Digital Commons Network^™

Agouti And Bmp Signaling Drive A Naturally Occurring Fate Conversion Of Melanophores To Leucophores In Zebrafish, Delai Huang, Emaan H. Kapadia, Yipeng Liang, Leah P. Shriver, Shengkun Dai, Gary J. Patti, Bruno M. Humbel, Vincent Laudet, David M. Parichy

2020-Current year OA Pubs

No abstract provided.

The Spatial Landscape Of Cancer Hallmarks Reveals Patterns Of Tumor Ecological Dynamics And Drug Sensitivity, Mustafa Sibai, Chia-Kuei Mo, Li Ding, Et Al.

2020-Current year OA Pubs

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we …

Improving Cancer Prevention And Control Through Implementing Academic-Local Public Health Department Partnerships - Protocol For A Cluster-Randomized Implementation Trial Using A Positive Deviance Approach, Stephanie Mazzucca-Ragan, Peg Allen, Kathleen Amos, Abigail R Barker, Madisen Brewer, Paul C Erwin, Jessica Gannon, Feng Gao, Rebekah R Jacob, Rebecca Lengnick-Hall, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Local public health departments in the United States are responsible for implementing cancer-related programs and policies in their communities; however, many staff have not been trained to use evidence-based processes, and the organizational climate may be unsupportive of evidence-based processes. A promising approach to address these gaps is through academic-public health department (AHD) partnerships, in which practitioners and academics collaborate to improve public health practice and education through joint research projects and educational opportunities. Prior research has demonstrated the benefits of AHD partnerships to public health practice and education. However, knowledge about how AHD partnerships should be structured to …

Virologic Effects Of Broadly Neutralizing Antibodies Vrc01ls And Vrc07-523ls On Chronic Hiv-1 Infection, Myra Happe, Rachel M. Presti, Et Al.

2020-Current year OA Pubs

BACKGROUNDHIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) have emerged as promising interventions with the potential to effectively treat and prevent HIV-1 infections. We conducted a phase I clinical trial evaluating the potent CD4-binding site-specific (CD4bs-specific) bNAbs VRC01LS and VRC07-523LS in people with HIV-1 (PWH) not receiving antiretroviral therapy (ART).METHODSParticipants received a single intravenous 40 mg/kg dose of either VRC01LS (n = 7) or VRC07-523LS (n = 9) and did not initiate ART for a minimum of 14 days. The primary study objective was to evaluate safety and tolerability; the secondary study objectives were to evaluate pharmacokinetics (PK) and the impact of …

Healthcare Facility Readiness And Availability For Hypertension And Type 2 Diabetes Care In Puno, Peru: A Cross-Sectional Survey Of Healthcare Facilities, Katherine E Lord, Parker K Acevedo, Lindsay J Underhill, Gonzalo Cuentas, Sonia Paredes, Juan C Mendoza, Percy Herrera, Victoria B Chou, Victor G Dávila-Román, Stella M Hartinger, William Checkley

2020-Current year OA Pubs

BACKGROUND: Non-communicable diseases are a rapidly growing cause of mortality and morbidity in Peru, accounting for 73% of total deaths. There is limited research on health system readiness to manage this rising burden. Our study characterized the readiness of healthcare facilities to manage patients with hypertension and/or type 2 diabetes (T2D) across two public healthcare systems in Puno, a largely rural and low-income department in Peru.

METHODS: We adapted the World Health Organization Service Availability and Readiness Assessment to characterize resources and services for hypertension and T2D care. We administered the survey to personnel at healthcare facilities in Puno. Service …

Progression Of Otologic And Nasal Symptoms In Primary Ciliary Dyskinesia Throughout Childhood, Isabelle Dagher, Adam J Kimple, Thomas W Ferkol, Scott D Sagel, Sharon D Dell, Carlos E Milla, Lang Li, Feng-Chang Lin, Kelli M Sullivan, Maimoona A Zariwala, Michael R Knowles, Margaret Rosenfeld, Margaret W Leigh, Stephanie D Davis, Genetic Disorders Of Mucociliary Clearance Consortium

2020-Current year OA Pubs

OBJECTIVE: Primary ciliary dyskinesia (PCD) is characterized by upper and lower airway disease. Multiple studies have demonstrated the progression of pulmonary disease; however, longitudinal changes in the otologic and nasal symptoms have not been well described in patients. This study defines age-related prevalence, age of onset, and age-related trends in self-reported otologic and sinonasal comorbidities in individuals with PCD.

