Digital Commons Network^™

A New Interpolated Pseudodifferential Preconditioner For The Helmholtz Equation In Heterogeneous Media, Sebastian Acosta, Tahsin Khajah, Benjamin Palacios

Faculty, Staff and Students Publications

This paper introduces a new pseudodifferential preconditioner for the Helmholtz equation in variable media with absorption. The pseudodifferential operator is associated with the multiplicative inverse to the symbol of the Helmholtz operator. This approach is well suited for the intermediate and high-frequency regimes. The main novel idea for the fast evaluation of the preconditioner is to interpolate its symbol, not as a function of the (high-dimensional) phase-space variables, but as a function of the wave speed itself. Since the wave speed is a real-valued function, this approach allows us to interpolate in a univariate setting even when the original problem …

Correction: Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel

Faculty, Staff and Students Publications

This corrects the article "Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials", 1570989.

Small Molecule-Based Regulation Of Gene Expression In Human Astrocytes Switching On And Off The G-Quadruplex Control Systems, Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov

Faculty, Staff and Student Publications

A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our …

Successful Treatment Of An Atypical Presentation Of Disseminated Retroperitoneal Seminoma: A Case Report, Mahmoud Abd-El-Hafez, Kylie Johnson, Joe Cates, Alosh Madala

HCA Healthcare Journal of Medicine

Background

Testicular seminoma is the most common malignant tumor of the testis. It occurs at a rate of 5 per 100 000 men, primarily between the ages of 15 to 34. While seminomas typically occur in the testis, other primary sites include the mediastinum, the retroperitoneum, or other extra-gonadal sites. Due to the curable nature of the malignancy (5-year survival rate > 95%), detection at early stages of the disease is key. This case presentation explores the delayed diagnosis and treatments of an atypical presentation of disseminated seminoma.

Case Presentation

We present the unusual case of a 56-year-old male who had …

Prosthetic Valve Endocarditis With Cardiobacterium Hominis: A Case Report, Kaci Griffin, Timothy Jang, Rees Adomako, Jasmine R. Marcelin, Jonathan H. Ryder

Graduate Medical Education Research Journal

Background: Cardiobacterium hominis (C. hominis) is an uncommon cause of infective endocarditis and often presents sub-acutely with fevers, cardiac murmurs, or embolic phenomena. We present a rare case of C. hominis infective prosthetic valve endocarditis that presented with new-onset atrial flutter and systemic emboli.

Case: A 38-year-old male presented to the emergency department with palpitations, shortness of breath, and chest tightness and was found to be in atrial flutter. He underwent a transesophageal echocardiogram-guided cardioversion and was incidentally found to have a one-centimeter echodensity on the ventricular side of his prosthetic aortic valve. (Figure 1.) He …

Perbandingan Konservatif Fisioterapi Dengan Core Stability Exercise Pada Kasus Nyeri Punggung Bawah, Angria Pradita, Nurul Halimah

Jurnal Fisioterapi Terapan Indonesia

ABSTRACT: Low back pain is a major complaint caused by multifactorial conditions. The most common factors of low back pain complaints are due to age, occupation and gender. This study aims to compare the differences in therapeutic effects of conservative physiotherapy with the provision of electrotherapy, namely; microwave diathermy combined with transcutaneous electrical nerve stimulation (TENS), core stability exercise techniques and a combination of electrotherapy with core stability exercise (CSE). This type of research is quasi experimental with a pre-post test design in a population of 90 low back pain patients who seek treatment at the Physiotherapy clinic. By using …

Thoracic Mobility And The Effects It Has On The Human Body: An Evidence To Practice Review, Megan Kurzec, Barton E. Anderson

