cssi/SciSciGPT-SciSciNet huggingface dataset:
Systems to Reduce the Cost of Preconditioning Calves1

Abstract Three selected methods for preconditioning of purchased calves were studied. Two methods (DRYLOT1 and DRY-LOT2) involve feeding mixed diets in a drylot, and the other grazing ryegrass (RYEGRASS) . A total of 192 heifer calves (three trials) were purchased during a 2- to 3-wk period from local stockyards. Upon arrival, calves were fed hay free-choice in a drylot and processed the next day. After processing, equal numbers of calves were randomly assigned to one of the three preconditioning treatments. DRYLOT1 calves were fed 4.54 kg/head per day of a mixed grain diet, and DRYLOT2 calves were fed 2.27 kg/head per day of a different diet. The remaining calves (RYEGRASS) were turned out on ryegrass pasture immediately after processing. Preconditioning was completed and final BW taken 21 d after the last calf was purchased. Heifers on the RYEGRASS treatment had the greatest ADG (P 0.05). Estimated cost of feed or pasture for 30 d of preconditioning was $11.00, $26.94, and $14.17 per head for RYEGRASS, DRYLOT1, and DRYLOT2 treatments, respectively. Net monetary returns of $46.38, $3.21, and $18.25 per head for RYEGRASS, DRYLOT1, and DRYLOT2 treatments, respectively, were heavily in favor of the RYEGRASS group due to a combination of superior ADG and reduted feed tos.
Using Machine Learning and Natural Language Processing Algorithms to Automate the Evaluation of Clinical Decision Support in Electronic Medical Record Systems.

Introduction: As the number of clinical decision support systems incorporated into electronic medical records increases, so does the need to evaluate their effectiveness. The use of medical record review and similar manual methods for evaluating decision rules is laborious and inefficient. Here we use machine learning and natural language processing (NLP) algorithms to accurately evaluate a clinical decision support rule through an electronic medical record system and compare it against manual evaluation. Methods: Modeled after the electronic medical record system EPIC at Maine Medical Center, we developed a dummy dataset containing physician notes in free text for 3621 artificial patients records undergoing a head computed tomography scan for mild traumatic brain injury after the incorporation of an electronic best practice approach. We validated the accuracy of the BPA using three machine learning algorithms (SVC, DecisionTreeClassifier; KNeighborsClassifier) by comparing their accuracy for adjudicating the occurrence of a mild traumatic brain injury against manual review. We then used the best of the three algorithms to evaluate the effectiveness of the BPA and compared the algorithm’s evaluation of the BPA to that of manual review. Results: The electronic best practice approach was found to have a sensitivity of 98.8% (96.83-100.0), specificity of 10.3%, PPV = 7.3%, and NPV = 99.2% when reviewed manually by abstractors. Though all the machine learning algorithms were observed to have a high level of prediction, the SVC displayed the highest with a sensitivity 93.33% (92.49-98.84) , specificity of 97.62% (96.53-98.38), PPV = 50.00, NPV = 99.83. The SVC algorithm was observed to have a sensitivity of 97.9% (94.7-99.86), specificity 10.30%, PPV 7.25%, and NPV 99.2% for evaluating the best practice approach, after accounting for 17 cases (0.66%) where the patient records had to be reviewed manually due to the NPL systems inability to capture the proper diagnosis. Discussion: Evaluation of clinical decision support systems incorporated into electronic medical records can be achieved in an automatic fashion by using natural language processing and machine learning techniques.
SELF-CERTIFICATION IN THE VOLUNTARY COMPLIANCE PROGRAM1

In 1964, the Food and Drug Administration (FDA) embarked on a voluntary Compliance Program designed to assist and encourage the regulated industries to adopt concepts of self-regulation. Administered by the Bureau of Voluntary Compliance, this program is aimed at providing industry with facts and techniques that will give industry the greatest opportunity to comply with FDA regulations and standards. FDA will do all it can to provide industry with: (a) advisory assistance and information, (b) an explanation of how laws and regulations affect it, (c) results of our scientific research and improved analytical methodology, and (d) recommendations for controlling bacterial contamination and adopting good manufacturing practices. FDA's traditional reliance on enforcement through its own staff is being reinforced to include an Industry-State-FDA partnership. Self-Certification, an example of such a partnership, is a co-operative approach of Government and industry to assure the quality of our American food supp...
Atomistically derived cohesive behavior of interphases in carbon fiber reinforced CNT nanocomposites

