Medicine and Health Sciences Commons^™

Affinity Purification Mass Spectrometry Characterisation Of The Interactome Of Receptor Tyrosine Kinase Proline-Rich Motifs In Cancer, Christopher M Jones, Arndt Rohwedder, Kin Man Suen, Safoura Zahed Mohajerani, Antonio N Calabrese, Sabine Knipp, Mark T Bedford, John E Ladbury

Faculty, Staff and Student Publications

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40 % of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome. Here, we explore the …

Chatgpt And Google Assistant As A Source Of Patient Education For Patients With Amblyopia: Content Analysis, Gloria Wu, David A Lee, Weichen Zhao, Adrial Wong, Rohan Jhangiani, Sri Kurniawan

Faculty, Staff and Student Publications

Background: We queried ChatGPT (OpenAI) and Google Assistant about amblyopia and compared their answers with the keywords found on the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) website, specifically the section on amblyopia. Out of the 26 keywords chosen from the website, ChatGPT included 11 (42%) in its responses, while Google included 8 (31%).

Objective: Our study investigated the adherence of ChatGPT-3.5 and Google Assistant to the guidelines of the AAPOS for patient education on amblyopia.

Methods: ChatGPT-3.5 was used. The four questions taken from the AAPOS website, specifically its glossary section for amblyopia, are as follows: (1) What …

Outpatient Administration Of Car T-Cell Therapies Using A Strategy Of No Remote Monitoring And Early Crs Intervention, Fateeha Furqan, Vineel Bhatlapenumarthi, Binod Dhakal, Timothy S. Fenske, Faiqa Farrukh, Walter Longo, Othman Akhtar, Anita D'Souza, Marcelo Pasquini, Guru Subramanian Guru Murthy, Lyndsey Runaas, Sameem Abedin, Meera Mohan, Nirav N. Shah, Mehdi Hamadani

Abington Jefferson Health Papers

Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days …

The Impact Of Face Masks On Face-To-Face Neural Tracking Of Speech: Auditory And Visual Obstacles, M. Fantoni, A. Federici, I. Camponogara, G. Handjaras, A. Martinelli, E. Bednaya, E. Ricciardi, F. Pavani, D. Bottari

All Works

Face masks provide fundamental protection against the transmission of respiratory viruses but hamper communication. We estimated auditory and visual obstacles generated by face masks on communication by measuring the neural tracking of speech. To this end, we recorded the EEG while participants were exposed to naturalistic audio-visual speech, embedded in 5-talker noise, in three contexts: (i) no-mask (audio-visual information was fully available), (ii) virtual mask (occluded lips, but intact audio), and (iii) real mask (occluded lips and degraded audio). Neural tracking of lip movements and of the sound envelope of speech was measured through backward modeling, that is, by reconstructing …

Development Of A Selective Novel Fluorescent Substrate For Sodium-Dependent Transporters, Richard S. Agnes, Raymond F. Muzic Jr.

Faculty Scholarship

Aim: To synthesize, characterize, and validate 6FGA, a fluorescent glucose modified with a Cyanine5.5 at carbon-6 position, for probing the function of sodium-dependent glucose transporters, SGLT1 and SGLT2. Main methods: The synthesis of fluorescent glucose analogue was achieved through “click chemistry” of Cyanine5.5-alkyne and 6-azido-6-deoxy-D-glucose. Cell system studies were conducted to characterize the in vivo transport properties. Key findings: Optical analyses revealed that 6FGA displayed similar spectral profiles to Cyanine5.5 in DMSO, allowing for concentration determination, thus supporting its utility in quantitative kinetic studies within biological assays. Uptake studies in cell system SGLT models, LLC-PK1 and HEK293 cells, exhibited concentration …

3dmousenest: A Volumetric Label-Free Imaging Method Evaluating Embryo-Uterine Interaction And Decidualization Efficacy, Audrey Savolainen, Emmi Kapiainen, Veli-Pekka Ronkainen, Valerio Izzi, Martin M Matzuk, Diana Monsivais, Renata Prunskaite-Hyyryläinen

