Digital Commons Network^™

Benzodiazepine Receipt In Adults With Psychogenic Non-Epileptic Seizures In The Usa, Kevin Young Xu, Fábio A Nascimento, Binx Yezhe Lin, Tae Woo Park, Donovan T Maust, Hillary Samples, Greta A Bushnell

2020-Current year OA Pubs

BACKGROUND: Characterising benzodiazepine (BZD) prescribing to individuals with psychogenic non-epileptic seizures (PNES) is important for optimising PNES outcomes, but existing data is lacking.

METHODS: Using a nationwide administrative claims database (2016-2022), incident PNES was defined as an International classification of diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis in an inpatient or outpatient healthcare encounter after a 1-year period with no documented diagnosis. We described clinical characteristics of adults with incident PNES and estimated the prevalence of outpatient BZD treatment in the baseline year and 30-day follow-up period, with secondary analyses stratifying by baseline ES, anxiety and/or insomnia diagnoses, representing common …

Design Of A Tool Capable Of Assessing Environmental Sociocultural Physical Factors Influencing Women's Decisions On When And Where To Toilet Within Real-World Settings: Protocol For The Build And Usability Testing Of A Mobile App For Use By Community-Dwelling Women, Janis M Miller, Jean F Wyman, Lawrence An, Haitao Chu, Cynthia S Fok, Missy Lavender, Cora Elizabeth Lewis, Alayne D Markland, Leslie M Rickey, Ying Sheng, Siobhan Sutcliffe, Lisa Kane Low, Elizabeth R Mueller

2020-Current year OA Pubs

BACKGROUND: Although surveys and apps are available for women to report urination and bladder symptoms, they do not include their decisions regarding toileting. Real-world factors can interfere with toileting decisions, which may then influence bladder health. This premise lacks data per want of a robust data collection tool.

OBJECTIVE: The Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium engaged a transdisciplinary team to build and test WhereIGo, a mobile data collection app for Android and iOS. The design goal was a comprehensive reporting system for capturing environmental, sociocultural, and physical factors that influence women's decisions for toileting. Aims include …

Host-Derived Ceacam-Laden Vesicles Engage Enterotoxigenic Escherichia Coli For Elimination And Toxin Neutralization, Alaullah Sheikh, Debayan Ganguli, Tim J Vickers, Marjahan Akhtar, Nazia Khatoon, Bipul Setu, Supratim Basu, Wandy L Beatty, James M Fleckenstein, Et Al.

2020-Current year OA Pubs

Enterotoxigenic

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 …

Myotube Guidance: Shaping Up The Musculoskeletal System, Aaron N Johnson

2020-Current year OA Pubs

Myofibers are highly specialized contractile cells of skeletal muscles, and dysregulation of myofiber morphogenesis is emerging as a contributing cause of myopathies and structural birth defects. Myotubes are the myofiber precursors and undergo a dramatic morphological transition into long bipolar myofibers that are attached to tendons on two ends. Similar to axon growth cones, myotube leading edges navigate toward target cells and form cell-cell connections. The process of myotube guidance connects myotubes with the correct tendons, orients myofiber morphology with the overall body plan, and generates a functional musculoskeletal system. Navigational signaling, addition of mass and volume, and identification of …

Adamts12 Promotes Fibrosis By Restructuring Extracellular Matrix To Enable Activation Of Injury-Responsive Fibroblasts, Konrad Hoeft, Benjamin D. Humphreys, Et Al.

2020-Current year OA Pubs

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. …

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 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 …

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 …

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 …

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 …

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 …

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 …

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

UNLABELLED:

IMPORTANCE:

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 …

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

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.

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 = …

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 …

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/

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 …

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 …

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

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.

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

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 …