Digital Commons Network^™

Genetic Architecture Of Reciprocal Social Behavior In Toddlers: Implications For Heterogeneity In The Early Origins Of Autism Spectrum Disorder, Natasha Marrus, Julia D Grant, Brooke Harris-Olenak, Jordan Albright, Drew Bolster, Jon Randolph Haber, Theodore Jacob, Yi Zhang, Andrew C Heath, Arpana Agrawal, John N Constantino, Jed T Elison, Anne L Glowinski

Open Access Publications

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic …

Mapping Geographical Inequalities In Access To Drinking Water And Sanitation Facilities In Low-Income And Middle-Income Countries, 2000-17, Aniruddha Deshpande, Ziyad Al-Aly, Local Burden Of Disease Wash Collaborators, Et Al

Open Access Publications

No abstract provided.

Chikungunya Virus Strains From Each Genetic Clade Bind Sulfated Glycosaminoglycans As Attachment Factors, Nicole Mcallister, Michael S. Diamond, Et Al

Open Access Publications

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes debilitating musculoskeletal disease. CHIKV displays broad cell, tissue, and species tropism, which may correlate with the attachment factors and entry receptors used by the virus. Cell surface glycosaminoglycans (GAGs) have been identified as CHIKV attachment factors. However, the specific types of GAGs and potentially other glycans to which CHIKV binds and whether there are strain-specific differences in GAG binding are not fully understood. To identify the types of glycans bound by CHIKV, we conducted glycan microarray analyses and discovered that CHIKV preferentially binds GAGs. Microarray results also indicate that sulfate groups …

Expanding The Genetic Architecture Of Nicotine Dependence And Its Shared Genetics With Multiple Traits, Bryan C. Quach, Michael J. Bray, Pamela Madden, Laura J. Bierut, Nancy L. Saccone, Et Al.

Open Access Publications

No abstract provided.

Tumor Microenvironment-Targeted Nanoparticles Loaded With Bortezomib And Rock Inhibitor Improve Efficacy In Multiple Myeloma, Cinzia Federico, Kinan Alhallak, Jennifer Sun, Kathleen Duncan, Feda Azab, Gail P. Sudlow, Pilar De La Puente, Barbara Muz, Vaishali Kapoor, Luna Zhang, Fangzheng Yuan, Matea Markovic, Joseph Kotsybar, Katherine Wasden, Nicole Guenthner, Shannon Gurley, Justin King, Daniel Kohnen, Noha N. Salama, Dinesh Thotala, Dennis E. Hallahan, Ravi Vij, John F. Dipersio, Samuel Achilefu, Abdel Kareem Azab

Open Access Publications

No abstract provided.

Stretchable, Dynamic Covalent Polymers For Soft, Long-Lived Bioresorbable Electronic Stimulators Designed To Facilitate Neuromuscular Regeneration, Yeon Sik Choi, Ying Yan, Matthew R. Macewan, Wilson Z. Ray, Et Al.

Open Access Publications

No abstract provided.

Phase 2 Study Of Ruxolitinib And Decitabine In Patients With Myeloproliferative Neoplasm In Accelerated And Blast Phase, John O. Mascarenhas, Camille N. Abboud, Et Al.

Open Access Publications

No abstract provided.

Determining The Recommended Dose Of Pacritinib: Results From The Pac203 Dose-Finding Trial In Advanced Myelofibrosis, Aaron T. Gerds, Stephen T. Oh, Et Al.

Open Access Publications

No abstract provided.

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml, Jayakumar Vadakekolathu, Michael P. Rettig, John F. Dipersio, Et Al.

Open Access Publications

No abstract provided.

Understanding Patient Transfers Across Multiple Clinics In Zambia Among Hiv Infected Adults, Kombatende Sikombe, Aaloke Mody, Jillian Kadota, Jesse Jake Pry, Sandra Simbeza, Ingrid Eshun-Wilson, Sitali Richard Situmbeko, Chama Bukankala, Laura Beres, Njekwa Mukamba, Mwanza Wa Mwanza, Carolyn Bolton-Moore, Charles B. Holmes, Elvin H. Geng, Izukanji Sikazwe

Open Access Publications

Many patients in HIV care in Africa considered lost to follow up (LTFU) at one facility are reportedly accessing care in another. The success of these unofficial transfers as measured by time to re-entry at the new-facility, prevalence of treatment interruptions, speed of ART-initiation, and overall continuity of care is not well characterized but may reveal opportunities for improvement. We traced a random sample of LTFU HIV-infected patients in Zambia. Among those found alive and reported in care at a new-facility, we reviewed records at the receiving facility to verify transfer; and when verified, documented the transfer experience. We used …

The Herbivore's Dilemma: Trends In And Factors Associated With Heterosexual Relationship Status And Interest In Romantic Relationships Among Young Adults In Japan-Analysis Of National Surveys, 1987-2015, Cyrus Ghaznavi, Haruka Sakamoto, Shuhei Nomura, Anna Kubota, Daisuke Yoneoka, Kenji Shibuya, Peter Ueda

Open Access Publications

BACKGROUND: It has been suggested that an increasing proportion of young adults in Japan have lost interest in romantic relationships, a phenomenon termed "herbivorization". We assessed trends in heterosexual relationship status and self-reported interest in heterosexual romantic relationships in nationally representative data.

