Digital Commons Network^™

An Intraoperative Telemedicine Program To Improve Perioperative Quality Measures: The Actfast-3 Randomized Clinical Trial, Christopher R King, Stephen Gregory, Bradley A Fritz, Thaddeus P Budelier, Arbi Ben Abdallah, Alex Kronzer, Daniel L Helsten, Brian Torres, Sherry Mckinnon, Shreya Goswami, Divya Mehta, Omokhaye Higo, Paul Kerby, Bernadette Henrichs, Mary C Politi, Joanna Abraham, Michael S Avidan, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Telemedicine for clinical decision support has been adopted in many health care settings, but its utility in improving intraoperative care has not been assessed.

OBJECTIVE: To pilot the implementation of a real-time intraoperative telemedicine decision support program and evaluate whether it reduces postoperative hypothermia and hyperglycemia as well as other quality of care measures.

DESIGN, SETTING, AND PARTICIPANTS: This single-center pilot randomized clinical trial (Anesthesiology Control Tower-Feedback Alerts to Supplement Treatments [ACTFAST-3]) was conducted from April 3, 2017, to June 30, 2019, at a large academic medical center in the US. A total of 26 254 adult surgical patients …

Genetic Susceptibility To Cognitive Decline Following Craniospinal Irradiation For Pediatric Central Nervous System Tumors, Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer

Faculty, Staff and Student Publications

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at …

Tissue Oxygenation Changes After Transfusion And Outcomes In Preterm Infants: A Secondary Near-Infrared Spectroscopy Study Of The Transfusion Of Prematures Randomized Clinical Trial (Top Nirs), Valerie Y Chock, Haresh Kirpalani, Edward F Bell, Sylvia Tan, Susan R Hintz, M Bethany Ball, Emily Smith, Abhik Das, Yvonne C Loggins, Beena G Sood, Lina F Chalak, Myra H Wyckoff, Stephen D Kicklighter, Kathleen A Kennedy, Ravi M Patel, Waldemar A Carlo, Karen J Johnson, Kristi L Watterberg, Pablo J Sánchez, Abbot R Laptook, Ruth B Seabrook, C Michael Cotten, Toni Mancini, Gregory M Sokol, Robin K Ohls, Anna Maria Hibbs, Brenda B Poindexter, Anne Marie Reynolds, Sara B Demauro, Sanjay Chawla, Mariana Baserga, Michele C Walsh, Rosemary D Higgins, Krisa P Van Meurs, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

IMPORTANCE: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.

OBJECTIVE: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age.

DESIGN, SETTING, AND PARTICIPANTS: …

Surgical Management Of Congenital Malrotation Presenting In Adulthood., Jacob Holzemer, Krishna Patel, Oscar Ruiz, Jodi Oostra

Surgery Articles

Intestinal malrotation is characterised by positional and congenital fixation abnormalities resulting from a failure in embryonic development in the normal 270° rotation around the axis of the superior mesenteric artery. Intestinal malrotation is primarily thought to affect neonates with an incidence of 1 in 500, however, only 1 in 6000 live births are symptomatic, and these usually present within the first month of life in 40% of cases and within the first year in over 5% of cases as an obstructive pathology or volvulus. In adults, however, the incidence has been documented at 0.2%. These patients usually present with postprandial …

Development Of A Culturally Adapted Dietary Intervention To Reduce Alzheimer's Disease Risk Among Older Black Adults, Ashley R Shaw, Mickeal N Key, Samantha Fikru, Saria Lofton, Debra K Sullivan, Jannette Berkley-Patton, Crystal M Glover, Jeffrey M Burns, Eric D Vidoni

Faculty, Staff and Student Publications

The objective of this study is to identify and understand knowledge and attitudes that influence dietary practices among older Black adults using a community-engaged approach. This is a non-interventional mixed methods study designed to inform the development of an adapted brain-healthy soul food diet intervention. A purposive sampling approach was used to conduct seven semi-structured focus group discussions and an online quantitative survey. In total, 39 participants who self-identified as Black, aged 55 years and older, English speaking, and who were cognitively normal with an AD8 < 2; (25.6% men; 74.4% women) participated in the online survey and one of the seven 60 min virtual focus group discussions (5-7 per focus group). Quantitative frequency data from the online surveys were analyzed using descriptive statistics. Qualitative focus group data were analyzed using a 6-step thematic analysis process. Five themes emerged: dementia awareness; practices shaping food choices and consumption; barriers to eating healthy; instrumental support; and elements of a culturally adapted brain-healthy dietary intervention. Older Black adults perceived an adapted MIND dietary model as the most acceptable with the incorporation of salient cultural characteristics and strategies within both the design and delivery phases.

Childhood Exposure To Parental Threatening Behaviors And Anxiety In Emerging Adulthood: Indirect Effects Of Perceived Stress, Erika S Trent, Andres G Viana, Elizabeth M Raines, Haley E Conroy Busch, Karina Silva, Eric A Storch, Michael J Zvolensky

Center for Medical Ethics and Health Policy Staff Publications

Background: Although childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress-a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self-efficacy (confidence in one's ability to manage stressors)-is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults.

Methods: Participants (N = 855; Mage = 18.75 years, SD = 1.05, range 18-24; 70.8% female) were recruited from a …

Cell-Based Noninvasive Prenatal Testing (Cbnipt)-A Review On The Current Developments And Future Prospects, Mohamad Ali Maktabi, Liesbeth Vossaert, Ignatia B Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Considering the diagnostic limitations of cfDNA-based noninvasive prenatal testing (NIPT), scientists have long been interested in isolating and analyzing rare intact fetal and trophoblast cells from maternal blood or endocervical samples to diagnose fetal genetic conditions. These cells may be scarce and difficult to isolate, but they are a direct source of pure fetal genetic material. In this review, we summarize the history of cell-based NIPT, present an updated review on its current developments, evaluate its genetic diagnostic potential, and discuss its future prospects for clinical use.

Dynamics Of Inflammatory Responses After Sars-Cov-2 Infection By Vaccination Status In The Usa: A Prospective Cohort Study, Xianming Zhu, Kelly A Gebo, Alison G Abraham, Feben Habtehyimer, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Patrick Broderick, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, Joann Petrini, William Rausch, David Shade, Karen Lane, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, David J Sullivan, Aaron A R Tobian

Faculty, Staff and Student Publications

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples …

Evaluation Of Field Sobriety Tests For Identifying Drivers Under The Influence Of Cannabis: A Randomized Clinical Trial, Thomas D Marcotte, Anya Umlauf, David J Grelotti, Emily G Sones, Kyle F Mastropietro, Raymond T Suhandynata, Marilyn A. Huestis, Igor Grant, Robert L Fitzgerald

Institute of Emerging Health Professions Faculty Papers

IMPORTANCE: With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC.

OBJECTIVE: To examine the classification accuracy of FSTs with respect to cannabis exposure and driving impairment (as determined via a driving simulation).

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled parallel randomized clinical trial was …

Global Sumoylation In Mouse Oocytes Maintains Oocyte Identity And Regulates Chromatin Remodeling And Transcriptional Silencing At The End Of Folliculogenesis, Shawn M Briley, Avery A Ahmed, Tessa E Steenwinkel, Peixin Jiang, Sean M Hartig, Karen Schindler, Stephanie A Pangas

Faculty, Staff and Students Publications

Meiotically competent oocytes in mammals undergo cyclic development during folliculogenesis. Oocytes within ovarian follicles are transcriptionally active, producing and storing transcripts required for oocyte growth, somatic cell communication and early embryogenesis. Transcription ceases as oocytes transition from growth to maturation and does not resume until zygotic genome activation. Although SUMOylation, a post-translational modification, plays multifaceted roles in transcriptional regulation, its involvement during oocyte development remains poorly understood. In this study, we generated an oocyte-specific knockout of Ube2i, encoding the SUMO E2 enzyme UBE2I, using Zp3-cre+ to determine how loss of oocyte SUMOylation during folliculogenesis affects oocyte development. Ube2i Zp3-cre+ female …

Tepotinib Treatment In Patients With Met Exon 14-Skipping Non-Small Cell Lung Cancer: Long-Term Follow-Up Of The Vision Phase 2 Nonrandomized Clinical Trial, Julien Mazieres, Paul K Paik, Marina C Garassino, Xiuning Le, Hiroshi Sakai, Remi Veillon, Egbert F Smit, Alexis B Cortot, Jo Raskin, Santiago Viteri, Yi-Long Wu, James C H Yang, Myung-Ju Ahn, Rui Ma, Jun Zhao, Aurora O'Brate, Karin Berghoff, Rolf Bruns, Gordon Otto, Andreas Johne, Enriqueta Felip, Michael Thomas

Faculty, Staff and Student Publications

Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.

Objective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.

Design, setting, and participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (>18 …

Examining Whether Genetic Variants Moderate The Skeletal Effects Of Selective Serotonin Reuptake Inhibitors In Older Adolescents And Young Adults, Ifeoma Ezenwabachili, Emira Deumic Shultz, James A Mills, Vicki Ellingrod, Chadi A Calarge

Faculty, Staff and Students Publications

Objective: To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes. Methods: Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in HTR1A (rs6295), HTR1B (rs6296), HTR1D (rs6300), HTR2A (rs6311 and rs6314), HTR2B (rs6736017), and the serotonin …

Cannabis Use Disorder And Perioperative Complications, Paul P Potnuru, Srikar Jonna, George W Williams

Faculty, Staff and Student Publications

Importance: Cannabis use is growing in the US and is increasingly perceived as harmless. However, the perioperative impact of cannabis use remains uncertain.

Objective: To assess whether cannabis use disorder is associated with increased morbidity and mortality after major elective, inpatient, noncardiac surgery.

Design, setting, and participants: This retrospective, population-based, matched cohort study used data from the National Inpatient Sample for adult patients aged 18 to 65 years who underwent major elective inpatient surgery (including cholecystectomy, colectomy, inguinal hernia repair, femoral hernia repair, mastectomy, lumpectomy, hip arthroplasty, knee arthroplasty, hysterectomy, spinal fusion, and vertebral discectomy) from January 2016 to December …

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Mary Duarte Thibault, Luyun Chen, Markus Huebner, John O Delancey, Carolyn W Swenson

Faculty, Staff and Students Publications

INTRODUCTION AND HYPOTHESIS: We sought to 1) test the hypothesis that young women (≤45 years) with pelvic organ prolapse have a higher prevalence of major levator ani muscle (LAM) defects than old women (≥70 years) with prolapse and 2) compare level II/III measurements between young and old women with prolapse and age-matched controls to evaluate age-related mechanistic differences in the disease process.

METHODS: A secondary analysis examined four groups of parous women: young prolapse (YPOP, n = 17); old prolapse (OPOP, n = 17); young controls (YC, n = 15); old controls, (OC, n = 13). Prolapse was defined as …

Atypical Squamous Verrucous Lesions Of The Oral Cavity: Challenges In Interpretation Of Small Incisional Biopsies, Ryland Richards, Shweta Agarwal

Pathology Research and Scholarship

BACKGROUND: Squamous verrucous proliferative lesions of oral cavity can pose a diagnostic challenge for the general pathologist, especially on small biopsies. The superficial nature of incisional biopsies and inconsistent histologic terminologies used for these lesions contribute to often-discrepant clinical diagnosis, resulting in delayed treatment. This study aims to explore the proliferative squamous lesions of oral cavity, correlate biopsy & resection diagnoses, and evaluate possible reasons for discrepant diagnosis (if any).

DESIGN: A retrospective review of oral verrucous squamous lesions was undertaken. Pathology database was searched for oral cavity biopsies from January2018 through August2022 with the keywords: atypical, verrucous, squamous, and …

Epigenome-Wide Association Study Using Peripheral Blood Leukocytes Identifies Genomic Regions Associated With Periodontal Disease And Edentulism In The Atherosclerosis Risk In Communities Study, Naisi Zhao, Flavia Teles, Jiayun Lu, Devin C Koestler, James Beck, Eric Boerwinkle, Jan Bressler, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.

MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs.

RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that …

Associations Of Sex, Race, And Apolipoprotein E Alleles With Multiple Domains Of Cognition Among Older Adults, Skylar Walters, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sex differences are established in associations between apolipoprotein E (APOE) ε4 and cognitive impairment in Alzheimer disease (AD). However, it is unclear whether sex-specific cognitive consequences of APOE are consistent across races and extend to the APOE ε2 allele.

OBJECTIVE: To investigate whether sex and race modify APOE ε4 and ε2 associations with cognition.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study included longitudinal cognitive data from 4 AD and cognitive aging cohorts. Participants were older than 60 years and self-identified as non-Hispanic White or non-Hispanic Black (hereafter, White and Black). Data were previously collected across multiple US locations …

The Effects Of Equine-Assisted Activities On Execution Function In Children Aged 7–8 Years: A Randomized Controlled Trial, Xiaodong Cheng, Kexin Zhen, Yongzhao Fan, Qian Tang, Hao Wu

Faculty, Staff and Student Publications

BACKGROUND: This study examines the effects of equine-assisted activity (EAA) training on executive functioning (EF) (inhibitory control, working memory, and cognitive flexibility) in children aged 7-8 years.

METHODS: Twenty-Four healthy children aged 7-8 years with a 1:1 ratio of boys to girls were randomly divided into EAA group (EAAG) or control group (CG). The subjects in EAAG were trained for 12 weeks, and CG participated in normal daily activities. All subjects conducted the Flanker, 1-Back, and More-odd shifting tasks at rest and recorded the average reaction times (RTs) and accuracy data of each task.

RESULTS: After 12 weeks of EAA …

Daily Early-Life Exposures To Diet Soda And Aspartame Are Associated With Autism In Males: A Case-Control Study, Sharon Parten Fowler, David Gimeno Ruiz De Porras, Michael D Swartz, Paula Stigler Granados, Lynne Parsons Heilbrun, Raymond F Palmer

Faculty, Staff and Student Publications

Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DSearly) or equivalent aspartame (ASPearly: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DSearly and …

Flavonoids Quercetin And Kaempferol Are Nr4a1 Antagonists And Suppress Endometriosis In Female Mice, Lei Zhang, Kumaravel Mohankumar, Gregory Martin, Fuada Mariyam, Yuri Park, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Nuclear receptor 4A1 (NR4A1) plays an important role in endometriosis progression; levels of NR4A1 in endometriotic lesions are higher than in normal endometrium, and substituted bis-indole analogs (NR4A1) antagonists suppress endometriosis progression in mice with endometriosis. In addition, the flavonoids kaempferol and quercetin are natural products that directly bind NR4A1 and significantly repress the intrinsic NR4A1-dependent transcriptional activity in human endometriotic epithelial and stromal cells and Ishikawa endometrial cancer cells. NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin suppressed proliferation of human endometriotic epithelial cells and Ishikawa cells by inhibiting epidermal growth factor receptor/c-Myc/survivin-mediated growth-promoting and survival pathways, …

The Histone Chaperone Function Of Daxx Is Dispensable For Embryonic Development, Chang Sun, Yuan Qi, Natalie Fowlkes, Nina Lazic, Xiaoping Su, Guillermina Lozano, Amanda R Wasylishen

Faculty, Staff and Student Publications

Daxx functions as a histone chaperone for the histone H3 variant, H3.3, and is essential for embryonic development. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres, and repeat loci. To advance our understanding of histone chaperone activity in vivo, we developed two Daxx mutant alleles in the mouse germline, which abolish the interactions between Daxx and Atrx (DaxxY130A), and Daxx and H3.3 (DaxxS226A). We found that the interaction between Daxx and Atrx is dispensable for viability; mice are born at the …

Bioaccumulation Of Non-Essential Trace Elements Detected In Women's Follicular Fluid, Urine, And Plasma Is Associated With Poor Reproductive Outcomes Following Single Euploid Embryo Transfer: A Pilot Study, Andrea Palomar, Roberto Gonzalez-Martin, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Isabel Rucandio, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Caroline Zuckerman, Christine Whitehead, Richard T. Scott, Francisco Dominguez

Department of Obstetrics and Gynecology Faculty Papers

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of …

Immunotherapy Targeting Different Immune Compartments In Combination With Radiation Therapy Induces Regression Of Resistant Tumors, Nils-Petter Rudqvist, Maud Charpentier, Claire Lhuillier, Erik Wennerberg, Sheila Spada, Caroline Sheridan, Xi Kathy Zhou, Tuo Zhang, Silvia C Formenti, Jennifer S Sims, Alicia Alonso, Sandra Demaria

Faculty, Staff and Student Publications

Radiation therapy (RT) increases tumor response to CTLA-4 inhibition (CTLA4i) in mice and in some patients, yet deep responses are rare. To identify rational combinations of immunotherapy to improve responses we use models of triple negative breast cancer highly resistant to immunotherapy in female mice. We find that CTLA4i promotes the expansion of CD4+ T helper cells, whereas RT enhances T cell clonality and enriches for CD8+ T cells with an exhausted phenotype. Combination therapy decreases regulatory CD4+ T cells and increases effector memory, early activation and precursor exhausted CD8+ T cells. A combined gene signature comprising these three CD8+ …

Building A Predictive Model Of Low Birth Weight In Low- And Middle-Income Countries: A Prospective Cohort Study, Jackie K. Patterson, Vanessa R Thorsten, Barry Eggleston, Tracy Nolen, Adrien Lokangaka, Antoinette Tshefu, Shivaprasad S. Goudar, Richard J. Derman, Elwyn Chomba, Waldemar A. Carlo, Manolo Mazariegos, Nancy F. Krebs, Sarah Saleem, Robert L. Goldenberg, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Rashidul Haque, Bill Petri, Marion Koso-Thomas, Elizabeth M. Mcclure, Carl L. Bose, Melissa Bauserman

Global Health Articles

BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants.

METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine.

RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) …

Biomass Smoke Inhalation Promotes Neuroinflammatory And Metabolomic Temporal Changes In The Hippocampus Of Female Mice, David Scieszka, Yan Jin, Shahani Noor, Ed Barr, Marcus Garcia, Jessica Begay, Guy Herbert, Russell P. Hunter, Kiran Bhaskar, Rahul Kumar, Rama Gullapalli, Alicia Bolt, Mark A. Mccormick, Barry Bleske, Haiwei Gu, Matthew J. Campen

Pathology Research and Scholarship

Smoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the temporal dynamics of neuroinflammation and metabolomics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6 J mice were exposed to wood smoke every other day for 2 weeks at an average exposure concentration of 0.5 mg/m

Variable Cre Recombination Efficiency In Placentas Of Cyp19-Cre Rosa Mt/Mg Transgenic Mice, Prashanth Anamthathmakula, Philemon D. Shallie, Neha Nayak, Sabita Dhal, Jay L. Vivian, Gil Mor, Michael J. Soares, Nihar R. Nayak

Manuscripts, Articles, Book Chapters and Other Papers

The aromatase-Cre recombinase (Cyp19-Cre) transgenic mouse model has been extensively used for placenta-specific gene inactivation. In a pilot study, we observed unexpected phenotypes using this mouse strain, which prompted an extensive characterization of Cyp19-Cre placental phenotypes using ROSAmT/mG transgenic reporter mice. The two strains were mated to generate bi-transgenic Cyp19-Cre;ROSAmT/mG mice following a standard transgenic breeding scheme, and placental and fetal tissues were analyzed on embryonic day 17.5. Both maternal and paternal Cre inheritance were analyzed by mating the respective Cyp19-Cre and ROSAmT/mG males and females. The genotype results showed the expected percentage of Cyp19-Cre;ROSAmT/mG fetuses (73%) and Cre mRNA …

A Multiparameter Molecular Classifier To Predict Response To Neoadjuvant Lapatinib Plus Trastuzumab Without Chemotherapy In Her2+ Breast Cancer, Jamunarani Veeraraghavan, Carolina Gutierrez, Carmine De Angelis, Robert Davis, Tao Wang, Tomas Pascual, Pier Selenica, Katherine Sanchez, Hiroaki Nitta, Monesh Kapadia, Anne C Pavlick, Patricia Galvan, Brent Rexer, Andres Forero-Torres, Rita Nanda, Anna M Storniolo, Ian E Krop, Matthew P Goetz, Julie R Nangia, Antonio C Wolff, Britta Weigelt, Jorge S Reis-Filho, Susan G Hilsenbeck, Aleix Prat, C Kent Osborne, Rachel Schiff, Mothaffar F Rimawi

Faculty, Staff and Student Publications

PURPOSE: Clinical trials reported 25% to 30% pathologic complete response (pCR) rates in HER2+ patients with breast cancer treated with anti-HER2 therapies without chemotherapy. We hypothesize that a multiparameter classifier can identify patients with HER2-"addicted" tumors who may benefit from a chemotherapy-sparing strategy.

EXPERIMENTAL DESIGN: Baseline HER2+ breast cancer specimens from the TBCRC023 and PAMELA trials, which included neoadjuvant treatment with lapatinib and trastuzumab, were used. In the case of estrogen receptor-positive (ER+) tumors, endocrine therapy was also administered. HER2 protein and gene amplification (ratio), HER2-enriched (HER2-E), and PIK3CA mutation status were assessed by dual gene protein assay (GPA), research-based …

The Unique Professional Journey Of Female High School Principals In Utah, Deon G. Leavy

Theses and Dissertations

Women in the United States are underrepresented in high school principalships. A review of literature identified specific barriers that have historically contributed to this disparity including role congruity, normative male dominance, and gender bias against women. Furthermore, the high school principalship has been defined over time from a male perspective assumed to be the universal reality leaving the unique career experiences of female high school principals glossed over and often misunderstood. Similar barriers most likely have also contributed to the underrepresentation of female high school principals in Utah, yet intentional studies analyzing their unique career journeys have not been completed. …

Bacteroides Uniformis-Induced Perturbations In Colonic Microbiota And Bile Acid Levels Inhibit Th17 Differentiation And Ameliorate Colitis Developments, Yiting Yan, Yu Lei, Ying Qu, Zhen Fan, Ting Zhang, Yangbin Xu, Qian Du, Daniel Brugger, Yulin Chen, Ke Zhang, Enping Zhang

Faculty, Staff and Student Publications

Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely …