Medicine and Health Sciences Commons^™

Combining The Tyrosine Kinase Inhibitor Cabozantinib And The Mtorc1/2 Inhibitor Sapanisertib Blocks Erk Pathway Activity And Suppresses Tumor Growth In Renal Cell Carcinoma, Yige Wu, Siqi Chen, Xiaolu Yang, Kazuhito Sato, Preet Lal, Andrew T Shinkle, Michael C Wendl, Tina M Primeau, Yanyan Zhao, Alanna Gould, Hua Sun, Jacqueline L Mudd, Jeremy Hoog, R Jay Mashl, Matthew A Wyczalkowski, Chia-Kuei Mo, Ruiyang Liu, John M Herndon, Sherri R Davies, Di Liu, Xi Ding, Ramaswamy Govindan, Shunqiang Li, James Hsieh, Ryan C Fields, Kian-Huat Lim, Cynthia X Ma, Li Ding, Feng Chen, Et Al.

2020-Current year OA Pubs

UNLABELLED: Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced …

T1 And Flair Signal Intensities Are Related To Tau Pathology In Dominantly Inherited Alzheimer Disease, Farzaneh Rahmani, Matthew R Brier, Brian A Gordon, Nicole Mckay, Shaney Flores, Sarah Keefe, Russ Hornbeck, Beau Ances, Nelly Joseph-Mathurin, Chengjie Xiong, Guoqiao Wang, Cyrus A Raji, Jorge J Libre-Guerra, Richard J Perrin, Eric Mcdade, Alisha Daniels, Celeste Karch, John C Morris, Randall J Bateman, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (μ) and standard deviation (σ) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-μ in mutation …

What Do Infectious Disease Specialists Think About Managing Long Covid?, Maureen D Lyons, Susan E Beekmann, Philip M Polgreen, Jonas Marschall

2020-Current year OA Pubs

This survey of infectious disease providers on long COVID care revealed a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. The low response rate suggests that infectious disease specialists do not consider themselves as the primary providers of long COVID care.

Does Patella Lowering As Part Of Multilevel Surgery Improve Knee Kinematics In Children With Cerebral Palsy And Crouch Gait? A Meta-Analysis Of Comparative Studies, María Galán-Olleros, Sergio Lerma-Lara, Beltran Torres-Izquierdo, Ana Ramírez-Barragán, Rosa M Egea-Gámez, Pooya Hosseinzadeh, Ignacio Martínez-Caballero

2020-Current year OA Pubs

PURPOSE: To evaluate differences in knee kinematic outcomes of patellar-lowering surgery, specifically patellar tendon advancement or patellar tendon shortening, compared with no-patellar-lowering surgery in multilevel surgery for children with cerebral palsy and crouch gait.

METHODS: Four databases were searched to retrieve studies published from inception until 2023. Three reviewers independently screened for studies with observational or randomized control designs, comparing two groups of patients with cerebral palsy and crouch gait who underwent multilevel surgery (with patellar-lowering surgery versus no-patellar-lowering surgery), where various gait analysis outcomes were reported (CRD42023450692). The risk of bias was assessed with the Risk Of Bias In …

Apobec-1 Deletion Enhances Cisplatin-Induced Acute Kidney Injury, Xiaojia Guo, Valerie Blanc, Nicholas O Davidson, Heino Velazquez, Tian-Min Chen, Dennis G Moledina, Gilbert W Moeckel, Robert L Safirstein, Gary V Desir

2020-Current year OA Pubs

Cisplatin (CP) induces acute kidney injury (AKI) whereby proximal tubules undergo regulated necrosis. Repair is almost complete after a single dose. We now demonstrate a role for Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (Apobec-1) that is prominently expressed at the interface between acute and chronic kidney injury (CKD), in the recovery from AKI. Apobec-1 knockout (KO) mice exhibited greater mortality than in wild type (WT) and more severe AKI in both CP- and unilateral ischemia reperfusion (IR) with nephrectomy. Specifically, plasma creatinine (pCr) 2.6 ± 0.70 mg/dL for KO, n = 10 and 0.16 ± 0.02 for WT, …

Designing For Dissemination Among Public Health And Clinical Practitioners In The Usa, Thembekile Shato, Maura M Kepper, Gabriella M Mcloughlin, Rachel G Tabak, Russell E Glasgow, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The slow adoption of evidence-based interventions reflects gaps in effective dissemination of research evidence. Existing studies examining designing for dissemination (D4D), a process that ensures interventions and implementation strategies consider adopters' contexts, have focused primarily on researchers, with limited perspectives of practitioners. To address these gaps, this study examined D4D practice among public health and clinical practitioners in the USA.

METHODS: We conducted a cross-sectional study among public health and primary care practitioners in April to June 2022 (analyzed in July 2022 to December 2022). Both groups were recruited through national-level rosters. The survey was informed by previous D4D …

Modbed Track: Visualization Of Modified Bases In Single-Molecule Sequencing, Daofeng Li, Xiaoyu Zhuo, Jessica K Harrison, Shane Liu, Ting Wang

2020-Current year OA Pubs

Recent advances in long-read sequencing technologies have not only dramatically increased sequencing read length but also have improved the accuracy of detecting chemical modifications to the canonical nucleotide bases, thus opening exciting venues to investigate the epigenome. Currently, the ability to visualize modified bases from long-read sequencing data in genome browsers is still limited, preventing users from easily and fully exploring these type of data. To address this limitation, the WashU Epigenome Browser introduces the modbed track type, which provides visualization of modification details in each single read as well as aggregated modifications of individual or multiple molecules across a …

A Multilevel Mhealth Intervention Boosts Adherence To Hydroxyurea In Individuals With Sickle Cell Disease, Jane S Hankins, Allison A King, Ana A Baumann, Lisa M Klesges, Et Al.

2020-Current year OA Pubs

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P < 0.001) and sustained (39.7% to 51.4%, P < 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P < 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU Toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167.

Single-Cell Atlas Of Healthy Human Blood Unveils Age-Related Loss Of Nkg2c+Gzmb−Cd8+ Memory T Cells And Accumulation Of Type 2 Memory T Cells, Marina Terekhova, Amanda Swain, Pavla Bohacova, Ekaterina Aladyeva, Laura Arthur, Anwesha Laha, Denis A Mogilenko, Samantha Burdess, Vladimir Sukhov, Denis Kleverov, Barbora Echalar, Petr Tsurinov, Roman Chernyatchik, Kamila Husarcikova, Maxim N Artyomov

2020-Current year OA Pubs

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells. Twelve subpopulations changed with age, including the accumulation of GZMK

A Patterned Human Primitive Heart Organoid Model Generated By Pluripotent Stem Cell Self-Organization, Brett Volmert, Chao Zhou, Et Al.

2020-Current year OA Pubs

Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage …

Antibody Binding Captures High Energy State Of An Antigen: The Case Of Nsp1 Sars-Cov-2 As Revealed By Hydrogen-Deuterium Exchange Mass Spectrometry, Ravi Kant, Nawneet Mishra, Michael L Gross

2020-Current year OA Pubs

We describe an investigation using structural mass spectrometry (MS) of the impact of two antibodies, 15497 and 15498, binding the highly flexible SARS-CoV-2 Nsp1 protein. We determined the epitopes and paratopes involved in the antibody-protein interactions by using hydrogen-deuterium exchange MS (HDX-MS). Notably, the Fab (Fragment antigen binding) for antibody 15498 captured a high energy form of the antigen exhibiting significant conformational changes that added flexibility over most of the Nsp1 protein. The Fab for antibody 15497, however, showed usual antigen binding behavior, revealing local changes presumably including the binding site. These findings illustrate an unusual antibody effect on an …

Applications Of Implementation Science Frameworks, Models And Theories In Disparities-Focused Cancer Screening Interventions: A Scoping Review Protocol, Serena Xiong, Lisa Klesges, Michelle Doering, Rebekah J Pratt

2020-Current year OA Pubs

BACKGROUND: Implementation science (IS) frameworks, models and theories (FMTs) have gained popularity in guiding the implementation and evaluation of evidence-based interventions (EBIs) for cancer screening. However, there are significant research gaps in understanding their applications in cancer health disparities contexts. This paper outlines a scoping review protocol designed to explore the utilisation of IS FMTs in cancer screening EBIs to inform intervention designs and adaptations.

METHODS AND ANALYSIS: This scoping review protocol adheres to Arksey and O'Malley's five-step methodological framework for conducting scoping studies. Search strategies were conducted in five bibliographic databases: Ovid MEDLINE, PubMed, Scopus, Web of Science and …

Reproductive Decision Making In Women With Medical Comorbidities: A Qualitative Study, Elena M Kraus, Niraj R Chavan, Victoria Whelan, Jennifer Goldkamp, James M Dubois

2020-Current year OA Pubs

BACKGROUND: A growing number of reproductive-age women in the U.S. have chronic medical conditions, increasing their risk of perinatal morbidity and mortality. Still, they experience unintended pregnancies at similar rates to low-risk mothers. We have limited understanding of how these individuals consider decisions about pregnancy and contraceptive use. The purpose of this study was to understand factors that influence reproductive decision-making among pregnant women with chronic medical conditions.

METHODS: We conducted 28 semi-structured interviews with pregnant women with pre-existing medical conditions admitted to a tertiary maternal hospital to examine factors influencing reproductive decision making. Maternal demographic characteristics, medical history, and …

A Drosophila Heart Optical Coherence Microscopy Dataset For Automatic Video Segmentation, Matthew Fishman, Abigail Matt, Fei Wang, Elena Gracheva, Jiantao Zhu, Xiangping Ouyang, Andrey Komarov, Yuxuan Wang, Hongwu Liang, Chao Zhou

2020-Current year OA Pubs

The heart of the fruit fly, Drosophila melanogaster, is a particularly suitable model for cardiac studies. Optical coherence microscopy (OCM) captures in vivo cross-sectional videos of the beating Drosophila heart for cardiac function quantification. To analyze those large-size multi-frame OCM recordings, human labelling has been employed, leading to low efficiency and poor reproducibility. Here, we introduce a robust and accurate automated Drosophila heart segmentation algorithm, called FlyNet 2.0+, which utilizes a long short-term memory (LSTM) convolutional neural network to leverage time series information in the videos, ensuring consistent, high-quality segmentation. We present a dataset of 213 Drosophila heart videos, equivalent …

Proteogenomic Analysis Reveals Cytoplasmic Sequestration Of Runx1 By The Acute Myeloid Leukemia-Initiating Cbfb::Myh11 Oncofusion Protein, Ryan B. Day, Julia A. Hickman, Ziheng Xu, Casey Ds Katerndahl, Francesca Ferraro, Sai Makund Ramakrishnan, Petra Erdmann-Gilmore, Robert W. Sprung, Yiling Mi, R. Reid Townsend, Christopher A. Miller, Timothy J. Ley

2020-Current year OA Pubs

Several canonical translocations produce oncofusion genes that can initiate acute myeloid leukemia (AML). Although each translocation is associated with unique features, the mechanisms responsible remain unclear. While proteins interacting with each oncofusion are known to be relevant for how they act, these interactions have not yet been systematically defined. To address this issue in an unbiased fashion, we fused a promiscuous biotin ligase (TurboID) in-frame with 3 favorable-risk AML oncofusion cDNAs (PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11) and identified their interacting proteins in primary murine hematopoietic cells. The PML::RARA- and RUNX1::RUNX1T1-TurboID fusion proteins labeled common and unique nuclear repressor complexes, implying their …

Preconception Counseling In A Patient With A Mechanical Aortic Valve And Recent Ischemic Stroke, Kristen E Wong, Alan C Braverman, Tsuyoshi Kaneko, Alan Zajarias, Amanda K Verma

2020-Current year OA Pubs

A 31-year-old woman with a mechanical aortic valve for congenital aortic stenosis presented to the cardiology clinic for preconception counseling. After experiencing an acute stroke 4 weeks prior, she was subsequently discovered to have prosthetic valve thrombosis requiring replacement of the aortic valve. We discuss her clinical course and preconception considerations.

Role Of Sex In The Association Of Socioeconomic Status With Cardiovascular Health In Black Americans: The Jackson Heart Study, Joshua J Joseph, Amaris Williams, Rosevine A Azap, Songzhu Zhao, Guy Brock, David Kline, James B Odei, Randi Foraker, Mario Sims, Laprincess C Brewer, Darrell M Gray Ii, Timiya S Nolan

2020-Current year OA Pubs

BACKGROUND: Socioeconomic status (SES) is associated with cardiovascular health (CVH). Potential differences by sex in this association remain incompletely understood in Black Americans, where SES disparities are posited to be partially responsible for cardiovascular inequities. The association of SES measures (income, education, occupation, and insurance) with CVH scores was examined in the Jackson Heart Study.

METHODS AND RESULTS: American Heart Association CVH components (non-high-density-lipoprotein cholesterol, blood pressure, diet, tobacco use, physical activity, sleep, glycemia, and body mass index) were scored cross-sectionally at baseline (scale: 0-100). Differences in CVH and 95% CIs (Estimate, 95% CI) were calculated using linear regression, adjusting …

Dna Methylation-Mediated Rbpjk Suppression Protects Against Fracture Nonunion Caused By Systemic Inflammation, Ding Xiao, Liang Fang, Zhongting Liu, Yonghua He, Jun Ying, Haocheng Qin, Aiwu Lu, Meng Shi, Tiandao Li, Bo Zhang, Jianjun Guan, Cuicui Wang, Yousef Abu-Amer, Jie Shen

2020-Current year OA Pubs

Challenging skeletal repairs are frequently seen in patients experiencing systemic inflammation. To tackle the complexity and heterogeneity of the skeletal repair process, we performed single-cell RNA sequencing and revealed that progenitor cells were one of the major lineages responsive to elevated inflammation and this response adversely affected progenitor differentiation by upregulation of Rbpjk in fracture nonunion. We then validated the interplay between inflammation (via constitutive activation of Ikk2, Ikk2ca) and Rbpjk specifically in progenitors by using genetic animal models. Focusing on epigenetic regulation, we identified Rbpjk as a direct target of Dnmt3b. Mechanistically, inflammation decreased Dnmt3b expression in progenitor cells, …

Older Adults' And Caregivers' Perceptions About Urinary Tract Infection And Asymptomatic Bacteriuria Guidelines: A Qualitative Exploration, Michael J Durkin, Viktoria Schmitz, Kevin Hsueh, Zoe Troubh, Mary C Politi

2020-Current year OA Pubs

OBJECTIVE: To explore older adults' and caregivers' knowledge and perceptions of guidelines for appropriate antibiotics use for bacteria in the urine.

DESIGN: Semi-structured qualitative interviews.

SETTING: Infectious disease clinics, community senior living facilities, memory care clinics, and general public.

PARTICIPANTS: Patients 65 years or older diagnosed with a urinary tract infection (UTI) in the past two years, or caregivers of such patients.

METHODS: We conducted interviews between March and July 2023. We developed an interview guide based on the COM-B (capability, opportunity, motivation-behavior) behavior change framework. We thematically analyzed written transcripts of audio-recorded interviews using inductive and deductive coding techniques. …

Transient Receptor Potential Vanilloid 4-Dependent Microglial Function In Myelin Injury And Repair, Jameson P Holloman, Sophia H Dimas, Angela S Archambault, Fabia Filipello, Lixia Du, Jing Feng, Yonghui Zhao, Bryan Bollman, Laura Piccio, Andrew J Steelman, Hongzhen Hu, Gregory F Wu

2020-Current year OA Pubs

Microglia are found pathologically at all stages of multiple sclerosis (MS) lesion development and are hypothesized to contribute to both inflammatory injury and neuroprotection in the MS brain. Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed, play an important role as environmental sensors, and are involved in calcium homeostasis for a variety of cells. TRPV4 modulates myeloid cell phagocytosis in the periphery and microglial motility in the central nervous system. We hypothesized that TRPV4 deletion would alter microglia phagocytosis in vitro and lessen disease activity and demyelination in experimental autoimmune encephalitis (EAE) and cuprizone-induced demyelination. We found that …

Prevalence, Characteristics, And Correlates Of Probable Avoidant/Restrictive Food Intake Disorder Among Adult Respondents To The National Eating Disorders Association Online Screen: A Cross-Sectional Study, Laura D'Adamo, Lauren Smolar, Katherine N Balantekin, C Barr Taylor, Denise E Wilfley, Ellen E Fitzsimmons-Craft

2020-Current year OA Pubs

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is a serious, albeit under-researched, feeding or eating disorder. This exploratory study utilized data from adult respondents to the National Eating Disorders Association online eating disorder screen to validate items assessing the presence of ARFID and examine the prevalence, clinical characteristics, and correlates of a positive ARFID screen.

METHODS: Among 50,082 adult screen respondents between January 2022 and January 2023, the prevalence of a positive ARFID screen was calculated. Chi-square tests and t-tests compared demographics, eating disorder attitudes and behaviors, suicidal ideation, current eating disorder treatment status, and eating disorder treatment-seeking intentions between respondents …

Predicting Cognitive Dysfunction And Regional Hubs Using Braak Staging Amyloid-Beta Biomarkers And Machine Learning, Puskar Bhattarai, Ahmed Taha, Bhavin Soni, Deepa S Thakuri, Erin Ritter, Ganesh B Chand

2020-Current year OA Pubs

Mild cognitive impairment (MCI) is a transitional stage between normal aging and early Alzheimer's disease (AD). The presence of extracellular amyloid-beta (Aβ) in Braak regions suggests a connection with cognitive dysfunction in MCI/AD. Investigating the multivariate predictive relationships between regional Aβ biomarkers and cognitive function can aid in the early detection and prevention of AD. We introduced machine learning approaches to estimate cognitive dysfunction from regional Aβ biomarkers and identify the Aβ-related dominant brain regions involved with cognitive impairment. We employed Aβ biomarkers and cognitive measurements from the same individuals to train support vector regression (SVR) and artificial neural network …

Tattoo-Associated Lacrimal Gland Enlargement And Sarcoidosis, Amritha Devi Kanakamedala, Robi N Maamari, Steven M Couch

2020-Current year OA Pubs

PURPOSE: To describe a case of tattoo-associated sarcoidosis presenting with cutaneous findings of tattoo granulomas and ophthalmic manifestation of isolated bilateral lacrimal gland enlargement.

OBSERVATIONS: A 35-year-old female presented with bilateral upper eyelid swelling for over a year. She reported no associated episodes of ocular pain or visual decline since onset of eyelid edema. On examination, the lacrimal glands were firm and enlarged bilaterally. Slit-lamp examination demonstrated no evidence of active or prior ocular inflammation. Further systemic examination revealed multiple raised papules within a 4-year-old chest/shoulder tattoo. Histopathology from a lacrimal gland biopsy showed non-caseating granulomas consistent with sarcoidosis.

CONCLUSIONS …

Normalization Of Drug And Therapeutic Concepts With Thera-Py, Matthew Cannon, James Stevenson, Kori Kuzma, Susanna Kiwala, Jeremy L Warner, Obi L Griffith, Malachi Griffith, Alex H Wagner

2020-Current year OA Pubs

OBJECTIVE: The diversity of nomenclature and naming strategies makes therapeutic terminology difficult to manage and harmonize. As the number and complexity of available therapeutic ontologies continues to increase, the need for harmonized cross-resource mappings is becoming increasingly apparent. This study creates harmonized concept mappings that enable the linking together of like-concepts despite source-dependent differences in data structure or semantic representation.

MATERIALS AND METHODS: For this study, we created Thera-Py, a Python package and web API that constructs searchable concepts for drugs and therapeutic terminologies using 9 public resources and thesauri. By using a directed graph approach, Thera-Py captures commonly used …

The Inorganic Nitrate And Exercise Performance In Heart Failure (Inix-Hf) Phase Ii Clinical Trial: Rationale And Study Design, Andrew R Coggan, Lauren K Park, Susan B Racette, Victor G Davila-Roman, Pattie Lenzen, Kathryn Vehe, Peter M Dore, Kenneth B Schechtman, Linda R Peterson

2020-Current year OA Pubs

BACKGROUND: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF).

METHODS: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO

DISCUSSION: The iNIX-HF phase …

Low Grade Endometrial Stromal Sarcoma In Pregnancy: A Case In Support Of Safe Abortion Access, Rachel L. Furuya, David L. Eisenberg, Diana L. Gray, Vincent M. Mellnick, Premal H. Thaker

2020-Current year OA Pubs

No abstract provided.

Diroximel Fumarate In Patients With Relapsing-Remitting Multiple Sclerosis: Final Safety And Efficacy Results From The Phase 3 Evolve-Ms-1 Study, Barry A Singer, Robert T Naismith, Et Al.

2020-Current year OA Pubs

BACKGROUND: Diroximel fumarate (DRF) is approved for adults with relapsing-remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF.

OBJECTIVE: To report final outcomes from EVOLVE-MS-1.

METHODS: EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory.

RESULTS: Overall, 75.7% (800/1057) of patients completed the study; median …

Progressive, Edematous Plaques, Mild Pancytopenia, And Inflammation, Leigh A Compton, Heather A Jones, Connor A Vinyard, Yi-Shan Lee, Matthew J Walter, Christine C Yokoyama

2020-Current year OA Pubs

No abstract provided.

Blockade Of Il-6r Prevents Preterm Birth And Adverse Neonatal Outcomes, Marcelo Farias-Jofre, Valeria Garcia-Flores, Nardhy Gomez-Lopez, Et Al.

2020-Current year OA Pubs

BACKGROUND: Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.

METHODS: Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α. The blockade of IL-6R by using an aIL-6R was tested as prenatal treatment for preterm birth and adverse neonatal outcomes. QUEST-MRI evaluated brain oxidative stress in utero. Targeted transcriptomic profiling assessed maternal, foetal, and neonatal inflammation. Neonatal biometrics and neurodevelopment …

Optimized Strategy For Real-Time Qpcr Detection Of Onchocerca Volvulus Dna In Pooled Simulium Sp. Blackfly Vectors, Mary Doherty, Peter U. Fischer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, …