METHODS: We used data from seven rounds of the National Fertility Survey (1987-2015) and included adults aged 18-39 years (18-34 years in the 1987 survey; sample size 11,683-17,675). Current heterosexual relationship status (married; unmarried but in a relationship; single) was estimated by sex, age group and survey year, with singles further categorized into those reporting interest vs. no …

A Feasibility Study To Evaluate Early Treatment Response Of Brain Metastases One Week After Stereotactic Radiosurgery Using Perfusion Weighted Imaging, Jiayi Huang, Mikhail Milchenko, Yuan J. Rao, Pamela Lamontagne, Christopher Abraham, Clifford G. Robinson, Yi Huang, Joshua S. Shimony, Keith M. Rich, Tammie Benzinger

Open Access Publications

BACKGROUND: To explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS).

METHODS: This is a prospective pilot study of adult brain metastasis patients who were treated with SRS and imaged with PWI before and 1 week later. Relative cerebral blood volume (rCBV) parameter maps were calculated by normalizing to the mean value of the contralateral white matter on PWI. Cox regression was conducted to explore factors associated with time to LR, with Bonferroni adjusted p<0.0006 for multiple testing correction. LR rates were estimated with the Kaplan-Meier method and compared using the log-rank test.

RESULTS: Twenty-three patients were enrolled from 2013 through …

Comparison Of The Ekblom-Bak Submaximal Test To A Maximal Test In A Cohort Of Healthy Younger And Older Adults In The United States, Stephanie A Schultz, Jennifer Byers, Tammie L S Benzinger, Dominic Reeds, Andrei G Vlassenko, W Todd Cade, Manu S Goyal

Open Access Publications

Cardiorespiratory fitness (CRF) is routinely investigated in diverse populations, including in older adults of varying physical activity levels. Commonly performed maximal exercise testing protocols might be contraindicated and/or inadequate for older individuals who have physical or cognitive impairment. Moreover, early termination of an attempted maximal exercise test could result in underestimation of CRF in this population. The goal of the current study was to compare CRF estimates using the Ekblom-Bak (EB) submaximal exercise test - previously validated in a cohort of Scandinavian adults - versus a subsequent maximal exercise test in a diverse, Midwestern United States cohort. Fifteen generally healthy …

Structural Basis Of Chikungunya Virus Inhibition By Monoclonal Antibodies, Qun Fei Zhou, Julie M. Fox, James T. Earnest, Thiam-Seng Ng, Arthur S. Kim, Guntur Fibriansah, Victor A. Kostyuchenko, Jian Shi, Bo Shu, Michael S. Diamond, Shee-Mei Lok

Open Access Publications

No abstract provided.

Accuracy Of Electromyometrial Imaging Of Uterine Contractions In Clinical Environment, Hui Wang, Wenjie Wu, Michael Talcott, Robert C Mckinstry, Pamela K Woodard, George A Macones, Alan L Schwartz, Phillip Cuculich, Alison G Cahill, Yong Wang

Open Access Publications

Clinically, uterine contractions are monitored with tocodynamometers or intrauterine pressure catheters. In the research setting, electromyography (EMG), which detects electrical activity of the uterus from a few electrodes on the abdomen, is feasible, can provide more accurate data than these other methods, and may be useful for predicting preterm birth. However, EMG lacks sufficient spatial resolution and coverage to reveal where uterine contractions originate, how they propagate, and whether preterm contractions differ between women who do and do not progress to preterm delivery. To address those limitations, electromyometrial imaging (EMMI) was recently developed and validated to non-invasively assess three-dimensional (3D) …

Plasmacytoid Dendritic Cell Impairment In Metastatic Melanoma By Lactic Acidosis, Matilde Monti, Raffaella Vescovi, Francesca Consoli, Davide Farina, Daniele Moratto, Alfredo Berruti, Claudia Specchia, William Vermi

Open Access Publications

The introduction of targeted therapies and immunotherapies has significantly improved the outcome of metastatic melanoma (MM) patients. These approaches rely on immune functions for their anti-melanoma response. Plasmacytoid dendritic cells (pDCs) exhibit anti-tumor function by production of effector molecules, type I interferons (I-IFNs), and cytokines. Tissue and blood pDCs result compromised in MM, although these findings are still partially conflicting. This study reports that blood pDCs were dramatically depleted in MM, particularly in patients with high lactate dehydrogenase (LDH) and high tumor burden; the reduced pDC frequency was associated with poor overall survival. Circulating pDCs resulted also in significant impairment …

New Imaging Tools To Measure Nephron Number In Vivo: Opportunities For Developmental Nephrology, K M Bennett, E J Baldelomar, D Morozov, R L Chevalier, J R Charlton

Open Access Publications

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.

Individualization Of Attention-Deficit/Hyperactivity Disorder Treatment: Pharmacotherapy Considerations By Age And Co-Occurring Conditions, Greg W Mattingly, Joshua Wilson, Leticia Ugarte, Paul Glaser

Open Access Publications

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient's age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges …

Neural Networks To Predict Radiographic Brain Injury In Pediatric Patients Treated With Extracorporeal Membrane Oxygenation, Neel Shah, Abdelaziz Farhat, Jefferson Tweed, Ziheng Wang, Jeon Lee, Rafe Mcbeth, Michael Skinner, Fenghua Tian, Ravi Thiagarajan, Lakshmi Raman

Open Access Publications

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of …

Genotype-Phenotype Correlations In Children With Hht, Alexandra Kilian, Andrew J White, Murali M Chakinala, Et Al

Open Access Publications

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (

Doing What We Know, Knowing What To Do: Californians Linking Action With Science For Prevention Of Breast Cancer (Clasp-Bc), Jon F Kerner, Marion H E Kavanaugh-Lynch, Lourdes Baezconde-Garbanati, Christopher Politis, Aviva Prager, Ross C Brownson

Open Access Publications

Given the lack of progress in breast cancer prevention, the California Breast Cancer Research Program (CBCRP) plans to apply current scientific knowledge about breast cancer to primary prevention at the population level. This paper describes the first phase of Californians Linking Action with Science for Prevention of Breast Cancer (CLASP-BC). The foci of Phase 1 are building coalitions and coalition capacity building through community engagement in community-based participatory research (CBPR) and dissemination and implementation (D&I) research training. Based on the successful implementation and evaluation of Phase 1, the foci of Phase 2 (presented separately in this special issue) will be …

Higher Cortical Dysfunction Presenting As Visual Symptoms In Neurodegenerative Diseases, Yin Liu, Victoria S Pelak, Gregory Van Stavern, Heather E Moss

Open Access Publications

No abstract provided.

Characteristics And Outcomes Among A Hospitalized Patient Cohort With Streptococcus Pneumoniae Infection, Scott T. Micek, James Simmons, Nicholas Hampton, Marin H. Kollef

Open Access Publications

No abstract provided.

Antagonism Between Substitutions In Β-Lactamase Explains A Path Not Taken In The Evolution Of Bacterial Drug Resistance, Cameron A. Brown, Liya Hu, Zhizeng Sun, Meha P. Patel, Sukrit Singh, Justin R. Porter, Banumathi Sankaran, B. V. Venkataram Prasad, Gregory R. Bowman, Timothy Palzkill

Open Access Publications

No abstract provided.

Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury And Preserves Left Ventricular Systolic Function In Rats, As Evaluated By 7t Cardiovascular Magnetic Resonance Imaging, Ziqian Xu, Wei Chen, Ruzhi Zhang, Lei Wang, Ridong Chen, Jie Zheng, Fabao Gao

Open Access Publications

No abstract provided.

Lung Transplant Pulmonologists’ Views Of Specialty Palliative Care For Lung Transplant Recipients, Eric Nolley, Jessica Fleck, Dio Kavalieratos, Mary Amanda Dew, Daniel Dilling, Rebecca Colman, Maria M. Crespo, Hilary Goldberg, Steven Hays, Ramsey Hachem, Erika Lease, James Lee, John Reynolds, Matthew Morrell, Yael Schenker

Open Access Publications

No abstract provided.

American Society Of Hematology 2020 Guidelines For Sickle Cell Disease: Prevention, Diagnosis, And Treatment Of Cerebrovascular Disease In Children And Adults, M.R. Debaun, L.C. Jordan, A.A. King, J. Schatz, E. Vichinsky, C.K. Fox, R.C. Mckinstry, P. Telfer, M.A. Kraut, L. Daraz, F.J. Kirkham, M.H. Murad

Open Access Publications

No abstract provided.

Structural Basis For Effector Protein Recognition By The Dot/Icm Type Ivb Coupling Protein Complex, Hyunmin Kim, Tomoko Kubori, Kohei Yamazaki, Mi-Jeong Kwak, Suk-Youl Park, Hiroki Nagai, Joseph P. Vogel, Byung-Ha Oh

Open Access Publications

No abstract provided.

Maturational Patterns Of Left Ventricular Rotational Mechanics In Pre-Term Infants Through 1 Year Of Age, Gloria C Lehmann, Philip T Levy, Meghna D Patel, Timothy Sekarski, Hongjie Gu, Swati Choudhry, Aaron Hamvas, Gautam K Singh

Open Access Publications

BACKGROUND: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures.

METHODS: Pre-term infants (<29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus.

RESULTS: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p < 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p < 0.05).

CONCLUSION: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact …

Cathepsin S And Protease-Activated Receptor-2 Drive Alloimmunity And Immune Regulation In Kidney Allograft Rejection, Yutian Lei, Benjamin Ehle, Santhosh V Kumar, Susanne Müller, Solange Moll, Andrew F Malone, Benjamin D Humphreys, Joachim Andrassy, Hans-Joachim Anders

Open Access Publications

Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes.