Digital Commons Network^™

Phenopacket-Tools: Building And Validating Ga4gh Phenopackets., Daniel Danis, Julius O B Jacobsen, Alex H Wagner, Tudor Groza, Martha A Beckwith, Lauren Rekerle, Leigh Carmody, Justin Reese, Harshad Hegde, Markus S Ladewig, Berthold Seitz, Monica Munoz-Torres, Nomi L Harris, Jordi Rambla, Michael Baudis, Christopher J Mungall, Melissa A Haendel, Peter N Robinson

Faculty Research 2023

The Global Alliance for Genomics and Health (GA4GH) is a standards-setting organization that is developing a suite of coordinated standards for genomics. The GA4GH Phenopacket Schema is a standard for sharing disease and phenotype information that characterizes an individual person or biosample. The Phenopacket Schema is flexible and can represent clinical data for any kind of human disease including rare disease, complex disease, and cancer. It also allows consortia or databases to apply additional constraints to ensure uniform data collection for specific goals. We present phenopacket-tools, an open-source Java library and command-line application for construction, conversion, and validation of phenopackets. …

The Effectiveness Of An Ehealth Family-Based Intervention Program In Patients With Uncontrolled Type 2 Diabetes Mellitus (T2dm) In The Community Via Wechat: Randomized Controlled Trial, Yuheng Feng, Yuxi Zhao, Linqi Mao, Minmin Gu, Hong Yuan, Jun Lu, Qi Zhang, Qian Zhao, Xiaohong Li

Community & Environmental Health Faculty Publications

Background: Intervention based on family support and risk perception can enhance type 2 diabetes mellitus (T2DM) patients’ self-care activities. In addition, eHealth education is considered to improve family members’ support for patients with T2DM. However, there is little evidence from rigorously designed studies on the effectiveness of an intervention combining these approaches.

Objective: This randomized controlled trial (RCT) aimed to assess the effectiveness of an eHealth family-based health education intervention for patients with T2DM to improve their glucose control, risk perception, and self-care behaviors.

Methods: This single-center, 2-parallel-group RCT was conducted between 2019 and 2020. Overall, 228 patients were recruited …

Editorial: Targeting Glucose Metabolism In Cancer Immunity And Immunotherapy., Olivier Feron, Chih-Hao Chang, Frédérique Végran

Faculty Research 2023

No abstract provided.

An Intravenous Pancreatic Cancer Therapeutic: Characterization Of Crispr/Cas9n-Modified Clostridium Novyi-Non Toxic, Kaitlin M. Dailey, James M. Small, Jessica E. Pullan, Seth Winfree, Krysten E. Vance, Megan Orr, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E Brooks

Journal Articles: Pathology and Microbiology

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed …

Agricultural Dust Derived Bacterial Extracellular Vesicle Mediated Inflammation Is Attenuated By Dha, Art J. Heires, Derrick R. Samuelson, Daniel Villageliu, Tara M. Nordgren, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed …

Icenticaftor, Novel Therapy For Copd: This Glass Is Half Full, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Assessing Impact Of Nutrition Care By Registered Dietitian Nutritionists On Patient Medical And Treatment Outcomes In Outpatient Cancer Clinics: A Cohort Feasibility Study, Dolores D. Guest, Tricia Cox, Anne Coble Voss, Kathryn Kelley, Xingya Ma, Andreea Nguyen, Kerry Mcmillen, Valaree Williams, James A. Lee, Jennifer Petersen, Karilynne Lenning, Elizabeth Yakes Jimenez

Pediatrics Research and Scholarship

More information is needed about the impact of outpatient nutrition care from a registered dietitian nutritionist (RDN) on patient outcomes. This study aimed to assess the feasibility of a cohort study design to evaluate impact of RDN nutrition care on patient outcomes, describe clinic malnutrition screening practices, and estimate statistical parameters for a larger study. Seventy-seven patients with lung, esophageal, colon, rectal, or pancreatic cancer from six facilities were included (41 received RDN care and 36 did not). RDN nutrition care was prospectively documented for six months and documented emergency room visits, unplanned hospitalizations and treatment changes were retrospectively abstracted …

Researching Covid To Enhance Recovery (Recover) Adult Study Protocol: Rationale, Objectives, And Design, Leora I Horwitz, Tanayott Thaweethai, Shari B Brosnahan, Mine S Cicek, Megan L Fitzgerald, Jason D Goldman, Rachel Hess, S L Hodder, Vanessa L Jacoby, Michael R Jordan, Jerry A Krishnan, Adeyinka O Laiyemo, Torri D Metz, Lauren Nichols, Rachel E Patzer, Anisha Sekar, Nora G Singer, Lauren E Stiles, Barbara S Taylor, Shifa Ahmed, Heather A Algren, Khamal Anglin, Lisa Aponte-Soto, Hassan Ashktorab, Ingrid V Bassett, Brahmchetna Bedi, Nahid Bhadelia, Christian Bime, Marie-Abele C Bind, Lora J Black, Andra L Blomkalns, Hassan Brim, Mario Castro, James Chan, Alexander W Charney, Benjamin K Chen, Li Qing Chen, Peter Chen, David Chestek, Lori B Chibnik, Dominic C Chow, Helen Y Chu, Rebecca G Clifton, Shelby Collins, Maged M Costantine, Sushma K Cribbs, Steven G Deeks, John D Dickinson, Sarah E Donohue, Matthew S Durstenfeld, Ivette F Emery, Kristine M Erlandson, Julio C Facelli, Rachael Farah-Abraham, Aloke V Finn, Melinda S Fischer, Valerie J Flaherman, Judes Fleurimont, Vivian Fonseca, Emily J Gallagher, Jennifer C Gander, Maria Laura Gennaro, Kelly S Gibson, Minjoung Go, Steven N Goodman, Joey P Granger, Frank L Greenway, John W Hafner, Jenny E Han, Michelle S Harkins, Kristine S P Hauser, James R Heath, Carla R Hernandez, On Ho, Matthew K Hoffman, Susan E Hoover, Carol R Horowitz, Harvey Hsu, Priscilla Y Hsue, Brenna L Hughes, Prasanna Jagannathan, Judith A James, Janice John, Sarah Jolley, S E Judd, Joy J Juskowich, Diane G Kanjilal, Elizabeth W Karlson, Stuart D Katz, J Daniel Kelly, Sara W Kelly, Arthur Y Kim, John P Kirwan, Kenneth S Knox, Andre Kumar, Michelle F Lamendola-Essel, Margaret Lanca, Joyce K Lee-Lannotti, R Craig Lefebvre, Bruce D Levy, Janet Y Lin, Brian P Logarbo, Jennifer K Logue, Michele T Longo, Carlos A Luciano, Karen Lutrick, Shahdi K Malakooti, Gail Mallett, Gabrielle Maranga, Jai G Marathe, Vincent C Marconi, Gailen D Marshall, Christopher F Martin, Jeffrey N Martin, Heidi T May, Grace A Mccomsey, Dylan Mcdonald, Hector Mendez-Figueroa, Lucio Miele, Murray A Mittleman, Sindhu Mohandas, Christian Mouchati, Janet M Mullington, Girish N Nadkarni, Erica R Nahin, Robert B Neuman, Lisa T Newman, Amber Nguyen, Janko Z Nikolich, Igho Ofotokun, Princess U Ogbogu, Anna Palatnik, Kristy T S Palomares, Tanyalak Parimon, Samuel Parry, Sairam Parthasarathy, Thomas F Patterson, Ann Pearman, Michael J Peluso, Priscilla Pemu, Christian M Pettker, Beth A Plunkett, Kristen Pogreba-Brown, Athena Poppas, J Zachary Porterfield, John G Quigley, Davin K Quinn, Hengameh Raissy, Candida J Rebello, Uma M Reddy, Rebecca Reece, Harrison T Reeder, Franz P Rischard, Johana M Rosas, Clifford J Rosen, Nadine G Rouphael, Dwight J Rouse, Adam M Ruff, Christina Saint Jean, Grecio J Sandoval, Jorge L Santana, Shannon M Schlater, Frank C Sciurba, Caitlin Selvaggi, Sudha Seshadri, Howard D Sesso, Dimpy P Shah, Eyal Shemesh, Zaki A Sherif, Daniel J Shinnick, Hyagriv N Simhan, Upinder Singh, Amber Sowles, Vignesh Subbian, Jun Sun, Mehul S Suthar, Larissa J Teunis, John M Thorp, Amberly Ticotsky, Alan T N Tita, Robin Tragus, Katherine R Tuttle, Alfredo E Urdaneta, P J Utz, Timothy M Vanwagoner, Andrew Vasey, Suzanne D Vernon, Crystal Vidal, Tiffany Walker, Honorine D Ward, David E Warren, Ryan M Weeks, Steven J Weiner, Jordan C Weyer, Jennifer L Wheeler, Sidney W Whiteheart, Zanthia Wiley, Natasha J Williams, Juan P Wisnivesky, John C Wood, Lynn M Yee, Natalie M Young, Sokratis N Zisis, Andrea S Foulkes