Clinical Practice in Athletic Training

Decreased thoracic mobility, stability, and strength are prevalent issues in athletes, contributing to various musculoskeletal problems. This Evidence to Practice Review synthesizes findings from a guiding systematic review that identified exercises targeting the thoracic spine in athletes. The review included a comprehensive search across six databases, five journals, and five social media platforms, yielding 38 exercises designed to improve thoracic mobility, motor control, work capacity, and strength. Despite the low level of evidence (Level D), these exercises are widely used in clinical practice. This review provides a framework for exercise prescription, offering athletic trainers a range of exercise options to …

Partnerships To Improve Access To Healthcare For Refugees And Immigrants In Philadelphia, Jessica Deffler, Chelsea Salas-Tam, Jenna Gosnay, Marc Altshuler

Department of Family & Community Medicine Faculty Papers

The United States has welcomed refugees since World War II. Currently, the world is experiencing an unparalleled refugee crisis that calls for action by nations across the globe. There are over 82 million people who are forcibly displaced from their homes today (UNHCR Global Trends, Forced displacement in 2020. [cited 2021 Sep 28]. Available from: https://www.unhcr.org/flagship-reports/globaltrends/). Over the last decade, Philadelphia has become home to hundreds of refugees from countries in Southeast and Central Asia, Africa, the Middle East, as well as many others. For newly arrived refugees, finding stable housing, medical care, and employment is difficult due to cultural, …

Infrarenal Abdominal Aortic Pseudoaneurysm With Suspected Behcet Disease: A Unique Case Report, Harsya D. Gunardi, Danny Pratama, Andrio W. Prabowo, Nanang W. Hidayat, M Aprizal Putera, Grady Krisandi

The New Ropanasuri Journal of Surgery

Introduction. Abdominal aortic pseudoaneurysm caused by autoimmune vasculitis is a rare complication. Clinical presentation of patients is often late with life–threatening complications.

Case Illustration: A 62–year–old male patient with infrarenal abdominal aortic pseudoaneurysm presenting with a 2–week worsening severe abdominal and lumbar pain with a history of uncontrolled hypertension and a history of oral ulcer. He was successfully treated with tube grafting through open surgical repair.

Conclusion: The pseudoaneurysm was successfully removed and replaced with a polyester tube graft with no perioperative complications and was discharged 5 days later

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH

Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien

Faculty, Staff and Student Publications

Background: Previous studies have shown that hypertonic saline nasal irrigation and gargling reduced the duration of symptoms in upper respiratory infections caused by coronavirus. This study aims to investigate the effects of two saline regimens on symptoms associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods: Between 2020 and 2022, individuals aged 18-65 years who tested positive for SARS-CoV-2 infection via polymerase chain reaction (PCR) were randomly assigned to either low- or high-saline regimens for 14 days. The low-saline solutions contained 2.13 g of salt dissolved in eight ounces of warm water, while the high-saline solution contained six grams of …

Patient And Parent Knowledge, Understanding, And Concerns After A New Diagnosis Of Ehlers Danlos Syndrome., Jordan T. Jones, Lora L. Black, William R. Black

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis.6 METHODS: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs …

Dlk-Dependent Axonal Mitochondrial Fission Drives Degeneration After Axotomy, Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon

Faculty, Staff and Students Publications

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrate that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We find that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related …

Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey

Faculty, Staff and Students Publications

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and …

A Saudi Heart Association Position Statement On Cardiovascular Diseases And Diabetes Mellitus, Waleed Alhabeeb, Abdelfatah Elasfar, Abdulhalim Kinsara, Ahmed Aljizeeri, Ibrahim Jelaidan, Kamal Alghalayini, Mohammed F. Alkheraiji., Mousa Akbar, Sameh Lawand, Sarah M. Alyousif, Saud Alsifri, Taher Hassan

Journal of the Saudi Heart Association

Background: Cardiovascular disease (CVD) and diabetes mellitus are prominent public health concerns in Saudi Arabia owing to their increasingly high prevalence and burden. Based on this, the Saudi Heart Association (SHA) set out to develop an official position statement on CVD and diabetes mellitus, with a focus on the prevention and management of these conditions and relevant special populations in the context of Saudi Arabia.

Methods: A multidisciplinary panel of experts met under the auspices of the SHA in a series of meetings to review and discuss available evidence on the prevention and management of comorbid CVD and diabetes mellitus. …

A Conceptual Framework To Assess The Health, Socioeconomic And Environmental Burden Of Chronic Kidney Disease, Charlotte Johnston-Webber, Isaac Bencomo-Bermudez, George Wharton, Robin Van Kessel, Salvatore Barone, Francisco Brotons Muntó, Steven Chadban, Juan Jose Garcia Sanchez, Janwillem Kocks, Kyra Obolensky, Petra Sandow, Neil Skolnik, Ming-Hui Zhao, Alexei Volaco, David Wheeler, Alistair Mcguire, Elias Mossialos

Department of Medicine Faculty Papers

Chronic kidney disease (CKD) is a global health challenge that affects patients, caregivers, healthcare systems, the environment and national economies. Despite its far-reaching impact, there is no framework to systematically evaluate national CKD prevention and management programmes or evaluate the societal burden of disease. This paper has two objectives: first, to introduce a comprehensive framework to assess national programmes, which recognises gaps and weaknesses and identifies feasible policy interventions to reduce overall CKD burden; second, to present some key challenges and success stories in delivering CKD services delivered in eight different country settings. A literature review informed an initial version …

Improving Pediatric Magnetic Resonance Imaging Safety By Enhanced Non-Technical Skills And Team Collaboration, Masashi Uramatsu, Hidekuni Takahashi, Paul Barach, Yoshikazu Fujisawa, Megumi Takahashi, Shiro Mishima, Gaku Yamanaka

College of Population Health Faculty Papers

BACKGROUND: Safe pediatric magnetic resonance imaging (MRI) ideally relies on non-sedative techniques, as avoiding risky sedation is inherently safer. However, in practice, sedation often becomes unavoidable, particularly for younger children or those with anxiety, to ensure motion-free, high-quality imaging. This narrative review explores the current practices and proposes strategies to enhance safety in pediatric MRI examinations.

METHODS: We identified and analyzed 247 studies addressing various aspects of pediatric MRI safety, including sedation protocols, patient monitoring, and team-based management approaches.

RESULTS: Safe sedation requires careful drug selection tailored to individual needs, continuous monitoring, and robust emergency preparedness. While efforts are underway …

Inhibition Of Microrna-660-5p Decreases Breast Cancer Progression Through Direct Targeting Of Tmem41b, Valeria Villarreal-García, José Roberto Estupiñan-Jiménez, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejía, Marienid Flores-Colón, Irma Estefanía Ancira-Moreno, Patricio Adrián Zapata-Morín, Claudia Altamirano-Torres, José Manuel Vázquez-Guillen, Cristina Rodríguez-Padilla, Recep Bayraktar, Mohamed H Rashed, Cristina Ivan, Gabriel Lopez-Berestein, Diana Reséndez-Pérez

Faculty, Staff and Student Publications

Background: Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells. Accumulating evidence suggests that dysregulated microRNAs (miRNAs) promote breast cancer progression, metastasis, and drug resistance. Compared with healthy breast tissue, miR-660-5p is notably overexpressed in breast cancer tumor tissues. However, the downstream effectors of miR-660-5p in breast cancer cells have not been fully elucidated. Our aim was to investigate the role of miR-660-5p in breast cancer cell proliferation, migration, invasion, and angiogenesis and to identify its potential …

Protocol For Culturing Patient-Derived Organoids Of Cervical Cancer, Rui Wang, Timothy Harris, Dalissa Negrón-Figueroa, David Lo, Allison Judge, D'Shaunique Walters, Bo Jiang, Lauren E Colbert

Faculty, Staff and Student Publications

Herein, we present a protocol for culturing patient-derived organoids (PDOs) of cervical cancer that includes workflows for tumor biopsy/resection tissue and cytobrush-sampled cells. We describe steps for PDO culture initiation, including rinsing, gentle dissociation, Lymphoprep separation, and cell assessment, as well as seeding cells from surgical and cytobrush tissue digestion. We then provide guidance on PDO maintenance and passage and techniques for producing conditioned medium. Overall, this protocol serves as a valuable guide for establishing and maintaining cervical cancer PDOs. For complete details on the use and execution of this protocol, please refer to Colbert et al.

