UNG2) to Mg²⁺ ions in solution is biphasic and paradoxical, where low concentrations of the ion stimulate the enzyme, but high concentrations inhibit the enzyme. We analyzed this phenomenon by modeling experimental data with a statistical framework that we empirically derived to understand molecular systems that display biphasic behaviors. Parameters from our statistical …

Caspase-11 Drives Macrophage Hyperinflammation In Models Of Polg-Related Mitochondrial Disease., Jordyn J Vanportfliet, Yuanjiu Lei, Muthumeena Ramanathan, Camila Guerra Martinez, Jessica Wong, Tim J Stodola, Brian Hoffmann, Kathryn Pflug, Raquel Sitcheran, Stephen C. Kneeland, Stephen A Murray, Peter J Mcguire, Carolyn L Cannon, A Phillip West

Faculty Research 2025

Mitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and lack of effective therapies. Environmental exposures, such bacterial and viral infection, can further compromise mitochondrial function and exacerbate the progression of MtD. However, the underlying immune alterations that enhance immunopathology in MtD remain unclear. Here we employ in vitro and in vivo approaches to clarify the molecular and cellular basis for innate immune hyperactivity in models of polymerase gamma (Polg)-related MtD. We reveal that type I interferon (IFN-I)-mediated upregulation of caspase-11 and guanylate-binding proteins (GBP) increase macrophage sensing of …