Pediatrics Research and Scholarship

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. …

Nonsystematic Reporting Biases Of The Sars-Cov-2 Variant Mu Could Impact Our Understanding Of The Epidemiological Dynamics Of Emerging Variants, Mary E. Petrone, Carolina Lucas, Bridget Menasche, Mallery I. Breban, Inci Yildirim, Melissa Campbell, Saad B. Omer, Edward C. Holmes, Albert I. Ko, Nathan D. Grubaugh, Akiko Iwasaki, Craig B. Wilen, Chantal B. F. Vogels, Joseph R. Fauver

Journal Articles: Epidemiology

Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC …

Short-Term Removal Of Exercise Impairs Glycemic Control In Older Adults: A Randomized Trial, Leryn J. Reynolds, Troy M. Williams, Joel E. Harden, Hannah M. Twiddy, Monica L. Kearney

Human Movement Studies & Special Education Faculty Publications

Postprandial glycemia (PPG) predicts cardiovascular disease, and short-term physical inactivity increases PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if postprandial interstitial glucose (PPIG) was impaired in active older adults following the removal of exercise for 3 days (NOEX) compared to active young adults. In this randomized, crossover study, 11 older (69.1 ± 1.9 years) and 9 young (32.8 ± 1.8 years) habitually active (≥90 min/week of exercise) adults completed 3-days of NOEX and 3-days of normal habitual exercise (EX), separated by …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Studies & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Oral/Oropharyngeal “Selfies” In Gay And Bisexual Men: A Pilot Study Exploring Oropharyngeal Screening For Hpv-Related Possible Malignancies, Michael W Ross, Sarah L Bennis, C Mark Nichols, I Niles Zoschke, J Michael Wilkerson, B R Simon Rosser, Cyndee L Stull, Alan G Nyitray, Charlene Flash, Samir S Khariwala

Faculty, Staff and Student Publications

Objectives: This study aims to determine the potential uptake and quality of oropharyngeal "selfies" taken by gay/bisexual men as a screening approach for HPV-associated oropharyngeal cancer.

Methods: From 1,699 gay/bisexual men in the US, surveyed about knowledge and attitudes to HPV-associated oropharyngeal cancer, a random sample of 320 men were invited to take an oropharyngeal "selfie" by smartphone and send it to the study website: 113 (35.5%) did so. Images were rated for quality by three healthcare professional raters blinded to each other's rating, with an otolaryngologist as the gold standard. In the second wave, those whose images were rated …

Prodromal Glutamatergic Modulation With Riluzole Impacts Glucose Homeostasis And Spatial Cognition In Alzheimer's Disease Mice., Caleigh A Findley, Samuel A Mcfadden, Makayla F Cox, Lindsey N Sime, Mackenzie R Peck, Kathleen Quinn, Andrzej Bartke, Kevin N Hascup, Erin R Hascup

Articles

BACKGROUND: Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model. Previous studies have illustrated increased glucose uptake and metabolism using a neuroprotective glutamate modulator (riluzole), supporting the link between glucose and glutamatergic homeostasis.

OBJECTIVE: We hypothesized …

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background: Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods: Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …

Associations Of Snfl With Clinico-Radiological Measures In A Large Ms Population., Elias S Sotirchos, Kathryn C Fitzgerald, Carol M Singh, Matthew D Smith, Maria Reyes-Mantilla, Carrie M Hersh, Megan H Hyland, Ryan Canissario, Sarah B Simmons, Georgina Arrambide, Xavier Montalban, Manuel Comabella, Robert T Naismith, Min Qiao, Lauren B Krupp, Jacqueline A Nicholas, Katja Akgün, Tjalf Ziemssen, Richard Rudick, Elizabeth Fisher, Robert A Bermel, Ellen M Mowry, Peter A Calabresi

