Digital Commons Network^™

Mean Arterial Pressure And Neonatal Outcomes In Pregnancies Complicated By Mild Chronic Hypertension, Matthew D Moore, Hui-Chien Kuo, Rachel G Sinkey, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew K Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather A Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Wendy Kinzler, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Sarah Osmundson, Joanne N Quiñones, Justin Leach, Ayodeji Sanusi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial.

Methods: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 …

Gene Expression Networks Regulated By Human Personality, Coral Del Val, Elisa Díaz De La Guardia-Bolívar, Igor Zwir, Pashupati P Mishra, Alberto Mesa, Ramiro Salas, Guillermo F Poblete, Gabriel De Erausquin, Emma Raitoharju, Mika Kähönen, Olli Raitakari, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Claude Robert Cloninger

Faculty, Staff and Students Publications

Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic …

Plozasiran (Aro-Apoc3) For Severe Hypertriglyceridemia: The Shasta-2 Randomized Clinical Trial, Daniel Gaudet, Denes Pall, Gerald F Watts, Stephen J Nicholls, Robert S Rosenson, Karen Modesto, Javier San Martin, Jennifer Hellawell, Christie M Ballantyne

Faculty, Staff and Students Publications

Importance: Severe hypertriglyceridemia (sHTG) confers increased risk of atherosclerotic cardiovascular disease (ASCVD), nonalcoholic steatohepatitis, and acute pancreatitis. Despite available treatments, persistent ASCVD and acute pancreatitis-associated morbidity from sHTG remains.

Objective: To determine the tolerability, efficacy, and dose of plozasiran, an APOC3-targeted small interfering-RNA (siRNA) drug, for lowering triglyceride and apolipoprotein C3 (APOC3, regulator of triglyceride metabolism) levels and evaluate its effects on other lipid parameters in patients with sHTG.

Design, setting, and participants: The Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2) was a placebo-controlled, double-blind, dose-ranging, phase 2b randomized clinical trial enrolling adults with sHTG at 74 …

Early And Late Complications Of Mandibulectomy Free Flap Reconstruction: Does The Selective Use Of Soft Tissue Only Flaps Reduce Complications?, Dylan B Mcbee, Michael J Dileo, Caroline C Keehn, Andrew T Huang, Angela D Haskins, David J Hernandez

Faculty, Staff and Students Publications

Purpose: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy.

Methods: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, < 90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used …

Utility Of Cystatin C-Based Equation For The Estimation Of Glomerular Filtration Rate In A Pediatric Population, Ridwan B Ibrahim, Poyyapakkam Srivaths, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations …

Pecarn Prediction Rule For Cervical Spine Imaging Of Children Presenting To The Emergency Department With Blunt Trauma: A Multicentre Prospective Observational Study, Julie C Leonard, Monica Harding, Lawrence J Cook, Jeffrey R Leonard, Kathleen M Adelgais, Fahd A Ahmad, Lorin R Browne, Rebecca K Burger, Pradip P Chaudhari, Daniel J Corwin, Nicolaus W Glomb, Lois K Lee, Sylvia Owusu-Ansah, Lauren C Riney, Alexander J Rogers, Daniel M Rubalcava, Robert E Sapien, Matthew A Szadkowski, Leah Tzimenatos, Caleb E Ward, Kenneth Yen, Nathan Kuppermann

Faculty, Staff and Students Publications

Background: Cervical spine injuries in children are uncommon but potentially devastating; however, indiscriminate neck imaging after trauma unnecessarily exposes children to ionising radiation. The aim of this study was to derive and validate a paediatric clinical prediction rule that can be incorporated into an algorithm to guide radiographic screening for cervical spine injury among children in the emergency department.

Methods: In this prospective observational cohort study, we screened children aged 0-17 years presenting with known or suspected blunt trauma at 18 specialised children's emergency departments in hospitals in the USA affiliated with the Pediatric Emergency Care Applied Research Network (PECARN). …

Independent Associations With Early Mortality After Open Repair Of Crawford Extent Iv Thoracoabdominal Aortic Aneurysms, Cuneyt Köksoy, Kimberly R Rebello, Susan Y Green, Hiruni S Amarasekara, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Objective: We aimed to identify outcomes and factors that independently associate with early mortality after open repair of Crawford extent IV thoracoabdominal aortic aneurysms, defined as aneurysms confined to the segment below the diaphragm.