Womb, Gravity, And Space: Shifting Towards The Cerebellum-Basal Ganglia Paradigm In Dystonia, Diego Iacono

Department of Neurology Faculty Papers

No abstract provided.

Il-12 Encoding Ondv Synergizes With Car-T Cells In Orthotopic Models Of Non-Small Cell Lung Cancer, Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells …

Navigating Life After The Nicu: A Developmental Guide For Preterm And High-Risk Infants And Toddlers, Reagan Lachaussee, Mary Jan Greer Phd, Otr, Theresa Mensi

Fall 2024 OTD Capstone Symposium

Premature and medically fragile infants are at high risk for developmental delays and benefit from ongoing support. Parents often feel overwhelmed and uncertain about how to support their child’s development at home. This project addressed gaps in caregiver education and support by developing the PEARLS Program (Promoting Early Achievements, Resilience, and Life Skills), a practical resource tailored to the needs of families and healthcare providers.

A needs assessment and provider feedback guided the program’s development, identifying challenges such as information overload, confusion around corrected age, and feeding difficulties. The PEARLS Program empowers families with digestible, actionable resources, including …

Feasibility Of Large Language Models For Ceus Li-Rads Categorization Of Small Liver Nodules In Patients At Risk For Hepatocellular Carcinoma, Jiayan Huang, Rui Yang, Xiaotong Huang, Keyu Zeng, Yan Liu, Jun Luo, Andrej Lyshchik, Qiang Lu

Department of Radiology Faculty Papers

BACKGROUND: Large language models (LLMs) offer opportunities to enhance radiological applications, but their performance in handling complex tasks remains insufficiently investigated.

PURPOSE: To evaluate the performance of LLMs integrated with Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) in diagnosing small (≤20mm) hepatocellular carcinoma (sHCC) in high-risk patients.

MATERIALS AND METHODS: From November 2014 to December 2023, high-risk HCC patients with untreated small (≤20mm) focal liver lesions (sFLLs), were included in this retrospective study. ChatGPT-4.0, ChatGPT-4o, ChatGPT-4o mini, and Google Gemini were integrated with imaging features from structured CEUS LI-RADS reports to assess their diagnostic performance for sHCC. …

Deceased Donor Renal Allograft Utility In Adult Single And Multi-Organ Transplantation In The United States, Peter J. Altshuler, Adam S. Bodzin, Kenneth A. Andreoni, Pooja Singh, Anju Yadav, Jaime M. Glorioso, Ashesh P. Shah, Carlo B. Ramirez, Warren R. Maley, Adam M. Frank

Department of Surgery Faculty Papers

BACKGROUND: Deceased donor multiorgan transplants utilizing kidneys (MOTs) can improve outcomes for multiorgan recipients but reduces kidneys for chronic renal failure patients.

METHODS: We reviewed the Organ Procurement and Transplantation Network database from 2015 through 2019, for adult deceased donor kidney transplants. Recipients were classified as kidney transplant alone (KTA) (n = 62,252) or MOTs pancreas-kidney, simultaneous pancreas-kidney (n = 3,976), liver-kidney, simultaneous liver-kidney (n = 3,212), heart-kidney, simultaneous heart-kidney (n = 808), and "other"-kidney, simultaneous "other" kidney (n = 73).

RESULTS: Liver, heart, and lung-alone transplants were at least 7 times more frequent than their MOT correlate, whereas the …

Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Jessica R Watts, Jennifer L Spencer Clinton, Jeroen Pollet, Rongsheng Peng, Jie Tan, Paul D Ling

Faculty, Staff and Students Publications

Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily …

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Jesse D Bengtsson, Sameer S Bajikar, Christopher M Grochowski, Ming Yin Lun, Mira Gandhi, Angad Jolly, Alexander J Trostle, Holly K Harris, Bernhard Suter, Sukru Aras, Melissa B Ramocki, Haowei Du, Michele G Mehaffey, Kyunghee Park, Ellen Wilkey, Cemal Karakas, Jesper J Eisfeldt, Maria Pettersson, Lynn Liu, Marwan S Shinawi, Virginia E Kimonis, Wojciech Wiszniewski, Kyle Mckenzie, Timo Roser, Angela M Vianna-Morgante, Alberto S Cornier, Ahmed Abdelmoity, James P Hwang, Shalini N Jhangiani, Donna M Muzny, Tadahiro Mitani, Kazuhiro Muramatsu, Shin Nabatame, Daniel G Glaze, Jawid M Fatih, Richard A Gibbs, Zhandong Liu, Anna Lindstrand, Fritz J Sedlazeck, James R Lupski, Huda Y Zoghbi, Claudia M B Carvalho

Faculty, Staff and Students Publications

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints < 5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …

Pathways From Socioeconomic Factors To Major Cardiovascular Events Among Postmenopausal Veteran And Nonveteran Women: Findings From The Women's Health Initiative, Hind A Beydoun, May A Beydoun, Rebecca L Kinney, Simin Liu, Rona Yu, Matthew Allison, Robert B Wallace, Qian Xiao, Longjian Liu, Philippe Gradidge, Su Yon Jung, Hilary A Tindle, Shawna Follis, Robert Brunner, Jack Tsai

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women.

METHODS AND RESULTS: A total of 121 286 study-eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which …

Large-Scale Crispr/Cas9 Deletions Within The Wfdc Gene Cluster Uncover Gene Functionality And Critical Roles In Mammalian Reproduction, Katarzyna Kent, Kaori Nozawa, Rachel Parkes, Laura Dean, Frey Daniel, Mei Leng, Antrix Jain, Anna Malovannaya, Martin M Matzuk, Thomas X Garcia

Faculty, Staff and Students Publications

Despite 96 million years of evolution separating humans and rodents, 11 closely related reproductive tract-specific genes in humans—SPINT3, WFDC6, EPPIN, WFDC8, WFDC9, WFDC10A, WFDC11, WFDC10B, WFDC13, SPINT4, and WFDC3—and the 13 reproductive tract-specific orthologous genes in mice, form highly conserved syntenic gene clusters indicative of conserved, combined critical functions. Further, despite significant progress toward a nonhormonal male contraceptive targeting the protein encoded by one of these genes, epididymal peptidase inhibitor (EPPIN), and associations found between mutations in EPPIN and an increased risk of male infertility, neither EPPIN nor …

The Doing, Being, Becoming, And Belonging Of Intergenerational Collective Occupations, Gladys Garcia, Jazminne Orozco-Arteaga

Fall 2024 OTD Capstone Symposium

Background: Older adults have been globally recognized as a vulnerable population. Literature has indicated that intergenerational engagement can decrease social isolation for older adults, but there is a gap in understanding intergenerational co-occupational engagement and how these engagements can improve quality of life and fulfillment of self-identity. The purpose of this qualitative research study was to generate knowledge of how relationships and occupations performed with individuals from a younger generation impacted sense of well-being. Through the lens of Doing, Being, Becoming and Belonging (Wilcock, 2006), the study sought to increase understanding of this lived experience to promote intergenerational practice within …

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Xin Yu, Dong Lu, Xiaoli Qi, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …