Recent Submissions

  • Far-field optical imaging of surface plasmons with a subdiffraction limited separation

    Xiang, Yifeng; Chen, Junxue; Tang, Xi; Wang, Ruxue; Zhan, Qiwen; Lakowicz, Joseph R.; Zhang, Douguo (De Gruyter Open Ltd, 2020-12-18)
    When an ultrathin silver nanowire with a diameter less than 100 nm is placed on a photonic band gap structure, surface plasmons can be excited and propagate along two side-walls of the silver nanowire. Although the diameter of the silver nanowire is far below the diffraction limit, two bright lines can be clearly observed at the image plane by a standard wide-field optical microscope. Simulations suggest that the two bright lines in the far-field are caused by the unique phase distribution of plasmons on the two side-walls of the silver nanowire. Combining with the sensing ability of surface plasmons to its environment, the configuration reported in this work is capable of functioning as a sensing platform to monitor environmental changes in the near-field region of this ultrathin nanowire.
  • Clinical strategies for optimizing infusion center care through a pandemic

    Hanna, Kirollos S; Segal, Eve M; Barlow, Ashley; Barlow, Brooke (SAGE Publications Inc., 2020-09-25)
    The national pandemic resulting from the novel coronavirus, COVID-19, has made the delivery of care for patients with cancer a challenge. There are competing risks of mortality from cancer versus serious complications and higher risk of death from COVID-19 in immunocompromised hosts. Furthermore, compounding these concerns is the inadequate supply of personal protective equipment, decreased hospital capacity, and paucity of effective treatments or vaccines to date for COVID-19. Guidance measures and recommendations have been published by national organizations aiming to facilitate the delivery of care in a safe and effective manner, many of which, are permanently adoptable interventions. Given the critical importance to continue chemotherapy, there remains additional interventions to further enhance patient safety while conserving healthcare resources such as adjustments in medication administration, reduction in laboratory or drug monitoring, and home delivery of specialty infusions. In this manuscript, we outline how to implement these actionable interventions of chemotherapy and supportive care delivery to further enhance the current precautionary measures while maintaining safe and effective patient care. Coupled with current published standards, these strategies can help alleviate the numerous challenges associated with this pandemic. © The Author(s) 2020.
  • Suicide Attempts and Perceived Social Support among Chinese Drug Users: The Mediating Role of Self-Esteem and Depression.

    Deng, Yali; Li, Xuemeng; Liu, Liu; Chui, Wing Hong (MDPI AG, 2020-12-30)
    Suicidal behavior is a severe problem among drug users. This study examines influential factors related to suicide attempts and analyzes possible mediators of the relationship between perceived social support and suicide attempts amongst Chinese drug users under compulsory institutional drug treatment. Taking perceived social support as the independent variable, we found that the relationship between suicide attempts and perceived social support is mediated by self-esteem as a protective factor and depression as a risk factor. Path analysis shows that self-esteem contributes relatively more to the indirect effects than depression does, accounting for 31.1% and 24.2% of the total effect, respectively. Generally speaking, the findings of this study point to an urgent need for addressing suicide attempts among Chinese drug users while treating self-esteem as the protective factor that deserves as substantial attention as depression receives. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
  • Proton-Coupled Conformational Activation of SARS Coronavirus Main Proteases and Opportunity for Designing Small-Molecule Broad-Spectrum Targeted Covalent Inhibitors.

    Verma, Neha; Henderson, Jack A; Shen, Jana (American Chemical Society, 2020-12-15)
    The SARS coronavirus 2 (SARS-CoV-2) main protease (Mpro) is an attractive broad-spectrum antiviral drug target. Despite the enormous progress in structure elucidation, the Mpro's structure-function relationship remains poorly understood. Recently, a peptidomimetic inhibitor has entered clinical trial; however, small-molecule orally available antiviral drugs have yet to be developed. Intrigued by a long-standing controversy regarding the existence of an inactive state, we explored the proton-coupled dynamics of the Mpros of SARS-CoV-2 and the closely related SARS-CoV using a newly developed continuous constant pH molecular dynamics (MD) method and microsecond fixed-charge all-atom MD simulations. Our data supports a general base mechanism for Mpro's proteolytic function. The simulations revealed that protonation of His172 alters a conserved interaction network that upholds the oxyanion loop, leading to a partial collapse of the conserved S1 pocket, consistent with the first and controversial crystal structure of SARS-CoV Mpro determined at pH 6. Interestingly, a natural flavonoid binds SARS-CoV-2 Mpro in the close proximity to a conserved cysteine (Cys44), which is hyper-reactive according to the CpHMD titration. This finding offers an exciting new opportunity for small-molecule targeted covalent inhibitor design. Our work represents a first step toward the mechanistic understanding of the proton-coupled structure-dynamics-function relationship of CoV Mpros; the proposed strategy of designing small-molecule covalent inhibitors may help accelerate the development of orally available broad-spectrum antiviral drugs to stop the current pandemic and prevent future outbreaks.
  • Editorial