Methods: This retrospective analysis included 721 extent IV thoracoabdominal aortic aneurysm repairs performed in our institution from 1986 to 2021. Indications for repair were aneurysm without dissection in 627 cases (87.0%) and aortic dissection in 94 cases (13.0%). Overall, 466 patients (64.6%) were symptomatic preoperatively; 124 (17.2%) procedures were performed in patients with acute presentation, including 58 (8.0%) ruptured aneurysms.

Results: Operative death occurred after 49 …

Effects Of Age On Lacrimal Gland Bioactive Lipids, Brandon Ebright, Zhiyuan Yu, Priyal Dave, Dante Dikeman, Sarah Hamm-Alvarez, Cintia S De Paiva, Stan Louie

Faculty, Staff and Students Publications

Purpose: Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution.

Methods: Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids.

Results: Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 …

Progressive Thrombocytopenia, Splenomegaly, And Abnormal Tone In An Infant With Growth Faltering, Gal Barak, Gail Demmler-Harrison, Linda Rossetti, Venée N Tubman, Ameya S Walimbe, Rathi Asaithambi

Faculty, Staff and Students Publications

A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but …

The Role Of Transoral Incisionless Fundoplication (Tif) In The Management Of Gastroesophageal Reflux Disease (Gerd) Following Peroral Endoscopic Myotomy (Poem): A Pilot, Prospective, Patient-Driven Study, Fares Ayoub, Tara Keihanian, Noor Zabad, Salmaan Jawaid, Kalpesh Patel, Mohamed O Othman

Faculty, Staff and Students Publications

BACKGROUND: Gastroesophageal reflux (GERD) is a concern after peroral endoscopic myotomy (POEM). Transoral incisionless fundoplication (TIF) has been recently described as a possible therapy for post-POEM GERD in case series.

METHODS: We prospectively enrolled patients undergoing POEM who agreed to participate in objective post-procedure GERD evaluation. Patients with objective evidence of GERD and suitable anatomy were offered TIF vs. proton pump inhibitor (PPI) only. Patients who underwent TIF were compared to those on PPI-only therapy after follow-up.

RESULTS: Of 21 enrolled POEM patients with objective testing, GERD was found in 11 (52%). Of those eligible for TIF, 4 (40%) opted …

Depressive Symptoms Are Associated With C-Reactive Protein In Older Adults With Obesity, Henry D Heisey, Clifford Qualls, Dennis T Villareal, Martha Belen Segoviano-Escobar, Maria Liza Duremdes Nava, Jennifer R Gatchel, Mark E Kunik

Faculty, Staff and Students Publications

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity.

METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m

RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R

CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group …

An Electronic Health Record Model For Predicting Risk Of Hepatic Fibrosis In Primary Care Patients, Aaron P Thrift, Theresa H Nguyen Wenker, Kyler Godwin, Maya Balakrishnan, Hao T Duong, Rohit Loomba, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic …

Thrombosis Risk Prediction In Lymphoma Patients: A Multi-Institutional, Retrospective Model Development And Validation Study, Shengling Ma, Jennifer La, Kaitlin N Swinnerton, Danielle Guffey, Raka Bandyo, Giordana De Las Pozas, Katy Hanzelka, Xiangjun Xiao, Cristhiam M Rojas-Hernandez, Christopher I Amos, Vipul Chitalia, Katya Ravid, Kelly W Merriman, Christopher R Flowers, Nathanael Fillmore, Ang Li

Faculty, Staff and Students Publications

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the …

Association Of High-Density Lipoprotein Parameters And Risk Of Heart Failure: A Multicohort Analysis, Ambarish Pandey, Kershaw V Patel, Matthew W Segar, Michael D Shapiro, Christie M Ballantyne, Salim S Virani, Vijay Nambi, Erin D Michos, Michael J Blaha, Khurram Nasir, Miguel Cainzos-Achirica, Colby R Ayers, B Daan Westenbrink, Jose L Flores-Guerrero, Stephan J L Bakker, Margery A Connelly, Robin P F Dullaart, Anand Rohatgi

Faculty, Staff and Students Publications

Background: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.

Objectives: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes.

Methods: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection …

Optimizing Sexual Reproductive Health Of Men And Women With Cystic Fibrosis: A Systematic Review, Anand G Iyer, Benjamin Yu, Amit Reddy, Mohit Khera

Faculty, Staff and Students Publications

This systematic review summarizes the impact of cystic fibrosis (CF) on sexual and reproductive health (SRH) in males and females, covering pubertal development, hormonal function, family planning, and fertility. Included articles featured historical CF diagnostic criteria, preclinical or clinical data (retrospective cohorts or open label trials), while excluded articles lacked full text availability, explicit methodology, or comparisons between CF and non-CF patients. Genotype differences in CFTR mutations influenced symptom severity. Males with CF experienced delayed puberty, hypogonadism, infertility from obstructive azoospermia, and semen parameter issues. Female CF patients showed decreased fertility, possibly linked to disrupted ionic balance and ovarian cystic …

Homozygous Missense Variants In Ykt6 Result In Loss Of Function And Are Associated With Developmental Delay, With Or Without Severe Infantile Liver Disease And Risk For Hepatocellular Carcinoma, Mengqi Ma, Mythily Ganapathi, Yiming Zheng, Kai-Li Tan, Oguz Kanca, Kevin E Bove, Norma Quintanilla, Sebnem O Sag, Sehime G Temel, Charles A Leduc, Amanda J Mcpartland, Elaine M Pereira, Yufeng Shen, Jacob Hagen, Christie P Thomas, Nhu Thao Nguyen Galván, Xueyang Pan, Shenzhao Lu, Jill A Rosenfeld, Daniel G Calame, Michael F Wangler, James R Lupski, Davut Pehlivan, Paula M Hertel, Wendy K Chung, Hugo J Bellen

Faculty, Staff and Students Publications

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases.

METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6

RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, …

Extended-Release 7-Day Injectable Buprenorphine For Patients With Minimal To Mild Opioid Withdrawal., Gail D'Onofrio, Andrew A. Herring, Jeanmarie Perrone, Kathryn Hawk, Elizabeth A. Samuels, Ethan Cowan, Erik Anderson, Ryan Mccormack, Kristen Huntley, Patricia Owens, Shara Martel, Mark Schactman, Michelle R. Lofwall, Sharon L. Walsh, James Dziura, David A. Fiellin

Behavioral Science Faculty Publications

IMPORTANCE: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD).

OBJECTIVE: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive …

Characteristics And Treatment Of Acute Myeloid Neoplasms With Cutaneous Involvement In Infants Up To 6 Months Of Age: A Retrospective Study., Juliette Renaud, Bianca F. Goemans, Franco Locatelli, Martina Pigazzi, Shelagh Redmond, Claudia E. Kuehni, Alice Destaillats, Todd A. Alonzo, Robert B. Gerbing, Alan S. Gamis, Richard Aplenc, Raffaele Renella, Todd Cooper, Francesco Ceppi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Myeloid neoplasms account for 50% of cases of pediatric leukemias in infants. Approximately 25%-50% of patients with newborn leukemia have cutaneous extramedullary disease (EMD). In less than 10% of patients, aleukemic leukemia cutis or isolated extramedullary disease with cutaneous involvement (cEMD) occurs when skin lesions appear prior to bone marrow involvement and systemic symptoms. Interestingly, in acute myeloid leukemia with cutaneous EMD (AML-cEMD) and cEMD, spontaneous remissions have been reported.

