Digital Commons Network^™

Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.

OBJECTIVES: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the 2 species.

METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc

RESULTS: Diet-induced obesity reduced survival in …

Mechanical Explanation For The Hemodynamic Efficacy Of Right Atrial Appendage Autografts Used In Neo-Semilunar Valve Leaflet Reconstruction, Andrew Behrmann, Kate Appleman, Katarina Lettner, Balaji Cherupala, Jessica Cayton, Shamik Bhattacharya, Pirooz Eghtesady

2020-Current year OA Pubs

BACKGROUND: Pediatric pulmonic and aortic valve insufficiency has recently been treated with novel procedures that use autologous right atrial appendage tissue. Whether atrial tissue's tensile strength correlates with pressures it can withstand to function as a neo-semilunar valve has not been studied. We therefore studied these properties using an ex vivo porcine heart model.

METHODS: Aortic cusps, pulmonic cusps, and right and left atrial appendage tissues were excised from 10 porcine hearts. Native leaflets and atrial appendage samples underwent circumferential and radial stretching by a uniaxial tensile machine. Right atrial appendage tissue from 14 additional porcine hearts was used to …

Clinical Characteristics And Real-World Outcomes In Patients With Mucopolysaccharidosis Ii Over 18 Years: Final Report Of The Hunter Outcome Survey, Joseph Muenzer, Jaco Botha, Hernan Amartino, Roberto Giugliani, Paul Harmatz, Christoph Kampmann, Bianca Link, Shuan-Pei Lin, David Molter, Julian Raiman, Maurizio Scarpa, Anna Tylki-Szymańska, Siddharth Jain, David A H Whiteman, Barbara K Burton

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare, progressive, X-linked lysosomal storage disease. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase has been approved for the treatment of patients with MPS II since 2005. The Hunter Outcome Survey (HOS; NCT03292887) was established as a condition of approval to monitor the long-term safety and effectiveness of idursulfase. Here, we report the final results from HOS.

METHODS: HOS was a multicenter, long-term, observational registry that enrolled patients with a biochemically and/or genetically confirmed diagnosis of MPS II who were untreated or treated with idursulfase and/or bone marrow transplant. Patients were enrolled prospectively …

From Sex Differences To Sex Inequalities In Life Expectancy: A Cross-Country Observational Benchmarking Analysis, Angela Y. Chang, Emily K. Johnson, Sarah Bolongaita, Kent Buse, Sarah J. Hawkes, Omar Karlsson, Felicia M. Knaul, Margaret E. Kruk, Ole F. Norheim, Osondu Ogbuoji, David Watkins, Dean T. Jamison

2020-Current year OA Pubs

BACKGROUND: The answer to whether females or males have better health, and which sex is the more disadvantaged, has depended in part on the metric and how the inequality is measured. This study introduces a new method for analyzing and interpreting sex inequalities in health outcomes-defined as the avoidable sex differences in health outcomes-that is systematic and potentially more objective. For this paper, we focus on life expectancy at different ages.

METHODS AND FINDINGS: We introduce the adjusted sex ratio as a measure of sex inequalities and determining sex disadvantage. First, we calculated the sex ratio of life expectancy at …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Improved Accuracy For Myocardial Blood Flow Mapping With Deep Learning-Enabled Cmr Arterial Spin Labeling (Deepmasl): Validation By Microsphere In Vivo, Ran Li, Caleb Berberet, Qi Huang, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Current myocardial arterial spin labeling (ASL) methods are sensitive to noise (background and physiology), which limits the accuracy of myocardial blood flow (MBF) measurement. In this study, we demonstrated a new deep learning-enabled myocardial ASL approach (DeepMASL) and evaluated its accuracy to quantify MBF in a canine model of coronary arterial disease in vivo. The reference method was invasive microsphere measurements.

