Medicine and Health Sciences Commons^™

Identifying The Neurophysiological Effects Of Memory-Enhancing Amygdala Stimulation Using Interpretable Machine Learning, Mohammad S E Sendi, Cory S Inman, Kelly R Bijanki, Lou Blanpain, James K Park, Stephan Hamann, Robert E Gross, Jon T Willie, Babak Mahmoudi

2020-Current year OA Pubs

BACKGROUND: Direct electrical stimulation of the amygdala can enhance declarative memory for specific events. An unanswered question is what underlying neurophysiological changes are induced by amygdala stimulation.

OBJECTIVE: To leverage interpretable machine learning to identify the neurophysiological processes underlying amygdala-mediated memory, and to develop more efficient neuromodulation technologies.

METHOD: Patients with treatment-resistant epilepsy and depth electrodes placed in the hippocampus and amygdala performed a recognition memory task for neutral images of objects. During the encoding phase, 160 images were shown to patients. Half of the images were followed by brief low-amplitude amygdala stimulation. For local field potentials (LFPs) recorded from …

Implementing Stereotactic Accelerated Partial Breast Irradiation Using Magnetic Resonance Guided Radiation Therapy, Alex T Price, William R Kennedy, Lauren E Henke, Sean R Brown, Olga L Green, Maria A Thomas, John Ginn, Imran Zoberi

2020-Current year OA Pubs

INTRODUCTION: Accelerated partial breast irradiation (APBI) seeks to reduce irradiated volumes and radiation exposure for patients while maintaining acceptable clinical outcomes. Magnetic resonance image-guided radiotherapy (MRgRT) provides excellent soft-tissue contrast for treatment localization, which can reduce setup uncertainty, thus reducing margins in the external beam setting. Additionally, stereotactic body radiotherapy (SBRT)-style regimens with high gradients can also be executed. This MR-guided stereotactic APBI (MRgS-APBI) approach can be utilized for a lower number of fractions and spare a greater volume of healthy tissues compared to conventional 3D external beam APBI.

METHODS: Our MRgS-APBI program was developed for two prospective non-randomized phase …

Oncogenic Kras-Induced Feedback Inflammatory Signaling In Pancreatic Cancer: An Overview And New Therapeutic Opportunities, Sapana Bansod, Paarth B Dodhiawala, Kian-Huat Lim

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) remains highly refractory to treatment. While the

Biotechnological Applications Of Polymeric Nanofiber Platforms Loaded With Diverse Bioactive Materials, M R El-Aassar, Omar M Ibrahim, Ziad H Al-Oanzi

2020-Current year OA Pubs

This review article highlights the critical research and formative works relating to nanofiber composites loaded with bioactive materials for diverse applications, and discusses the recent research on the use of electrospun nanofiber incorporating bioactive compounds such as essential oils, herbal bioactive components, plant extracts, and metallic nanoparticles. Inevitably, with the common advantages of bioactive components and polymer nanofibers, electrospun nanofibers containing bioactive components have attracted intense interests for their applications in biomedicine and cancer treatment. Many studies have only concentrated on the production and performance of electrospun nanofiber loaded with bioactive components; in this regard, the features of different types …

Coffee, Tea, And Mammographic Breast Density In Premenopausal Women, Adashi Margaret Odama, Valerie Otti, Shuai Xu, Olamide Adebayo, Adetunji T Toriola

2020-Current year OA Pubs

Studies have investigated the associations of coffee and tea with mammographic breast density (MBD) in premenopausal women with inconsistent results. We analyzed data from 375 premenopausal women who attended a screening mammogram at Washington University School of Medicine, St. Louis, MO in 2016, and stratified the analyses by race (non-Hispanic White (NHW) vs. Black/African American). Participants self-reported the number of servings of coffee, caffeinated tea, and decaffeinated tea they consumed. Volpara software was used to determine volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We used generalized linear regression models to quantify the associations of coffee and …

Factors Associated With Viremia In People Living With Hiv On Antiretroviral Therapy In Guatemala, Dean W Ortíz, Olivia Roberts-Sano, Hugo E Marroquin, Lindsey Larson, Katherine B Franco, Andrej Spec, Johanna R Melendez, Rodolfo Pinzón, Ana J Samayoa, Carlos Mejia-Chew, Jane A O Halloran

2020-Current year OA Pubs

INTRODUCTION: Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala.

METHODS: We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ …

Energy Compensation And Adiposity In Humans, Vincent Careau, Susan B Racette, Et Al.

2020-Current year OA Pubs

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.

Non-Invasive Monitoring Of Arthritis Treatment Response Via Targeting Of Tyrosine-Phosphorylated Annexin A2 In Chondrocytes, Shaw-Wei D Tsen, Luke E Springer, Krishna Sharmah Gautam, Rui Tang, Kexian Liang, Gail Sudlow, Amir Kucharski, Christine T N Pham, Samuel Achilefu

2020-Current year OA Pubs

BACKGROUND: The development and optimization of therapies for rheumatoid arthritis (RA) is currently hindered by a lack of methods for early non-invasive monitoring of treatment response. Annexin A2, an inflammation-associated protein whose presence and phosphorylation levels are upregulated in RA, represents a potential molecular target for tracking RA treatment response.

METHODS: LS301, a near-infrared dye-peptide conjugate that selectively targets tyrosine 23-phosphorylated annexin A2 (pANXA2), was evaluated for its utility in monitoring disease progression, remission, and early response to drug treatment in mouse models of RA by fluorescence imaging. The intraarticular distribution and localization of LS301 relative to pANXA2 was determined …

Understanding The Groups Of Care Transition Strategies Used By U.S. Hospitals: An Application Of Factor Analytic And Latent Class Methods, Glen Mays, Jing Li, Jessica Miller Clouser, Gaixin Du, Arnold Stromberg, Brian Jack, Huong Q Nguyen, Mark V Williams

2020-Current year OA Pubs

BACKGROUND: After activation of the Hospital Readmission Reduction Program (HRRP) in 2012, hospitals nationwide experimented broadly with the implementation of Transitional Care (TC) strategies to reduce hospital readmissions. Although numerous evidence-based TC models exist, they are often adapted to local contexts, rendering large-scale evaluation difficult. Little systematic evidence exists about prevailing implementation patterns of TC strategies among hospitals, nor which strategies in which combinations are most effective at improving patient outcomes. We aimed to identify and define combinations of TC strategies, or groups of transitional care activities, implemented among a large and diverse cohort of U.S. hospitals, with the ultimate …

Gem: Scalable And Flexible Gene-Environment Interaction Analysis In Millions Of Samples, Kenneth E Westerman, Duy T Pham, Liang Hong, Ye Chen, Magdalena Sevilla-González, Yun Ju Sung, Yan V Sun, Alanna C Morrison, Han Chen, Alisa K Manning

2020-Current year OA Pubs

MOTIVATION: Gene-environment interaction (GEI) studies are a general framework that can be used to identify genetic variants that modify the effects of environmental, physiological, lifestyle or treatment effects on complex traits. Moreover, accounting for GEIs can enhance our understanding of the genetic architecture of complex diseases and traits. However, commonly used statistical software programs for GEI studies are either not applicable to testing certain types of GEI hypotheses or have not been optimized for use in large samples.

RESULTS: Here, we develop a new software program, GEM (Gene-Environment interaction analysis in Millions of samples), which supports the inclusion of multiple …

Adaptable P Body Physical States Differentially Regulate Bicoid Mrna Storage During Early Drosophila Development, M Sankaranarayanan, Ryan J Emenecker, Elise L Wilby, Marcus Jahnel, Irmela R E A Trussina, Matt Wayland, Simon Alberti, Alex S Holehouse, Timothy T Weil

2020-Current year OA Pubs

Ribonucleoprotein condensates can exhibit diverse physical states in vitro and in vivo. Despite considerable progress, the relevance of condensate physical states for in vivo biological function remains limited. Here, we investigated the physical properties of processing bodies (P bodies) and their impact on mRNA storage in mature Drosophila oocytes. We show that the conserved DEAD-box RNA helicase Me31B forms viscous P body condensates, which adopt an arrested physical state. We demonstrate that structurally distinct proteins and protein-protein interactions, together with RNA, regulate the physical properties of P bodies. Using live imaging and in situ hybridization, we show that the arrested …

A Rational Approach To Unilateral Neck Rt For Head And Neck Cancers In The Era Of Immunotherapy, Re-I Chin, Joshua P Schiff, Randall J Brenneman, Hiram A Gay, Wade L Thorstad, Alexander J Lin

2020-Current year OA Pubs

Radiotherapy plays an important role in the definitive and adjuvant treatment of head and neck squamous cell carcinoma (HNSCC). However, standard courses of radiation therapy may contribute to the depletion of circulating lymphocytes and potentially attenuate optimal tumor antigen presentation that may be detrimental to the efficacy of novel immunotherapeutic agents. This review explores the advantages of restricting radiation to the primary tumor/tumor bed and ipsilateral elective neck as it pertains to the evolving field of immunotherapy.

Trem2 Modulates Differential Deposition Of Modified And Non-Modified Aβ Species In Extracellular Plaques And Intraneuronal Deposits, Pranav Joshi, Florian Riffel, Sathish Kumar, Nàdia Villacampa, Sandra Theil, Samira Parhizkar, Christian Haass, Marco Colonna, Michael T Heneka, Thomas Arzberger, Jochen Herms, Jochen Walter

2020-Current year OA Pubs

Progressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer's disease (AD). During disease progression, extracellular Aβ plaques undergo specific changes in their composition by the sequential deposition of different modified Aβ species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aβ. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of Aβ could modulate the interaction with TREM2, and the uptake by microglia. Here, we …

Timing Of Antibiotic Therapy In The Icu, Marin H Kollef, Andrew F Shorr, Matteo Bassetti, Jean-Francois Timsit, Scott T Micek, Andrew P Michelson, Jose Garnacho-Montero

2020-Current year OA Pubs

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic …

Cellular Therapy Updates In B-Cell Lymphoma: The State Of The Car-T, Zachary D Crees, Armin Ghobadi

2020-Current year OA Pubs

Non-Hodgkin Lymphoma accounts for >460,000 cases and >240,000 deaths globally and >77,000 cases and >20,000 deaths in the U.S. annually, with ~85% of cases being B-cell malignancies. Until recently, patients with relapsed/refractory B-cell lymphoma following standard chemotherapy in combination with anti-CD20 monoclonal antibodies and autologous stem cell transplantation experienced a median overall survival (OS) of <6 months. However, with the approval of four different CD-19 CAR-T therapies between 2017 and 2021, approximately 60-80% of patients receiving CAR-T therapy now achieve an objective response with >3 years median OS. Here, we review the current state of the art of CD19 CAR-T therapies for B-cell lymphomas, focusing on current updates in US FDA-approved products, along with their associated efficacy and toxicities. Lastly, we highlight a selection of promising clinical developments in …

Untargeted Metabolomic Analysis Of Human Milk From Mothers Of Preterm Infants, Lila S Nolan, Angela N Lewis, Qingqing Gong, James J Sollome, Olivia N Dewitt, Robert D Williams, Misty Good

2020-Current year OA Pubs

The application of metabolomics in neonatology offers an approach to investigate the complex relationship between nutrition and infant health. Characterization of the metabolome of human milk enables an investigation into nutrients that affect the neonatal metabolism and identification of dietary interventions for infants at risk of diseases such as necrotizing enterocolitis (NEC). In this study, we aimed to identify differences in the metabolome of breast milk of 48 mothers with preterm infants with NEC and non-NEC healthy controls. A minimum significant difference was observed in the human milk metabolome between the mothers of infants with NEC and mothers of healthy …