METHOD: This is a multicentric retrospective cohort study aiming to describe characteristics, treatment, and outcome of infants with either cEMD or presence of cutaneous disease with involvement of the …

Use Of Clearguard Hd Caps In Pediatric Hemodialysis Patients., Amy E. Nau, Troy Richardson, Diana Cardwell, Jennifer Ehrlich, Jyothsna Gattineni, Melisha Hanna, Mahima Keswani, Emily Neibauer, Kelly Nitz, Raymond Quigley, Michelle Rheault, Rebekah Sims, Mayna Woo, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of hospitalizations and mortality among patients receiving hemodialysis (HD) therapy, especially those with a central venous catheter (CVC) for dialysis access. The use of chlorhexidine impregnated catheter caps (ClearGuard) has been associated with a decrease in the rate of HD catheter-related BSIs (CA-BSIs) in adults; similar data have not been published for children.

METHODS: We compared CA-BSI data from participating centers within the Standardizing Care to Improve Outcomes in Pediatric Endstage Kidney Disease (SCOPE) collaborative based on the center's use of ClearGuard caps for patients with HD catheter access. Centers were characterized …

Efficacy And Safety Of Odevixibat In Patients With Alagille Syndrome (Assert): A Phase 3, Double-Blind, Randomised, Placebo-Controlled Trial., Nadia Ovchinsky, Madeleine Aumar, Alastair Baker, Ulrich Baumann, Philip Bufler, Mara Cananzi, Piotr Czubkowski, Özlem Durmaz, Ryan T. Fischer, Giuseppe Indolfi, Wikrom W. Karnsakul, Florence Lacaille, Way S. Lee, Giuseppe Maggiore, Philip Rosenthal, Mathias Ruiz, Etienne Sokal, Ekkehard Sturm, Wendy Van Der Woerd, Henkjan J. Verkade, Andrew Wehrman, Christine Clemson, Qifeng Yu, Quanhong Ni, Jessica Ruvido, Susan Manganaro, Jan P. Mattsson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In patients with Alagille syndrome, cholestasis-associated clinical features can include high serum bile acids and severe pruritus that can necessitate liver transplantation. We aimed to evaluate the efficacy and safety of the ileal bile acid transporter inhibitor odevixibat versus placebo in patients with Alagille syndrome.

METHODS: The ASSERT study was a phase 3, double-blind, randomised, placebo-controlled trial that enrolled patients at 21 medical centres or hospitals in ten countries (Belgium, France, Germany, Italy, Malaysia, the Netherlands, Poland, Türkiye, the UK, and the USA). Eligible patients had a genetically confirmed diagnosis of Alagille syndrome, a history of significant pruritus, and …

Juvenile Polyposis Syndrome In Children: The Impact Of Smad4 And Bmpr1a Mutations On Clinical Phenotype And Polyp Burden., Shlomi Cohen, Anat Yerushalmy-Feler, Isabel Rojas, Claudia Phen, David A. Rudnick, Colleen B. Flahive, Steven H. Erdman, Ramit Magen-Rimon, Ivana Copova, Thomas M. Attard, Andrew Latchford, Warren Hyer

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS.

METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group.

RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) …

Risk Factors For Postpartum Depression And Severe Distress Among Mothers Of Very Preterm Infants At Nicu Discharge., Julie A. Hofheimer, Elisabeth C. Mcgowan, Lynne M. Smith, Samantha Meltzer-Brody, Brian S. Carter, Lynne M. Dansereau, Steven Pastyrnak, Jennifer B. Helderman, Charles R. Neal, Sheri A. Dellagrotta, Thomas Michael D O'Shea, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE:  To identify psychological, medical, and socioenvironmental risk factors for maternal postpartum depression (PPD) and severe psychological distress (SPD) at intensive care nursery discharge among mothers of very preterm infants.

STUDY DESIGN:  We studied 562 self-identified mothers of 641 infants born(NOVI) conducted in nine university-affiliated intensive care nurseries. Enrollment interviews collected socioenvironmental data, depression, and anxiety diagnoses prior to and during the study pregnancy. Standardized medical record reviews ascertained prenatal substance use, maternal and neonatal medical complications. The Edinburgh Postnatal Depression Scale and Brief Symptom Inventory were administered at nursery discharge to screen for PPD and SPD symptoms, respectively.