METHODS: Eighteen mongrel dogs were divided into two groups: healthy (n = 9) and coronary stenosis (n = 9). The latter was induced in an open-chest model with 3 types of stenosis: 50% (n= 3), 70% (n = …

Semi-Annual And Annual Mass Drug Administration Of Diethylcarbamazine And Albendazole Are Equally Effective Regimens For Eliminating Lymphatic Filariasis In Papua New Guinea, Michael C. Payne, Nelly Sanuku, Brooke E. Mancuso, Yao-Chieh Cheng, Gary J. Weil, Peter U. Fischer, Moses Laman, Leanne J. Robinson, Daniel J. Tisch, Christopher L King

2020-Current year OA Pubs

Annual mass drug administration (MDA) is currently recommended for the local elimination of lymphatic filariasis (LF). Modeling studies of LF transmission suggest that conducting MDA twice a year could accelerate LF elimination. To test this idea, we compared the effects of 3 rounds of yearly MDA and 5 rounds of semiannual MDA using diethylcarbamazine with albendazole on LF infection measures in Papua New Guinea (PNG) across 2 treatment areas with high LF prevalence. From 2013 to 2018, we conducted 4 annual community surveys at 4 sentinel sites in each treatment area. We sampled 2,854 people at the start and 2,746, …

The Non-Communicable Disease E-Cohort For Hypertension In Latin America: Concept, Survey Development And Study Protocol, Patricia J Garcia, Laura Espinoza-Pajuelo, Hannah H Leslie, Margaret E Kruk, Catherine Arsenault, Agustina Mazzoni, Jesus Medina-Ranilla, Javier Roberti, Marina Guglielmino, Ezequiel Garcia-Elorrio

2020-Current year OA Pubs

Non-communicable diseases like hypertension cause substantial morbidity and mortality in low- and middle-income countries, where limited access to high-quality care contributes to millions of preventable deaths annually. Traditional assessments of health system performance often rely on structural indicators and cross-sectional, overlooking patient experiences and care processes. In Latin America, amid rising cardiovascular disease, longitudinal tools are needed to guide improvements in healthcare delivery models, particularly for chronic diseases such as hypertension. The NCD e-Cohort is a prospective, longitudinal, mixed-mode (in-person and phone) survey designed to assess health system quality in Latin America. Developed by the QuEST Network, it integrates validated …

Does Health Insurance Coverage Improve Cardiometabolic Risk Factor Levels? Quasi-Experimental Evidence From India, Kavita Singh, Anubha Agarwal, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored.

OBJECTIVE: To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India.

METHODS: Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality …

Cholinergic Dysfunction In Occupational Manganese Exposure, T Noah Hutson, Susan Searles Nielsen, Natalie Senini, John O'Donnell, Hubert P Flores, Tamara Hershey, Joel S Perlmutter, Anil Kumar Soda, Stephen M Moerlein, Zhude Tu, Michael Kasper, Lianne Sheppard, Brad A Racette, Susan R Criswell

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: Excessive exposure to manganese (Mn) produces a clinical syndrome of parkinsonism and cognitive impairment. However, our understanding of the mechanisms of Mn neurotoxicity remains limited. This study aimed to evaluate the relationships between Mn exposure, cholinergic function, and cognitive impairment in exposed workers.

METHODS: We assessed brain cholinergic function using vesicular acetylcholine transporter (VAChT) radiotracer (-)-(1-(8-(2-[(18)F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone (VAT) with positron emission tomography (PET) in 21 Mn-exposed workers. We estimated occupational Mn exposure from work histories and the MRI pallidal index. A cognitive control battery consisting of the Verbal Fluency (VF), Letter Number Sequencing (LNS), Two-Back Letter Task (2B), …

The Influence Of Body Mass Index On Tumor Treating Fields Therapy In Patients With Metastatic Non-Small Cell Lung Cancer: A Post-Hoc And Simulation Analysis From The Phase Iii Lunar Study, Christian Rolfo, David E Gerber, Rupesh Kotecha, Jeffrey P Ward, Wallace Akerley, Lukas Weiss, Ariel Naveh, Nadav Shapira, Ticiana Leal, Corey J Langer, Lunar Study Investigators

2020-Current year OA Pubs

INTRODUCTION: In the phase III LUNAR study, overall survival (OS) with PD-(L)1 inhibitor or docetaxel was improved by adding Tumor Treating Fields (TTFields) therapy in patients with metastatic non-small cell lung cancer progressing on/after platinum-based therapy. This post-hoc analysis evaluated the effects of body mass index (BMI) on TTFields delivery.

