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Comparative Genomics And Transcriptomics Of 4 Paragonimus Species Provide Insights Into Lung Fluke Parasitism And Pathogenesis, Bruce A. Rosa, Young-Jun Choi, Samantha N. Mcnulty, Hyeim Jung, John Martin, Takeshi Agatsuma, Hiromu Sugiyama, Thanh Hoa Le, Pham Ngoc Doanh, Wanchai Maleewong, David Blair, Paul J. Brindley, Peter U. Fischer, Makedonka Mitreva

Open Access Publications

BACKGROUND: Paragonimus spp. (lung flukes) are among the most injurious foodborne helminths, infecting ∼23 million people and subjecting ∼292 million to infection risk. Paragonimiasis is acquired from infected undercooked crustaceans and primarily affects the lungs but often causes lesions elsewhere including the brain. The disease is easily mistaken for tuberculosis owing to similar pulmonary symptoms, and accordingly, diagnostics are in demand.

RESULTS: We assembled, annotated, and compared draft genomes of 4 prevalent and distinct Paragonimus species: Paragonimus miyazakii, Paragonimus westermani, Paragonimus kellicotti, and Paragonimus heterotremus. Genomes ranged from 697 to 923 Mb, included 12,072-12,853 genes, and were 71.6-90.1% complete according …

Brainstorm: A Multi-Institutional Phase 1/2 Study Of Rrx-001 In Combination With Whole Brain Radiation Therapy For Patients With Brain Metastases, Michelle M Kim, Christina I Tsien, Et Al

Open Access Publications

PURPOSE: To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response.

METHODS AND MATERIALS: Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m

RESULTS: Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The …

Exploiting The Circuit Breaker Cancer Evolution Model In Human Clear Cell Renal Cell Carcinoma, James J Hsieh, Emily H Cheng

Open Access Publications

The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20

Growth Velocity In Children With Environmental Enteric Dysfunction Is Associated With Specific Bacterial And Viral Taxa Of The Gastrointestinal Tract In Malawian Children, Chandni Desai, Scott A. Handley, Rachel Rodgers, Cynthia Rodriguez, Maria I. Ordiz, Mark J. Manary, Lori R. Holtz

Open Access Publications

Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of …

Strategies To Optimize Icu Liberation (A To F) Bundle Performance In Critically Ill Adults With Coronavirus Disease 2019, John W Devlin, Hollis R O'Neal Jr, Christopher Thomas, Mary Ann Barnes Daly, Joanna L Stollings, David R Janz, E Wesley Ely, John C Lin

Open Access Publications

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, …

Coronary Heart Disease And Mortality Following A Breast Cancer Diagnosis, Aixia Guo, Kathleen W Zhang, Kristi Reynolds, Randi E Foraker

Open Access Publications

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. …

De Novo Identification Of Toxicants That Cause Irreparable Damage To Parasitic Nematode Intestinal Cells, Douglas P. Jasmer, Bruce A. Rosa, Rahul Tyagi, Christina A. Bulman, Brenda Beerntsen, Joseph F. Urban Jr, Judy Sakanari, Makedonka Mitreva

Open Access Publications

Efforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, a novel approach focused on integrating a pan-Nematoda multi-omics data targeted to a specific nematode organ system (the intestinal tract) with evidence-based filtering and chemogenomic screening was undertaken. Based on de novo computational target prioritization of the 3,564 conserved intestine genes in A. suum, exocytosis was identified as a high priority pathway, and predicted inhibitors of exocytosis were tested using the large roundworm (Ascaris suum larval …

Sucroferric Oxyhydroxide In Maintenance Hemodialysis: A Retrospective, Comparative Cohort Study, Daniel W Coyne, Linda H Ficociello, Vidhya Parameswaran, Melissa M Rosen, Claudy Mullon, Robert J Kossmann, Stuart M Sprague

Open Access Publications

RATIONALE & OBJECTIVE: High pill burden associates with reduced phosphate-binder adherence among dialysis patients, contributing to elevated serum phosphorus levels. We compared the real-world effectiveness of sucroferric oxyhydroxide (SO) versus other phosphate binders in hemodialysis patients over 2 years.