Faculty, Staff and Students Publications

Effective interplay between the uterus and the embryo is essential for pregnancy establishment; however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here, we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extra-embryonic tissues) growth. We demonstrate that …

Proteomics Meets Dose Response: A New Paradigm For Deciphering Drug Effects, Chenwei Wang, Bing Zhang

Faculty, Staff and Students Publications

In a groundbreaking study, Eckert and colleagues introduce DecryptE, an innovative approach to dose-resolved proteomics that significantly advances our understanding of drug effects at the proteomic level. This method integrates cutting edge sample preparation and mass spectrometry technologies, establishing a robust platform for high-throughput proteome analysis. DecryptE enables the quantification of more than 7,000 proteins per hour and was employed to study 144 clinical drugs and research compounds, generating more than 1 million dose-response curves using Jurkat acute T-cell leukemia cells as a model system. The platform demonstrates outstanding reproducibility, ensuring reliable and consistent results across multiple experiments. By providing …

Genetics And Genomics Of Pulmonary Fibrosis: Charting The Molecular Landscape And Shaping Precision Medicine, Ayodeji Adegunsoye, Jonathan A Kropski, Juergen Behr, Timothy S Blackwell, Tamera J Corte, Vincent Cottin, Allan R Glanville, Marilyn K Glassberg, Matthias Griese, Gary M Hunninghake, Kerri A Johannson, Michael P Keane, John S Kim, Martin Kolb, Toby M Maher, Justin M Oldham, Anna J Podolanczuk, Ivan O Rosas, Fernando J Martinez, Imre Noth, David A Schwartz

Faculty, Staff and Students Publications

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis and clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the …

Impact Of Gene-By-Trauma Interaction In Mdd-Related Multimorbidity Clusters, Sarah Bonk, Nora Eszlari, Kevin Kirchner, Andras Gezsi, Linda Garvert, Mikko Kuokkanen, Isaac Cano, Hans J. Grabe, Peter Antal, Gabriella Juhasz, Sandra Van Der Auwera

School of Medicine Publications

Background

Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters.

Methods

We analyzed 77,519 participants and 6,266,189 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was …

Zinc And Diabetes: A Connection Between Micronutrient And Metabolism, Rahnuma Ahmad, Ronald A. Shaju, Azeddine Atfi, Mohammed S. Razzaque

School of Medicine Publications

Diabetes mellitus is a global health problem and a major contributor to mortality and morbidity. The management of this condition typically involves using oral antidiabetic medication, insulin, and appropriate dietary modifications, with a focus on macronutrient intake. However, several human studies have indicated that a deficiency in micronutrients, such as zinc, can be associated with insulin resistance as well as greater glucose intolerance. Zinc serves as a chemical messenger, acts as a cofactor to increase enzyme activity, and is involved in insulin formation, release, and storage. These diverse functions make zinc an important trace element for the regulation of blood …

Single-Cell Analysis Of Innate Spinal Cord Regeneration Identifies Intersecting Modes Of Neuronal Repair, Vishnu Muraleedharan Saraswathy, Lili Zhou, Mayssa H Mokalled

2020-Current year OA Pubs

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an …

An Accurate And Rapidly Calibrating Speech Neuroprosthesis, Nicholas S Card, Matthew F Glasser, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy.

METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted …

Effects Of Prostaglandin Administration After Farrowing On Milk Output, Vaginal Discharge, And Mastitis During The Early Postpartum Period In Sows Under Field Conditions, G. Romano, R. Saleri, F. De Rensis, E. Dall’Olio, Padet Tummaruk, M. Andrani, C. Mazzoni

The Thai Journal of Veterinary Medicine

The present study evaluates the clinical effects of early post-partum prostaglandin administration on milk output, vaginal discharge and mastitis in sow. Two groups of sows were used: sows (n = 25) treated with prostaglandin F-2alpha (PGF-2α) intramuscularly 36 h after farrowing and a control group (n = 48) that did not receive any treatment. Seventy-two hours after farrowing, all animals were scored for rectal temperature, respiratory rate, feed ingestion, milk output, vaginal discharge and mastitis. Rectal temperature, feed intake, and milk output did not differ between the groups (P = 0.43). Regarding the clinical data, vaginal discharge was detected in …

Spontaneous Interatrial Hematoma: Still An Unresolved Critical Conundrum, Fayaz Mohammed Khazi, Imthiaz Manoly, Nayyer R Siddiqi, Tarek Abdel Aziz, Obaid Aljassim

Journal of the Saudi Heart Association

Spontaneous interatrial hematoma is a rare clinical entity leading to the obliteration of the left atrial cavity and causing haemodynamic compromise, necessitating immediate surgical intervention. Herein, we report a patient with acute chest pain with normal coronaries and echocardiographic evidence of left atrial mass. The investigations revealed the mass to be a thrombus rather than tumour. The patient underwent surgery to remove a large thrombus completely enclosed within the interatrial septum. The septum was then repaired using a pericardial patch. No apparent etiological factor was found. Spontaneous atrial wall dissection should be considered in the differential diagnosis of acute chest …

Gender Differences In Relations Between Social Comparison, Social Support, And Sleep Disturbance Among Midlife And Older Adults., Iris Bercovitz, Gabrielle M Salvatore, Jacqueline A Mogle, Danielle Arigo

College of Science & Mathematics Departmental Research

OBJECTIVE: To examine associations between sleep disturbance, social support, and social comparison among midlife and older adults, including the moderating role of gender.

METHODS: Adults ages ≥40 years (N = 557, MAge = 57, 53% men) completed a cross-sectional survey including validated measures of sleep disturbance, perceptions of social support, and social comparison orientation.

RESULTS: Sleep disturbance was negatively associated with social support (rs = −0.42 to–0.33, ps = 0.001) and associations were stronger for men than women–particularly perceived support from friends (η 2= 0.01). Sleep disturbance was also associated with upward comparison orientation (r = 0.12, p = 0.003), …

Thriving Transitions: Supporting Children With Autism Through Their Transition To School, Jennica Cano, Angela Blackwell

Summer 2024 OTD Capstone Symposium

Thriving Transitions is an educational guidebook created for parents of children with autism who are transitioning to school. Thriving transitions contains evidence and sensory based strategies for children with autism who are transitioning to school.

Development Of A Post Professional Neurorehabilitation Track At The University Of Zimbabwe, Alejandra Garcia, Angela L. Blackwell, Karen Aranha

Summer 2024 OTD Capstone Symposium

Collaborated to create an Occupational Therapy Post Professional Neurorehabilitation Track (OTPPNCT) blueprint for the University of Zimbabwe. This poster describes the background, methods, product and discussion for this capstone project.

Recruitment And Retention Of Physician Assistants In Rural Medicine: A Novel Approach, Sean Grabbe

Theses and Graduate Projects

Improving the health of patients requires having access to well trained medical providers. This is one of the main goals of the physician assistant profession. For many years research has documented how to recruit and retain physician assistants in the rural areas of the United States. Although created to fill the gaps in primary care medicine physician assistants have moved as all of medicine has into specialization. This gap in primary care has not closed and is most significant in rural areas. This paper reviews the plethora of research and elaborates on the known and best methods for recruitment and …

Development Of Vla4 And Cxcr4 Antagonists For The Mobilization Of Hematopoietic Stem And Progenitor Cells, Peter G Ruminski, Michael P Rettig, John F Dipersio

2020-Current year OA Pubs

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and …

Vaginitis And Risk Of Sexually Transmitted Infections: Results Of A Multi-Center U.S. Clinical Study Using Sti Nucleic Acid Amplification Testing, Jane R Schwebke, Paul Nyirjesy, Melissa Dsouza, Damon Getman

SKMC Student Presentations and Publications

Significant increases in rates of sexually transmitted infections (STIs) caused by Trichomonas vaginalis (TV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) are occurring in the United States. We present results of a U.S. study examining the intersection of STIs and vaginitis. Among 1,051 women with diagnoses for the presence or absence of bacterial vaginosis (BV) and/or symptomatic vulvovaginal candidiasis (VVC), 195 (18.5%) had one or more STIs, including 101 (9.6%) with TV, 24 (2.3%) with CT, 9 (0.8%) with NG, and 93 (8.8%) with MG. STI prevalence in BV-positive women was 26.3% (136/518), significantly higher than STI …