The carbon fiber/polymer matrix interphase region plays an important role in failure initiation and accurate modeling techniques are integral to study the effects of this complex region on the composite response. In composites infused with nanoparticles such as carbon nanotubes (CNT), the interphase region is more complex due to the presence of multiple constituents and their interactions with each other. An atomistic methodology to simulate the constituent interphases in carbon fiber reinforced CNT/epoxy nanocomposites is presented in this paper. The interphase model consisting of voids in multiple graphene layers enable the simulation of physical entanglement between the polymer matrix and the irregular carbon fiber surface. The voids in graphene layers are generated by removing carbon atoms and hydrogenating the end carbon atoms, which better represent the roughness of the carbon fiber surface. The epoxy curing studies and the response of fiber/matrix interphase under mechanical loading are investigated through molecular dynamic (MD) simulations with appropriate classical/harmonic and bond order-based force fields. Furthermore, the atomistic force-displacement behavior is also extracted to formulate a traction-separation law for interface cohesive zone models. The cohesive behavior determined from molecular models is parameterized in equations that can be integrated with an atomistically informed multiscale modeling framework.
Sense of School Coherence, Perceptions of Danger at School, and Teacher Support Among Youth at Risk of School Failure

Using a sample of middle and high school students who had been identified by school personnel as at risk of school failure, this investigation examines two competing models about the effects of students' perceptions of danger at school and teacher support on their sense of school coherence. From the compensatory model, it is assumed that risk and protective factors combine additively to influence outcomes. From the immunity model, it is assumed that protective factors buffer or moderate the negative effects of risk factors on outcomes. Support is found for the compensatory or additive model, with perceptions of school danger negatively influencing students' sense of school coherence and teacher support positively influencing variation in the criterion variable. Implications for theory, practice, and further research are discussed.
The parametric nature of two students’ covariational reasoning

Abstract Researchers have argued that covariational reasoning is foundational for learning a variety of mathematics topics. We extend prior research by examining two students’ covariational reasoning with attention to the extent they became consciously aware of the parametric nature of their reasoning. We first describe our theoretical background including different conceptions of covariation researchers have found useful when characterizing student reasoning. We then present two students’ activities during a teaching experiment in which they constructed and reasoned about covarying quantities. We highlight aspects of the students’ reasoning that we conjectured created an intellectual need that resulted in their constructing a parameter quantity or attribute, a need we explored in closing teaching episodes. We discuss implications of these results for perspectives on covariational reasoning, students’ understandings of graphs and parametric functions, and areas of future research.
Abnormalities Associated With the Cavum Septi Pellucidi on Fetal MRI: What Radiologists Need to Know.

OBJECTIVE. Screening the cavum septi pellucidi (CSP), more commonly referred to as the “cavum septum pellucidum,” is a required component of the fetal anatomic survey during second-trimester ultras...
Results of Clinical Trials and Basis for Future Therapeutics

Cancer of the lung is the most common and most lethal form of human cancer in the United States. During 1983, there will be approximately 139,000 new cases and about 121,000 deaths from lung cancer in the United States (Silverberg, 1984). The overall five-year survival rate with this disease is less than five percent, a resultant from the fact that at diagnosis the disease is usually advanced.
Vaccination against cutaneous leishmaniasis: Current status

The different cutaneous leishmaniases are distinct in their etiology, epidemiology, transmission, and geographical distribution. In most instances cutaneous leishmaniasis is limited to one or a few skin ulcers that develop at the site where the parasites were deposited during the bite of the sandfly vector. Lesions typically heal spontaneously after several months but some lesions can be large and follow a chronic, more severe course. Protective immunity is usually acquired following cutaneous infection with Leishmania spp., so prevention of disease through prophylactic immunization appears to be feasible. Since vaccination with live, virulent parasites is associated with an unacceptable rate of adverse events, attention has turned to the use of killed or attenuated parasite vaccines and defined subunit vaccines. Whole parasite vaccines have the advantage of delivering multiple antigenic epitopes that may be necessary for initiation of a broad-based immune response. Persistent or repeated immune-stimulation by parasite antigens and/or sustained expression of interleukin-12 appear to be critical elements in the development of durable immunity. A number of purified or recombinant antigens, when co-administered with a vaccine adjuvant, appear promising as vaccine candidates against cutaneous leishmaniasis. The sustained expression of recombinant Leishmania antigens by vaccination with DNA is an attractive approach because it mimics the persistent antigenic stimulation of subclinical infection. Effective vaccine-induced immunity must generate an antigen-specific memory T cell population that, upon exposure to the infecting parasite, rapidly produces a type 1 effector T cell response that leads to interferon-gamma-mediated activation of infected macrophages to kill the intracellular parasites. This parasite-directed recall response must be prompt and of sufficient magnitude to overcome the subversive effect that the intracellular infection has on macrophage effector function. It is unlikely that vaccination against cutaneous leishmaniasis would induce sterile immunity, but a small number of parasites are likely to persist subclinically.
Microbial Nickel Metabolism

