Digital Commons Network^™

Refractory Chronic Spontaneous Urticaria After Heterologous Covid-19 Booster Vaccination, Miranda Crista Tomaras, Leah Michelle Douglas, Rosa Michelle Schmidt, Maria Suzanne Bloomquist, Abdul Hafeez Diwan, Soo Jung Kim

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) involves recurrent, pruritic wheals lasting more than 6 weeks in response to various etiologies, including unknown causality. Though most cutaneous reactions to the COVID-19 vaccine series are self-limited and of short duration, more complex presentations including chronic spontaneous urticaria have been described. To the best of our knowledge, this is the first report of chronic spontaneous urticaria following heterologous mRNA COVID-19 booster vaccination that includes vaccination with both forms of the mRNA vaccine. Our patient received Pfizer-BioNTech for the primary series and Moderna for the booster. After failing several therapies, our patient's urticaria was refractory even …

Treating Sex And Gender Differences As A Continuous Variable Can Improve Precision Cancer Treatments, Wei Yang, Joshua B Rubin

2020-Current year OA Pubs

BACKGROUND: The significant sex and gender differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. One barrier to translation is that cancer phenotypes cannot be segregated into distinct male versus female categories. Instead, within this convenient but contrived dichotomy, male and female cancer phenotypes are highly overlapping and vary between female- and male- skewed extremes. Thus, sex and gender-specific treatments are unrealistic, and our translational goal should be adaptation of treatment to the variable effects of sex and gender on targetable pathways.

METHODS: To overcome this obstacle, we profiled the similarities in 8370 transcriptomes …

Akap12 Upregulation Associates With Pde8a To Accelerate Cardiac Dysfunction, Hanan Qasim, Mehrdad Rajaei, Ying Xu, Arfaxad Reyes-Alcaraz, Hala Y Abdelnasser, M David Stewart, Satadru K Lahiri, Xander H T Wehrens, Bradley K Mcconnell

Faculty, Staff and Students Publications

BACKGROUND: In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3',5'-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins) regulate cardiac function and are proposed as targets for precise pharmacology. AKAP12 is expressed in the heart and has been reported to directly bind β2-adrenergic receptor, PKA, and PDE4D. However, its roles in cardiac function are unclear.

METHODS: cAMP accumulation in real time downstream of the β2-adrenergic receptor was detected for …

Capn2 Correlates With Insulin Resistance States In Pcos As Evidenced By Multi-Dataset Analysis, Xi Luo, Yunhua Dong, Haishan Zheng, Xiaoting Zhou, Lujuan Rong, Xiaoping Liu, Yun Bai, Yunxiu Li, Ze Wu

Faculty, Staff and Student Publications

OBJECTIVE: IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies.

METHODS: We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR …

Photophobia Is Associated With Lower Sleep Quality In Individuals With Migraine: Results From The American Registry For Migraine Research (Armr), Nina Sharp, Mark J Burish, Kathleen B Digre, Jessica Ailani, Mahya Fani, Sophia Lamp, Todd J Schwedt

Faculty, Staff and Student Publications

BACKGROUND: Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aimed to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine.

METHODS: A cross-sectional observational study was conducted using …

"In Our Community, We Normalize Pain": Discussions Around Menstruation And Uterine Fibroids With Black Women And Latinas, Minerva Orellana, Karen N Dsouza, Jane Q Yap, Abhirami Sriganeshan, M Elena Jones, Charis Johnson, Megan Allyse, Sateria Venable, Elizabeth A Stewart, Felicity Enders, Joyce E Balls-Berry

2020-Current year OA Pubs

BACKGROUND: Uterine fibroids are non-cancerous neoplasms that arise from the uterus affecting over 75% of women. However, there is a disparity with Black women having an increased prevalence of nearly 80%. Black women also experience increased symptom burden, including younger age at the time of diagnosis and increased number and volume of fibroids. Less is known about other ethnoracially diverse women such as Latinas and the potential cultural impacts on fibroid burden and treatment.

METHODS: Community engagement studios were conducted to facilitate discussions with stakeholders on their uterine fibroid and menstruation experience. We recruited Black women (n = 6) diagnosed …

Phase 1b Study Of Intraperitoneal Ipilimumab And Nivolumab In Patients With Recurrent Gynecologic Malignancies With Peritoneal Carcinomatosis, Anne Knisely, Emily Hinchcliff, Bryan Fellman, Ann Mosley, Kathryn Lito, Sara Hull, Shannon N Westin, Anil K Sood, Kathleen M Schmeler, Jolyn S Taylor, Steven Y Huang, Rahul A Sheth, Karen H Lu, Amir A Jazaeri

Faculty, Staff and Student Publications

Background: Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity.

Methods: In this phase 1b study, registered at Clinical.

Trials: gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Findings: …

‘Joining The Dots: Linking Prenatal Drug Exposure To Childhood And Adolescence’ – Research Protocol Of A Population Cohort Study, Kate Lawler, Mithilesh Dronavalli, Andrew Page, Evelyn Lee, Hannah Uebel, Barbara Bajuk, Lucinda Burns, Michelle Dickson, Charles Green, Lauren Dicair, John Eastwood, Ju Lee Oei

Faculty, Staff and Student Publications

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The

METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal …

‘Joining The Dots: Linking Prenatal Drug Exposure To Childhood And Adolescence’ – Research Protocol Of A Population Cohort Study, Kate Lawler, Mithilesh Dronavalli, Andrew Page, Evelyn Lee, Hannah Uebel, Barbara Bajuk, Lucinda Burns, Michelle Dickson, Charles Green, Lauren Dicair, John Eastwood, Ju Lee Oei

Faculty, Staff and Student Publications

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The

METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal …

Targeted Deletion Of Nr2f2 And Vcam1 In Theca Cells Impacts Ovarian Follicular Development: Insights Into Polycystic Ovary Syndrome?†, Nicholes R Candelaria, Joanne S Richards

Faculty, Staff and Students Publications

Defining features of polycystic ovary syndrome (PCOS) include elevated expression of steroidogenic genes, theca cell androgen biosynthesis, and peripheral levels of androgens. In previous studies, we identified vascular cell adhesion molecule 1 (VCAM1) as a selective androgen target gene in specific NR2F2/SF1 (+/+) theca cells. By deleting NR2F2 and VCAM1 selectively in CYP17A1 theca cells in mice, we documented that NR2F2 and VCAM1 impact distinct and sometimes opposing theca cell functions that alter ovarian follicular development in vivo: including major changes in ovarian morphology, steroidogenesis, gene expression profiles, immunolocalization images (NR5A1, CYP11A1, NOTCH1, CYP17A1, INSL3, VCAM1, NR2F2) as well as …

Discussing Menstrual Health In Family Medicine, Allison Casola, Alice Renaud, Ashwini Kamath Mulki

Department of Family & Community Medicine Faculty Papers

No abstract provided.

Bone Canonical Wnt Signaling Is Downregulated In Type 2 Diabetes And Associates With Higher Advanced Glycation End-Products (Ages) Content And Reduced Bone Strength, Giulia Leanza, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Nicola Napoli, Et Al.

2020-Current year OA Pubs

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (

The Stress Of Measuring Plantar Tissue Stress In People With Diabetes-Related Foot Ulcers: Biomechanical And Feasibility Findings From Two Prospective Cohort Studies, Chantal M Hulshof, Madelyn Page, Sjef G Van Baal, Sicco A Bus, Malindu E Fernando, Lisette Van Gemert-Pijnen, Kilian D R Kappert, Scott Lucadou-Wells, Bijan Najafi, Jaap J Van Netten, Peter A Lazzarini

Center on Aging Staff Publications

Reducing high mechanical stress is imperative to heal diabetes-related foot ulcers. We explored the association of cumulative plantar tissue stress (CPTS) and plantar foot ulcer healing, and the feasibility of measuring CPTS, in two prospective cohort studies (Australia (AU) and The Netherlands (NL)). Both studies used multiple sensors to measure factors to determine CPTS: plantar pressures, weight-bearing activities, and adherence to offloading treatments, with thermal stress response also measured to estimate shear stress in the AU-study. The primary outcome was ulcer healing at 12 weeks. Twenty-five participants were recruited: 13 in the AU-study and 12 in the NL-study. CPTS data …

Prognostic Significance Of Central Skull Base Remodeling In Chiari Ii Malformation, John T Freiling, Nilesh K Desai, Stephen F Kralik, William E Whitehead, Thierry A G M Huisman

Faculty, Staff and Students Publications

Background and purpose: Outward convexity of the basiocciput and posterior atlanto-occipital membrane are common in patients with Chiari II malformation associated with an open neural tube defect. We aimed to determine if the severity of these findings correlated with the need for future hydrocephalus treatment.

Materials and methods: A retrospective chart and imaging review identified patients who underwent open neural tube defect repair at a quaternary care pediatric hospital from July 2014 through September 2022. Patients were classified by the need for hydrocephalus treatment and whether they received prenatal or postnatal neural tube defect repair. Measurements of imaging parameters related …

Primary Anastomosis With Diverting Loop Ileostomy Vs. Hartmann's Procedure For Acute Diverticulitis: What Happens After Discharge? Results Of A Nationwide Analysis, Arturo J. Rios Diaz, Lisa A. Bevilacqua, Theodore E. Habarth-Morales, Alicja Zalewski, David Metcalfe, Caitlyn Costanzo, Charles J. Yeo, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: Current guidelines recommend resection with primary anastomosis with diverting loop ileostomy over Hartmann's procedure if deemed safe for acute diverticulitis. The primary objective of the current study was to compare the utilization of these strategies and describe nationwide ostomy closure patterns and readmission outcomes within 1 year of discharge.

METHODS: This was a retrospective, population-based, cohort study of United States Hospitals reporting to the Nationwide Readmissions Database from January 2011 to December 2019. There were 35,774 patients identified undergoing non-elective primary anastomosis with diverting loop ileostomy or Hartmann's procedure for acute diverticulitis. Rates of ostomy closure, unplanned readmissions, and …

Blocking Senescence And Tolerogenic Function Of Dendritic Cells Induced By Γδ Treg Cells Enhances Tumor-Specific Immunity For Cancer Immunotherapy, Fusheng Si, Xia Liu, Yan Tao, Yuanqin Zhang, Feiya Ma, Eddy C Hsueh, Sidharth V Puram, Guangyong Peng

2020-Current year OA Pubs

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence …

Application Of Deep Learning On Mammographies To Discriminate Between Low And High-Risk Dcis For Patient Participation In Active Surveillance Trials, Sena Alaeikhanehshir, Madelon M Voets, Frederieke H Van Duijnhoven, Esther H Lips, Emma J Groen, Marja C J Van Oirsouw, Shelley E Hwang, Joseph Y Lo, Jelle Wesseling, Ritse M Mann, Jonas Teuwen

Faculty, Staff and Student Publications

BACKGROUND: Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S. Hwang et al., BMJ Open, 9: e026797, 2019, A. Francis et al., Eur J Cancer. 51: 2296-2303, 2015, Chizuko Kanbayashi et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA), L. E. Elshof et al., Eur J Cancer, 51, 1497-510, 2015). Low-risk is defined as grade I or II DCIS. Because …

Induction Of Viral Mimicry Upon Loss Of Dhx9 And Adar1 In Breast Cancer Cells, Kyle A Cottrell, Sua Ryu, Jackson R Pierce, Luisangely Soto Torres, Holly E Bohlin, Angela M Schab, Jason D Weber

2020-Current year OA Pubs

UNLABELLED: Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The IFN-inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for adenosine deaminase acting on RNA 1 (ADAR1) in many cancers, including breast. Although ADAR1-p150 has been well established in this role, the functions of the constitutively expressed ADAR1-p110 isoform are less understood. We used proximity labeling to identify putative ADAR1-p110-interacting proteins in breast cancer cell lines. Of the proteins identified, the RNA helicase DHX9 was of particular interest. Knockdown of DHX9 in …

Idiopathic Intracranial Hypertension After Abrupt Cessation Of Medication: A Case Report Of Abrupt Glucagon-Like Peptide-1 (Glp-1) Receptor Agonist Cessation And Review Of The Literature, Brittany Heckel

Department of Jefferson Headache Center Papers and Presentations

PURPOSE OF REVIEW: The purpose of this review is two-fold: (1) to discuss a case report of idiopathic intracranial hypertension (IIH) after abrupt cessation of a glucagon-like peptide-1 (GLP-1) receptor agonist with resultant rapid weight gain and (2) to review the literature regarding the potential role of GLP-1 receptor agonists in the treatment of IIH as well as potential pitfalls.

RECENT FINDINGS: GLP-1 receptor agonists have become widely used to treat obesity. Obesity is a known risk factor for the development of IIH, though the precise pathophysiology is unclear. GLP-1 receptor agonists may help treat IIH by promoting weight loss, …

Syphilis Complicating Pregnancy And Congenital Syphilis. Reply, Irene A Stafford, Kimberly A Workowski, Laura H Bachmann

Faculty, Staff and Student Publications

The authors reply: The Jarisch–Herxheimer reaction is an underreported and often-over-looked sequela of antimicrobial therapy in persons with spirochetal disease and is caused by the release of treponemal constituents.1 Sandoval’s description of the clinical manifestations of this reaction is an important reminder for clinicians to recognize the reaction and avoid the pitfalls of incorrectly diagnosing it as an allergic reaction to penicillin; it also highlights a critical aspect of care for persons with syphilis, including neonates with congenital syphilis.