STUDY DESIGN: Retrospective cohort study.

SETTING & PARTICIPANTS: Adult in-center hemodialysis patients prescribed 2 years of uninterrupted SO therapy (maintenance SO; n = 222) compared with patients who discontinued SO therapy (discontinued SO; n = 596) within 90 days of first prescription and switched to other phosphate binder(s) for 2 years.

EXPOSURES: Phosphate binders.

OUTCOMES: Achievement of serum phosphorus levels ≤ …

Perspectives On Program Mis-Implementation Among U.S. Local Public Health Departments, Peg Allen, Rebekah R Jacob, Renee G Parks, Stephanie Mazzucca, Hengrui Hu, Mackenzie Robinson, Maureen Dobbins, Debra Dekker, Margaret Padek, Ross C Brownson

Open Access Publications

BACKGROUND: Public health resources are limited and best used for effective programs. This study explores associations of mis-implementation in public health (ending effective programs or continuing ineffective programs) with organizational supports for evidence-based decision making among U.S. local health departments.

METHODS: The national U.S. sample for this cross-sectional study was stratified by local health department jurisdiction population size. One person was invited from each randomly selected local health department: the leader in chronic disease, or the director. Of 600 selected, 579 had valid email addresses; 376 completed the survey (64.9% response). Survey items assessed frequency of and reasons for mis-implementation. …

Chromatin-Binding Protein Phf6 Regulates Activity-Dependent Transcriptional Networks To Promote Hunger Response, Linhua Gan, Cheng Cheng, Azad Bonni, Et Al

Open Access Publications

Understanding the mechanisms of activity-dependent gene transcription underlying adaptive behaviors is challenging at neuronal-subtype resolution. Using cell-type specific molecular analysis in agouti-related peptide (AgRP) neurons, we reveal that the profound hunger-induced transcriptional changes greatly depend on plant homeodomain finger protein 6 (PHF6), a transcriptional repressor enriched in AgRP neurons. Loss of PHF6 in the satiated mice results in a hunger-state-shifting transcriptional profile, while hunger fails to further induce a rapid and robust activity-dependent gene transcription in PHF6-deficient AgRP neurons. We reveal that PHF6 binds to the promoters of a subset of immediate-early genes (IEGs) and that this chromatin binding is …

Proof-Of-Concept Study Of The Efficacy Of A Microbiota-Directed Complementary Food Formulation (Mdcf) For Treating Moderate Acute Malnutrition, Ishita Mostafa, Naila Nurun Nahar, Md Munirul Islam, Sayeeda Huq, Mahfuz Mustafa, Michael Barratt, Jeffrey I Gordon, Tahmeed Ahmed

Open Access Publications

BACKGROUND: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy …

Perioperative Care Of The Geriatric Patient For Noncardiac Surgery, Jonathan D Wolfe, Natasha K Wolfe, Michael W Rich

Open Access Publications

Adults age 65 and over are the fastest growing segment of the population in the United States and around the world. As the size of this population expands, the number of older adults referred for surgical procedures will continue to increase. Due to the physiologic changes of aging and the increased frequency of comorbidities, older adults are at increased risk for adverse outcomes, and perioperative care is inherently more complex than in younger individuals. In this review, we discuss the physiologic changes of aging relevant to the surgical patient, comprehensive preoperative assessment, and postoperative management of common complications in older …

Parental Deployment And Distress, And Adolescent Disordered Eating In Prevention-Seeking Military Dependents, M K Higgins Neyland, Denise E Wilfley, Et Al

Open Access Publications

OBJECTIVE: Parental military deployment can lead to stress in the family system due to concerns about the deployed service-member's safety and increased responsibilities for those not deployed. Parent-related stress can impact adolescent disordered eating. Given the important role that stress plays in disordered eating and obesity, it is crucial to understand the impacts of unique stressors to which vulnerable populations are exposed.