STUDY DESIGN: A prospective, longitudinal, multicenter, observational study spanning up to 12 years.

SETTING: Six PCD centers in North America.

METHODS: Inclusion criteria were < 19 years of age and a confirmed diagnosis of PCD based on electron microscopy and/or genetics. A standardized medical history questionnaire and physical exam were completed during each study visit. Descriptive statistics were performed for the entire cohort as well as for subgroups based on ciliary ultrastructure.

RESULTS: A total of 147 participants were followed for an average of 7.6 ± 3.2 years. Pressure …

Impact Of Biocontainment On Small Animal Pet Performance Adapted For Bsl-2/3 Infectious Disease Imaging Research, Isabella Salerno, Nadia Benabdallah, Amanda Fears, Ryan Unnerstall, Lindsey Hauck, Sergey Komarov, Linda Cox, Hanwen Zhang, Kevin Poenicke, Joseph Aromando, Yuan-Chun Tai, Timothy Wencewicz, Deborah J Veis, Daniel L J Thorek

2020-Current year OA Pubs

BACKGROUND: Biocontainment protocols are critical for conducting infectious disease (ID) research, particularly when using small animal models in biosafety level (BSL) 2/3 environments. This study evaluates the impact of poly-methyl methacrylate (PMMA) containment vessels on the performance of preclinical positron emission tomography (PET) systems. We tested containment vessels designed with varying wall thicknesses (3, 6, and 9 mm) to simulate ID imaging facility equipment and protocols. Through the use of multicomponent phantoms and in vivo mouse models of Staphylococcus aureus infection, we assessed key performance metrics including count rate, image quality, activity recovery, and spatial resolution.

RESULTS: The results indicate …

Female Mice Lacking Glua3 Show Early Onset Of Hearing Loss, Cochlear Synaptopathy, And Afferent Terminal Swellings In Ambient Sound Levels, Indra Pal, Atri Bhattacharyya, Babak V-Ghaffari, Essence Devine Williams, Maolei Xiao, Mark Allen Rutherford, María Eulalia Rubio

2020-Current year OA Pubs

AMPA-type glutamate receptors (AMPARs) mediate excitatory cochlear transmission. However, unique roles of AMPAR subunits are unresolved. Lack of subunit GluA3 (

Effects Of Acute Pro-Inflammatory Stimulation And 25-Hydroxycholesterol On Hippocampal Plasticity And Learning Involve Nlrp3 Inflammasome And Cellular Stress Responses, Yukitoshi Izumi, Kazuko A O'Dell, Steven Mennerick, Charles F Zorumski

2020-Current year OA Pubs

Neuroinflammation is an increasingly important target for therapeutics in neuropsychiatry and contributes to cognitive dysfunction, disability and death across a range of illnesses. We previously found that acute effects of pro-inflammatory stimulation with lipopolysaccharide (LPS) on hippocampal long-term potentiation (LTP), a form of synaptic plasticity involved in learning and memory, requires synthesis of the oxysterol, 25-hydroxycholesterol (25HC) and exogenous 25HC mimics effects of LPS. However, downstream mechanisms engaged by LPS and 25HC remain uncertain. Here we use rat hippocampal slices and in vivo behavioral studies to provide evidence that acute modulation of synaptic plasticity by both LPS and 25HC requires …

Approaches To Engaging Faith Communities In Public Health Efforts Regarding Vaccination, Genetics, And Colorectal Cancer: A Systematic Review, Ana S Iltis, Lauren L Baker, Kari Baldwin, Lucas Cruz, Lauren H Yaeger, James M Dubois

2020-Current year OA Pubs

BACKGROUND: Public health professionals regularly engage faith communities to improve public health. This systematic review characterizes approaches that public health professionals have used to engage faith communities and evaluates them using the Theory of Planned Behavior. It examines engagement regarding vaccination and genetic and genomic healthcare, which have generated significant controversy within religious groups and, for comparison, colorectal cancer screening, which has not.

METHODS: This systematic review followed PRISMA reporting guidelines. We searched 8 online databases (e.g., Medline, Embase, Scopus). Publications in English that reported engaging a faith community on genetics, vaccination, or colorectal cancer screening were included. We screened …

Reneu: A Pivotal, Phase Iib Trial Of Mirdametinib In Adults And Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma, Christopher L Moertel, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

METHODS: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m

RESULTS: Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term …

Trem2 Promotes Lung Fibrosis Via Controlling Alveolar Macrophage Survival And Pro-Fibrotic Activity, Huachun Cui, Sami Banerjee, Na Xie, Musaddique Hussain, Ashish Jaiswal, Hongli Liu, Tejaswini Kulkarni, Veena B Antony, Rui-Ming Liu, Marco Colonna, Gang Liu

2020-Current year OA Pubs

Lung macrophages play a pivotal role in pulmonary fibrosis, with monocyte-derived alveolar macrophages driving disease progression. However, the mechanisms regulating their pro-fibrotic behavior and survival remain unclear, and effective therapeutic strategies are lacking. Here we show that triggering receptors expressed on myeloid cells 2 are predominantly expressed on monocyte-derived alveolar macrophages in fibrotic mouse lungs and are significantly elevated in lung macrophages from patients with idiopathic pulmonary fibrosis. Deletion or knockdown of this receptor disrupts intracellular survival signaling, promotes macrophage apoptosis, and attenuates their pro-fibrotic phenotype. We further demonstrate that a lipid mediator and a high-avidity ligand of this receptor, …

Successful Endovascular Management Of Concomitant Ischemic Stroke, Myocardial Infarction, And Massive Pulmonary Embolism, Ryan W Nolan, Naganathan B Mani, Amir Ata Rahnemai-Azar, Sriya Kosaraju, Arindam Chatterjee, Jasvindar Singh, Pavan Kumar Kavali

2020-Current year OA Pubs

BACKGROUND: Ischemic stroke, myocardial infarction (MI), and pulmonary embolism (PE) are emergent conditions which can be treated with catheter-directed therapies. Concomitant management of these conditions with catheter-directed therapy is not well-documented and lacks strong guidelines.

CASE SUMMARY: A 70-year-old woman presented with stroke symptoms and ST-segment elevation MI. Rapid stroke protocol imaging confirmed ischemic stroke and extensive bilateral PE. To address these conditions rapidly and because of contraindications for systemic thrombolysis, she underwent percutaneous coronary intervention without stenting, stroke thrombectomy, and finally pulmonary thrombectomy.

DISCUSSION: This case provides insight into the management of a patient with 3 emergent pathologies with …

Chromosomal And Gonadal Sex Have Differing Effects On Social Motivation In Mice, Sneha M Chaturvedi, Simona Sarafinovska, Din Selmanovic, Katherine B Mccullough, Raylynn G Swift, Susan E Maloney, Joseph D Dougherty

2020-Current year OA Pubs

BACKGROUND: Sex differences in brain development are thought to lead to sex variation in social behavior. Sex differences are fundamentally driven by both gonadal hormones and sex chromosomes, yet little is known about the independent effects of each on social behavior. Further, mouse models of the genetic liability for the neurodevelopmental disorder MYT1L Syndrome have shown sex-specific deficits in social motivation. In this study, we aimed to determine if gonadal hormones or sex chromosomes primarily mediate the sex differences seen in mouse social behavior, both at baseline and in the context of Myt1l haploinsufficiency.