As described in Chapters 3–6, four nickel-dependent enzymes have been isolated and characterized from various microorganisms—urease, hydrogenase, CO dehydrogenase, and methyl coenzyme M reductase. In addition, specific accessory proteins have been identified as being involved in the functional incorporation of nickel ion into urease and hydrogenase. Intracellular nickel processing functions may also be needed for nickel metallocenter assembly in CO dehydrogenase and for the synthesis of the nickel-containing coenzyme F430, a component of methyl coenzyme M reductase. These aspects of microbial nickel metabolism will not be repeated here. Rather, this chapter will focus on nickel ion transport into the microbial cell, nickel ion toxicity and resistance mechanisms in microbes, and other features related to microbial nickel metabolism.
Reconstitution of T-Cell Function After CD6-Depleted Allogeneic Bone Marrow Transplantation

Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.
Use of Multistation Computer System for Laboratory Data Acquisition and Control

This paper describes the functions and the methods of operation of the computerized data acquisition and control system used in the authors' fatigue laboratory. The computer, a real-time multiprogramming system with digital/analog and analog/digital interfaces, controls and takes data for various complex fatigue experiments simultaneously through use of programs developed by the laboratory personnel. Such programs, the capabilities of the system, and typical applications are discussed.
Glycinergic Innervation of Motoneurons Is Deficient in Amyotrophic Lateral Sclerosis Mice : A Quantitative Confocal Analysis

Altered motoneuron excitability is involved in amyotrophic lateral sclerosis pathobiology. To test the hypothesis that inhibitory interneuron innervation of spinal motoneurons is abnormal in an amyotrophic lateral sclerosis mouse model, we measured GABAergic, glycinergic, and cholinergic immunoreactive terminals on spinal motoneurons in mice expressing a mutant form of human superoxide dismutase-1 with a Gly93→Ala substitution (G93A-SOD1) and in controls at different ages. Glutamic acid decarboxylase, glycine transporter-2, and choline acetyltransferase were used as markers for GABAergic, glycinergic, and cholinergic terminals, respectively. Triple immunofluorescent labeling of boutons contacting motoneurons was visualized by confocal microscopy and analyzed quantitatively. Glycine transporter-2-bouton density on lateral motoneurons was decreased significantly in G93A-SOD1 mice compared with controls. This reduction was absent at 6 weeks of age but present in asymptomatic 8-week-old mice and worsened with disease progression from 12 to 14 weeks of age. Motoneurons lost most glycinergic innervation by 16 weeks of age (end-stage) when there was a significant decrease in the numbers of motoneurons and choline acetyltransferase-positive boutons. No significant differences in glutamic acid decarboxylase-bouton densities were found in G93A-SOD1 mice. Reduction of glycinergic innervation preceded mitochondrial swelling and vacuolization. Calbindin-positive Renshaw cell number was decreased significantly at 12 weeks of age in G93A-SOD1 mice. Thus, either the selective loss of inhibitory glycinergic regulation of motoneuron function or glycinergic interneuron degeneration contributes to motoneuron degeneration in amyotrophic lateral sclerosis.
Transplantation of hematopoietic stem cells obtained by a combined dye method fractionation of murine bone marrow

