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Evaluating The Impact Of A Novel Program To Address Acute Food Insecurity Among Cancer Patients, Elliott M. Sina, Michael Rowe, Gina Mancuso, Gregory Garber, W. Kevin Kelly, Amy E. Leader

Kimmel Cancer Center Faculty Papers

INTRODUCTION: Acute food insecurity (FI) significantly impacts cancer patients' health, exacerbating physical and psychological burdens. While current interventions address chronic FI, acute cases remain undermanaged. Legacy of Hope, a Philadelphia-based non-profit, addresses this gap through its Emergency Patient Support Network (EPSN), offering free bi-weekly groceries to patients facing acute FI.

MATERIALS AND METHODS: The pilot study evaluated EPSN's impact utilizing the Legacy of Hope Acute Food Insecurity (LOHAFI) survey, which was performed at baseline and two weeks post-intervention. The survey combines the Functional Assessment of Cancer Therapy-General (FACT-G7) and questions on food and financial security. Mean scores and frequencies were …

Use Of Cigarettes And E-Cigarettes, Impulsivity, And Anxiety: Influences On Suicidal Ideation Among Youth And Young Adults In Texas, Anna V Wilkinson, Baojiang Chen, Alan C Swann, David P Graham, David A Nielsen, Thomas R Kosten, Alexandra Loukas, Dale S Mantey, Bara S Bataineh, Melissa B Harrell

Faculty, Staff and Students Publications

Introduction: Cigarette use and smoking intensity increase risk of suicidal ideation. Less is known about e-cigarette use. Here we examine direct influences of cigarette versus e-cigarette use on suicidal ideation among 16- to 23-year-olds in Texas.

Aims and methods: Since 2019, the Texas Adolescent Tobacco and Marketing Surveillance Study collected data on suicidal ideation every 6 months covering the previous 2 weeks. Youths answering that they had "thoughts that you would be better off dead, or of hurting yourself" on more than 2 of 14 days were categorized as having suicidal ideation. Generalized linear mixed-effects logistic regressions examined the influence …

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 …

Phenotypic And Genetic Heterogeneity Of A Pakistani Cohort Of 15 Consanguineous Families Segregating Variants In Leber Congenital Amaurosis-Associated Genes, Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease. It can be an isolated eye disorder or as part of a syndrome, such as Senior Loken or Joubert syndrome. Sequencing studies from consanguineous populations have proven useful for novel variants identification; thus, the present study aimed to explore the genetic heterogeneity of 15 consanguineous Pakistani families, each segregating a severe IRD phenotype using targeted next …

Survival Analysis Of Clear Cell Renal Cell Carcinoma Based On Radiomics And Deep Learning Features From Ct Images, Zhennan Lu, Sijia Wu, Dan Ni, Meng Zhou, Tao Wang, Xiaobo Zhou, Liyu Huang, Yu Yan

Faculty, Staff and Student Publications

Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.

Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator. Then the selected features formed a fusion signature, which was assessed by Cox proportional hazard regression model method, Kaplan-Meier analysis, receiver operating characteristic curves, and concordance index (C-index) …

Quantifying Interpretation Reproducibility In Vision Transformer Models With Tavac., Yue Zhao, Dylan Agyemang, Yang Liu, J Matthew Mahoney, Sheng Li

Faculty Research 2024

Deep learning algorithms can extract meaningful diagnostic features from biomedical images, promising improved patient care in digital pathology. Vision Transformer (ViT) models capture long-range spatial relationships and offer robust prediction power and better interpretability for image classification tasks than convolutional neural network models. However, limited annotated biomedical imaging datasets can cause ViT models to overfit, leading to false predictions due to random noise. To address this, we introduce Training Attention and Validation Attention Consistency (TAVAC), a metric for evaluating ViT model overfitting and quantifying interpretation reproducibility. By comparing high-attention regions between training and testing, we tested TAVAC on four public …

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.

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Effects On Maternal And Pregnancy Outcomes Of First-Trimester Malaria Infection Among Nulliparous Women From Kenya, Zambia, And The Democratic Republic Of The Congo, Sequoia I. Leuba, Daniel Westreich, Carl L. Bose, Andrew F. Olshan, Steve M. Taylor, Antoinette Tshefu, Adrien Lokangaka, Waldemar A. Carlo, Elwyn Chomba, Musaku Mwenechanya, Edward A. Liechty, Sherri L. Bucher, Osayame A. Ekhaguere, Fabian Esamai, Paul Nyongesa, Saleem Jessani, Sarah Saleem, Robert L. Goldenberg, Janet L. Moore, Tracy L. Nolen, Jennifer Hemingway-Foday, Elizabeth M. Mcclure, Marion Koso-Thomas, Richard Derman, Matthew Hoffman, Steven R. Meshnick, Melissa Bauserman

Department of Medicine Faculty Papers

BACKGROUND: Few studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes.

METHODS: In a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democratic Republic of the Congo, we tested for first-trimester Plasmodium falciparum infection using quantitative polymerase chain reaction. We estimated site-specific effects on pregnancy outcomes using parametric g-computation.

RESULTS: Compared to uninfected women, we observed the adjusted site-specific prevalence differences (PDs) among women with first-trimester malaria of the following pregnancy outcomes: preterm birth …

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al.

2020-Current year OA Pubs

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous …

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …

The Camden Study - A Pregnancy Cohort Study Of Pregnancy Complications And Birth Outcomes In Camden, New Jersey, Usa., Stephanie Shiau, Xinhua Chen, Ayana April-Sanders, Ellen C Francis, Shristi Rawal, Megan Hansel, Kehinde Adeyemi, Zorimar Rivera-Núñez, Emily S Barrett

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Pregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.

METHODS: From 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the US. The cohort reflects a population under-represented in perinatal cohort studies (45% Hispanic, 38% non-Hispanic Black, 17% White …

The Lived Experiences Of African American Female First-Generation College Students As They Matriculate Through College: A Phenomenological Study, Rosa Denise Mcallister-Mcrae

Doctoral Dissertations and Projects

The purpose of this transcendental phenomenological study was to examine the lived experiences of African American female first-generation college students’ (FGCS) academic, social, emotional, and low economic challenges while attending either a Historically Black College and University (HBCU) or a Predominately White Institution (PWI) located in the southeastern area of the United States. First-generation college students are students whose parents never attended college. Tinto’s retention theory was the framework that guided the research, particularly, the challenges faced by first-generation students. The central research question was, how do African American female FGCSs describe their lived experiences matriculating through an HBCU or …

Enhancer Reprogramming Underlies Therapeutic Utility Of A Smarca2 Degrader In Smarca4 Mutant Cancer, Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu

Faculty, Staff and Student Publications

Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog SMARCA2 is synthetic lethal to SMARCA4 suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in SMARCA4-mutant cells with loss of chromatin accessibility at enhancers of genes …

Assessing Tolerability With The Functional Assessment Of Cancer Therapy Item Gp5: Psychometric Evidence From Libretto-531, A Phase 3 Trial Of Selpercatinib In Medullary Thyroid Cancer, Antoine Regnault, Laurine Bunod, Angely Loubert, Marcia S. Brose, Lisa M. Hess, Patricia Maeda, Yan Lin, Rebecca M. Speck, Adrienne M. Gilligan, Nalin Payakachat

Department of Medical Oncology Faculty Papers

BACKGROUND: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

METHODOLOGY: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with …

Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV), a common sexually transmitted infection in the US, contributes to oropharyngeal and urogenital cancers. To improve HPV vaccine uptake, quality improvement (QI) interventions that address barriers to vaccination in primary care may help. This study aims to understand pediatric primary care providers' (PCP) perspectives on participating in an HPV QI intervention that utilized practice facilitation to improve HPV vaccine uptake in pediatric primary care clinics.

METHODS: Participants were pediatric PCPs whose clinics completed a QI intervention that utilized practice facilitation led by an outside facilitator. One PCP from each practice completed a 15-min semi-structured exit interview. …

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …

The Effect Of A Low-Carbohydrate Diet On Evoked Pain And Quality Of Life In Non-Hispanic Black Women With Knee Osteoarthritis: A Pilot Study, Asia M Wiggins, Larissa J Strath, Gray E Mcpherson, Barbara A Gower, Amy M Goss, Burel R Goodin, Robert E Sorge

2020-Current year OA Pubs

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent chronic pain condition that can significantly impact quality of life and contribute to recognized chronic pain racial disparities. We have shown that a low-carbohydrate diet (LCD) can reduce KOA-related pain. Our previous work suggested that the LCD was more beneficial for women and non-Hispanic Black (NHB) adults, but our sample was not sufficiently diverse. Thus, we sought to determine whether the LCD may be beneficial for NHB women with KOA on measures of self-reported and evoked pain.

METHODS: Fourteen NHB women (M = 55.93, S.D. = 7.79 years of age) with KOA were …

Transforming Growth Factor-Beta Is Increased In Sputum From Individuals With Rheumatoid Arthritis-Associated Pulmonary Fibrosis, Timothy M. Wilson, Matthew Bolt, Andrew Stahly, Joyce S. Lee, Tami J. Bang, Peter B. Sachs, Kevin D. Deane, Stephen M. Humphries, Joshua J. Solomon, M. Kristen Demoruelle

Division of Rheumatology Faculty Papers

BACKGROUND: Interstitial lung disease (ILD) develops in 5-10% of patients with RA and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD.

METHODS: We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for TGF-β levels by immunoassay. DNA was extracted to determine presence of the MUC5B …

Utility Of Colposcopy For The Screening And Management Of Cervical Cancer In Africa: A Cross-Sectional Analysis Of Providers’ Training And Practices, Joël Fokom Domgue, Issimouha Dille, Freddy Gnangnon, Sharon Kapambwe, Celine Bouchard, Nomonde Mbatani, Elodie Gauroy, Nathalie Ledaga Ambounda, Robert Yu, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Pierre-Marie Tebeu, Gregory Halle-Ekane, Mohenou Isidore Diomande, Jean-Marie Dangou, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Sanjay Shete

Faculty, Staff and Student Publications

Introduction: Cervical cancer is a public health issue in Africa with devastating socioeconomic consequences due to the lack of organized screening programs. The success of screening programs depends on the appropriate investigation and management of women who test positive for screening. Colposcopic assessment following positive screening results is a noteworthy issue in Africa. This study aimed to assess the utilization of colposcopy by providers in the region.

Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior colposcopy training, whether they performed colposcopy and the …

Transcriptomic Clustering Of Chronic Lymphocytic Leukemia: Molecular Subtypes Based On Bruton’S Tyrosine Kinase Expression Levels, Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L Ayres, Lakesla R Iles, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples …

Influenza Knowledge And Barriers To Vaccination In Immunosuppressed Patients In The Pediatric Rheumatology Clinic., Julia G. Harris, Leslie Favier, Jordan T. Jones, Maria Ibarra, Michael J. Holland, Emily Fox, Kelly Jensen, Ashley K. Sherman, Ashley M. Cooper

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Most patients with a pediatric rheumatic disease are at increased risk of influenza due to immunosuppressive medication use. Despite initial quality improvement efforts, our influenza vaccination rate plateaued at 72%, which prompted a survey of patients and families to assess provider vaccine recommendations, influenza knowledge, and barriers to influenza vaccination.