METHODS: Four-core genotypes (FCG) mice, which …

Targeting Fatty Acid Synthase Reduces Aortic Atherosclerosis And Inflammation, Rodrigo Meade, Dina Ibrahim, Connor Engel, Larisa Belaygorod, Batool Arif, Fong-Fu Hsu, Sangeeta Adak, Ryan Catlett, Mingzhou Zhou, Ma Xenia G Ilagan, Clay F Semenkovich, Mohamed A Zayed

2020-Current year OA Pubs

Fatty acid synthase (FAS) is predominantly expressed in the liver and adipose tissue. It plays vital roles in de novo synthesis of saturated fatty acids and regulates insulin sensitivity. We previously demonstrated that serum circulating FAS (cFAS) is a clinical biomarker for advanced atherosclerosis, and that it is conjugated to low-density lipoproteins (LDL). However, it remains unknown whether cFAS can directly impact atheroprogression. To investigate this, we evaluate whether cFAS impacts macrophage foam cell formation - an important cellular process leading to atheroprogression. Macrophages exposed to human serum containing high levels of cFAS show increased foam cell formation as compared …

Unveiling The Genetic Landscape Of Coronary Artery Disease Through Common And Rare Structural Variants, Kruthika R Iyer, Erica P Young, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. …

Ipscs And Ipsc-Derived Cells As A Model Of Human Genetic And Epigenetic Variation, Kara Quaid, Xiaoyun Xing, Yi-Hsien Chen, Yong Miao, Amber Neilson, Vijayalingam Selvamani, Aaron Tran, Xiaoxia Cui, Ming Hu, Ting Wang

2020-Current year OA Pubs

Understanding the interaction between genetic and epigenetic variation remains a challenge due to confounding environmental factors. We propose that human induced Pluripotent Stem Cells (iPSCs) are an excellent model to study the relationship between genetic and epigenetic variation while controlling for environmental factors. In this study, we have created a comprehensive resource of high-quality genomic, epigenomic, and transcriptomic data from iPSC lines and three iPSC-derived cell types (neural stem cell (NSC), motor neuron, monocyte) from three healthy donors. We find that epigenetic variation is most strongly associated with genetic variation at the iPSC stage, and that relationship weakens as epigenetic …

Small Molecule-Mediated Inhibition Of The Oxidoreductase Ero1a Restrains Aggressive Breast Cancer By Impairing Vegf And Pd-L1 In The Tumor Microenvironment, Ersilia Varone, Jaehyung Cho, Et Al.

2020-Current year OA Pubs

Cancer cells adapt to harsh environmental conditions by inducing the Unfolded Protein Response (UPR), of which ERO1A is a mediator. ERO1A aids protein folding by acting as a protein disulfide oxidase, and under cancer-related hypoxia conditions, it favors the folding of angiogenic VEGFA, leading tumor cells to thrive and spread. The upregulation of ERO1A in cancer cells, oppositely to the dispensability of ERO1A activity in healthy cells, renders ERO1A a perfect target for cancer therapy. Here, we report the upregulation of ERO1A in a cohort of aggressive triple-negative breast cancer (TNBC) patients in which ERO1A levels correlate with a higher …

The Lymph Trial: Comparing Microsurgical With Conservative Treatment For Chronic Breast Cancer-Associated Lymphoedema - Study Protocol Of A Pragmatic Randomised International Multicentre Superiority Trial, Elisabeth A Kappos, Justin M Sacks, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Up to one-fifth of breast cancer survivors will develop chronic breast cancer-related lymphoedema (BCRL). To date, complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage. This international randomised trial aims to evaluate advantages of microsurgical interventions plus CDT versus CDT alone for BCRL treatment.

METHODS AND ANALYSIS: The effectiveness of LVA and/or VLNT in combination with CDT, which may be combined with liposuction, versus CDT alone will …

Impulsivity Facets And Substance Use Involvement: Insights From Genomic Structural Equation Modeling, Laura Vilar-Ribó, Alexander S Hatoum, Andrew D Grotzinger, Travis T Mallard, 23andme Research Team, Sarah Elson, Pierre Fontanillas, Abraham A Palmer, Daniel E Gustavson, Sandra Sanchez-Roige

2020-Current year OA Pubs

BACKGROUND: Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear.