Structural Basis For A Polθ Helicase Small-Molecule Inhibitor Revealed By Cryo-Em, Fumiaki Ito, Ziyuan Li, Leonid Minakhin, Gurushankar Chandramouly, Mrityunjay Tyagi, Robert Betsch, John J. Krais, Bernadette Taberi, Umeshkumar Vekariya, Marissa L Calbert, Tomasz Skorski, Neil Johnson, Xiaojiang S. Chen, Richard T. Pomerantz

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

DNA polymerase theta (Polθ) is a DNA helicase-polymerase protein that facilitates DNA repair and is synthetic lethal with homology-directed repair (HDR) factors. Thus, Polθ is a promising precision oncology drug-target in HDR-deficient cancers. Here, we characterize the binding and mechanism of action of a Polθ helicase (Polθ-hel) small-molecule inhibitor (AB25583) using cryo-EM. AB25583 exhibits 6 nM IC50 against Polθ-hel, selectively kills BRCA1/2-deficient cells, and acts synergistically with olaparib in cancer cells harboring pathogenic BRCA1/2 mutations. Cryo-EM uncovers predominantly dimeric Polθ-hel:AB25583 complex structures at 3.0-3.2 Å. The structures reveal a binding-pocket deep inside the helicase central-channel, which underscores the high specificity …

Preceptor Toolkit Effects On New Graduate Nurse Orientation Experience, Ashley Dunnier

MSN Capstone Projects

The role of the nurse preceptor is vital to the successful onboarding of new graduate nurses to the organization. By focusing on preceptor support methods in addition to the established nursing preceptor programs, organizations can improve the nurse preceptor’s confidence and competency levels. The opportunities for improvement, solution recommendation, timeline, and associated costs are provided in this summary.

Many organizations have seen an increase in new graduate nurses leaving their jobs within their first year of hire. The transition period of new graduate nurses is often a period of transition shock while they acclimate into professional practice from academia (Fink …

Improving Palliative Care Knowledge In The Acute Care Setting, Laura C. Brumett

MSN Capstone Projects

Aim: The aim of this paper is to present an education intervention for bedside nursing staff to improve their palliative care knowledge and the end-of-life care provided for terminally ill patients.

Background: When dying in the hospital, patients experience higher discomfort, lower quality of life, and prolonged family grieving. Suffering worsens when patient needs are unmet and can contribute to a traumatic death. Providing end-of-life education will increase a nurse’s knowledge of palliative care, address knowledge gaps, and promote better patient outcomes through improved clinical practice.

Design: The proposed intervention has three prongs which include: (1) virtual training using the …

Sac1 Links Phosphoinositide Turnover To Cryptococcal Virulence, Elizabeth A Gaylord, Hau Lam Choy, Guohua Chen, Sydney L Briner, Tamara L Doering

2020-Current year OA Pubs

No abstract provided.

Manualized Occupational Therapy Intervention For Children And Adolescents With Post-Traumatic Stress Disorder, Adam J. Mcmahon, Steven M. Gerardi

Summer 2024 OTD Capstone Symposium

The capstone poster demonstrates the purpose for a manualized occupational therapy (OT) intervention for OT practitioners to treat children with post-traumatic stress disorder. The intervention uses an occupation-based approach informed by behavioral activation therapy and the model of human occupation principles. The manual includes two parts. Part one demonstrates the foundational principles for OT practitioners to obtain knowledge, skills, and tools before implementing the intervention. Part two outlines the treatment process beginning with evaluation, introducing manualized OT intervention to the child and the family member(s) and/or caregiver(s), treatment application, progress note, and discharge. The manualized OT intervention will allow OT …

Hyperpolarized Magnetic Resonance Imaging, Nuclear Magnetic Resonance Metabolomics, And Artificial Intelligence To Interrogate The Metabolic Evolution Of Glioblastoma, Kang Lin Hsieh, Qing Chen, Travis C Salzillo, Jian Zhang, Xiaoqian Jiang, Pratip K Bhattacharya, Shyan Shams