Hematopoietic stem cells were purified from murine bone marrow cells (BMC). Their characteristic density, size, internal complexity, Hoechst 33342 dye uptake, and wheat germ agglutinin (WGA) affinity were used to distinguish them from other cells in the bone marrow. BMC suspensions were centrifuged over Ficoll Lymphocyte Separation Media (Organon Teknika, Durham, NC; density 1.077 to 1.08). The lower-density cells were drawn off, stained with Hoechst and labeled with biotinylated WGA bound to streptavidin conjugated to phycoerythrin (WGA-B*A-PE) or with WGA conjugated to Texas Red. These cells were then analyzed and sorted by an Ortho Cytofluorograph 50-H cell sorter. The cells exhibiting medium to high forward light scatter, low to medium right angle light scatter, low Hoechst intensity, and high WGA affinity were selected. Sorted BMC (SBMC) were stained with Romanowsky-type stains for morphologic assay, and were assayed in lethally irradiated (LI) mice for their ability to produce colony-forming units in the spleen (CFU-S) and for their ability to produce survival. The spleen seeding factor for day 8 CFU-S upon retransplantation of the isolated cells was 0.1. The isolated cells were found to have consistent morphology, were enriched up to 135-fold as indicated by day 8 CFU-S assay, 195-fold as indicated by day 14 CFU-S assay, and 150 sorter-selected BMC were able to produce long-term survival in LI mice with retention of donor karyotype. When recipients of this first transplantation were themselves used as BMC donors, their number of day 8 and day 12 CFU-S were found to be reduced. However, 3 X 10(5) of their BMC provided 100% survival among secondary recipients. When the previously SBMC were competed after one transplantation against fresh nonsorted BMC in a mixed donor transplant, they showed the decline in hematopoietic potency normally seen in previously transplanted BMC. We conclude that the use of combinations of vital dyes for fluorescence-activated cell sorting (FACS) selection of survival-promoting murine hematopoietic stem cells provides results comparable with those produced by antibody-selected FACS and has the advantage of a method directly transferable to human BMC.
Na+-leak channel, non-selective (NALCN) regulates myometrial excitability and facilitates successful parturition

Background/Aims: Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. Methods: Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN’s contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCreeGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/-, and smNALCN-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN-/- mice. Results: We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. Conclusions: Together, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes.
Population genomics of Fundulus grandis exposed to oil from Deepwater Horizon

Abstract The April 2010 Deepwater Horizon (DWH) oil spill released over 4 million barrels of oil into northern Gulf of Mexico ecosystems. Due to the magnitude of the spill and observed effects from previous spills, the ecological impacts were predicted to be catastrophic. While negative effects of petroleum hydrocarbon exposure to fish have been documented at the organismal scale, most studies of fish assemblages have noted few, if any, DWH impacts. Our understanding of DWH effects is therefore limited by a disconnect in results reported at different organizational levels. We used population genomic tools to test hypotheses about population-level DWH impacts to Gulf Killifish (Fundulus grandis) in coastal Mississippi. Fundulus grandis is one of the most abundant marsh species in the northern Gulf of Mexico, and along with the sister species F. heteroclitus, has served as a model for toxicology research. We collected genotyping by sequencing data from four populations of F. grandis (two oiled and two not) to test predictions about DWH-related gene flow, demographics, genetic diversity and evidence of selection. Mississippi populations of F. grandis showed clear genetic structure, but there were few indicators (e.g. reduced genetic diversity, lower Ne estimates) consistent with large-scale mortality or migration related to DWH oil. Only one estimate of effective population size was reduced in oil-exposed populations and of the twenty outlier loci only two were in regions with potential adaptive significance (i.e., immune functions). While the toxic effects of oil on F. grandis at the organismal level is well established, the minimal impacts we detected to populations along the Mississippi coast likely reflects the complexity of the northern Gulf of Mexico and DWH oil spill. However, we do recognize that the patchiness of oil exposure and low genome coverage of the data limit our ability to conclude there were no DWH effects on these populations.
The Temporal Dimension of System Justification: Gender Ideology Over the Course of the 2016 Election:

Although psychological science has documented individual and situational factors that affect the process of system justification, the temporal dimension of system justification has not been systematically examined. This study used the 2016 U.S. presidential election as a naturalistic setting in which to test for the existence of a temporal dimension. We propose that the potential for a Clinton victory represented a system threat for individuals who supported traditional gender roles, and the approaching election provided a mechanism for measuring the effect of the temporal proximity of the system-threatening event. The results show that gender role ideology played a substantial role in decision-making during the 2016 election, and they support the existence of a temporal dimension of system justification. Participants who began the study with a stronger gender-system justification motive exhibited greater changes in their psychological responses to Clinton over time and greater sensitivity to the temporal proximity of the election.
Interim Results of an Open-Label Study to Assess the Effects of Delayed-release Dimethyl Fumarate on Lymphocyte Subsets and Immunoglobulins in Patients with Relapsing-remitting Multiple Sclerosis (P5.380)

