Medicine and Health Sciences Commons^™

Clinical-Transcriptional Prioritization Of The Circulating Proteome In Human Heart Failure, Andrew S Perry, Junedh Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human "ome" and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified …

Mapping Health-Related Quality Of Life Of Children And Families Receiving Pediatric Invasive Home Mechanical Ventilation: A Scoping Review Protocol, Keisha White Makinde, Maysara Mitchell, Alexandra F Merz, Michael Youssef

2020-Current year OA Pubs

BACKGROUND: Children utilizing invasive home mechanical ventilation (administered via tracheostomy tube) receive intensive care at home without the support of trained staff typically present in an intensive care unit; within the context of worsening home nursing shortages, much of the 24/7 care burden falls to families which are likely under supported. Prior reviews have explored the quality of life of children receiving various forms of mechanical ventilation, without addressing the impact on the family. Additionally, the literature inconsistently differentiates the unique experience of families with children using invasive home mechanical ventilation from non-invasive, which has lower morbidity and mortality and …

A Qualitative Exploration Of Disseminating Research Findings Among Public Health Researchers In China, Yiluan Hu, Xuejun Yin, Yachen Wang, Enying Gong, Xin Xin, Jing Liu, Xia Liu, Ruitai Shao, Juan Zhang, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Research dissemination is essential to accelerate the translating of evidence into practice. Little is known about dissemination among Chinese public health researchers. This study aimed to explore the understanding and practices of disseminating research findings and to identify barriers and facilitators that influence dissemination activities to non-research audiences.

METHODS: This study deployed an exploratory qualitative design with purposive and snowball sampling. One focus group with 5 participants and 12 in-depth interviews were conducted with participants working in diverse fields from universities (n = 10), the National Chinese Center for Disease Control and Prevention (n = 4), the Chinese National …

A Research Agenda To Advance The Study Of Implementation Mechanisms, Cara C Lewis, Hannah E Frank, Gracelyn Cruden, Bo Kim, Aubyn C Stahmer, Aaron R Lyon, Bianca Albers, Gregory A Aarons, Rinad S Beidas, Brian S Mittman, Bryan J Weiner, Nate J Williams, Byron J Powell, Mnoe Group

2020-Current year OA Pubs

BACKGROUND: Implementation science scholars have made significant progress identifying factors that enable or obstruct the implementation of evidence-based interventions, and testing strategies that may modify those factors. However, little research sheds light on how or why strategies work, in what contexts, and for whom. Studying implementation mechanisms-the processes responsible for change-is crucial for advancing the field of implementation science and enhancing its value in facilitating equitable policy and practice change. The Agency for Healthcare Research and Quality funded a conference series to achieve two aims: (1) develop a research agenda on implementation mechanisms, and (2) actively disseminate the research agenda …

Refining, Implementing, And Evaluating An Anesthesia Choice Conversation Aid For Older Adults With Hip Fracture: Protocol For A Stepped Wedge Cluster Randomized Trial, Eliana C Goldstein, Mary C Politi, James H Baraldi, Glyn Elwyn, Hugo Campos, Rui Feng, Samir Mehta, Karah Whatley, Viktoria Schmitz, Mark D Neuman

2020-Current year OA Pubs

BACKGROUND: Hip fracture surgery under general or spinal anesthesia is a common procedure for older adults in the United States (US). Although spinal or general anesthesia can be appropriate for many patients, and the choice between anesthesia types is preference-sensitive, shared decision-making is not consistently used by anesthesiologists counseling patients on anesthesia for this procedure. We designed an Option Grid™-style conversation aid, My Anesthesia Choice─Hip Fracture, to promote shared decision making in this interaction. This study will refine the aid and evaluate its implementation and effectiveness in clinical practice.

METHODS: The study will be conducted over 2 phases: qualitative interviews …

Recent Advancements In Cell-Based Therapies In Melanoma, George Nassief, Angela Anaeme, Karen Moussa, Abdallah N Mansour, George Ansstas

2020-Current year OA Pubs

Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that address this gap in treatment options. Cell-based therapies have gained wide attention as a therapeutic option that could address this gap in treatment options for advanced melanoma. These therapies work by extracting certain cell types produced in the human body such as T-cells, modifying them based on a specific target, and transfusing them back into the patient. …

Use Of Guideline-Recommended Heart Failure Drugs In High-, Middle-, And Low-Income Countries: A Systematic Review And Meta-Analysis, Gautam Satheesh, Rupasvi Dhurjati, Laura Alston, Fisaha Tesfay, Rashmi Pant, Ehete Bahiru, Claudia Bambs, Anubha Agarwal, Sanne A E Peters, Abdul Salam, Isabelle Johansson

2020-Current year OA Pubs

Optimal use of guideline-directed medical therapy (GDMT) can prevent hospitalization and mortality among patients with heart failure (HF). We aimed to assess the prevalence of GDMT use for HF across geographic regions and country-income levels. We systematically reviewed observational studies (published between January 2010 and October 2020) involving patients with HF with reduced ejection fraction. We conducted random-effects meta-analyses to obtain summary estimates. We included 334 studies comprising 1,507,849 patients (31% female). The majority (82%) of studies were from high-income countries, with Europe (45%) and the Americas (33%) being the most represented regions, and Africa (1%) being the least. Overall …

Prenatal Environment Is Associated With The Pace Of Cortical Network Development Over The First Three Years Of Life, Ursula A Tooley, Aidan Latham, Jeanette K Kenley, Dimitrios Alexopoulos, Tara A Smyser, Ashley N Nielsen, Lisa Gorham, Barbara B Warner, Joshua S Shimony, Jeffrey J Neil, Joan L Luby, Deanna M Barch, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Environmental influences on brain structure and function during early development have been well-characterized, but whether early environments are associated with the pace of brain development is not clear. In pre-registered analyses, we use flexible non-linear models to test the theory that prenatal disadvantage is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal disadvantage was assessed using a latent factor of socioeconomic disadvantage that included measures of mother's income-to-needs ratio, educational attainment, area deprivation index, insurance status, and nutrition. We find that prenatal disadvantage is associated with developmental increases in …

Diagnostic Utility Of Brain Mri Volumetry In Comparing Traumatic Brain Injury, Alzheimer Disease And Behavioral Variant Frontotemporal Dementia, Cyrus A Raji, Somayeh Meysami, Verna R Porter, David A Merrill, Mario F Mendez

2020-Current year OA Pubs

BACKGROUND: Brain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments.

OBJECTIVE: To investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD).

METHOD: We utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes …

Constitutive Upregulation Of Transcription Factors Underlies Permissive Bradyzoite Differentiation In A Natural Isolate Of Toxoplasma Gondii, Jing Xia, Yong Fu, Wanyi Huang, Taher Uddin, L David Sibley

2020-Current year OA Pubs

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Adverse Cardiovascular And Kidney Outcomes In People With Sars-Cov-2 Treated With Sglt2 Inhibitors, Taeyoung Choi, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

BACKGROUND: Whether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear.

METHODS: We used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)-a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)-a composite of death, eGFR decline > 50%, and …

Conditioning With Anti-Cd47 And Anti-Cd117 Plus Jak Inhibition Enables Toxic Payload-Free Allogeneic Transplantation, Stephen P Persaud, Aditya R Yelamali, Julie K Ritchey, John F Dipersio

2020-Current year OA Pubs

No abstract provided.

Variants In Lrrc7 Lead To Intellectual Disability, Autism, Aggression And Abnormal Eating Behaviors, Jana Willim, Weimin Yuan, Anika Lindsey, Omar Itani, Gary A Silverman, Stephen C Pak, Tim Schedl, Et Al.

2020-Current year OA Pubs

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca

Gestational Diabetes Knowledge Improves With Interactive Online Training Modules, Petra Krutilova, Roxann Williams, Rebecca Morey, Carole Field, Veronda Byrth, Melissa Tepe, Amy Mcqueen, Cynthia Herrick

2020-Current year OA Pubs

BACKGROUND: The risk of developing type 2 diabetes mellitus (T2DM) is up to 50% among women with gestational diabetes mellitus (GDM). However, diabetes education during and after pregnancy is limited. To bridge this gap, our team developed four training modules on GDM for nurses and community health workers. This pilot study assesses changes in knowledge, self-efficacy for providing diabetes education, attitudes, and intentions to recommend diabetes prevention before and after training completion.

METHODS: Interactive online modules were disseminated to clinical staff providing care for women with GDM in the United States. Optional pre- and post-training surveys were conducted to gauge …

Smoking And Alcohol By Hpv Status In Head And Neck Cancer: A Mendelian Randomization Study, Abhinav Thakral, Laura Bierut, Et Al.

2020-Current year OA Pubs

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = …

Novel Cyclic Homogeneous Oscillation Detection Method For High Accuracy And Specific Characterization Of Neural Dynamics, Hohyun Cho, Markus Adamek, Jon T Willie, Peter Brunner

2020-Current year OA Pubs

Determining the presence and frequency of neural oscillations is essential to understanding dynamic brain function. Traditional methods that detect peaks over 1/

Menopausal Hormone Therapy Use Among Postmenopausal Women, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Menopausal hormone therapy (MHT) is the treatment of choice for symptoms of menopause. However, its adoption is hindered by the risk-benefit trade-off in relation to acute and chronic diseases.

OBJECTIVE: To evaluate trends in and correlates of MHT use among postmenopausal women in the US from 1999 to March 2020.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional analysis of MHT use used data from the nationally representative National Health and Nutrition Examination Survey (NHANES). Participants included noninstitutionalized US postmenopausal women from 10 NHANES study cycles (1999-2000 to 2017-March 2020 [pre-COVID-19 pandemic]). Data were analyzed from December 2023 to April …

Stat3-Mediated Atg7 Expression Regulates Anti-Tumor Immunity In Mouse Melanoma, Sarah M Zimmerman, Erin Suh, Sofia R Smith, George P Souroullas

2020-Current year OA Pubs

Epigenetic modifications to DNA and chromatin control oncogenic and tumor-suppressive mechanisms in melanoma. Ezh2, the catalytic component of the Polycomb Repressive Complex 2 (PRC2), which mediates methylation of lysine 27 on histone 3 (H3K27me3), can regulate both melanoma initiation and progression. We previously found that mutant Ezh2

Regional Desynchronization Of Microglial Activity Is Associated With Cognitive Decline In Alzheimer's Disease, Artem Zatcepin, Samira Parhizkar, Et Al.

2020-Current year OA Pubs

BACKGROUND: Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker.

METHODS: To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia …

Efficacy Of Parp Inhibitor Therapy After Targeted Braf/Mek Failure In Advanced Melanoma, Jordan Phillipps, George Nassief, Renee Morecroft, Tolulope Adeyelu, Andrew Elliott, Farah Abdulla, Ari Vanderwalde, Soo Park, Omar Butt, Alice Zhou, George Ansstas

2020-Current year OA Pubs

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option …

Adjunctive Intravenous Argatroban Or Eptifibatide For Ischemic Stroke, Opeolu Adeoye, Peter Panagos, Stephanie Pizzella, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.

METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with …

A Genetic Screen In Drosophila Uncovers A Role For Senseless-2 In Surface Glia In The Peripheral Nervous System To Regulate Cns Morphology, Haluk Lacin, Yuqing Zhu, Jose T Dipaola, Beth A Wilson, Yi Zhu, James B Skeath

2020-Current year OA Pubs

Despite increasing in mass approximately 100-fold during larval life, the Drosophila CNS maintains its characteristic form. Dynamic interactions between the overlying basement membrane and underlying surface glia are known to regulate CNS structure in Drosophila, but the genes and pathways that establish and maintain CNS morphology during development remain poorly characterized. To identify genes that regulate CNS shape in Drosophila, we conducted an EMS-based, forward genetic screen of the second chromosome, uncovered 50 mutations that disrupt CNS structure, and mapped these alleles to 17 genes. Analysis of whole genome sequencing data wedded to genetic studies uncovered the affected gene for …

Left Coronary Artery Compression And Stent Fracture Following Self-Expanding Transcatheter Pulmonary Valve Implantation, Jeannette Wong-Siegel, Adam Naylor, David Balzer

2020-Current year OA Pubs

Coronary compression and vascular perforation have not been reported for self-expanding transcatheter pulmonary valves. We describe a patient with tetralogy of Fallot after self-expanding valve implantation who developed left coronary artery compression from the valve. In addition, a wire frame fracture resulted in perforation of the aorta.

Diurnal Rhythms In Varicella Vaccine Effectiveness, Dana Danino, Yoav Kalron, Jeffrey A. Haspel, Guy Hazan

2020-Current year OA Pubs

BACKGROUNDImmune processes are influenced by circadian rhythms. We evaluate the association between varicella vaccine administration time of day and vaccine effectiveness.METHODSA national cohort, children younger than 6 years, were enrolled between January 2002 and December 2023. We compared children vaccinated during morning (7:00-10:59), late morning to afternoon (11:00-15:59), or evening hours (16:00-19:59). A Cox proportional hazards regression model was used to adjust for ethnicity, sex, and comorbidities. The first varicella infection occurring at least 14 days after vaccination and a second dose administration were treated as terminal events.RESULTSOf 251,141 vaccinated children, 4,501 (1.8%) experienced breakthrough infections. Infection rates differed based …

Proteomic Correlates And Prognostic Significance Of Kidney Injury In Heart Failure With Preserved Ejection Fraction, Oday Salman, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear.

METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death …

Use Of Palliative Care Among Adults With Newly Diagnosed Heart Failure: Insights From A Us National Insured Patient Sample, Zidong Zhang, Divya S Subramaniam, Steven W Howard, Kenton J Johnston, William H Frick, Kimberly Enard, Leslie Hinyard

2020-Current year OA Pubs

BACKGROUND: Despite the known benefits for individuals with heart failure (HF), incomplete data suggest a low use of palliative care (PC) for HF in the United States. We aimed to investigate the national PC use for adults with HF by determining when they received their first PC consultation (PCC) and the associations with clinical factors following diagnosis of HF.

METHODS AND RESULTS: We conducted a retrospective cohort study in a national all-payer electronic health record database to identify adults (aged ≥18 years) with newly diagnosed HF between 2011 and 2018. The proportion of those who received PCC within 5 years …

Concurrent Ependymal And Ganglionic Differentiation In A Subset Of Supratentorial Neuroepithelial Tumors With Ewsr1-Plagl1 Rearrangement, Julieann C Lee, Sonika Dahiya, Kaleigh Roberts, Et Al.

2020-Current year OA Pubs

Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, …

Targeting Akr1b10 By Drug Repurposing With Epalrestat Overcomes Chemoresistance In Non-Small Cell Lung Cancer Patient-Derived Tumor Organoids, Kanve N Suvilesh, Yariswamy Manjunath, Yulia I Nussbaum, Mohamed Gadelkarim, Murugesan Raju, Akhil Srivastava, Guangfu Li, Wesley C Warren, Chi-Ren Shyu, Feng Gao, Matthew A Ciorba, Jonathan B Mitchem, Satyanarayana Rachagani, Jussuf T Kaifi

2020-Current year OA Pubs

PURPOSE: Systemic treatments given to patients with non-small cell lung cancer (NSCLC) are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTO) and matched tumor tissues from surgically treated patients with NSCLC to identify drug repurposing targets to overcome resistance toward standard-of-care platinum-based doublet chemotherapy.

EXPERIMENTAL DESIGN: PDTOs were established from 10 prospectively enrolled patients with non-metastatic NSCLC from resected tumors. PDTOs were compared with matched tumor tissues by histopathology/immunohistochemistry, whole exome sequencing, and transcriptome sequencing. PDTO growths and drug responses were determined by measuring 3D tumoroid volumes, cell viability, and proliferation/apoptosis. Differential …

Stabilization Of Interdomain Closure By A G Protein Inhibitor, Tyson D Todd, Neha Vithani, Sukrit Singh, Gregory R Bowman, Kendall J Blumer, Andrea Soranno

2020-Current year OA Pubs

Inhibitors of heterotrimeric G proteins are being developed as therapeutic agents. Epitomizing this approach are YM-254890 (YM) and FR900359 (FR), which are efficacious in models of thrombosis, hypertension, obesity, asthma, uveal melanoma, and pain, and under investigation as an FR-antibody conjugate in uveal melanoma clinical trials. YM/FR inhibits the Gq/11/14 subfamily by interfering with GDP (guanosine diphosphate) release, but by an unknown biophysical mechanism. Here, we show that YM inhibits GDP release by stabilizing closure between the Ras-like and α-helical domains of a Gα subunit. Nucleotide-free Gα adopts an ensemble of open and closed configurations, as indicated by single-molecule Förster …

Hierarchical Tricarboxylic Acid Cycle Regulation By Hepatocyte Arginase 2 Links The Urea Cycle To Oxidative Metabolism, Yiming Zhang, Cassandra B Higgins, Stefani Tica, Joshua A Adams, Jiameng Sun, Shannon C Kelly, Xiaoyu Zong, Dennis J Dietzen, Terri Pietka, Samuel J Ballentine, Leah P Shriver, Gary J Patti, Yin Cao, Brian J Debosch

2020-Current year OA Pubs

Urea cycle impairment and its relationship to obesity and inflammation remained elusive, partly due to the dramatic clinical presentation of classical urea cycle defects. We generated mice with hepatocyte-specific arginase 2 deletion (Arg2