Neuroscience Articles

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with …

Researching Covid To Enhance Recovery (Recover) Pregnancy Study: Rationale, Objectives And Design, Torri D Metz, Rebecca G Clifton, Richard Gallagher, Rachel S Gross, Leora I Horwitz, Vanessa L Jacoby, Susanne P Martin-Herz, Myriam Peralta-Carcelen, Harrison T Reeder, Carmen J Beamon, James Chan, A Ann Chang, Maged M Costantine, Megan L Fitzgerald, Andrea S Foulkes, Kelly S Gibson, Nick Güthe, Mounira Habli, David N Hackney, Matthew K Hoffman, M Camille Hoffman, Brenna L Hughes, Stuart D Katz, Victoria Laleau, Gail Mallett, Hector Mendez-Figueroa, Vanessa Monzon, Anna Palatnik, Kristy T S Palomares, Samuel Parry, Christian M Pettker, Beth A Plunkett, Athena Poppas, Uma M Reddy, Dwight J Rouse, George R Saade, Grecio J Sandoval, Shannon M Schlater, Frank C Sciurba, Hyagriv N Simhan, Daniel W Skupski, Amber Sowles, Tanayott Thaweethai, Gelise L Thomas, John M Thorp, Alan T Tita, Steven J Weiner, Samantha Weigand, Lynn M Yee, Valerie J Flaherman

Faculty, Staff and Student Publications

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.

METHODS: RECOVER-Pregnancy cohort is a …

Old, Nonagenarians, And Centenarians In Cilento, Italy And The Association Of Lifespan With The Level Of Some Physicochemical Elements In Tap Drinking Water., Silvana Mirella Aliberti, Richard H W Funk, Elena Ciaglia, Joseph S. Gonnella, Aldo Giudice, Carmine Vecchione, Annibale Alessandro Puca, Mario Capunzo

Department of Medicine Faculty Papers

Longevity, as a complex life-history trait, shares an ontogenetic relationship with other quantitative traits, such as epigenetic and environmental factors. Therefore, it is important to identify environmental factors that may modify the epigenome to establish healthy aging. This study explored the association between tap drinking water and longevity in Cilento, Italy, to understand whether trace elements in local drinking water may have an influence on old, nonagenarian, and centenarian people and promote their health and longevity. Data on population and water sources were collected through the National Demographic Statistics, the Cilento Municipal Archives, and the Cilento Integrated Water Service. Ordinary …

Effect Of Positive Emotion Intervention During Late Pregnancy On Improving Colostrum Secretion: A Randomised Control Trial Protocol, Kechen Xu, Ying Xie, Xiujun Han, Ying Yu, Suqing Liu, Suliu Wu, Qian Yang, Qi Zhang

Community & Environmental Health Faculty Publications

Introduction Though evidence has revealed the beneficial effects of cognitive improvement interventions on breastfeeding, the effect of psychological interventions has rarely been studied. This study aims to test whether promoting a positive emotion intervention, 'Three Good Things' intervention, during the last trimester of pregnancy can enhance early colostrum secretion and breastfeeding behaviours by modulating the hormones associated with lactation (prolactin and insulin-like growth factor I). We will attempt to promote exclusive breastfeeding by using physiological behavioural measures.

Methods and analysis This study is designed as a randomised controlled trial conducted in the Women's Hospital School of Medicine at Zhejiang University …

Towards Fair Patient-Trial Matching Via Patient-Criterion Level Fairness Constraint, Chia-Yuan Chang, Jiayi Yuan, Sirui Ding, Qiaoyu Tan, Kai Zhang, Xiaoqian Jiang, Xia Hu, Na Zou

Faculty, Staff and Student Publications

Clinical trials are indispensable in developing new treatments, but they face obstacles in patient recruitment and retention, hindering the enrollment of necessary participants. To tackle these challenges, deep learning frameworks have been created to match patients to trials. These frameworks calculate the similarity between patients and clinical trial eligibility criteria, considering the discrepancy between inclusion and exclusion criteria. Recent studies have shown that these frameworks outperform earlier approaches. However, deep learning models may raise fairness issues in patient-trial matching when certain sensitive groups of individuals are underrepresented in clinical trials, leading to incomplete or inaccurate data and potential harm. To …

The Kynurenine Pathway In Alzheimer’S Disease: A Meta-Analysis Of Central And Peripheral Levels, Brisa S Fernandes, Mehmet Enes Inam, Nitesh Enduru, Joao Quevedo, Zhongming Zhao

Faculty, Staff and Student Publications

OBJECTIVE: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer's disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD.

METHODS: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood.

RESULTS: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral …

Nasal Host Response-Based Screening For Undiagnosed Respiratory Viruses: A Pathogen Surveillance And Detection Study, Nagarjuna R. Cheemarla, Amelia Hanron, Joseph R. Fauver, Jason Bishai, Timothy A. Watkins, Anderson F. Brito, Dejian Zhao, Tara Alpert, Chantal B. F. Vogels, Albert I. Ko, Wade L. Schulz, Marie L. Landry, Nathan D. Grubaugh, David Van Dijk, Ellen F. Foxman

Journal Articles: Epidemiology

BACKGROUND: Symptomatic patients who test negative for common viruses are an important possible source of unrecognised or emerging pathogens, but metagenomic sequencing of all samples is inefficient because of the low likelihood of finding a pathogen in any given sample. We aimed to determine whether nasopharyngeal CXCL10 screening could be used as a strategy to enrich for samples containing undiagnosed viruses.

METHODS: In this pathogen surveillance and detection study, we measured CXCL10 concentrations from nasopharyngeal swabs from patients in the Yale New Haven health-care system, which had been tested at the Yale New Haven Hospital Clinical Virology Laboratory (New Haven, …

Adverse Maternal Environment Alters Oprl1 Variant Expression In Mouse Hippocampus., Xingrao Ke, Yingliu Huang, Qi Fu, Amber Majnik, Venkatesh Sampath, Robert H. Lane

Manuscripts, Articles, Book Chapters and Other Papers

An adverse maternal environment (AME) and Western diet (WD) in early life predispose offspring toward cognitive impairment in humans and mice. Cognitive impairment associates with hippocampal dysfunction. An important regulator of hippocampal function is the hippocampal Nociceptin/Orphanin FQ (N/OFQ) system. Previous studies find links between dysregulation of hippocampal N/OFQ receptor (NOP) expression and impaired cognitive function. NOP is encoded by the opioid receptor-like 1 (Oprl1) gene that contains multiple mRNA variants and isoforms. Regulation of Oprl1 expression includes histone modifications within the promoter. We tested the hypothesis that an AME and a postweaning WD increase the expression of hippocampal Oprl1 …

Nutritional Management Of The Infant With Chronic Kidney Disease Stages 2-5 And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Dieter Haffner, Christina L. Nelms, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, José Renken-Terhaerdt, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

The nutritional management of children with chronic kidney disease (CKD) is of prime importance in meeting the challenge of maintaining normal growth and development in this population. The objective of this review is to integrate the Pediatric Renal Nutrition Taskforce clinical practice recommendations for children with CKD stages 2-5 and on dialysis, as they relate to the infant from full term birth up to 1 year of age, for healthcare professionals, including dietitians, physicians, and nurses. It addresses nutritional assessment, energy and protein requirements, delivery of the nutritional prescription, and necessary dietary modifications in the case of abnormal serum levels …

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

Preclinical Efficacy Of Azacitidine And Venetoclax For Infant Kmt2a-Rearranged Acute Lymphoblastic Leukemia Reveals A New Therapeutic Strategy., Laurence C. Cheung, Carlos Aya-Bonilla, Mark N. Cruickshank, Sung K. Chiu, Vincent Kuek, Denise Anderson, Grace-Alyssa Chua, Sajla Singh, Joyce Oommen, Emanuela Ferrari, Anastasia M. Hughes, Jette Ford, Elena Kunold, Maria C. Hesselman, Frederik Post, Kelly E. Faulk, Erin H. Breese, Erin M. Guest, Patrick A. Brown, Mignon L. Loh, Richard B. Lock, Ursula R. Kees, Rozbeh Jafari, Sébastien Malinge, Rishi S. Kotecha

Manuscripts, Articles, Book Chapters and Other Papers

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required. KMT2A-rearranged infant ALL cells are characterized by an abundance of promoter hypermethylation and exhibit high BCL-2 expression, highlighting potential for therapeutic targeting. Here, we show that hypomethylating agents exhibit in vitro additivity when combined with most conventional chemotherapeutic agents. However, in a subset of samples an antagonistic effect was seen between several agents. This was most evident when hypomethylating agents were combined with methotrexate, with upregulation of ATP-binding cassette transporters identified …

Testing For Homologous Recombination Repair Or Homologous Recombination Deficiency For Poly (Adp-Ribose) Polymerase Inhibitors: A Current Perspective, Thomas J Herzog, Ignace Vergote, Leonard G Gomella, Tsveta Milenkova, Tim French, Raffi Tonikian, Christian Poehlein, Maha Hussain

Department of Urology Faculty Papers

Poly (ADP-ribose) polymerase inhibitors (PARPis) have demonstrated clinical activity in patients with BRCA1 and/or BRCA2 mutated breast, ovarian, prostate, and pancreatic cancers. Notably, BRCA mutations are associated with defects in the homologous recombination repair (HRR) pathway. This homologous recombination deficiency (HRD) phenotype can also be observed as genomic instability in tumour cells. Accordingly, PARPi sensitivity has been observed in various tumours with HRD, independent of BRCA mutations. Currently, four PARPis are approved by regulatory agencies for the treatment of cancer across multiple tumour types. Most indications are specific to tumours with a confirmed BRCA mutation, mutations in other HRR-related genes, …

Omega-3 Polyunsaturated Fatty Acid Levels In Maternal And Cord Plasma Are Associated With Maternal Socioeconomic Status, Alexandra Hergenrader, Matthew Van Ormer, Rebecca Slotkowski, Maranda Thompson, Alyssa Freeman, Olivia Paetz, Sarah Sweeney, Lauren Wegner, Khadijjta Ali, Nicole S. Bender, Ridhi Chaudhary, Melissa K. Thoene, Corrine K. Hanson, Ann Anderson-Berry

Journal Articles: Pediatrics

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a crucial role in fetal growth and neurodevelopment, while omega-6 (n-6) PUFAs have been associated with adverse pregnancy outcomes. Previous studies have demonstrated that socioeconomic status (SES) influences dietary intake of n-3 and n-6 PUFAs, but few studies have evaluated the association between maternal and cord plasma biomarkers of PUFAs and socioeconomic markers. An IRB-approved study enrolled mother-infant pairs (n = 55) at the time of delivery. Maternal and cord plasma PUFA concentrations were analyzed using gas chromatography. Markers of SES were obtained from validated surveys …

Nasal Accumulation And Metabolism Of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration In An Adolescent Rat Model, Alexa Torrens, Christina M Ruiz, Maricela X Martinez, Alex Mabou Tagne, Pritam Roy, Dakota Grimes, Faizy Ahmed, Valeria Lallai, Victoria Inshishian, Malia Bautista, Yen-Chu Chen, Marilyn A. Huestis, Aditi Das, Christie D Fowler, Stephen V Mahler, Daniele Piomelli

Institute of Emerging Health Professions Faculty Papers

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Raju Pillai, Soyoung Kim, Noel Estrada-Merly, Michelle Afkhami, Lixin Yang, Zhuo Meng, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Christopher Bredeson, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Corey Cutler, Zachariah Defilipp, Miguel Angel Diaz Perez, Nosha Farhadfar, César O Freytes, Shahinaz M Gadalla, Siddhartha Ganguly, Robert Peter Gale, Usama Gergis, Michael R Grunwald, Betty K Hamilton, Shahrukh Hashmi, Gerhard C Hildebrandt, Hillard M Lazarus, Mark Litzow, Reinhold Munker, Hemant S Murthy, Sunita Nathan, Taiga Nishihori, Sagar S Patel, David Rizzieri, Sachiko Seo, Mithun Vinod Shah, Melhem Solh, Leo F Verdonck, Ravi Vij, Ronald M Sobecks, Betul Oran, Bart L Scott, Wael Saber, Ryotaro Nakamura

Department of Medical Oncology Faculty Papers

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Population Variations Of Cheiloscopy Patterns: A Cross-Sectional Observation Pilot Study, Emily Smith Regan, Brenda T. Bradshaw, Ann M. Bruhn, Walter Melvin, Sinjini Sikdar

Dental Hygiene Faculty Publications

Purpose Lip prints are unique and have potential for use as a human identifier. The purpose of this study was to observe possible cheiloscopy differences of individuals with and without parafunctional oral habits such as smoking, vaping, playing a wind instrument or using an asthma inhaler.

Methods This IRB approved blinded cross-sectional observation pilot study collected lip prints from sixty-six individuals, three of which were excluded. Participants cleansed their lips, then lipstick was applied to the vermillion zones of the upper and lower lips. Adhesive tape was applied to the lips and prints were transferred to white bond paper for …