    Lee, Bethany R. (Routledge, 2021-01-01)
  • Policy statement from the Society for Healthcare Epidemiology of America (SHEA): Only medical contraindications should be accepted as a reason for not receiving all routine immunizations as recommended by the Centers for Disease Control and Prevention

    Weber, David J; Talbot, Thomas R; Weinmann, Allison; Mathew, Trini; Heil, Emily; Stenehjem, Edward; Duncan, Robert; Gross, Alan; Stinchfield, Patricia; Baliga, Christopher; et al. (Cambridge University Press, 2020-09-17)
    SHEA endorses adhering to the recommendations by the CDC and ACIP for immunizations of all children and adults. All persons providing clinical care should be familiar with these recommendations and should routinely assess immunization compliance of their patients and strongly recommend all routine immunizations to patients. All healthcare personnel (HCP) should be immunized against vaccine-preventable diseases as recommended by the CDC/ACIP (unless immunity is demonstrated by another recommended method). SHEA endorses the policy that immunization should be a condition of employment or functioning (students, contract workers, volunteers, etc) at a healthcare facility. Only recognized medical contraindications should be accepted for not receiving recommended immunizations. ©
  • Immature defense mechanisms mediate the relationship between childhood trauma and onset of bipolar disorder

    Wang, Leilei; Yin, Yi; Bian, Qingtao; Zhou, Yanfang; Huang, Junchao; Zhang, Ping; Chen, Song; Fan, Hongzhen; Cui, Yimin; Luo, Xingguang; et al. (Elsevier B.V., 2020-10-15)
  • Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704

    Bitterman, Danielle S; Winter, Kathryn A; Hong, Theodore S; Fuchs, Charles S; Regine, William F; Abrams, Ross A; Safran, Howard; Hoffman, John P; Benson, Al B; Kasunic, Timothy; et al. (Elsevier Inc., 2020-08-26)
    Purpose: Diabetes mellitus (DM) has been proposed to be tumorigenic; however, prior studies of the association between DM and survival are conflicting. The goal of this ancillary analysis of RTOG 9704, a randomized controlled trial of adjuvant chemotherapy in pancreatic cancer, was to determine the prognostic effects of DM and insulin use on survival. Methods and Materials: Eligible patients from RTOG 9704 with available data on DM and insulin use were included. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and variable levels were compared using log-rank test. Cox proportional hazards models were created to assess the associations among DM, insulin use, and body mass index phenotypes on outcomes. Results: Of 538 patients enrolled from 1998 to 2002, 238 patients were eligible with analyzable DM and insulin use data. Overall 34% of patients had DM and 66% did not. Of patients with DM, 64% had insulin-dependent DM, and 36% had non–insulin-dependent DM. On univariable analysis, neither DM nor insulin dependence were associated with OS or DFS (P >.05 for all). On multivariable analysis, neither DM, insulin use, nor body mass index were independently associated with OS or DFS. Nonwhite race (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.35-3.50; P =.0014), nodal involvement (HR, 1.74; 95% CI, 1.24-2.45; P =.0015), and carbohydrate antigen 19-9 (CA19-9) ≥90 U/mL (HR, 3.61; 95% CI, 2.32-5.63; P <.001) were associated with decreased OS. Nonwhite race (HR, 1.67; 95% CI, 1.05-2.63; P =.029) and CA19-9 ≥90 U/mL (HR, 2.86; 95% CI, 1.85-4.40; P <.001) were associated with decreased DFS. Conclusions: DM and insulin use were not associated with OS or DFS in patients with pancreatic cancer in this study. Race, nodal involvement, and increased CA19-9 were significant predictors of outcomes. These data might apply to the more modern use of neoadjuvant therapies for potentially resectable pancreatic cancer.
  • Adjustments for oral fluid quality and collection methods improve prediction of circulating tetanus antitoxin: Approaches for correcting antibody concentrations detected in a non-invasive specimen

    Garrison-Desany, Henri; Ochieng, Benard Omondi; Odiere, Maurice R; Kuo, Helen; Gibson, Dustin G; Were, Joyce; Kagucia, E Wangeci; Pasetti, Marcela F; Kim, Hani; Reymann, Mardi; et al. (Elsevier Ltd., 2020-11-27)
    Objectives: To examine whether anti-tetanus toxoid (anti-TT) immunoglobulin G (IgG) levels measured in oral fluid and adjusted for collection difficulties and specimen quality are associated with total IgG and anti-TTIgG in oral fluid and assess if statistical adjustment for them improves prediction of anti-TT IgG in serum. Methods: 267 children, ages 12 to 15 months, enrolled in the M-SIMU randomized controlled trial participated in this nested cross-sectional analysis. Venous blood and oral fluid (OF) specimens were collected, and OF collection difficulties such as crying or gagging were recorded. OF volume was documented and total IgG was measured in OF specimens and anti-TT IgG was measured in OF and serum by enzyme immunoassay (EIA). Collection difficulties, volume and sociodemographic characteristics were assessed in relation to total IgG and anti-TT IgG in OF via multivariate regression. These models were extended to evaluate the association between anti-TT IgG in OF and in serum. A prediction model was developed to adjust anti-TT IgG in OF estimates as proxy for serum. Results: Blood in the specimen, sores in the mouth and crying were positively associated with total IgG concentration while high oral fluid volume and sucking on the swab were inversely associated. None were significant predictors of anti-TT IgG in OF after adjusting for total IgG (geometric mean [GM] ratio: 1.99; 95% confidence interval: 1.78–2.24) and vaccination history (GM ratio: 2.44; 95% CI: 1.98–3.01). When predicting anti-TT IgG levels in serum with OF, total IgG modified the effect of anti-TT IgG in OF. Conclusions: Anti-TT IgG in OF is a good proxy for levels in serum, after controlling for total IgG in the specimen and other variables. Post hoc adjustments for OF volume and total IgG concentration are an important consideration when conducting serosurveys with oral fluid.
  • Robust control of a system with a pneumatic spring

    Kim, Dongwon; Lee, Jinoh (Elsevier Ltd., 2020-11-01)
    Recently, series elasticity has been realized using pneumatics in human-robot interaction systems. Pneumatic circuits provide not only a flexible power transmission, but also the elastic element in a series elastic actuator (SEA). Pneumatic series elastic systems involve more than twice the number of parameters that influence system behaviors in comparison with rigid robotic systems. In this study, a position controller that eliminates the need of identifying a system model by employing the time delay estimation (TDE) technique is proposed for pneumatic SEA systems. The TDE technique is effective in compensating for system dynamics and all uncertainties involved in system behaviors without imposing computation load. TDE error is cancelled out through a learning way, which improves control performance and leads to asymptotic stability. A simulation study demonstrates the robustness of the proposed controllers against uncertainties imposed on the motor system as well as uncertainties on the end-effector. The simulation shows the efficacy of the learning compensation for TDE error.
  • Optimization of RG1-VLP vaccine performance in mice with novel TLR4 agonists

    Zacharia, Athina; Harberts, Erin; Valencia, Sarah M; Myers, Breana; Sanders, Chelsea; Jain, Akshay; Larson, Nicholas R; Middaugh, C Russell; Picking, William D; Difilippantonio, Simone; et al. (Elsevier Ltd., 2020-12-10)
    Current human papilloma virus (HPV) vaccines provide substantial protection against the most common HPV types responsible for oral and anogenital cancers, but many circulating cancer-causing types remain that lack vaccine coverage. The novel RG1-VLP (virus-like particle) vaccine candidate utilizes the HPV16-L1 subunit as a backbone to display an inserted HPV16-L2 17–36 a.a. “RG1” epitope; the L2 RG1 epitope is conserved across many HPV types and the generation of cross-neutralizing antibodies (Abs) against which has been demonstrated. In an effort to heighten the immunogenicity of the RG1-VLP vaccine, we compared in BALB/c mice adjuvant formulations consisting of novel bacterial enzymatic combinatorial chemistry (BECC)-derived toll-like receptor 4 (TLR4) agonists and the aluminum hydroxide adjuvant Alhydrogel. In the presence of BECC molecules, consistent improvements in the magnitude of Ab responses to both HPV16-L1 and the L2 RG1 epitope were observed compared to Alhydrogel alone. Furthermore, neutralizing titers to HPV16 as well as cross-neutralization of pseudovirion (PsV) types HPV18 and HPV39 were augmented in the presence of BECC agonists as well. Levels of L1 and L2-specific Abs were achieved after two vaccinations with BECC/Alhydrogel adjuvant that were equivalent to or greater than levels achieved with 3 vaccinations with Alhydrogel alone, indicating that the presence of BECC molecules resulted in accelerated immune responses that could allow for a decreased dose schedule for VLP-based HPV vaccines. In addition, dose-sparing studies indicated that adjuvantation with BECC/Alhydrogel allowed for a 75% reduction in antigen dose while still retaining equivalent magnitudes of responses to the full VLP dose with Alhydrogel. These data suggest that adjuvant optimization of HPV VLP-based vaccines can lead to rapid immunity requiring fewer boosts, dose-sparing of VLPs expensive to produce, and the establishment of a longer-lasting humoral immunity.
  • Buyer beware: inflated claims of sensitivity for rapid COVID-19 tests

    Fitzpatrick, Meagan C; Pandey, Abhishek; Wells, Chad R; Sah, Pratha; Galvani, Alison P (Elsevier Ltd., 2020-12-14)
  • Completeness of Medical Records of Trauma Patients Admitted to the Emergency Unit of a University Hospital, Upper Egypt

    Mohammed, Zeinab; Arafa, Ahmed; Senosy, Shaimaa; El-Morsy, El-Morsy Ahmed; El-Bana, Emad; Saleh, Yaseen; Hirshon, Jon Mark (MDPI AG, 2020-12-24)
    Trauma records in Egyptian hospitals are widely suspected to be inadequate for developing a practical and useful trauma registry, which is critical for informing both primary and secondary prevention. We reviewed archived paper records of trauma patients admitted to the Beni-Suef University Hospital in Upper Egypt for completeness in four domains: demographic data including contact information, administrative data tracking patients from admission to discharge, clinical data including vital signs and Glasgow Coma Scale scores, and data describing the causal traumatic event (mechanism of injury, activity at the time of injury, and location/setting). The majority of the 539 medical records included in the study had significant deficiencies in the four reviewed domains. Overall, 74.3% of demographic fields, 66.5% of administrative fields, 55.0% of clinical fields, and just 19.9% of fields detailing the causal event were found to be completed. Critically, oxygen saturation, arrival time, and contact information were reported in only 7.6%, 25.8%, and 43.6% of the records, respectively. Less than a fourth of the records provided any details about the cause of trauma. Accordingly, the current, paper-based medical record system at Beni-Suef University Hospital is insufficient for the development of a practical trauma registry. More efforts are needed to develop efficient and comprehensive documentation of trauma data in order to inform and improve patient care. © 2020 by the authors. Li-censee MDPI, Basel, Switzerland.
  • Insulin Resistance in Skeletal Muscle of Chronic Stroke

    Ryan, Alice S; Hafer-Macko, Charlene; Ortmeyer, Heidi K (MDPI AG, 2020-12-26)
    A stroke can lead to reduced mobility affecting skeletal muscle mass and fatty infiltration which could lead to systemic insulin resistance, but this has not been examined and the mechanisms are currently unknown. The objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in paretic (P) and nonparetic (NP) skeletal muscle in chronic stroke, and to compare to nonstroke controls. Participants were mild to moderately disabled adults with chronic stroke (n = 30, 60 ± 8 years) and sedentary controls (n = 35, 62 ± 8 years). Insulin sensitivity (M) and bilateral GS activity were determined after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Stroke subjects had lower aerobic capacity than controls, but M was not significantly different. Insulin-stimulated activities of GS (independent, total, fractional), as well as absolute differences (insulin minus basal) and the percent change (insulin minus basal, relative to basal) in GS activities, were all significantly lower in P versus NP muscle. Basal GS fractional activity was 3-fold higher, and the increase in GS fractional activity during the clamp was 2-fold higher in control versus P and NP muscle. Visceral fat and intermuscular fat were associated with lower M. The effect of in vivo insulin to increase GS fractional activity was associated with M in control and P muscle. A reduction in insulin action on GS in paretic muscle likely contributes to skeletal muscle-specific insulin resistance in chronic stroke.
  • Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy

    Thangaraju, Kiruphagaran; Neerukonda, Sabari Nath; Katneni, Upendra; Buehler, Paul W (MDPI AG, 2020-12-25)
    Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-de-rived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
  • Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

    Aggarwal, Charu; Rolfo, Christian D; Oxnard, Geoffrey R; Gray, Jhanelle E; Sholl, Lynette M; Gandara, David R (Springer Nature, 2020-09-11)
    Upfront tumour genotyping is now considered an essential step in guiding treatment decision-making in the management of patients with advanced-stage non-small-cell lung cancer (NSCLC) in light of the ever-expanding toolbox of targeted therapies and immune-checkpoint inhibitors. However, genotyping of tumour biopsy samples is not feasible for all patients and, therefore, genomic analysis of circulating tumour DNA (ctDNA) has emerged as a compelling non-invasive option. Current guidelines universally recommend genotyping and support the use of ctDNA testing in certain settings, although they often omit the detail necessary for integrating these tests into clinical care on an individual basis. In this Perspective, we describe the rationale, promise and challenges associated with ctDNA-based NSCLC genotyping and suggest a framework for the implementation of these assays into routine clinical practice. We also offer considerations for the interpretation of ctDNA genotyping results, which, particularly when using next-generation sequencing panels, can be nuanced. Through the addition of this new approach to clinical practice, we propose that oncologists might finally be able to utilize effective genotyping in nearly all patients with advanced-stage NSCLC. © 2020, Springer Nature Limited.
  • Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD

    Navaneethan, Sankar D; Kirwan, John P; Remer, Erick M; Schneider, Erika; Addeman, Bryan; Arrigain, Susana; Horwitz, Ed; Fink, Jeffrey C; Lash, James P; McKenzie, Charles A; et al. (Elsevier Ltd., 2020-08-13)
    Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2±14.6 (SD) mL/min/1.73m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors.
  • Innovating organ delivery to improve access to care: Surgeon perspectives on the current system and future use of unmanned aircrafts

    Talaie, Tara; Niederhaus, Silke; Villalongas, Ester; Scalea, Joseph (BMJ Publishing Group, 2020-11-23)
    Objective Organ transportation requires innovation. We recently showed that unmanned aircraft systems (UAS) could transport human organs. There are no data addressing UAS acceptance among healthcare providers. Conceptually, UAS implementation may improve delivery of care through improved efficiency. We sought to learn surgical perspectives on current and innovated organ transport systems. Methods An Institutional Review Board exempt, pretested, 5-point Likert scale web-based survey was undertaken. Transplant surgeons taking kidney transplant offers in the USA (n=174) were sampled. Results Of 174 surveys, 122 were delivered successfully, and 55 responses collected. Mean age was 48.1 (range 34-64), and 80% were male. Forty-two (76.4%) surgeons felt cold ischaemia time reduction to 8 hours would increase organ acceptance rates. More than 23% of respondents were fearful and 34.5% nervous regarding drones. Nearly all (92.7%) respondents believed drones could help people; 90.9% felt the mode of transportation was irrelevant to their decision to accept an organ but that speed and quality were most important. Only 16.4% of surgeons believed the current system is adequate for our transportation needs. Conclusions Surgeons feel the present system of organ transportation needs reform, and an innovated system using UAS might improve care. An innovated organ transportation system involving UAS may lead to fear and anxiety among transplant surgeons, suggesting that research and education are required ahead of adoption.
  • Age-dependent effects of protein restriction on dopamine release

    Naneix, Fabien; Peters, Kate Z; Young, Andrew M J; McCutcheon, James E (Springer Nature, 2020-07-31)
    Despite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1–20 Hz). By contrast, protein restriction during adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction at adulthood has no impact on dopamine release but the same diet during adolescence induced a frequency-dependent increase in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages. © 2020, The Author(s).

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