Digital Commons Network^™

Uterine Natural Killer Cell Heterogeneity: Lessons From Mouse Models, Dorothy K Sojka

Open Access Publications

Natural killer (NK) cells are the most abundant lymphocytes at the maternal-fetal interface. Epidemiological data implicate NK cells in human pregnancy outcomes. Discoveries using mouse NK cells have guided subsequent advances in human NK cell biology. However, it remains challenging to identify mouse and human uterine NK (uNK) cell function(s) because of the dynamic changes in the systemic-endocrinological and local uterine structural microenvironments during pregnancy. This review discusses functional similarities and differences between mouse and human NK cells at the maternal-fetal interface.

Genomic Prediction Of Alcohol-Related Morbidity And Mortality, Tuomo Kiiskinen, Nina J. Mars, Teemu Palviainen, Jukka Koskela, Joel T. Rämö, Pietari Ripatti, Sanni Ruotsalainen, Finngen, Gscan Consortium, Aarno Palotie, Pamela A.F. Madden, Richard J. Rose, Jaakko Kaprio, Veikko Salomaa, Pia Mäkelä, Aki S. Havulinna, Samuli Ripatti

Open Access Publications

No abstract provided.

A Framework For Applying Natural Language Processing In Digital Health Interventions, Burkhardt Funk, Shiri Sadeh-Sharvit, Ellen E Fitzsimmons-Craft, Mickey Todd Trockel, Grace E Monterubio, Neha J Goel, Katherine N Balantekin, Dawn M Eichen, Rachael E Flatt, Marie-Laure Firebaugh, Corinna Jacobi, Andrea K Graham, Mark Hoogendoorn, Denise E Wilfley, C Barr Taylor

Open Access Publications

BACKGROUND: Digital health interventions (DHIs) are poised to reduce target symptoms in a scalable, affordable, and empirically supported way. DHIs that involve coaching or clinical support often collect text data from 2 sources: (1) open correspondence between users and the trained practitioners supporting them through a messaging system and (2) text data recorded during the intervention by users, such as diary entries. Natural language processing (NLP) offers methods for analyzing text, augmenting the understanding of intervention effects, and informing therapeutic decision making.

OBJECTIVE: This study aimed to present a technical framework that supports the automated analysis of both types of …

Insulin Resistance Drives Hepatic De Novo Lipogenesis In Nonalcoholic Fatty Liver Disease, Gordon I Smith, Mahalakshmi Shankaran, Mihoko Yoshino, George G Schweitzer, Maria Chondronikola, Joseph W Beals, Adewole L Okunade, Bruce W Patterson, Edna Nyangau, Tyler Field, Claude B Sirlin, Saswata Talukdar, Marc K Hellerstein, Samuel Klein

Open Access Publications

BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated …

The Long-Term Effects Of A Family Based Economic Empowerment Intervention (Suubi+Adherence) On Suppression Of Hiv Viral Loads Among Adolescents Living With Hiv In Southern Uganda: Findings From 5-Year Cluster Randomized Trial, Fred M. Ssewamala, Darejan Dvalishvili, Claude A. Mellins, Elvin H. Geng, Fredderick Makumbi, Torsten B. Neilands, Mary Mckay, Christopher Damulira, Proscovia Nabunya, Ozge Sensoy Bahar, Gertrude Nakigozi, Godfrey Kigozi, William Byansi, Miriam Mukasa, Flavia Namuwonge

Open Access Publications

BACKGROUND: The rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment.

METHODS: We carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect …

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study Of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio Xr) In Preschool Children With Attention-Deficit/Hyperactivity Disorder, Ann C. Childress, Scott H. Kollins, Henry C. Foehl, Jeffrey H. Newcorn, Greg Mattingly, Robert J. Kupper, Akwete L. Adjei

Open Access Publications

No abstract provided.

Metabolic And Addiction Indices In Patients On Opioid Agonist Medication-Assisted Treatment: A Comparison Of Buprenorphine And Methadone, Igor Elman, Margaret Howard, Jacob T. Borodovsky, David Mysels, David Rott, David Borsook, Mark Albanese

Open Access Publications

No abstract provided.

Family Encouragement Of Healthy Eating Predicts Child Dietary Intake And Weight Loss In Family-Based Behavioral Weight-Loss Treatment, Sophia A. Rotman, Lauren A. Fowler, Mary Katherine Ray, Richard I. Stein, Jacqueline F. Hayes, Rachel P. Kolko, Katherine N. Balantekin, Alexis Engel, Brian E. Saelens, R. Robinson Welch, Michael G. Perri, Leonard H. Epstein, Denise E. Wilfley

Open Access Publications

No abstract provided.

Reporting Guidelines, Review Of Methodological Standards, And Challenges Toward Harmonization In Bone Marrow Adiposity Research. Report Of The Methodologies Working Group Of The International Bone Marrow Adiposity Society, Josefine Tratwal, Erica L Scheller, Et Al

Open Access Publications

The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical …

Influence Of Adiposity, Insulin Resistance, And Intrahepatic Triglyceride Content On Insulin Kinetics, Gordon I Smith, David C Polidori, Mihoko Yoshino, Monica L Kearney, Bruce W Patterson, Bettina Mittendorfer, Samuel Klein

Open Access Publications

BACKGROUNDInsulin is a key regulator of metabolic function. The effects of excess adiposity, insulin resistance, and hepatic steatosis on the complex integration of insulin secretion and hepatic and extrahepatic tissue extraction are not clear.METHODSA hyperinsulinemic-euglycemic clamp and a 3-hour oral glucose tolerance test were performed to evaluate insulin sensitivity and insulin kinetics after glucose ingestion in 3 groups: (a) lean subjects with normal intrahepatic triglyceride (IHTG) and glucose tolerance (lean-NL; n = 14), (b) obese subjects with normal IHTG and glucose tolerance (obese-NL; n = 24), and (c) obese subjects with nonalcoholic fatty liver disease (NAFLD) and prediabetes (obese-NAFLD; n …

Proactive Prevention: Act Now To Disrupt The Impending Non-Communicable Disease Crisis In Low-Burden Populations, Benson Njuguna, Angela Brown, Victor G. Davila-Roman, Et Al.

Open Access Publications

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as "proactive prevention." This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a …

Temporary Abdominal Closure Is Associated With Increased Risk For Fungal Intra-Abdominal Infections In Trauma Patients, Christina X. Zhang, Rohit R. Rasane, Qiao Zhang, Ricardo A. Fonseca, Jose A. Aldana, Javier E. Rincon, Maya J. Sorini, Kelly M. Bochicchio, Jennifer M. Leonard, Obeid N. Ilahi, Grant V. Bochicchio

Open Access Publications

No abstract provided.

Assessment Of Plasma Amyloid-Β42/40 And Cognitive Decline Among Community-Dwelling Older Adults, Kelly Virecoulon Giudici, Philipe De Souto Barreto, Sophie Guyonnet, Yan Li, Randall J. Bateman, Bruno Vellas

Open Access Publications

Importance: Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce.

Objective: To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns.

Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in …

Association Between Benzodiazepine Use With Or Without Opioid Use And All-Cause Mortality In The United States, 1999-2015, Kevin Y. Xu, Sarah M. Hartz, Jacob T. Borodovsky, Laura J. Bierut, Richard A. Grucza

Open Access Publications

Importance: Although overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death.

Objective: To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants.

Design, Setting, and Participants: This retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from …

Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao

Open Access Publications

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have …

Using The Systemic Immune-Inflammation Index (Sii) As A Mid-Treatment Marker For Survival Among Patients With Stage-Iii Locally Advanced Non-Small Cell Lung Cancer (Nsclc), Tithi Biswas, Kylie H Kang, Rohin Gawdi, David Bajor, Mitchell Machtay, Charu Jindal, Jimmy T Efird

Open Access Publications

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3-4) is a …

Social Jetlag And Prostate Cancer Incidence In Alberta's Tomorrow Project: A Prospective Cohort Study, Liang Hu, Andrew Harper, Emily Heer, Jessica Mcneil, Chao Cao, Yikyung Park, Kevin Martell, Geoffrey Gotto, Grace Shen-Tu, Cheryl Peters, Darren Brenner, Lin Yang

Open Access Publications

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta's Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-<1 h (from 0 to anything smaller than 1), 1-<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (

Histone H3.3 Beyond Cancer: Germline Mutations In Histone 3 Family 3a And 3b Cause A Previously Unidentified Neurodegenerative Disorder In 46 Patients, Laura Bryant, Marcia C Willing, Linda Manwaring, Et Al

Open Access Publications

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (

Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz

Open Access Publications

No abstract provided.

Decreased Adipose Tissue Oxygenation Associates With Insulin Resistance In Individuals With Obesity, Vincenza Cifarelli, Scott C Beeman, Gordon I Smith, Jun Yoshino, Darya Morozov, Joseph W Beals, Brandon D Kayser, Jeramie D Watrous, Mohit Jain, Bruce W Patterson, Samuel Klein

Open Access Publications

BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy …

From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al.

Open Access Publications

No abstract provided.