Corrections In The Charmm36 Parametrization Of Chloride Interactions With Proteins, Lipids, And Alkali Cations, And Extension To Other Halide Anions, Esam A Orabi, Tuǧba N Öztürk, Nathan Bernhardt, José D Faraldo-Gómez

2020-Current year OA Pubs

The nonpolarizable CHARMM force field is one of the most widely used energy functions for all-atom biomolecular simulations. Chloride is the only halide ion included in the latest version, CHARMM36m, and is used widely in simulation studies, often as an electrolyte ion but also as the biological substrate of transport proteins and enzymes. Here, we find that existing parameters systematically underestimate the interaction of Cl

Phospho-Ser784-Vcp Drives Resistance Of Pancreatic Ductal Adenocarcinoma To Genotoxic Chemotherapies And Predicts The Chemo-Sensitizing Effect Of Vcp Inhibitor, Faliang Wang, Kiran Vij, Lin Li, Paarth Dodhiawala, Kian-Huat Lim, Jieya Shao

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) patients have a dismal prognosis due in large part to chemotherapy resistance. However, a small subset containing defects in the DNA damage response (DDR) pathways are chemotherapy-sensitive. Identifying intrinsic and therapeutically inducible DDR defects can improve precision and efficacy of chemotherapies for PDAC. DNA repair requires dynamic reorganization of chromatin-associated proteins, which is orchestrated by the AAA+ ATPase VCP. We recently discovered that the DDR function of VCP is selectively activated by Ser

Updates On Wound Infiltration Use For Postoperative Pain Management: A Narrative Review, Dusica M Stamenkovic, Mihailo Bezmarevic, Suzana Bojic, Dragana Unic-Stojanovic, Dejan Stojkovic, Damjan Z Slavkovic, Vladimir Bancevic, Nebojsa Maric, Menelaos Karanikolas

2020-Current year OA Pubs

Local anesthetic wound infiltration (WI) provides anesthesia for minor surgical procedures and improves postoperative analgesia as part of multimodal analgesia after general or regional anesthesia. Although pre-incisional block is preferable, in practice WI is usually done at the end of surgery. WI performed as a continuous modality reduces analgesics, prolongs the duration of analgesia, and enhances the patient's mobilization in some cases. WI benefits are documented in open abdominal surgeries (Caesarean section, colorectal surgery, abdominal hysterectomy, herniorrhaphy), laparoscopic cholecystectomy, oncological breast surgeries, laminectomy, hallux valgus surgery, and radical prostatectomy. Surgical site infiltration requires knowledge of anatomy and the pain origin …

Barriers To Symptom Management Care Pathway Implementation In Pediatric Cancer, L Lee Dupuis, Allison Grimes, Emily Vettese, Lisa M Klesges, Lillian Sung

2020-Current year OA Pubs

BACKGROUND: Objectives were to describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation.

METHODS: We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators prior to randomization to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of …

Naturally Occurring Genetic Variants In The Oxytocin Receptor Alter Receptor Signaling Profiles, Manasi Malik, Michael D Ward, Yingye Fang, Justin R Porter, Maxwell I Zimmerman, Thomas Koelblen, Michelle Roh, Antonina I Frolova, Thomas P Burris, Gregory R Bowman, Princess I Imoukhuede, Sarah K England

2020-Current year OA Pubs

The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor (

Prioritization Of Molecular Targets For Antimalarial Drug Discovery, Barbara Forte, Daniel E Goldberg, Eva S Istvan, Et Al

2020-Current year OA Pubs

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated in

Single-Cell Epigenomics Reveals Mechanisms Of Human Cortical Development, Ryan S Ziffra, Tychele N Turner, Et Al.

2020-Current year OA Pubs

During mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes in the gene regulatory landscape

Patient-Reported Reasons For Stopping Care Or Switching Clinics In Zambia: A Multisite, Regionally Representative Estimate Using A Multistage Sampling-Based Approach In Zambia, Izukanji Sikazwe, Ingrid Eshun-Wilson, Kombatende Sikombe, Laura K Beres, Paul Somwe, Aaloke Mody, Sandra Simbeza, Chama Bukankala, David V Glidden, Lloyd B Mulenga, Nancy Padian, Peter Ehrenkranz, Carolyn Bolton-Moore, Charles B Holmes, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Understanding patient-reported reasons for lapses of retention in human immunodeficiency virus (HIV) treatment can drive improvements in the care cascade. A systematic assessment of outcomes among a random sample of patients lost to follow-up (LTFU) from 32 clinics in Zambia to understand the reasons for silent transfers and disengagement from care was undertaken.

METHODS: We traced a simple random sample of LTFU patients (>90 days from last scheduled visit) as determined from clinic-based electronic medical records from a probability sample of facilities. Among patients found in person, we solicited reasons for either stopping or switching care and predictors …

Epigenetic Dynamics Shaping Melanophore And Iridophore Cell Fate In Zebrafish, Hyo Sik Jang, Yujie Chen, Jiaxin Ge, Alicia N Wilkening, Yiran Hou, Hyung Joo Lee, You Rim Choi, Rebecca F Lowdon, Xiaoyun Xing, Daofeng Li, Charles K Kaufman, Stephen L Johnson, Ting Wang

2020-Current year OA Pubs

BACKGROUND: Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood.

RESULTS: We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and …

The Role Of Community Health Workers In The Surgical Cascade: A Scoping Review, Helen W Li, Michael L Scanlon, Nicholas Kisilu, Debra K Litzelman

2020-Current year OA Pubs

BACKGROUND: Community health workers (CHWs) can increase access to various primary healthcare services; however, their potential for improving surgical care is under-explored. We sought to assess the role of CHWs in the surgical cascade, defined as disease screening, linkage to operative care, and post-operative care. Given the well-described literature on CHWs and screening, we focused on the latter two steps of the surgical cascade.

METHODS: We conducted a scoping review of the peer-reviewed literature. We searched for studies published in any language from January 1, 2000 to May 1, 2020 using electronic literature databases including Pubmed/MEDLINE, Web of Science, SCOPUS, …

Ceftolozane/Tazobactam Probability Of Target Attainment And Outcomes In Participants With Augmented Renal Clearance From The Randomized Phase 3 Aspect-Np Trial, Andrew F Shorr, Christopher J Bruno, Zufei Zhang, Erin Jensen, Wei Gao, Hwa-Ping Feng, Jennifer A Huntington, Brian Yu, Elizabeth G Rhee, Carisa De Anda, Sumit Basu, Marin H Kollef

2020-Current year OA Pubs

BACKGROUND: The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function.

METHODS: Baseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess …

Aces: Analysis Of Conservation With An Extensive List Of Species, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Eleanor I Sams, Tychele N Turner

2020-Current year OA Pubs

MOTIVATION: An abundance of new reference genomes is becoming available through large-scale sequencing efforts. While the reference FASTA for each genome is available, there is currently no automated mechanism to query a specific sequence across all new reference genomes.

RESULTS: We developed ACES (Analysis of Conservation with an Extensive list of Species) as a computational workflow to query specific sequences of interest (e.g., enhancers, promoters, exons) against reference genomes with an available reference FASTA. This automated workflow generates BLAST hits against each of the reference genomes, a multiple sequence alignment file, a graphical fragment assembly file, and a phylogenetic tree …

Impact Of Covid-19 On Gastroenterology Fellowship Training: A Multicenter Analysis Of Endoscopy Volumes, Swathi Paleti, Anas Gremida, Et Al.

2020-Current year OA Pubs

No abstract provided.

Neutralisation Of Sars-Cov-2 Lineage P.1 By Antibodies Elicited Through Natural Sars-Cov-2 Infection Or Vaccination With An Inactivated Sars-Cov-2 Vaccine: An Immunological Study, William M Souza, Michael S Diamond, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response.

METHODS: We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) …