METHOD: We studied 126 adolescent (14.3 ± 1.6 years; 59.5% girls; 44.4% non-Hispanic White; BMI-z, 1.91 ± .39) military dependents prior to entering an obesity and binge-eating disorder prevention trial. The Eating Disorder Examination was used to assess …

Targeting Refractory Sarcomas And Malignant Peripheral Nerve Sheath Tumors In A Phase I/Ii Study Of Sirolimus In Combination With Ganetespib (Sarc023), Aerang Kim, Brian A. Van Tine, Et Al

Open Access Publications

No abstract provided.

The Tip Of The Vgrg Spike Is Essential To Functional Type Vi Secretion System Assembly In Acinetobacter Baumannii, Juvenal Lopez, Pek Man Ly, Mario F Feldman

Open Access Publications

The type VI secretion system (T6SS) is a critical weapon in bacterial warfare between Gram-negative bacteria. Although invaluable for niche establishment, this machine represents an energetic burden to its host bacterium.

Nab-Paclitaxel/Xarboplatin In Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis, Corey J Langer, Ajeet Gajra, Cesare Gridelli, Kartik Konduri, Daniel Morgensztern, David Spigel, Denis Talbot, Michael Thomas, Jared Weiss, Richard Pilot, Rafia Bhore, Marianne Wolfsteiner, Teng Jin Ong, Mark Socinski

Open Access Publications

Introduction: Despite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including

Methods: To better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of

Results: Median progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04-5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88-10.12 months). PFS for elderly patients and patients with renal impairment …

The Cartilage Matrisome In Adolescent Idiopathic Scoliosis, Carol A. Wise, Diane Sepich, Aki Ushiki, Anas M. Khanshour, Yared H. Kidane, Nadja Makki, Christina A. Gurnett, Ryan S. Gray, Jonathan J. Rios, Nadav Ahituv, Lila Solnica-Krezel

Open Access Publications

No abstract provided.

Design And Rationale Of The Hapin Study: A Multicountry Randomized Controlled Trial To Assess The Effect Of Liquefied Petroleum Gas Stove And Continuous Fuel Distribution, Thomas Clasen, Victor G. Davila-Roman, Et Al.

Open Access Publications

No abstract provided.

Ancestry Specific Associations Of Fto Gene Variant And Metabolic Syndrome: A Longitudinal Aric Study, Dale S. Hardy, Jane T. Garvin, Tesfaye B. Mersha, Susan B. Racette

Open Access Publications

No abstract provided.

Eflornithine Plus Sulindac For Prevention Of Progression In Familial Adenomatous Polyposis, Carol A. Burke, Paul E. Wise, Et Al

Open Access Publications

No abstract provided.

Adherence To Updated Childcare Nutrition Regulations In Colorado, United States, Amy A Eyler, Cheryl R Valko, Katherine A Curoe, Ramya Ramadas, Jamie F Chriqui

Open Access Publications

No abstract provided.

The Tethering Function Of Mitofusin2 Controls Osteoclast Differentiation By Modulating The Ca2+–Nfatc1 Axis, Anna Ballard, Rong Zeng, Allahdad Zarei, Christine Shao, Linda Cox, Hui Yan, Antonietta Franco, Gerald W. Dorn Ii, Roberta Faccio, Deborah J. Veis

Open Access Publications

No abstract provided.

A Prospective Study Of Weight Gain In Women Diagnosed With Early-Stage Invasive Breast Cancer, Ductal Carcinoma In Situ, And Women Without Breast Cancer, Christine C. Ekenga, Xiaoyan Wang, Maria Pérez, Mario Schootman, Donna B. Jeffe

Open Access Publications

No abstract provided.

The De-Implementation And Persistence Of Low-Value Hiv Prevention Interventions In The United States: A Cross-Sectional Study, Virginia R Mckay, Todd B Combs, M Margaret Dolcini, Ross C Brownson

Open Access Publications

BACKGROUND: As more effective or efficient interventions emerge out of scientific advancement to address a particular public health issue, it may be appropriate to de-implement low-value interventions, or interventions that are less effective or efficient. Furthermore, factors that contribute to appropriate de-implementation are not well identified. We examined the extent to which low-value interventions were de-implemented among public health organizations providing HIV prevention services, as well as explored socio-economic, organizational, and intervention characteristics associated with de-implementation.

METHODS: We conducted an online cross-sectional survey from the fall of 2017 to the spring of 2019 with organizations (

RESULTS: Organizations reported 359 …

Early Diagnosis And Intervention In Cystic Fibrosis: Imagining The Unimaginable, Andrea M Coverstone, Thomas W Ferkol

Open Access Publications

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of …

Identifying Barriers, Facilitators, And Implementation Strategies For A Faith-Based Physical Activity Program, Jessica Haughton, Michelle L Takemoto, Jennifer Schneider, Steven P Hooker, Borsika Rabin, Ross C Brownson, Elva M Arredondo

Open Access Publications

BACKGROUND: Community engagement is critical to the acceleration of evidence-based interventions into community settings. Harnessing the knowledge and opinions of community leaders increases the likelihood of successful implementation, scale-up, and sustainment of evidence-based interventions.

METHODS: We conducted in-depth interviews using a semi-structured interview guide based on the Consolidated Framework for Implementation Research (CFIR) at various Catholic and Protestant churches with large Latino membership in San Diego County, California to explore barriers and facilitators to implementation of

RESULTS: Pastors and church staff described barriers and facilitators to implementation within three domains of CFIR: characteristics of individuals (lack of self-efficacy for and …

Macrophage Lc3-Associated Phagocytosis Is An Immune Defense Against Streptococcus Pneumoniae That Diminishes With Host Aging, Megumi Inomata, Shuying Xu, Pallavi Chandra, Simin N. Meydani, Genzou Takemura, Jennifer A. Philips, John M. Leong

Open Access Publications

No abstract provided.

Innate Immune Receptor Nod2 Mediates Lgr5+ Intestinal Stem Cell Protection Against Ros Cytotoxicity Via Mitophagy Stimulation, Antonin Levy, Aline Stedman, Eric Deutsch, Françoise Donnadieu, Herbert W. Virgin, Philippe J. Sansonetti, Giulia Nigro

Open Access Publications

No abstract provided.

Gene-By-Gene Interactions Associated With The Risk Of Conotruncal Heart Defects, Chen Lyu, Daniel M Webber, Stewart L Macleod, Charlotte A Hobbs, Ming Li, National Birth Defects Prevention Study

Open Access Publications

BACKGROUND: The development of conotruncal heart defects (CTDs) involves a complex relationship among genetic variants and maternal lifestyle factors. In this article, we focused on the interactions between 13 candidate genes within folate, homocysteine, and transsulfuration pathways for potential association with CTD risk.

METHODS: Targeted sequencing was used for 328 case-parental triads enrolled in the National Birth Defects Prevention Study (NBDPS). To evaluate the interaction of two genes, we applied a conditional logistic regression model for all possible SNP pairs within two respective genes by contrasting the affected infants with their pseudo-controls. The findings were replicated in an independent sample …

Identifying Determinants Of Bacterial Fitness In A Model Of Human Gut Microbial Succession, Lihui Feng, Arjun S. Raman, Matthew C. Hibberd, Jiye Cheng, Nicholas W. Griffin, Yangqing Peng, Semen A. Leyn, Dmitry A. Rodionov, Andrei L. Osterman, Jeffrey I. Gordon

Open Access Publications

No abstract provided.