Endothelial Cell Cd36 Deficiency Prevents Normal Angiogenesis And Vascular Repair, Lara Bou Khzam, Ni-Huiping Son, Adam E Mullick, Nada A Abumrad, Ira J Goldberg

Open Access Publications

Endothelial cells (ECs) maintain vascular integrity and mediate vascular repair and angiogenesis, by which new blood vessels are formed from pre-existing blood vessels. Hyperglycemia has been shown to increase EC angiogenic potential. However, few studies have investigated effects of fatty acids (FAs) on EC angiogenesis. Cluster of differentiation 36 (CD36) is a FA transporter expressed by ECs, but its role in EC proliferation, migration, and angiogenesis is unknown. We sought to determine if circulating FAs regulate angiogenic function in a CD36-dependent manner. CD36-dependent effects of FAs on EC proliferation and migration of mouse heart ECs (MHECs) and lung ECs (MLECs) …

Roles Of The Vagina And The Vaginal Microbiota In Urinary Tract Infection: Evidence From Clinical Correlations And Experimental Models, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Mounting evidence indicates that the vagina can harbor uropathogenic bacteria. Here, we consider three roles played by the vagina and its bacterial inhabitants in urinary tract infection (UTI) and urinary health. First, the vagina can serve as a reservoir for

Lipin-1 Contributes To Il-4 Mediated Macrophage Polarization, Sunitha Chandran, Robert M Schilke, Cassidy M R Blackburn, Aila Yurochko, Rusella Mirza, Rona S Scott, Brian N Finck, Matthew D Woolard

Open Access Publications

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 …

The Role Of Ct-Quantified Body Composition On Longitudinal Health-Related Quality Of Life In Colorectal Cancer Patients: The Colocare Study, Biljana Gigic, Graham A Colditz, Adetunji T Toriola, Et Al

Open Access Publications

BACKGROUND: Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.

METHODS: A total of 138 …

Maternal Activation Of The Egfr Prevents Translocation Of Gut-Residing Pathogenic Escherichia Coli In A Model Of Late-Onset Neonatal Sepsis, Kathryn A. Knoop, Paige E. Coughlin, Alexandria N. Floyd, I. Malick Ndao, Carla Hall-Moore, Nurmohammad Shaikh, Andrew J. Gasparrini, Brigida Rusconi, Marilyn Escobedo, Misty Good, Barbara B. Warner, Phillip I. Tarr, Rodney D. Newberry

Open Access Publications

No abstract provided.

Use Of The Theory Of Planned Behavior Framework To Understand Breastfeeding Decision-Making Among Mothers Of Preterm Infants, Margaret G. Parker, Sunah S. Hwang, Emma S. Forbes, Bryanne N. Colvin, Kyria R. Brown, Eve R. Colson

Open Access Publications

No abstract provided.

Characterization Of A High-Resolution Breath Acetone Meter For Ketosis Monitoring, Donald J Suntrup Iii, Timothy V Ratto, Matt Ratto, James P Mccarter

Open Access Publications

Background: The ketone bodies beta-hydroxybutyrate (BHB) and acetone are endogenous products of fatty acid metabolism. Although ketone levels can be monitored by measuring either blood BHB or breath acetone, determining the precise correlation between these two measurement methods has been challenging. The purpose of this study is to characterize the performance of a novel portable breath acetone meter (PBAM) developed by Readout, Inc., to compare single versus multiple daily ketone measurements, and to compare breath acetone (BrAce) and blood BHB measurements.

Methods: We conducted a 14-day prospective observational cohort study of 21 subjects attempting to follow either a low-carbohydrate/ketogenic or …

Diet-Induced Metabolic Dysregulation In Female Mice Causes Osteopenia In Adult Offspring, Yu Shi, Jessica L. Saben, Guangxu He, Kelle H. Moley, Fanxin Long

Open Access Publications

Bone mass and quality in humans are controlled by numerous genetic and environmental factors that are not fully understood. Increasing evidence has indicated that maternal metabolic dysregulation impairs multiple physiological processes in the adult offspring, but a similar effect on bone health is yet to be established. Here, we have analyzed the bones of first-generation offspring from murine dams that present metabolic syndrome due to a high-fat and high-sugar (HF/HS) diet. Micro-CT analyses show that the long bones of HF/HS offspring possess lower cortical bone mass and weaker mechanical strength than normal, even though the trabecular bone is not affected. …

Quantitative Definition Of Neurobehavior, Vision, Hearing And Brain Volumes In Macaques Congenitally Exposed To Zika Virus, Michelle R. Koenig, Kevin Noguchi, Et Al.

Open Access Publications

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified …