Digital Commons Network^™

Association Of Second-Generation Antiandrogens With Cognitive And Functional Toxic Effects In Randomized Clinical Trials: A Systematic Review And Meta-Analysis, Malgorzata K Nowakowska, Rachel M Ortega, Mackenzie R Wehner, Kevin T Nead

Faculty, Staff and Student Publications

Importance: The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.

Objective: To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.

Data sources: PubMed, EMBASE, and Scopus (inception to September 12, 2022).

Study selection: Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, …

Sex-Based Differences In The Presentation And Outcomes Of Acute Pulmonary Embolism: A Systematic Review And Meta-Analysis, Yu Zhang, Yu Qiu, Jinming Luo, Jian Zhang, Qingqing Yan

The Texas Heart Institute Journal

BACKGROUND: The study aimed to review differences in the presentation and outcomes of acute pulmonary embolism (PE) between men and women.

METHODS: PubMed, CENTRAL, Web of Science, and Embase were searched for studies comparing clinical features or outcomes of PE between men and women. Baseline comorbidities, risk factors, clinical features, and mortality rates were also compared between men and women.

RESULTS: Fourteen studies were included. It was noted that men presented with PE at a statistically significantly younger age than women (P < .001). Smoking history (P < .001), lung disease (P = .004), malignancy (P = .02), and unprovoked PE (P = .004) were significantly more frequent among men than among women. There was no difference between the sexes for hypertension, diabetes, and a history of recent immobilization. A significantly higher proportion of men presented with chest pain (P = .02) and hemoptysis (P < .001), whereas syncope (P = .005) was more frequent in women. Compared with men, women had a higher proportion of high-risk PE (P = .003). There was no difference in the use of thrombolytic therapy or inferior vena cava filter. Neither crude nor adjusted mortality rates were significantly different between men and women.

CONCLUSION: This review found that the age at presentation, comorbidities, and symptoms of PE differed between men and …

Proteogenomic Approaches For The Identification Of Nf1/Neurofibromin-Depleted Estrogen Receptor-Positive Breast Cancers For Targeted Treatment, Beom-Jun Kim, Ze-Yi Zheng, Jonathan T Lei, Matthew V Holt, Anran Chen, Jianheng Peng, Diana Fandino, Purba Singh, Hilda Kennedy, Yongchao Dou, María Del Rosario Chica-Parrado, Emmanuel Bikorimana, Dan Ye, Yunguan Wang, Ariella B Hanker, Nada Mohamed, Susan G Hilsenbeck, Bora Lim, Jaya Ruth Asirvatham, Arun Sreekumar, Bing Zhang, George Miles, Meenakshi Anurag, Matthew J Ellis, Eric C Chang

Faculty, Staff and Student Publications

NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking both pathways by fulvestrant (F), a selective ER degrader, together with binimetinib (B), a MEK inhibitor, promotes tumor regression in NF1-depleted ER+ models. We aimed to establish approaches to determine how NF1 protein levels impact B+F treatment response to improve our ability to identify B+F sensitive tumors. We examined a panel of ER+ patient-derived xenograft (PDX) models by DNA and mRNA sequencing and found that more than half of these models carried an NF1 shallow deletion and generally have low mRNA …

Presentation Of External Ear Rosai-Dorfman Disease With Laryngeal Involvement, Kenji R Kobayashi, Yusif Hajiyev, Maren Y Fuller, Gunes Orman, Elton M Lambert

Faculty, Staff and Students Publications

Rosai-Dorfman disease (RDD) is a rare benign systemic histiocytic proliferation characterized by massive lymph node enlargement and sometimes associated with extranodal involvement. Even though it is considered to be benign, death can occur depending on the extent and location. Our case highlights a primary extranodal site of the right pinna with extension through the Eustachian tube to the subglottis. A previously healthy 15-year-old female presented with 1-year right pinna swelling, slowly enlarging and becoming more bothersome. An incisional biopsy was performed on the ear along with S100 staining yielding a diagnosis. After multidisciplinary case discussion, clofarabine monotherapy and systemic therapy …

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections, Sidra Zafar, Annette Walder, Salim Virani, Kristin Biggerstaff, Silvia Orengo-Nania, Jonathan Chang, Roomasa Channa

Faculty, Staff and Students Publications

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups.

OBJECTIVE: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and …

Characterizing The Influence Of Exposure To Military Sexual Trauma And Intimate Partner Violence On Mental Health Outcomes Among Female Veterans, Carrie Esopenko, Nicola De Souza, Elisabeth A Wilde, Kristen Dams-O'Connor, Ellen Teng, Deleene S Menefee

Faculty, Staff and Students Publications

Military sexual trauma (MST) has deleterious long-term psychological consequences. Among female U.S. military members, MST is associated with increased risk for future interpersonal victimization, such as experiencing intimate partner violence (IPV). Few studies have investigated the implications of the cumulative effects of IPV and MST on psychological functioning. This study examined rates of co-exposure to MST, IPV, and their cumulative impact on psychological symptoms. Data were collected from 308 female Veterans (FVets; age:

Achieving Equity In Emergency Medicine Quality Measures Requires A Sex And Gender Lens, Ynhi T Thomas, Angela F Jarman, Nina G Faynshtayn, Greg B Buehler, Sara Andrabi, Alyson J Mcgregor

Faculty, Staff and Students Publications

BACKGROUND: Quality measures within Emergency Medicine (EM) were developed to standardize and improve care. Their development has been limited by lack of consideration of sex- and gender-based differences. Research has suggested that sex and gender can impact clinical care and treatment. Inclusion of sex and gender differences is needed to create EM quality measures that are equitable to all.

OBJECTIVE: The aim of the review is to provide a brief history of EM quality measures and the value of considering sex- and gender-based evidence in their development to ensure equity, using acute myocardial infarction (AMI) as an example.

DISCUSSION: Current …

Exploring The Role Of Vitamin D And The Gut Microbiome: A Cross-Sectional Study Of Individuals With Irritable Bowel Syndrome And Healthy Controls, Sarah W Matthews, Anna Plantinga, Robert Burr, Kevin C Cain, Tor Savidge, Kendra Kamp, Margaret M Heitkemper

Faculty, Staff and Students Publications

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and …

Testis-Specific Serine Kinase 3 Is Required For Sperm Morphogenesis And Male Fertility, Kaori Nozawa, Thomas X Garcia, Katarzyna Kent, Mei Leng, Antrix Jain, Anna Malovannaya, Fei Yuan, Zhifeng Yu, Masahito Ikawa, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: The importance of phosphorylation in sperm during spermatogenesis has not been pursued extensively. Testis-specific serine kinase 3 (Tssk3) is a conserved gene, but TSSK3 kinase functions and phosphorylation substrates of TSSK3 are not known.

OBJECTIVE: The goals of our studies were to understand the mechanism of action of TSSK3.

MATERIALS AND METHODS: We analyzed the localization of TSSK3 in sperm, used CRISPR/Cas9 to generate Tssk3 knockout (KO) mice in which nearly all of the Tssk3 open reading frame was deleted (ensuring it is a null mutation), analyzed the fertility of Tssk3 KO mice by breeding mice for 4 months, …

Advancing Asms With Lc-Ms/Ms For The Discovery Of Novel Pdcl2 Ligands From Dna-Encoded Chemical Library Selections, Qiuji Ye, Hassane Belabed, Yong Wang, Zhifeng Yu, Murugesan Palaniappan, Jian-Yuan Li, Stacey A Kalovidouris, Kevin R Mackenzie, Mingxing Teng, Damian W Young, Yoshitaka Fujihara, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: A safe, effective, and reversible nonhormonal male contraceptive drug is greatly needed for male contraception as well as for circumventing the side effects of female hormonal contraceptives. Phosducin-like 2 (PDCL2) is a testis-specific phosphoprotein in mice and humans. We recently found that male PDCL2 knockout mice are sterile due to globozoospermia caused by impaired sperm head formation, indicating that PDCL2 is a potential target for male contraception. Herein, our study for the first time developed a biophysical assay for PDCL2 allowing us to screen a series of small molecules, to study structure-activity relationships, and to discover two PDCL2 binders …