METHODS: OS was assessed in LUNAR patients with BMI <  25 kg/m

RESULTS: In the BMI <  25 kg/m

CONCLUSIONS: In this post-hoc analysis, we found no difference in OS benefit of TTFields therapy between patients with BMI <  25 kg/m

Early And Mid-Term Outcomes Of Mitral Annular Calcification And Transcatheter Mitral Therapy: A Systematic Review, Yosuke Sakurai, Ashton Mcdonald, Tsuyoshi Kaneko

2020-Current year OA Pubs

BACKGROUND: Mitral annular calcification (MAC) poses technical and clinical challenges in patients undergoing mitral valve intervention. Patients with severe MAC were excluded from major previous randomized controlled trials evaluating mitral therapies. Consequently, outcomes following mitral transcatheter edge-to-edge repair (M-TEER) in this population remain controversial.

METHODS: MEDLINE and EMBASE were searched through June 2025 to identify studies reporting outcomes after M-TEER in patients with MAC. This systematic review assessed the difference in MAC grading and M-TEER eligibility across studies. The definition of procedural success was documented to highlight inconsistencies. The primary endpoint was all-cause mortality during follow-up. Secondary endpoints included procedural …

Peptide Vaccines For Pediatric High-Grade Glioma And Diffuse Midline Glioma: Current Progress And Future Perspectives, Aron K Mebrahtu, Vatsal Jain, Eliese M Moelker, Alexandra M Hoyt-Miggelbrink, Katayoun Ayasoufi, Eric M Thompson

2020-Current year OA Pubs

High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we define the scope of current progress by arguing that immunogenicity in children with HGG/DMG hinges on three factors: appropriate antigen class (neoantigen vs. TAA), the use of potent immunoadjuvants, and successful navigation of immune suppression. To address the gap between biological promise and clinical reality, we analyze clinical trials targeting shared tumor-associated antigens (e.g., CMV pp65, Survivin) …

Implementing And Evaluating Visual Key Information Pages Compared To Text-Based Key Information: Protocol For A Stepped-Wedge Cluster Randomized Trial, Krista E Cooksey, Eliana C Goldstein, Clara N Lee, Jessica Mozersky, Kimberly A Kaphingst, Jingxia Liu, Shuang Wu, Molly Volkmar, Victor Catalan-Gallegos, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Informed consent is a key aspect of conducting research studies, yet many participants do not understand critical study details after reviewing long, complex consent documents. The 2018 Common Rule aimed to address this challenge by requiring a key information section, a "concise and focused" presentation of important and relevant study information. In our ongoing work, we developed a template and toolkit to improve the presentation of key information by incorporating health literacy best practices, including color and visual icons. The goal of this study is to assess the impact of the visual key information (KI) pages at both the …

Development Of Intestinal Tissue-Resident T Cells In Early-Life Mice Before And After Weaning, Catherine Montenegro, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco

2020-Current year OA Pubs

Intestinal tissue-resident T cells have been poorly characterized during early-life. Here, we phenotypically characterized tissue-resident (intravascular staining negative) CD4

Participatory Implementation Science To Enhance Knowledge And Build The Capacity To Increase The Uptake And Sustainability Of Hpv Vaccination Among Girls In Nigeria, Peter Kalulu, Olufunto A Olusanya, Nkiruka Obodoechina, Maria A Afadapa, Temitope Ojo, Priscilla A Kabutey, Caven N Ngoe, Ashley Bardon, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV) vaccination can prevent cancer in low- and middle-income countries (LMICs), but its uptake remains low, especially in Nigeria. Understanding participatory approaches can help identify local strategies to increase, build capacity for, and sustain vaccine uptake. This study evaluated the effectiveness of an innovation bootcamp in enhancing the knowledge and skills of youth implementers about HPV and cervical cancer as a strategy to increase vaccine uptake among Nigerian girls aged 9-14 years. An innovation bootcamp is an intensive training program that engages end users to build capacity and skills.

METHODS: This was a five-week hybrid bootcamp guided …

Structure Of An Lgr Dimer, An Evolutionary Predecessor Of Glycoprotein Hormone Receptors, Zhen Gong, Shuobing Chen, Ziao Fu, Brian Kloss, Chi Wang, Jonathan Kim, Oliver B Clarke, Qing R Fan, Wayne A Hendrickson

2020-Current year OA Pubs

Glycoprotein hormones (GpHs) produced in the human pituitary act through receptors (GpHRs) in the gonads to support reproduction and in the thyroid for metabolism. GpHs are heterodimeric cystine-knot proteins; their receptors bind cognate hormones at an extracellular domain and signal through a transmembrane domain to heterotrimeric G proteins. GpHs and GpHRs have co-evolved from invertebrate counterparts. Structures of the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers. Here we characterize the homologous receptor from Caenorhabditis elegans. Its biochemical properties are notably similar to those of the thyroid stimulating …

So What? Elevating The Impact Of Implementation Science, Ross C Brownson, Juliet Iwelunmor, Thomas A Odeny, Enola K Proctor, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Given the substantial public funding of health-related research, tangible benefits of this support must be demonstrated. Implementation science provides actionable methods to enhance population health, reduce health inequities, and guide effective public health and clinical practices and policies. We must elevate the notion of impact (the "so-what gap") and the role of implementation science, particularly in university settings.

MAIN TEXT: We distinguish between scientific output and impacts. Impacts in implementation science are commonly defined as improvements in health outcomes, quality of life, quality of services, or policy change. In contrast, traditional academic outputs, such as citation counts and grant …

Variation In State Policies On Sideline Medical Coverage Of High School Athletic Events, Marcus Allen, Aravind Athiviraham, Darlington Nwaudo, Lutul D Farrow, Aossm Bold Study Group, Matthew Matava

2020-Current year OA Pubs

BACKGROUND: Certified athletic trainers (ATs) are the primary source of sideline coverage for high school athletic events, providing an essential role in student-athlete health. However, there is a paucity of literature evaluating the existence of state requirements regarding the presence of ATs and mandatory sideline medical coverage of high school athletic events.

HYPOTHESIS: It was hypothesized that there is significant variation among state policies on sideline medical coverage and AT requirements for high school athletic events.

STUDY DESIGN: Cross-sectional study.

METHODS: A 17-question survey was emailed to the executive directors (or analogous position) of the state high school athletic associations …

Strengthening Implementation Science Research To Improve Adolescent And Young Adult Hiv-Prevention And Care In Sub-Saharan Africa: Patc3h-In, Geri R Donenberg, Ucheoma Nwaozuru, Sylvia Adebajo, Joseph D Tucker, Juliet Iwelunmor, Lisa M Kuhns, Brenda Gati Mirembe, Lisa Hightow-Weidman, Brian Zanoni, Tapiwa A Tembo, Maria Felix Lupogo, Franklin Yates

2020-Current year OA Pubs

BACKGROUND: Despite significant progress in HIV prevention and treatment, uptake of evidence-based interventions among adolescents and young adults (AYA), particularly in low- and middle-income countries (LMICs), remains low. Implementation research can optimize strategies to enhance reach, uptake, and equitable access to these innovations. The Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource-Constrained Settings Implementation Science Network (PATC

METHODS: The PATC

RESULTS: The PATC

CONCLUSIONS: The PATC

CLINICAL TRIAL NUMBER: Not Applicable.

Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites …

Implementation Outcomes From The Hypertension Treatment In Nigeria Program: Results From A Type 2 Hybrid Interrupted Time Series Trial, Jiancheng Ye, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Hypertension Treatment in Nigeria Program was implemented across 60 primary healthcare centers (PHCs) in Nigeria to improve hypertension treatment and control using the World Health Organization's HEARTS package. This study reports the program's implementation outcomes.

METHODS: The Hypertension Treatment in Nigeria Program used a type 2 hybrid interrupted time series design, and data were collected from January 2020 to December 2023. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework guided the evaluation, focusing on key metrics such as patients' and clinics' characteristics, prescription rate of fixed dose combination (FDC) drugs, medication availability, and retention.

RESULTS: Among 21,922 …

Clinical And Implementation Outcomes Of An Antimicrobial Stewardship Intervention For Rapid Blood Culture Diagnostics, Monica Abdelnour, Christine R Lockowitz, Evan E Facer, Andrew Atkinson, Sara Malone, Virginia R Mckay, Rebekah E Dumm, Alexander S Plattner, Matthew M Sattler, Jason G Newland

2020-Current year OA Pubs

OBJECTIVE: To evaluate the clinical and implementation outcomes of an antimicrobial stewardship program (ASP) intervention to improve antibiotic therapy for a rapid diagnostic test (RDT) for bloodstream infections (BSIs).

DESIGN: Retrospective pre and postintervention study.

SETTING: Single pediatric tertiary center from August 2022 to May 2024.

PARTICIPANTS: Patients presenting with a positive blood culture accompanied by the Verigene (VG) Gram-positive Blood Culture Nucleic Acid (BC-GP) assay. Implementation outcomes surveys were completed by infectious diseases (ID) clinicians and non-ID clinicians.

METHODS: We implemented a 24 hours a day, 7 days a week (24/7) ASP intervention to improve response to BC-GP assay …

Molecular Basis Of Nfib-Mediated Regulation Of Oncogenic Transcription, Ci Zhu, Ding Xiao, Yueyu Wang, Hong Han, Chengxiao Qin, Shuang Liu, Xi Chen, Hejin Xiao, Xin Chen, Junfeng Shi, Juyu Tang, Jie Shen, He Song

2020-Current year OA Pubs

The Nuclear Factor I (NFI) family of transcription factors orchestrates key regulatory programs in development, differentiation, and metabolism, with dysregulation implicated in diverse pathological conditions, including cancer. Among the paralogs, NFIB has emerged as an oncogenic driver in multiple tumor types, yet the mechanisms through which it engages DNA and directs oncogenic transcriptional programs remain undefined. Here, using cancer cells with high NFIB expression, we demonstrate that NFIB promotes malignant phenotypes, as CRISPR-Cas9 knockout impairs proliferation, migration, and invasion. Transcriptomic profiling reveals that NFIB regulates a cancer-enriched gene network that includes FGFR3 and PDGFRB. Biophysical analyses show that NFIB, including …

Oligomerisation Of Ku From Mycobacterium Tuberculosis Promotes Dna Synapsis, Sayma Zahid, Ankita Chadda, Eric Galburt, Et Al.

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is estimated to infect nearly one-quarter of the global population. A key factor in its resilience and persistence is its robust DNA repair capacity. Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in many organisms, including Mtb, where it is mediated by the Ku protein and the multifunctional LigD enzyme. In this study, we demonstrate that Ku is essential for mycobacterial survival under DNA-damaging conditions. Using cryogenic electron microscopy (cryo-EM), we solved high-resolution structures of both the apo and DNA-bound forms of the Ku-Mtb homodimer. …

The Pitfalls Of Multiple-Choice Questions In Generative Ai And Medical Education, Shrutika Singh, Anton Alyakin, Daniel Alexander Alber, Jaden Stryker, Ai Phuong S Tong, Karl Sangwon, Nicolas Goff, Mathew De La Paz, Miguel Hernandez-Rovira, Ki Yun Park, Eric Claude Leuthardt, Eric Karl Oermann

2020-Current year OA Pubs

The performance of Large Language Models (LLMs) on multiple-choice question (MCQ) benchmarks is frequently cited as proof of their medical capabilities. We hypothesized that LLM performance on medical MCQs may in part be illusory and driven by factors beyond medical content knowledge and reasoning capabilities. To assess this, we created a novel benchmark of free-response questions with paired MCQs (FreeMedQA). Using this benchmark, we evaluated three state-of-the-art LLMs (GPT-4o, GPT-3.5, and LLama-3-70B-instruct) and found an average absolute deterioration of 39.43% in performance on free-response questions relative to multiple-choice (p = 1.3 * 10

Maternal Obesogenic Diet Exposure Regulates The Offspring Gut Liver Axis And Fibroinflammatory Liver Disease, Naresh Naik Ramavath, Oğuz Özler, Holly Hinrichs, Francisco R Victorino, Vung Lian, Monica Young, Tarin M Bigley, Michael D Thompson

2020-Current year OA Pubs

Maternal obesogenic diet exposure (MODE) promotes fibroinflammatory liver disease in offspring via vertical transfer of an altered microbiome. The mechanism for how an altered offspring microbiome increases susceptibility to liver disease is not clear. A critical early life event termed the 'weaning reaction' is dependent on the early microbiome and when altered, results in worse pathologic inflammation. MODE attenuates the weaning reaction promoting worse liver disease in mice in an early microbiome-dependent manner. Using our MODE model and cross-fostering approaches we assessed the effect of MODE on neonatal gut-liver axis development. MODE shifts the bile acid (BA) profile, expression of …

Cpx-351 Vs. Conventional Chemotherapy Cardiotoxicity In High-Risk Aml: A Post Hoc Phase Iii Trial Analysis, Joshua D Mitchell, Michael Pfeiffer, John Boehmer, John Gorcsan, Shunsuke Eguchi, Yoshiyuki Orihara, Nalina Dronamraju, Sonja Dhani, Stefan Faderl, Tara L Lin, Geoffrey L Uy, Jeffrey E Lancet, Jorge E Cortes

2020-Current year OA Pubs

BACKGROUND: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has demonstrated significantly improved overall survival in acute myeloid leukemia (AML) compared with 7 + 3, but its impact on cardiac function remains unclear. In a post hoc analysis of the pivotal clinical trial, we sought to determine the relative cardiotoxicity of CPX-351 vs. 7 + 3 in high-risk AML.

METHODS: We evaluated cardiotoxicity in 102 patients with AML (CPX-351, n = 57; 7 + 3, n = 45) who had normal baseline left ventricular ejection fraction (LVEF) ≥ 53% and at least one …

Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain

2020-Current year OA Pubs

Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in …

Mitochondrial Iron Transport Via Mfrn1 Is Required For Erythroid Cell Cycle Progression, Mark Perfetto, Aidan Danoff, Muhammad Ishfaq, Heidi Monroe, Aiden Mohideen, Meilin Chen, Jesus Tejero, Amber N Stratman, Satoshi Okawa, Yvette Y Yien

2020-Current year OA Pubs

Iron metabolism drives key erythropoietic processes, including hemoglobinization, survival, and proliferation. Here, we developed in vivo methods to interrogate how iron regulates erythropoiesis and report that mitochondrial iron transport via mitoferrin-1 (MFRN1) is essential for erythroid cell cycle progression. mfrn1 embryos had severely decreased erythroid cell number caused by cell cycle arrest at G2/M. They had enlarged nuclei, suggesting a mitotic defect. Iron supplementation rescued the cell cycle defect, implicating mitochondrial iron deficiency as its cause. In contrast, fpn1 mutants, anemic from systemic iron deficiency, had less severe decreases in erythroid mitochondrial iron than mfrn1 mutants and no proliferative defects. …