Bi-Allelic Acbd6 Variants Lead To A Neurodevelopmental Syndrome With Progressive And Complex Movement Disorders, Rauan Kaiyrzhanov, Aboulfazl Rad, Sheng-Jia Lin, Aida Bertoli-Avella, Wouter W Kallemeijn, Annie Godwin, Maha S Zaki, Kevin Huang, Tracy Lau, Cassidy Petree, Stephanie Efthymiou, Ehsan Ghayoor Karimiani, Maja Hempel, Elizabeth A Normand, Sabine Rudnik-Schöneborn, Ulrich A Schatz, Marc P Baggelaar, Muhammad Ilyas, Tipu Sultan, Javeria Raza Alvi, Manizha Ganieva, Ben Fowler, Ruxandra Aanicai, Gulsen Akay Tayfun, Abdulaziz Al Saman, Abdulrahman Alswaid, Nafise Amiri, Nilufar Asilova, Vorasuk Shotelersuk, Patra Yeetong, Matloob Azam, Meisam Babaei, Gholamreza Bahrami Monajemi, Pouria Mohammadi, Saeed Samie, Selina Husna Banu, Jorge Pinto Basto, Fanny Kortüm, Mislen Bauer, Peter Bauer, Christian Beetz, Masoud Garshasbi, Awatif Hameed Issa, Wafaa Eyaid, Hind Ahmed, Narges Hashemi, Kazem Hassanpour, Isabella Herman, Sherozjon Ibrohimov, Ban A Abdul-Majeed, Maria Imdad, Maksudjon Isrofilov, Qassem Kaiyal, Suliman Khan, Brian Kirmse, Janet Koster, Charles Marques Lourenço, Tadahiro Mitani, Oana Moldovan, David Murphy, Maryam Najafi, Davut Pehlivan, Maria Eugenia Rocha, Vincenzo Salpietro, Miriam Schmidts, Adel Shalata, Mohammad Mahroum, Jawabreh Kassem Talbeya, Robert W Taylor, Dayana Vazquez, Annalisa Vetro, Hans R Waterham, Mashaya Zaman, Tina A Schrader, Wendy K Chung, Renzo Guerrini, James R Lupski, Joseph Gleeson, Mohnish Suri, Yalda Jamshidi, Kailash P Bhatia, Barbara Vona, Michael Schrader, Mariasavina Severino, Matthew Guille, Edward W Tate, Gaurav K Varshney, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne …

Effect Of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis On Medication Satisfaction And Out-Of-Pocket Costs: A Secondary Analysis Of A Randomized Clinical Trial, Nathan N O'Hara, Katherine P Frey, Deborah M Stein, Joseph F Levy, Gerard P Slobogean, Renan Castillo, Reza Firoozabadi, Madhav A Karunakar, Joshua L Gary, William T Obremskey, Rachel B Seymour, Joseph Cuschieri, C Daniel Mullins, Robert V O'Toole, Metrc

Faculty, Staff and Student Publications

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin.

METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) …

Gabaergic/Glycinergic And Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes Of Stxbp1 Encephalopathy, Joo Hyun Kim, Wu Chen, Eugene S Chao, Armando Rivera, Heet Naresh Kaku, Kevin Jiang, Dongwon Lee, Hongmei Chen, Jaimie M Vega, Teresa V Chin, Kevin Jin, Kelly T Nguyen, Sheldon S Zou, Zain Moin, Shawn Nguyen, Mingshan Xue 薛名杉

Faculty, Staff and Students Publications

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as …

A Data Browsing Application For Accessing Gene And Module-Level Blood Transcriptome Profiles Of Healthy Pregnant Women From High- And Low-Resource Settings., Darawan Rinchai, Tobias Brummaier, Alexandra A Marr, Tanwir Habib, Mohammed Toufiq, Tomoshigue Kino, François Nosten, Souhaila Al Khodor, Annalisa Terranegra, Rose Mcgready, Basirudeen Syed Ahamed Kabeer, Damien Chaussabel

Faculty Research 2024

Transcriptome profiling data, generated via RNA sequencing, are commonly deposited in public repositories. However, these data may not be easily accessible or usable by many researchers. To enhance data reuse, we present well-annotated, partially analyzed data via a user-friendly web application. This project involved transcriptome profiling of blood samples from 15 healthy pregnant women in a low-resource setting, taken at 6 consecutive time points beginning from the first trimester. Additional blood transcriptome profiles were retrieved from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public repository, representing a cohort of healthy pregnant women from a high-resource setting. …

Neonatal Outcomes In The Surgical Management Of Placenta Accreta Spectrum Disorders: A Retrospective Single-Center Observational Study From 468 Vietnamese Pregnancies Beyond 28 Weeks Of Gestation, Phuc Nhon Nguyen, Anh Dinh Bao Vuong, Xuan Trang Thi Pham

Faculty, Staff and Student Publications

BACKGROUND: Placenta accreta spectrum disorders (PASDs) increase the mortality rate for mothers and newborns over a decade. Thus, the purpose of the study is to evaluate the neonatal outcomes in emergency cesarean section (CS) and planned surgery as well as in Cesarean hysterectomy and the modified one-step conservative uterine surgery (MOSCUS). The secondary aim is to reveal the factors relating to poor neonatal outcomes.

METHODS: This was a single-center retrospective study conducted between 2019 and 2020 at Tu Du Hospital, in the southern region of Vietnam. A total of 497 pregnant women involved in PASDs beyond 28 weeks of gestation …

Targeting Branched N-Glycans And Fucosylation Sensitizes Ovarian Tumors To Immune Checkpoint Blockade, Hao Nie, Pratima Saini, Taito Miyamoto, Liping Liao, Rafal J Zielinski, Heng Liu, Wei Zhou, Chen Wang, Brennah Murphy, Martina Towers, Tyler Yang, Yuan Qi, Toshitha Kannan, Andrew Kossenkov, Hiroaki Tateno, Daniel T Claiborne, Nan Zhang, Mohamed Abdel-Mohsen, Rugang Zhang

Faculty, Staff and Student Publications

Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their …

Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi

Faculty, Staff and Student Publications

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways …

Genetic Diversity Promotes Resilience In A Mouse Model Of Alzheimer's Disease., Neelakshi Soni, Lindsay A Hohsfield, Kristine M Tran, Shimako Kawauchi, Amber Walker, Dominic Javonillo, Jimmy Phan, Dina Matheos, Celia Da Cunha, Asli Uyar, Giedre Milinkeviciute, Angela Gomez-Arboledas, Katelynn Tran, Catherine C Kaczorowski, Marcelo A Wood, Andrea J Tenner, Frank M Laferla, Gregory W. Carter, Ali Mortazavi, Vivek Swarup, Grant R Macgregor, Kim N Green

Faculty Research 2024

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology, including genetic factors that play a significant role in disease risk and resilience. However, the role of genetic diversity in preclinical AD studies has received limited attention.

METHODS: We crossed five Collaborative Cross strains with 5xFAD C57BL/6J female mice to generate F1 mice with and without the 5xFAD transgene. Amyloid plaque pathology, microglial and astrocytic responses, neurofilament light chain levels, and gene expression were assessed at various ages.

RESULTS: Genetic diversity significantly impacts AD-related pathology. Hybrid strains showed resistance to amyloid plaque formation and neuronal damage. Transcriptome diversity was …

Improving Prenatal Diagnosis Through Standards And Aggregation., Michael H Duyzend, Pilar Cacheiro, Julius O B Jacobsen, Jessica Giordano, Harrison Brand, Ronald J Wapner, Michael E Talkowski, Peter N Robinson, Damian Smedley

Faculty Research 2024

Advances in sequencing and imaging technologies enable enhanced assessment in the prenatal space, with a goal to diagnose and predict the natural history of disease, to direct targeted therapies, and to implement clinical management, including transfer of care, election of supportive care, and selection of surgical interventions. The current lack of standardization and aggregation stymies variant interpretation and gene discovery, which hinders the provision of prenatal precision medicine, leaving clinicians and patients without an accurate diagnosis. With large amounts of data generated, it is imperative to establish standards for data collection, processing, and aggregation. Aggregated and homogeneously processed genetic and …

The Moderating Effects Of Hiv Relevant Factors On The Relationship Between Intimate Partner Violence And Intention To Start Hiv Pre-Exposure Prophylaxis (Prep) Among Cisgender Women, Shimrit Keddem, Victoria Frye, Annet Davis, Beryl A Koblin, Hong-Van Tieu, Rachele K Lipsky, Vijay Nandi, Anne M Teitelman

Faculty, Staff and Students Publications

Background:

Intimate partner violence (IPV) and HIV are serious and related public health problems that detrimentally impact women’s health. Because women who experience IPV are more likely to acquire HIV, it is critical to promote HIV prevention strategies, such as HIV pre-exposure prophylaxis (PrEP), that increase autonomy.

Setting:

This study of cis-gender women eligible for HIV PrEP took place between 2017 and 2019 in Philadelphia and New York City.

Methods:

This study aimed to examine the relationship between four types of IPV (control, psychological, psychological, physical, sexual) and intention to start PrEP among PrEP-eligible cisgender women; and assess the extent …