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a malignant Grade VI cancer type with a median survival duration of only 8-16 months. Earlier detection of GBM could enable more effective treatment. Hyperpolarized magnetic resonance spectroscopy (HPMRS) could detect GBM earlier than conventional anatomical MRI in glioblastoma murine models. We further investigated whether artificial intelligence (A.I.) could detect GBM earlier than HPMRS. We developed a deep learning model that combines multiple modalities of cancer data to predict tumor progression, assess treatment effects, and to reconstruct in vivo metabolomic information from ex vivo data. Our model can detect GBM progression two weeks earlier than conventional MRIs …

Hybridizing Mechanistic Modeling And Deep Learning For Personalized Survival Prediction After Immune Checkpoint Inhibitor Immunotherapy, Joseph D Butner, Prashant Dogra, Caroline Chung, Eugene J Koay, James W Welsh, David S Hong, Vittorio Cristini, Zhihui Wang

Faculty, Staff and Student Publications

We present a study where predictive mechanistic modeling is combined with deep learning methods to predict individual patient survival probabilities under immune checkpoint inhibitor (ICI) immunotherapy. This hybrid approach enables prediction based on both measures that are calculable from mechanistic models of key mechanisms underlying ICI therapy that may not be directly measurable in the clinic and easily measurable quantities or patient characteristics that are not always readily incorporated into predictive mechanistic models. A deep learning time-to-event predictive model trained on a hybrid mechanistic + clinical data set from 93 patients achieved higher per-patient predictive accuracy based on event-time concordance, …

Recurrent Inflammatory Myofibroblastic Tumor Of Larynx Harboring A Novel Thbs1::Alk Fusion, Namra Ajmal, Stacey Gargano, Ujwala Gosavi, Madalina Tuluc

Computational Medicine Center Faculty Papers

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor primarily occurring in the abdominopelvic region of young patients, and it is characterized by spindle-shaped myofibroblasts, or fibroblasts surrounded by inflammatory infiltrate. Herein, we report a case of a 24-year-old male with a firm submucosal mass in the anterior right vocal fold diagnosed as an IMT that recurred 14 months later. The tumor demonstrated a novel THBS1::ALK fusion containing Exons 1-7 of the thrombospondin 1 (THBS1) gene fused to Exon 19 of the anaplastic lymphoma kinase (ALK) gene via next-generation sequencing with the NextSeq sequencer. The fusion of THBS1 to …

Feasibility Study Of Mim Auto-Contouring For Head And Neck Patients That Have Dental Artifact Using A Metal Artifact Reduction Scan, Allison C. Munyer

Masters Projects

Introduction

Accurate contouring of organs at risk (OARs) is essential in the treatment of head and neck cancer, particularly in patients with metal dental artifacts that can obscure critical structures. The ability to precisely define these OARs is crucial for minimizing radiation exposure to healthy tissues and improving patient outcomes. To address the challenges posed by metal artifacts, Metal Artifact Reduction (MAR) technology, including iterative MAR (IMAR) scanning, has been widely adopted in radiation oncology.

Methods

This retrospective study evaluated the impact of IMAR scanning and Medical Image Merge (MIM) auto-contouring software on the accuracy and efficiency of contouring OARs …

Regulatory Complexity Of Cellular Differentiation In Candida Albicans Revealed Through Systematic Screening Of Protein Kinase Mutants, Michael C Lorenz

Faculty, Staff and Student Publications

A recent study in mBio reports the construction and preliminary screening of a library containing mutants of 99 of the 119 predicted protein kinases in Candida albicans (the majority of the remaining 20 are probably essential) (J. Kramara, M.-J. Kim, T. L. Ollinger, L. C. Ristow, et al., mBio e01249-24, 2024, https://doi.org/10.1128/mbio.01249-24). Using a quantitative competition assay in 10 conditions that represent nutritional, osmotic, cell wall, and pH stresses that are considered to model various aspects of the host environment allowed them to phenotypically cluster kinases, which highlight both the integration and specialization of signaling pathways, suggesting novel functions …