Objective: Given the immunomodulatory properties of delayed-release dimethyl fumarate (DMF) and its observed effects on lymphocytes, further research evaluating these effects is needed. We are conducting this study to comprehensively characterize the effects of DMF on circulating lymphocyte subsets and immunoglobulin levels within the first year of treatment and beyond. Background: DMF is an approved oral disease-modifying therapy (DMT) to treat RRMS. DMF has putative immunomodulatory properties through activation of the Nrf2-dependent and NRF2-independent pathways. A mean ALC decrease by ~30% during the first year of treatment has been observed in pivotal trials and in real-world settings; however, a detailed and comprehensive analysis of the impact and time course of changes in circulating lymphocyte subsets has not been described. Design/Methods: In this ongoing, open-label, multicenter study, 218 patients aged 18–65 years with RRMS were enrolled and treated with DMF 240mg twice daily. Blood samples were taken at baseline, and at Weeks 4, 8, 12, 24, 36, and 48. Lymphocyte subset changes were monitored by flow cytometry using a comprehensive panel of surface markers and intracellular cytokines. Results: This interim analysis includes ~165 patients from 6 different countries with ≥6 months follow-up or who discontinued the study earlier. The overall safety results and the changes in ALC and detailed lymphocyte subset counts, including phenotypic characterization of CD4 + T-cell, CD8 + T-cell, B-cell, and natural killer cell subsets, based on a comprehensive panel of surface markers and intracellular cytokines will be presented. Conclusions: The results will provide insight into the effects of DMF on a comprehensive panel of immune cell subsets and their correlation with changes in ALC within the first 6 months of treatment initiation and may help to understand treatment-related changes in immune cell function. Study Supported by: Biogen Disclosure: Dr. Von Hehn has received personal compensation for activities with Biogen as an employee. Dr. Mehta has received personal compensation for activities with Biogen as an employee. Dr. Mehta holds stock and/or stock options in Biogen. Dr. Prada has received personal compensation for activities with Biogen as an employee. Dr. Prada holds stock and/or stock options in Biogen. Dr. Yang has received personal compensation for activities with Biogen as an employee. Dr. Yang hold stocks and/or stock options in Biogen. Dr. Liu has received personal compensation for activities with Biogen as an employee. Dr. Ray has received personal compensation for activities with Biogen Idec. Dr. Ray holds stock and/or stock options in Biogen Idec. Dr. Sheikh has received personal compensation for activities with Biogen as an employee. Dr. Sheikh holds stock and/or stock options in Biogen.
“Not Giving Up”: Ghanaian Students’ Perspectives on Resilience, Risk, and Academic Achievement:

Resilience research began in North America and Western Europe but there is a growing call for exploration of what resilience might mean in specific cultural contexts. Placed within the context of A...
Review of New Perspectives in Forensic Human Skeletal Identification

REFERENCE: Krista Latham, Eric Bartelink, Michael Finnegan, eds. New Perspectives in Forensic Human Skeletal Identification . San Diego: Academic Press; 2018. 356 pp.
TTP399: an investigational liver-selective glucokinase (GK) activator as a potential treatment for type 2 diabetes

Introduction: Type 2 diabetes is a complex metabolic disorder defined by hyperglycemia which occurs because of impaired insulin secretion and sensitivity. There is an ongoing need to develop novel therapies that are effective and safe with minimal side effects and long-term durability. TTP399 is a hepatoselective, glucokinase activator with potential for treating type 2 diabetes. Areas covered: This is a review of the available data regarding the mechanism of action and the pharmacokinetics of TTP399. The efficacy and safety of the drug for treatment of type 2 diabetes will also be examined with an emphasis on the results of a randomized, controlled phase 2 study. Expert opinion: TTP399 could offer significant advantages over currently available therapies for type 2 diabetes. It successfully lowers glucose without side effects such as hypoglycemia, weight gain or dyslipidemia. Larger trials are required to understand long-term efficacy and safety of this medication in various patient populations and to elucidate its effect on the pathologic processes underpinning type 2 diabetes.
Convergent and parallel evolution in a voltage-gated sodium channel underlies TTX-resistance in the Greater Blue-ringed Octopus: Hapalochlaena lunulata.

Abstract The natural history and pharmacology of tetrodotoxin (TTX) has long intrigued biologists. This toxin has a remarkable distribution that spans two domains of life (Bacteria and Eukarya). Within Eukaryotes, TTX has only been identified in animals but is known to be present in over five-dozen species of phylogenetically distant Metazoans. Despite decades of work, the origin and biosynthetic pathways of TTX remain unresolved. Investigations in puffer fishes and salamanders have provided insights into the acquisition of auto-resistance to TTX through the evolution of voltage-gated sodium ion channels (VGSCs) that have reduced binding affinity for TTX. To date there have been no studies of these proteins in tetrodotoxic Blue-Ringed Octopuses. Here we report data demonstrating that the Greater Blue-ringed Octopus (Hapalochlaena lunulata) expresses a VGSC (HlNaV1) gene with mutations that reduce the channel's TTX-binding affinity and likely render the organism TTX resistant. We identified three amino-acid substitutions in the TTX-binding site of HlNaV1 that likely confer TTX-resistance to both the channel and the organism. These substitutions are associated with organismal TTX-resistance in other TTX-bearing taxa and are convergent with substitutions that have evolved in fish, salamanders, and some TTX-resistant invertebrates.
Preeclampsia and low sodium (PALS): A case and systematic review

Normal physiologic changes in pregnancy include mild hyponatremia. In some cases of preeclampsia, more significant hyponatremia has been associated with syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. A 45-year-old gravida 2, para 0010 with a dichorionic twin gestation was diagnosed with preeclampsia at 30 weeks 6 days and noted to have concomitant hyponatremia of 125 mEq/L at our institution. Her hyponatremia was initially managed with furosemide and water restriction. She was delivered at 33 weeks 5 days due to worsening preeclampsia and continued significant hyponatremia despite treatment. Her hyponatremia resolved within 48 h after delivery. Our objectives were to discuss trends, treatment, and outcomes of cases with hyponatremia in preeclampsia. We performed a systematic review of the literature using Ovid Medline (1963-2017), Scopus (1962-2017), and PubMed (1963-2017, including Cochrane database). Relevant articles describing any case report of hyponatremia in preeclampsia were identified from the above databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described a case of hyponatremia in the setting of preeclampsia. 18 manuscripts detailing 55 cases were identified. Pertinent demographic data and laboratory values were extracted. Maternal management strategy, diagnosis, delivery, and neonatal outcome data were also collected. Mean, range, standard deviation, and percentage calculations were used as applicable. Advanced maternal age (46 %), nulliparity (79 %), and multifetal gestation (34 %) were noted in patients with preeclampsia and low sodium. Hyponatremia was detected on average at 34 weeks gestation. 64 % were diagnosed with preeclampsia with severe features. When reported, diagnoses related to hyponatremia were syndrome of inappropriate antidiuretic hormone secretion (41 %) or hypervolemic hyponatremia (59 %). Indications for delivery included severe hyponatremia unresponsive to conservative measures in addition to other known obstetric or preeclamptic indications. Hyponatremia resolved within 48 h on average in cases where postpartum resolution was reported. It may be prudent to screen women with preeclampsia for electrolyte disturbances as part of their evaluation, especially in the setting of severe features. Initially, hyponatremia may be treated with medical management. In addition to established obstetric or preeclamptic indications, delivery may be considered if severe hyponatremia no longer responds to conservative measures.
A review of technical progression in the robot-assisted radical prostatectomy

Since the advent of the robotic surgery, its implementation in urology has been both wide and rapid. Particularly in extirpative surgery for prostate cancer, techniques in robotic-assisted radical prostatectomy have-and continue to-evolve to maximize functional and oncologic outcomes. In this review, we briefly present a historical perspective of the evolution of various robotic techniques, allowing us to contextualize contemporary robotic approaches to radical prostatectomy.
Chapter 8 – From Lipid Bilayers to Lipid Rafts

By 1935 all of the basic elements were in place for someone to propose a realistic model of a membrane. Comparing cell permeability measurements with solute partition coefficients, Overton had suggested the lipid nature of a membrane, while Gorter and Grendel had proposed that there was the precise amount of lipid in the erythrocyte membrane to exactly cover the erythrocyte cell surface twice. Thus, at least the erythrocyte membrane was a lipid bilayer. In fact, the then obscure Gorter-Grendel paper implied that the membrane was entirely lipid! Using trans-membrane electrical measurements, in 1925 Fricke correctly determined that a membrane was ∼33 A thick. Also in 1925, Sumner purified the first protein, urease. The prevailing opinion at that time was that biological catalysts were small, hard to isolate organic molecules that were hidden in all the “cellular junk”. Although it took almost a full decade for the importance of protein catalysts (enzymes) to be universally accepted, by 1935 it was obvious that proteins were to be a major player in understanding life. Proteins were soon found to be a major component of all membrane compositional analysis. One readily measurable membrane property, surface tension, was severely impacted by both membrane lipids and proteins. The surface tension of pure water is 72.8 dyn/cm at 25°C. Phospholipids reduce this to ∼7–15 dyn/cm. Proteins further reduce the surface tension down to that of a biological membrane (∼0.1 dyn/cm). The conclusion was that proteins must play an important role in membrane structure. However, by 1935 the only proteins that were understood to any extent were water-soluble globular proteins. Nothing was known about membrane proteins.
Oral Granulomatous Disease

Granulomatous diseases are chronic inflammatory disorders whose pathogenesis is triggered by an array of infectious and noninfectious agents, and may be localized or a manifestation of systemic, disseminated disease. As in the skin, oral manifestations of granulomatous inflammation are often nonspecific in their clinical appearance. Thus, in the absence of overt foreign material or a recognizable infectious agent, identifying the underlying cause of the inflammation can be challenging. This article highlights various conditions known to induce granulomatous inflammation within the oral soft tissues.
The “Wonder to Behold”: Reflections on Phenomenological Research of Alienic Spirituality

This paper suggests the adaptation of the phenomenological research method for the study of indigenous spirituality. As a method by which one clarifies obscure forms of experience, phenomenology developed in Western academia. For such a context, indigenous spirituality is understood as spirituality of an alien, in need of discovery and to be differentiated from the psychological sphere of meaning. Six principles of the method include historical reduction, intentional cultivation of wonder, attention to the embodied, attentive, enfleshed and affective unique “what it’s like” of experience, letting imagination run wild towards seemingly impossible options, experimenting with the transcendental and other forms of reduction, and aiming at a discovery.
Implementation of a gastrostomy care bundle reduces dislodgements and length of stay.

Abstract Purpose Pediatric gastrostomy tubes (G-tubes) are associated with considerable utilization of healthcare resources. G-tube dislodgement can result in tract disruption and abdominal sepsis. We aimed to reduce early G-tube dislodgement by 25%. Methods An interdisciplinary team convened to identify key drivers of G-tube dislodgement and implement initiatives to reduce this complication. A G-tube care bundle was implemented in 2018. Rates of early G-tube dislodgement (within 90 days of insertion) were tracked. 15 months of cases after bundle implementation were compared to 20 months of cases before implementation. Length of stay (LOS, balancing measure) and bundle compliance (process measure) were tracked. Results G-tube dislodgements decreased 47% after bundle implementation. Overall, dislodgements after G-tube insertion decreased from 43% to 19% dislodgements per tube inserted, p = 0.004. Reductions were observed for dislodgements occurring in both the inpatient (14% vs. 1.5%) and outpatient (29% vs. 18%) settings. Median LOS was reduced from 15.3 to 7.1 days following implementation, p = 0.004. Process measures demonstrated 75% or greater compliance one year after implementation. Conclusion An interdisciplinary team using quality improvement science methodology can significantly reduce G-tube dislodgement and improve value after pediatric gastrostomy tube insertion. Type of study Longitudinal cohort study. Level of evidence III.
Prevalence of Adrenal Insufficiency and Glucocorticoid Use in Pediatric Pseudotumor Cerebri Syndrome.

Background The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship. Methods We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-μg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol 20 μg/dL and AM or random cortisol >13 μg/dL). Results A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test. Conclusions Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.
Supercapacitor performance of corn stover-derived biocarbon produced from the solid co-products of a hydrothermal liquefaction process

Abstract Biocarbon is obtained by the graphitization of biochar, a co-product in a novel integrated biorefinery concept that simultaneously produces C1–C3 acids, phenol, bio-oil, and biochar. The unhydrolyzed solids from the IBR are hydrothermally liquefied to obtain bio-oil and biochar coproducts. The biochar samples obtained from the HTL of UHS at different process conditions were low temperature thermally treated to remove volatile compounds, followed by a facile high temperature graphitization to biocarbon. Physical analyses showed the degree of graphitization directly effects pore volume. The UHS-SDC9 biochar produced at 275 °C, 40 psig, and 1 h of hydrothermal treatment exhibited the biocarbon with the best electrochemical performance having specific capacitance of 242 F g−1 at a scan rate of 5 mV s−1 and an energy density of 9.9 W h kg−1. Statistical analysis was performed to correlate the IBR processing parameters to physical and electrochemical characteristics of the biocarbon obtained.
Joint Ventures Between Non-Profit and For-Profit Organizations

This paper examines the consequences of allowing a non-profit organization to form a joint venture with a for-profit organization. Three tax regimes are considered: prohibiting all such joint ventures; allowing all such joint ventures; and restricting joint ventures between non-profit and for-profit entities to those controlled by the non-profit organization. The paper derives the equilibrium profit sharing rule, output decision, and organizational form choice under each tax regime. Joint ventures can create both private and social benefits by reducing production costs. They can also create private benefits and social costs by reducing competition. Prohibitions or restrictions on joint ventures can either increase or decrease social welfare depending on whether the production cost effect or the competition effect is more important.
Therapeutic Implications of Diet in Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory Diseases

Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising clinical trials are currently underway, there is a need for further evidence-based recommendations. As such, we summarize the current evidence on various diets used in the treatment of IBD and also explore the potential applications of dietary data from related immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and psoriasis, to provide additional information to inform IBD providers. To date, there have been multiple diets investigated as adjunctive therapy in IBD, but many associated studies are small, non-randomized, and not controlled. Mediterranean, vegetarian/vegan, and reduced-calorie/fasting diets have been studied and have shown some positive results in other IMIDs, which may suggest potential applicability to those with IBD, but larger, well-designed clinical trials are needed for further guidance. Gluten-free and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diets do not appear to have an impact on IBD disease activity, but low FODMAP may potentially be helpful for those with concurrent functional gastrointestinal symptoms. Specific carbohydrate diets have been mainly assessed in children but show some potential in small adult studies.
Upfront Impella 5.0 vs. Prior Mechanical Circulatory Support Use in Cardiogenic Shock: A Single Center Experience

Purpose There has been an emphasis on treating cardiogenic shock (CS) with early mechanical circulatory support (MCS). Yet, algorithmic approaches for the use of specific MCS devices is institutionally dependent. We evaluated the impact of early, upfront Impella 5.0 vs. an alternative MCS device prior to Impella 5.0. Methods Retrospective analysis was performed on 28 consecutive patients at a single center between Jan. '19 - Aug. '20 implanted with Impella 5.0. Patients were separated into those receiving upfront Impella 5.0 and those that had a different MCS device prior to Impella 5.0. Clinical outcomes and hemodynamic data were collected at various time points. Results 16 patients (57%) with a mean age of 60 ± 10.2 years received upfront Impella 5.0, while 12 (43%) with a mean age of 58 ± 12.6 years received an alternative MCS device first (6 IABP, 6 Impella CP). Etiologies of CS in the upfront Impella 5.0 group were decompensated heart failure (HF) in 15 patients (94%) and MI in 1 patient (6%), and in the prior MCS group were decompensated HF in 5 patients (42%) and MI in 7 patients (58%). The mean duration of either IABP or Impella CP use before Impella 5.0 was 0.83 days. The upfront Impella 5.0 cohort had a trend towards higher initial filling pressures shown by elevated RAP, mPAP, PCWP, and reduced CI and CPO prior to implantation. Greater improvements were also seen in each of these variables at 72 hours compared to the alternative MCS group (Figure 1). Complications rates were higher in the alternative MCS group with significant hemolysis in the Impella CP arm with an average plasma free hemoglobin of 324 ± 268 mg/dL, and 1 major vascular complication requiring surgical intervention; and 1 ischemic stroke. Survival in the upfront Impella 5.0 group was 87% and only 56% in the alternative MCS group. Conclusion Early use of Impella 5.0 provides more hemodynamic support and may reduce complications and improve outcomes. It should be considered as initial strategy, when feasible, in patients with CS that require use of MCS.
Expansion microscopy: A powerful nanoscale imaging tool for neuroscientists.

Abstract One of the biggest unsolved questions in neuroscience is how molecules and neuronal circuitry create behaviors, and how their misregulation or dysfunction results in neurological disease. Light microscopy is a vital tool for the study of neural molecules and circuits. However, the fundamental optical diffraction limit precludes the use of conventional light microscopy for sufficient characterization of critical signaling compartments and nanoscopic organizations of synapse-associated molecules. We have witnessed rapid development of super-resolution microscopy methods that circumvent the resolution limit by controlling the number of emitting molecules in specific imaging volumes and allow highly resolved imaging in the 10–100 nm range. Most recently, Expansion Microscopy (ExM) emerged as an alternative solution to overcome the diffraction limit by physically magnifying biological specimens, including nervous systems. Here, we discuss how ExM works in general and currently available ExM methods. We then review ExM imaging in a wide range of nervous systems, including Caenorhabditis elegans, Drosophila, zebrafish, mouse, and human, and their applications to synaptic imaging, neuronal tracing, and the study of neurological disease. Finally, we provide our prospects for expansion microscopy as a powerful nanoscale imaging tool in the neurosciences.