METHODS: We used genomic structural equation modeling and genome-wide association studies (

RESULTS: We found that the SU and SUD factors were strongly genetically inter-correlated (

CONCLUSIONS: Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.

Clinical Impact Of Endoscopy In Severely Thrombocytopenic Patients With Hematologic Malignancy Experiencing Gastrointestinal Bleeding, Badr Alhumayyd, Ashton Naumann, Amanda Cashen, Chien-Huan Chen

2020-Current year OA Pubs

BACKGROUND: Gastrointestinal bleeding (GIB) is a major cause of hospitalization worldwide. Patients with hematologic malignancies have a higher risk of GIB as a result of thrombocytopenia and platelet dysfunction. There is no consensus on the optimal platelet level that would be safe for endoscopic intervention, although a platelet level of > 50 × 10

AIM: To assess the safety of endoscopic intervention of inpatients with hematological malignancies and severe thrombocytopenia presenting with acute overt GIB.

METHODS: This is a single center retrospective study. The data was collected from the electronic health record from 2018 to 2020. Inpatients with hematologic malignancy who …

Association Of Hyponatremia With Outcomes After Geriatric Trauma: A Systematic Review And Meta-Analysis, Ariana Naaseh, Steven Tohmasi, Carrie Stoll, Chongliang Luo, Lauren H Yaeger, Mark H Hoofnagle, Graham A Colditz, Marguerite W Spruce

2020-Current year OA Pubs

BACKGROUND: Trauma is a major cause of mortality in the elderly population. Hyponatremia is the most common electrolyte imbalance in geriatric patients and has been demonstrated to be a risk factor for altered cognition, low bone density, falls, and death. We systematically and critically reviewed the literature to ascertain the association between hyponatremia and geriatric trauma outcomes.

METHODS: We searched seven databases for articles published from inception to October 2023. Studies included reported on geriatric trauma, hyponatremia, and clinical outcomes. Two investigators independently reviewed 6535 abstracts, 235 full-text articles, and critically appraised each study. Study details, patient characteristics, and outcomes …

Proximity Proteomics Provides A New Resource For Exploring The Function Of Afadin And The Complexity Of Cell-Cell Adherens Junctions, Wangsun Choi, Dennis Goldfarb, Feng Yan, Michael B Major, Alan S Fanning, Mark Peifer

2020-Current year OA Pubs

The network of proteins at the interface between cell-cell adherens junctions and the actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change and motility. While this was initially thought to be a simple linear connection via classic cadherins and their associated catenins, we now have come to appreciate that many more proteins are involved, providing robustness and mechanosensitivity. Defining the full set of proteins in this network remains a key objective in our field. Proximity proteomics provides a means to define these networks. Mammalian Afadin and its Drosophila homolog Canoe are key parts of this protein network, …

Identifying Major Depressive Disorder In Older Adults Through Naturalistic Driving Behaviors And Machine Learning, Chen Chen, David C Brown, Noor Al-Hammadi, Sayeh Bayat, Anne Dickerson, Brenda Vrkljan, Matthew Blake, Yiqi Zhu, Jean-Francois Trani, Eric J Lenze, David B Carr, Ganesh M Babulal

2020-Current year OA Pubs

Depression in older adults is often underdiagnosed and has been linked to adverse outcomes, including motor vehicle crashes. With a growing population of older drivers in the United States, innovations in screening methods are needed to identify older adults at greatest risk of decline. This study used machine learning techniques to analyze real-world naturalistic driving data to identify depression status in older adults and examined whether specific demographics and medications improved model performance. We analyzed two years of GPS data from 157 older adults, including 81 with major depressive disorder, using XGBoost and logistic regression models. The top-performing model achieved …

Patient Partner Engagement In The Publication Process: Challenges And Possible Solutions, Krista E Cooksey, Mark Neuman, Mara Bollini, Bethany Pennington, Hugo De O Campos, Kathleen Oberst, Melissa Wurst, Mary C Politi

2020-Current year OA Pubs

Patient engagement in research is gaining traction as an international standard, and often requirement, of many health research funding agencies. Drivers of this increase include patient interest, increased attention to and recognition of the value of patients' voices in research, and more patients leading or partnering in the conduct research. Patient engagement includes collaborating and providing insights into research question and study design, and may extend to the publication process. When patients contribute to publications, they can bring unique perspectives that may enhance the impact, reach, and utility of the research in real-world contexts. Currently, there is limited systematic guidance …

Digit Regeneration Is Expedited In Lg/J Healer Mice Compared To Sm/J Non-Healer Mice, Feini Qu, Kristin L Lenz, Gwendalyn L Krekeler, Xin Duan, Muhammad Farooq Rai, Farshid Guilak

2020-Current year OA Pubs

Limb loss resulting from disease or trauma affects an estimated 185,000 Americans annually, significantly reducing their quality of life. Consequently, successful attempts to regrow missing appendages could substantially improve the prognosis for amputees. In mice, the digit tip spontaneously regenerates resected tissues following distal amputation, whereas this capacity diminishes at more proximal levels after amputation. Moreover, regenerative potential is influenced by genetic variations among inbred mouse strains: LG/J (healer) mice exhibit superior reparative potential compared to SM/J (non-healer) mice. This study investigated the response to various levels of digit amputation in these mice to determine whether this strain-dependent healing response …

Aberrant Homeodomain-Dna Cooperative Dimerization Underlies Distinct Developmental Defects In Two Dominant Crx Retinopathy Models, Yiqiao Zheng, Gary D Stormo, Shiming Chen

2020-Current year OA Pubs

Paired-class homeodomain (HD) transcription factors (TFs) play essential roles in vertebrate development, and their mutations are linked to human diseases. One unique feature of a paired-class HD is cooperative dimerization on specific palindrome DNA sequences. Yet, the functional significance of HD cooperative dimerization in animal development and its dysregulation in diseases remains elusive. Using the retinal TF cone-rod homeobox (CRX) as a model, we have studied how blindness-causing mutations in the paired HD, p.E80A and p.K88N, alter CRX's cooperative dimerization, leading to gene misexpression and photoreceptor developmental deficits in dominant manners. CRX

Phase 3 Trial Of Cabozantinib To Treat Advanced Neuroendocrine Tumors, Jennifer A Chan, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.

METHODS: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points …

Phages Carry Orphan Antitoxin-Like Enzymes To Neutralize The Dartg1 Toxin-Antitoxin Defense System, Anna Johannesman, Leila C Awasthi, Nico Carlson, Michele Leroux

2020-Current year OA Pubs

The astounding number of anti-phage defenses encoded by bacteria is countered by an elaborate set of phage counter-defenses, though their evolutionary origins are often unknown. Here, we report the discovery of an orphan antitoxin counter-defense element in T4-like phages that can overcome the bacterial toxin-antitoxin phage defense system, DarTG1. The DarT1 toxin, an ADP-ribosyltransferase, modifies phage DNA to prevent replication while its cognate antitoxin, DarG1, is a NADAR superfamily ADP-ribosylglycohydrolase that reverses these modifications in uninfected bacteria. We show that some phages carry an orphan DarG1-like NADAR domain protein, which we term anti-DarT factor NADAR (AdfN), that removes ADP-ribose modifications …

Feasibility Of An Undergraduate Academic Fellowship In Global Health System Development, Haleigh Pine, Brody R Mayoras, Maxwell C Klapow, Nathanael J Smith, Peter G Delaney, Zachary J Eisner

2020-Current year OA Pubs

BACKGROUND: Despite increasing student interest in global health, undergraduate opportunities remain limited and often lack practical, multidisciplinary experiences. To address professional gaps for future healthcare professionals and global health workers, it is crucial to incorporate resource management, business practices, and leadership into undergraduate volunteer service-learning programs.

METHODS: Lay First Responders (LFR) International's Fellowship Program in Emergency Medical Care and Innovation (ECMI) trains undergraduates to develop community-based emergency medical services in low- and middle-income countries, focusing on global capacity building, service leadership, and cultural competency. The year-long program guides fellows through a three-stage process of skill-development, design, and project implementation. The …