A Crispr/Cas9-Engineered Mouse Carrying A Conditional Knockout Allele For The Early Growth Response-1 Transcription Factor, Vineet K Maurya, Yan Ying, Denise G Lanza, Jason D Heaney, John P Lydon

Faculty, Staff and Students Publications

Early growth response 1 (EGR1) mediates transcriptional programs that are indispensable for cell division, differentiation and apoptosis in numerous physiologies and pathophysiologies. Whole-body EGR1 knockouts in mice (Egr1KO) have advanced our understanding of EGR1 function in an in vivo context. To extend the utility of the mouse to investigate EGR1 responses in a tissue- and/or cell-type-specific manner, we generated a mouse model in which exon 2 of the mouse Egr1 gene is floxed by CRISPR/Cas9 engineering. The floxed Egr1 alleles (Egr1f/f) are designed to enable spatiotemporal control of Cre-mediated EGR1 ablation in the …

Epigenetic Reprogramming Of Cell Cycle Genes By Ack1 Promotes Breast Cancer Resistance To Cdk4/6 Inhibitor, Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J O'Conor, Ian S Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P Mahajan

2020-Current year OA Pubs

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition …

Plasma Proteomic Patterns Show Sex Differences In Early Concentric Left Ventricular Remodeling, Anne-Mar Van Ommen, Ernest Diez Benavente, N. Charlotte Onland-Moret, Gideon B. Valstar, Maarten J. Cramer, Frans H. Rutten, Arco J. Teske, Roxana Menken, Leonard Hofstra, Igor I. Tulevski, Nancy Sweitzer, G. Aernout Somsen, Hester M. Den Ruijter

2020-Current year OA Pubs

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women.

METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM.

RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, …

The Impact Of Essential Trace Elements On Ovarian Response And Reproductive Outcomes Following Single Euploid Embryo Transfer, Roberto Gonzalez-Martin, Andrea Palomar, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Estefania Conde-Vilda, Alberto J Quejido, Christine Whitehead, Richard T. Scott, Francisco Dominguez

Department of Medicine Faculty Papers

Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the …

Female Athlete Health Domains: A Supplement To The International Olympic Committee Consensus Statement On Methods For Recording And Reporting Epidemiological Data On Injury And Illness In Sport., Isabel S Moore, Kay M Crossley, Kari Bo, Margo Mountjoy, Kathryn E Ackerman, Juliana Da Silva Antero, Jorunn Sundgot Borgen, Wendy J Brown, Caroline S Bolling, Benjamin Clarsen, Wayne Derman, Paul Dijkstra, Amber Donaldson, Kirsty J Elliott-Sale, Carolyn A Emery, Lene Haakstad, Astrid Junge, Nonhlanhla S Mkumbuzi, Sophia Nimphius, Debbie Palmer, Mireille Van Poppel, Jane S Thornton, Rita Tomás, Phathokuhle C Zondi, Evert Verhagen

Family Medicine Publications

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) …

Heterogeneity In The Effect Of Marked Weight Loss On Metabolic Function In Women With Obesity, Bettina Mittendorfer, Brandon D. Kayser, Mihoko Yoshino, Jun Yoshino, Jeramie D. Watrous, Mohit Jain, J. Christopher Eagon, Bruce W. Patterson, Samuel Klein

2020-Current year OA Pubs

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

Blm Overexpression As A Predictive Biomarker For Chk1 Inhibitor Response In Parp Inhibitor-Resistant Brca-Mutant Ovarian Cancer, Nitasha Gupta, Tzu-Ting Huang, Jayakumar R Nair, Daniel An, Grant Zurcher, Erika J Lampert, Ann Mccoy, Ashley Cimino-Mathews, Elizabeth M Swisher, Marc R Radke, Christina M Lockwood, Jonathan B Reichel, Chih-Yuan Chiang, Kelli M Wilson, Ken Chih-Chien Cheng, Darryl Nousome, Jung-Min Lee

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (BRCA)–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib …

Healthy Lifestyle Index And Risk Of Cardiovascular Disease Among Postmenopausal Women With Normal Body Mass Index, Rita Peila, Xiaonan Xue, Qibin Qi, Andrew J Dannenberg, Matthew A Allison, Karen C Johnson, Michael J Lamonte, Robert A Wild, Bernhard Haring, Kathy Pan, Hilary A Tindle, Randi Foraker, Nazmus Saquib, Ana Barac, Thomas E Rohan

2020-Current year OA Pubs

Background A lifestyle comprising a healthy diet, light alcohol consumption, no smoking, and moderate or intense physical activity has been associated with reduced risk of cardiovascular disease (CVD). We examined the association of a healthy lifestyle index (HLI), derived from scores for each of these components plus waist circumference, with the risk of incident CVD and CVD subtypes in postmenopausal women with normal body mass index (18.5-<25.0 kg/m

Relative Age Effect Of Female And Male Handball Players Participating In Olympics Games Tokyo 2020, Paweł Krawczyk, Adam Dyjas, Adam Szeląg, Maciej Cedro

Baltic Journal of Health and Physical Activity

Introduction: The aim of this study was to determine whether the relative age effect (RAE) was present among handball players participating in the Tokyo 2020 Olympics. Materials and Methods. The study involved a group of handball players participating in the Tokyo 2020 Olympics. All data was collected from the website of the IHF. The research material consisted of data on the players’ dates of birth, which were broken down by four quarters (Q1: January 1–March 31, Q2: April 1–June 30, Q3: July 1–September 30, Q4: October 1–December 31) and two semesters (S1: January 1–June 30, S2: July 1–December 31). The …

The Insulin Receptor Regulates The Persistence Of Mechanical Nociceptive Sensitization In Flies And Mice, Yan Wang, Roger Lopez-Bellido, Xiaojiao Huo, Annemieke Kavelaars, Michael J Galko

Faculty, Staff and Student Publications

Early phase diabetes is often accompanied by pain sensitization. In Drosophila, the insulin receptor (InR) regulates the persistence of injury-induced thermal nociceptive sensitization. Whether Drosophila InR also regulates the persistence of mechanical nociceptive sensitization remains unclear. Mice with a sensory neuron deletion of the insulin receptor (Insr) show normal nociceptive baselines; however, it is uncertain whether deletion of Insr in nociceptive sensory neurons leads to persistent nociceptive hypersensitivity. In this study, we used fly and mouse nociceptive sensitization models to address these questions. In flies, InR mutants and larvae with sensory neuron-specific expression of RNAi transgenes targeting InR exhibited persistent …

Microbiome Alteration Via Fecal Microbiota Transplantation Is Effective For Refractory Immune Checkpoint Inhibitor-Induced Colitis, Taylor M Halsey, Anusha S Thomas, Tomo Hayase, Weijie Ma, Hamzah Abu-Sbeih, Baohua Sun, Edwin Roger Parra, Zhi-Dong Jiang, Herbert L Dupont, Christopher Sanchez, Rawan El-Himri, Alexandria Brown, Ivonne Flores, Lauren Mcdaniel, Miriam Ortega Turrubiates, Matthew Hensel, Dung Pham, Stephanie S Watowich, Eiko Hayase, Chia-Chi Chang, Robert R Jenq, Yinghong Wang

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line …

Apoe4, Age, And Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia, Jayakrishnan Nair, Joseph F. Welch, Alexandria B. Marciante, Tingting Hou, Qing Lu, Emily J. Fox, Gordon S. Mitchell

Department of Physical Therapy Faculty Papers

Rational

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.

Objectives

Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).

Methods

In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures …

Development Of A Definition Of Postacute Sequelae Of Sars-Cov-2 Infection, Tanayott Thaweethai, Sarah E Jolley, Elizabeth W Karlson, Emily B Levitan, Bruce Levy, Grace A Mccomsey, Lisa Mccorkell, Girish N Nadkarni, Sairam Parthasarathy, Upinder Singh, Tiffany A Walker, Caitlin A Selvaggi, Daniel J Shinnick, Carolin C M Schulte, Rachel Atchley-Challenner, George A Alba, Radica Alicic, Natasha Altman, Khamal Anglin, Urania Argueta, Hassan Ashktorab, Gaston Baslet, Ingrid V Bassett, Lucinda Bateman, Brahmchetna Bedi, Shamik Bhattacharyya, Marie-Abele Bind, Andra L Blomkalns, Hector Bonilla, Hassan Brim, Patricia A Bush, Mario Castro, James Chan, Alexander W Charney, Peter Chen, Lori B Chibnik, Helen Y Chu, Rebecca G Clifton, Maged M Costantine, Sushma K Cribbs, Sylvia I Davila Nieves, Steven G Deeks, Alexandria Duven, Ivette F Emery, Nathan Erdmann, Kristine M Erlandson, Kacey C Ernst, Rachael Farah-Abraham, Cheryl E Farner, Elen M Feuerriegel, Judes Fleurimont, Vivian Fonseca, Nicholas Franko, Vivian Gainer, Jennifer C Gander, Edward M Gardner, Linda N Geng, Kelly S Gibson, Minjoung Go, Jason D Goldman, Halle Grebe, Frank L Greenway, Mounira Habli, John Hafner, Jenny E Han, Keith A Hanson, James Heath, Carla Hernandez, Rachel Hess, Sally L Hodder, Matthew K Hoffman, Susan E Hoover, Beatrice Huang, Brenna L Hughes, Prasanna Jagannathan, Janice John, Michael R Jordan, Stuart D Katz, Elizabeth S Kaufman, John D Kelly, Sara W Kelly, Megan M Kemp, John P Kirwan, Jonathan D Klein, Kenneth S Knox, Jerry A Krishnan, Andre Kumar, Adeyinka O Laiyemo, Allison A Lambert, Margaret Lanca, Joyce K Lee-Iannotti, Brian P Logarbo, Michele T Longo, Carlos A Luciano, Karen Lutrick, Jason H Maley, Gail Mallett, Jai G Marathe, Vincent Marconi, Gailen D Marshall, Christopher F Martin, Yuri Matusov, Alem Mehari, Hector Mendez-Figueroa, Robin Mermelstein, Torri D Metz, Richard Morse, Jarrod Mosier, Christian Mouchati, Janet Mullington, Shawn N Murphy, Robert B Neuman, Janko Z Nikolich, Ighovwerha Ofotokun, Elizabeth Ojemakinde, Anna Palatnik, Kristy Palomares, Tanyalak Parimon, Samuel Parry, Jan E Patterson, Thomas F Patterson, Rachel E Patzer, Michael J Peluso, Priscilla Pemu, Christian M Pettker, Beth A Plunkett, Kristen Pogreba-Brown, Athena Poppas, John G Quigley, Uma Reddy, Rebecca Reece, Harrison Reeder, W B Reeves, Eric M Reiman, Franz Rischard, Jonathan Rosand, Dwight J Rouse, Adam Ruff, George Saade, Grecio J Sandoval, Jorge L Santana, Shannon M Schlater, Frank C Sciurba, Fitzgerald Shepherd, Zaki A Sherif, Hyagriv Simhan, Nora G Singer, Daniel W Skupski, Amber Sowles, Jeffrey A Sparks, Fatima I Sukhera, Barbara S Taylor, Larissa Teunis, Robert J Thomas, John M Thorp, Paul Thuluvath, Amberly Ticotsky, Alan T Tita, Katherine R Tuttle, Alfredo E Urdaneta, Daisy Valdivieso, Timothy M Vanwagoner, Andrew Vasey, Monica Verduzco-Gutierrez, Zachary S Wallace, Honorine D Ward, David E Warren, Steven J Weiner, Shelley Welch, Sidney W Whiteheart, Zanthia Wiley, Juan P Wisnivesky, Lynn M Yee, Sokratis Zisis, Leora I Horwitz, Andrea S Foulkes

Faculty, Staff and Student Publications

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, …

Biological Mechanism Of Sex Difference In Stroke Manifestation And Outcomes, Wi-Sun Ryu, Jinyong Chung, Dawid Schellingerhout, Sang-Wuk Jeong, Hang-Rai Kim, Jung E Park, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyungbok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Man Seok Park, Kang-Ho Choi, Juneyoung Lee, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location.

METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 >days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods …

Clinical Significance And Biology Of Circulating Tumor Dna In High-Risk Early-Stage Her2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy, Mark Jesus M Magbanua, Lamorna Brown Swigart, Ziad Ahmed, Rosalyn W Sayaman, Derrick Renner, Ekaterina Kalashnikova, Gillian L Hirst, Christina Yau, Denise M Wolf, Wen Li, Amy L Delson, Smita Asare, Minetta C Liu, Kathy Albain, A Jo Chien, Andres Forero-Torres, Claudine Isaacs, Rita Nanda, Debu Tripathy, Angel Rodriguez, Himanshu Sethi, Alexey Aleshin, Matthew Rabinowitz, Jane Perlmutter, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J Esserman, Angela M Demichele, Hope S Rugo, Laura J Van 'T Veer

Faculty, Staff and Student Publications

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized ctDNA analysis in hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. ctDNA positivity rates before, during, and after NAC are higher in TNBC than in HR-positive/HER2-negative breast cancer patients. Early clearance of ctDNA 3 weeks after treatment initiation predicts a favorable response to NAC in TNBC only. Whereas ctDNA positivity associates with reduced distant recurrence-free survival …

In Vitro And In Vivo Efficacy Of A Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus In Different Preclinical Models Of Cancer, Ana Alfano, Eduardo G A Cafferata, Mariela Gangemi, Alejandro Nicola Candia, Cristian M Malnero, Ismael Bermudez, Mauricio Vargas Lopez, Gregorio David Ríos, Cecilia Rotondaro, Nicasio Cuneo, David T Curiel, Osvaldo L Podhajcer, Maria Veronica Lopez

2020-Current year OA Pubs

More than one million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at a late stage, either because a lack of symptoms, such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries, such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV), whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer, uterine cancer, and cervical cancer. AR2011 was also able …

Microcalcification Crystallography As A Potential Marker Of Dcis Recurrence, Sarah B Gosling, Emily L Arnold, Samantha K Davies, Hannah Cross, Ihssane Bouybayoune, Doriana Calabrese, Jayakrupakar Nallala, Sarah E Pinder, Liping Fu, Esther H Lips, Lorraine King, Jeffrey Marks, Allison Hall, Lars J Grimm, Thomas Lynch, Donna Pinto, Hilary Stobart, E Shelley Hwang, Jelle Wesseling, Kalotina Geraki, Nicholas Stone, Iain D Lyburn, Charlene Greenwood, Keith D Rogers, Grand Challenge Precision Consortium

Faculty, Staff and Student Publications

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite …

Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie

Faculty, Staff and Student Publications

BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for …

Dostarlimab For Primary Advanced Or Recurrent Endometrial Cancer, Mansoor R Mirza, Carolyn Mccourt, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.

METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by …

17Β-Estradiol Promotes Extracellular Vesicle Release And Selective Mirna Loading In Erα-Positive Breast Cancer, Rares Drula, Barbara Pardini, Xiao Fu, Mireia Cruz De Los Santos, Ancuta Jurj, Lan Pang, Sherien M El-Daly, Linda Fabris, Erik Knutsen, Mihnea P Dragomir, Recep Bayraktar, Yongfeng Li, Meng Chen, Filippo Del Vecchio, Léa Berland, Jessica Dae, Daniel Fan, Masayoshi Shimizu, Anh M Tran, Mercedes Barzi, Carlotta Pioppini, Angelica M Gutierrez, Cristina Ivan, Salyna Meas, Carolyn S Hall, Suresh K Alahari, Ioana Berindan-Neagoe, Muller Fabbri, Anthony Lucci, Banu Arun, Simone Anfossi, George A Calin

Faculty, Staff and Student Publications

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, …