METHODS: Patients on immunosuppressive medication or their parent were eligible to complete a survey between July 2019 and January 2020. Survey questions assessed demographics, rheumatology diagnosis, immunosuppressive medication(s), influenza vaccination recommendation, patient/parent influenza knowledge, and barriers to influenza vaccination. Influenza vaccination rates for immunosuppressed patients were acquired each influenza …

High Ldl Particle And Apob Concentrations In Patients With Adrenal Cortical Adenomas, Rashi Sandooja, Jasmine Saini, Annop Kittithaworn, Raul Gregg-Garcia, Prerna Dogra, Elizabeth Atkinson, Kai Yu, Vanessa Fell, Vinaya Simha, Margery A Connelly, Robin P F Dullaart, Irina Bancos

Faculty, Staff and Students Publications

Context: Patients with nonfunctioning adenomas (NFAs), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk.

Objective: This work aimed to determine the extent of lipoprotein abnormalities in NFA, MACS, and CS.

Methods: We conducted a single-center, cross-sectional study of patients with NFA (n = 167), MACS (n = 213), CS (n = 142), and referent individuals (n = 202) between January 2015 and July 2022. Triglyceride-rich lipoprotein particles (TRLP), low-density lipoprotein particles (LDLP), high-density lipoprotein particles (HDLP), their subclasses and sizes were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted …

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

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 …

Primary Anorectal Mammary-Like Adenocarcinoma: A Potential Diagnostic Pitfall With Conventional Colorectal Adenocarcinoma, Margaret L Axelrod, Xiuli Liu, Pooja Navale

2020-Current year OA Pubs

Anogenital mammary-like glands (AGMLGs) are present in the anogenital region that bear striking morphologic and protein-expression similarities to mammary glands in the breast. AGMLGs can give rise to both benign and malignant lesions which mimic primary breast lesions. Herein, we report two mammary-type adenocarcinomas arising from AGMLGs, including one in the previously unreported site of the rectum. Recognition of mammary-type adenocarcinoma in the rectal and anogenital regions is crucial as clinical management options may differ compared to conventional colorectal adenocarcinomas.

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 …

Co-Inhibition Of Tgli1 And Gp130 Using Fda-Approved Ketoconazole And Bazedoxifene Is Synergistic Against The Growth And Metastasis Of Her2-Enriched And Triple-Negative Breast Cancers, Sara Manore, Chuling Zhuang, Mariana K Najjar, Grace L Wong, Shivani Bindal, Kounosuke Watabe, Jiayuh Lin, Hui-Wen Lo

Faculty, Staff and Student Publications

Breast cancer stem cells (CSCs) are resistant to most cancer therapeutics and contribute to tumor recurrence and metastasis. Two breast CSC-promoting transcription factors, truncated glioma-associated oncogene homolog 1 (tGLI1) and signal transducer and activator of transcription 3 (STAT3), have been reported to be frequently co-expressed in HER2-enriched breast cancer and triple-negative breast cancer (TNBC), undergo protein-protein interactions for gene regulation and activation, and functionally cooperate to promote breast CSCs. STAT3 can be activated by activated interleukin-6 receptor/glycoprotein-130 (IL-6R/GP130). Co-targeting of tGLI1 and IL-6R/GP130 has not been investigated in breast cancer or any tumor type. Here, we report that tGLI1 and …

Understanding Rare Genetic Variants Within The Terminal Pathway Of Complement System In Preeclampsia, A Inkeri Lokki, Michael Triebwasser, Emma Daly, Finnpec Core Investigator Group, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri

2020-Current year OA Pubs

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25-467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17-440.78), p value = 0.01). In addition, one predisposing rare variant …

Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were …

Whispers In The Wind: Face Mask Sampling For Mycobacterium Tuberculosis Detection In Children With Pulmonary Tuberculosis, Lennard Meiwes, Irina Kontsevaya, Dumitru Chesov, Stela Kulciţkaia, Viola Dreyer, Doris Hillemann, Qiniso Dlamini, Caroline Williams, Michael Barer, Folke Brinkmann, Renate Krüger, Stephanie Thee, Alexander Kay, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

Background: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods: Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results: Experiments with H37Ra M. …