RESULTS: …

Preeclampsia, Fetal Growth Restriction, And 24-Month Neurodevelopment In Very Preterm Infants., Jennifer Check, Coral Shuster, Julie Hofheimer, Marie Camerota, Lynne M. Dansereau, Lynne M. Smith, Brian S. Carter, Sheri A. Dellagrotta, Jennifer Helderman, Howard Kilbride, Cynthia M. Loncar, Elisabeth Mcgowan, Charles R. Neal, T Michael O'Shea, Steven L. Pastyrnak, Stephen J. Sheinkopf, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized.

OBJECTIVE: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care …

The Use Of Hearing Tests To Assess Otitis Media With Effusion In Children With Down Syndrome., Mackenzie O'Donnell, Nasrin Sultana, Nasreen Talib, Jason May, Michael Slogic

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Down syndrome is associated with an increased risk for otitis media with effusion (OME), a childhood condition in which fluid accumulates in the middle ear, potentially leading to hearing loss. The American Academy of Pediatrics Down syndrome guidelines and the American Academy of Otolaryngology - Head and Neck Surgery OME guidelines recommend hearing testing to assess the hearing status of children with Down syndrome diagnosed with OME.

METHODS: Through an Institutional Review Board approved retrospective chart review at Children's Mercy, this project assessed how clinical factors affect the frequency in which children with Down syndrome receive hearing testing after …

Psychotropic Medication Usage In Pediatric Ckd: Reporting From The Ckd In Children Cohort., Ryan C. Ward, Amy J. Kogon, Matthew B. Matheson, Anne Dawson, Stephen R. Hooper, Stephen Molitor, Cynthia Wong, Susan L. Furth, Bradley A. Warady, Lyndsay A. Harshman

Manuscripts, Articles, Book Chapters and Other Papers

Background: Mental health disorders within the pediatric CKD population are prevalent. The frequency is unknown with which psychotropic medications that commonly treat these conditions are used in this population.

Methods: Data from the CKD in Children (CKiD) cohort study were used to describe the use of psychotropic medications and patient-related characteristics of use. Medications were classified into three groups: antidepressants, central nervous system (CNS) stimulants, and antipsychotic/mood stabilizing medications. Participant age, sex, CKD severity, and duration of medication use were ascertained. Medication use was evaluated in parallel with CKD disease type, presence of urological comorbidity, and hypertension. Chi-square tests compared …

Study Of A Pst-Trained Voice-Enabled Artificial Intelligence Counselor For Adults With Emotional Distress (Speac-2): Design And Methods, Corina R Ronneberg, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Novel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms.

METHODS: To further validate Lumen in a 3-arm randomized clinical trial, 200 participants with mild-to-moderate depression and/or anxiety will be randomly assigned in a 2:1:1 ratio to receive Lumen-coached PST, human-coached PST as active treatment comparison, or a waitlist control condition where participants can receive Lumen …

Gene Expression Networks Regulated By Human Personality, Coral Del Val, Elisa Díaz De La Guardia-Bolívar, Igor Zwir, Pashupati P Mishra, Alberto Mesa, Ramiro Salas, Guillermo F Poblete, Gabriel De Erausquin, Emma Raitoharju, Mika Kähönen, Olli Raitakari, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Claude Robert Cloninger

2020-Current year OA Pubs

Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic …

Alcohol Milestones And Internalizing, Externalizing, And Executive Function: Longitudinal And Polygenic Score Associations, Sarah E Paul, David A A Baranger, Joshua J Jackson, Aaron J Gorelik, Alexander S Hatoum, Michael Strube, Andrey P Anokhin, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (

RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe …

Integrating Multisector Molecular Characterization Into Personalized Peptide Vaccine Design For Patients With Newly Diagnosed Glioblastoma, Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn

2020-Current year OA Pubs

PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.

PATIENTS AND METHODS: In this …

Il2 Targeted To Cd8+ T Cells Promotes Robust Effector T-Cell Responses And Potent Antitumor Immunity, Kelly D Moynihan, Hussein Sultan, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells …