cssi/SciSciGPT-SciSciNet huggingface dataset:
Epigenetic effects of the continuous exposure to peroxisome proliferator WY-14,643 in mouse liver are dependent upon peroxisome proliferator activated receptor α

Peroxisome proliferators are potent rodent liver carcinogens that act via a non-genotoxic mechanism. The mode of action of these agents in rodent liver includes increased cell proliferation, decreased apoptosis, secondary oxidative stress and other events; however, it is not well understood how peroxisome proliferators are triggering the plethora of the molecular signals leading to cancer. Epigenetic changes have been implicated in the mechanism of liver carcinogenesis by a number of environmental agents. Short-term treatment with peroxisome proliferators and other non-genotoxic carcinogens leads to global and locus-specific DNA hypomethylation in mouse liver, events that were suggested to correlate with a burst of cell proliferation. In the current study, we investigated the effects of long-term exposure to a model peroxisome proliferator WY-14,643 on DNA and histone methylation. Male SV129 mice were fed a control or WY-14,643-containing (1000 ppm) diet for one week, five weeks or five months. Treatment with WY-14,643 led to progressive global hypomethylation of liver DNA as determined by an HpaII-based cytosine extension assay with the maximum effect reaching over 200% at five months. Likewise, trimethylation of histone H4 lysine 20 and H3 lysine 9 was significantly decreased at all time points. The majority of cytosine methylation in mammals resides in repetitive DNA sequences. In view of this, we measured the effect of WY-14,643 on the methylation status of major and minor satellites, as well as in IAP, LINE1 and LINE2 elements in liver DNA. Exposure to WY-14,643 resulted in a gradual loss of cytosine methylation in major and minor satellites, IAP, LINE1 and LINE2 elements. The epigenetic changes correlated with the temporal effects of WY-14,643 on cell proliferation rates in liver, but no sustained effect on c-Myc promoter methylation was observed. Finally, WY-14,643 had no effect on DNA and histone methylation status in Pparα-null mice at any of the time points considered in this study. These data indicate the importance of epigenetic alterations in the mechanism of action of peroxisome proliferators and the key role of Ppar. © 2007 Elsevier B.V. All rights reserved.
The effects of alcohol-containing e-cigarettes on young adult smokers

Abstract Background The liquids (e-liquids) used in an electronic cigarette (e-cigarette) contain myriad chemicals without adequate human inhalation safety data. Furthermore, the absence of e-liquid labeling requirements poses a formidable challenge to understanding how e-liquid constituents may promote nicotine addiction and/or have independent or synergistic biological effects when combined with nicotine. Ethyl alcohol is such a constituent, but has received little scientific interest in this context. Methods Using a randomized, double blind, crossover design, acute changes in subjective drug effects, motor performance and biochemical measures of alcohol and nicotine intake were evaluated after directed and ad lib puffing from two commercially available e-liquids containing nicotine (8 mg/ml), vanilla flavor and either 23.5% (high) or 0.4% (trace) alcohol. Results While no differences in subjective drug effects were observed between alcohol conditions, performance on the Purdue Pegboard Dexterity Test (PPDT) improved under the trace, but not under the 23.5% alcohol condition. Although plasma alcohol levels remained undetectable during testing, urine ethyl glucuronide (EtG), an alcohol metabolite, became measurable in three participants after puffing from the 23.5% alcohol e-cigarette. Conclusions Brief use of a widely available type of e-cigarette containing an e-liquid purchased from an internet vendor can negatively impact psychomotor performance and in some instances, produce detectable levels of a urine alcohol metabolite. Given the widespread and unregulated use of e-cigarettes, especially by youth and other vulnerable populations, further studies are needed to evaluate both the acute safety and long-term health risks of using alcohol-containing e-cigarettes.
Convergence of Multimodal Sensory Input Onto Higher-Level Neurons of the Crayfish Olfactory Pathway

Intracellular electrophysiological studies of lateral protocerebral interneurons (LPIs) in the crayfish Procambarus clarkii have revealed convergence of multimodal sensory information onto these higher-level cells of the crustacean central olfactory pathway. Antennular stimulation by odors or electrical shocks generates excitatory-inhibitory sequences in some LPIs as does electrical or hydrodynamic stimulation of the antennae. Photic stimulation of the ipsilateral compound eye generates excitatory responses in LPIs, usually in the form of trains of impulse bursts that are timed to the peaks of the spontaneous oscillatory activity that characterizes these neurons. Focal electrical stimulation of the olfactory lobe, the termination point of antennular afferent input, or the accessory lobe, where higher-level visual and tactile inputs converge, also generates brief excitation and a delayed, prolonged inhibition in LPIs. Both phases of this activity are thought to be transmitted to the lateral protocerebrum via deutocerebral projection neurons, which have extensive dendritic arborizations in the olfactory lobe and the accessory lobe. The excitatory pathway is thought to synapse directly with target LPIs, whereas the inhibitory pathway is probably indirect and mediated through GABAergic interneurons within the lateral protocerebrum. There is evidence that both presynaptic and postsynaptic inhibition suppress activity in LPIs. Preliminary observations suggest that a small cluster of neurons adjacent to the hemi-ellipsoid body are inhibitory to LPI activity. Multimodal inhibitory and excitatory modulation of LPI activity may play a part in the contextual identification of odors in the crayfish olfactory system.
Body energy status and the metabolic response to acute inflammation

An animal model of acute inflammation was used to examine how body energy status influences the syndrome of anorexia, negative nitrogen balance, and body weight loss typically seen in response to injury. Specifically, the metabolic response to acute inflammation was studied in rats of normal, elevated, or reduced body weights. Rats induced to overeat and gain weight prior to inflammation displayed protracted anorexia, greater subsequent weight loss, higher metabolic rates, and greater negative energy balance than rats of normal weight. Conversely, rats with reduced body weights displayed elevated food intakes, body weight gain, attenuated nitrogen loss, and normal rates of energy expenditure. Prior weight reduction did not affect postinflammation fever or levels of fibrinogen, iron, and interleukin-6-like activity, suggesting that the ability to mount an acute phase response was not impaired in weight-reduced rats. These results suggest that the usual postinflammation adjustments in body energy flux and body nitrogen are regulated components of a metabolic response to acute inflammation which renders normally protected sources of endogenous energy and substrate available for repair and recovery.
Lenticular neovascularization subsequent to traumatic cataract formation.

PURPOSE To report a series of cases involving neovascularization within the human crystalline lens-a normally avascular structure-after ocular trauma. This is a retrospective, consecutive observational case series with review of the prevailing literature. METHODS Four individuals with a history of ocular trauma and subsequent cataract development were examined between May 2004 and April 2007. All had hypermature cataracts and intraocular inflammation, presumably secondary to phacolysis; two of the four had concurrent hyphema and ocular hypertension in the involved eye. RESULTS All subjects in this series were found to display a discrete network of blood vessels within the structure of the crystalline lens, just beneath the anterior lens capsule. CONCLUSIONS Neovascularization of the crystalline lens has received little attention in the ophthalmic literature, having been described only rarely in individual case reports. This manuscript details the first known case series involving lenticular neovascularization, and offers insight into its possible developmental mechanism.
Effect of Methionine Deficiency upon Enzyme Activity in the Rat.

SummaryIt has been observed that a methionine deficiency in the rat reduces liver succinic dehydrogenase activity slightly, completely reduces liver xanthine oxidase activity, and has practically no effect upon endogenous respiration of liver tissue in vitro.
The Place of Nationalökonomie: Theorie Des Handelns Und Wirtschaftens in Modern Political Economy

This paper contends that Mises' work, both in Nationalokonomie and Human Action, provides us with an integrated treatise on economics and social theory which has had a tremendous intellectual influence in the second half of the 20th century. Mises' treatise can be seen as responsible for three major movements. First, Mises' work was not the last work of a dead school of economic thought, but actually the first work in a revolutionary research program for economic science that is still developing. Second, Mises' book rallied the anti-Communist intellectual forces around a book that represented a direct challenge to Marx's works on a technical, philosophical, and polemical level. Third, Mises' work was one of the main intellectual inspirations behind the rebirth of classical liberal political economy, and the unification of the related discipline through a common means of analysis - methodological individualism. In short, Mises' work is the fountainhead for the rational choice revolution in social science.
Analysis of the prevalence of hypertension, hyperglycemia, hyperlipidemia and fatty liver in 3 474 examined elderly people

Objective: To understand the detected prevalence of hypertension, hyperglycemia, hyperlipidemia and fatty liver of the elderly people in Zhongshan Community to provide a reference for the prevention and treatment. Methods: In 2012, 3 474 elderly people over 60, among them 1 400 male accounting for 40.30% and 2 074 female accounting for 59.70% were examined for hypertension, hyperglycemia, hyperlipidemia and fatty liver. The prevalence of hypertension, hyperglycemia, hyperlipidemia and fatty liver were analyzed in different elderly genders and ages. Results: The detective rates of hypertension, hyperglycemia, hyperlipidemia and fatty liver were 40.50%, 12.87%, 55.96% and 31.23%, respectively. The detective rates of hyperlipidemia, and hyperglycemia were higher in female than in male. The detective rate of fatty liver decreased with the increase of the age. In the physical examination, the elderly people having one abnormality accounted for 44.19%. Conclusion: The detective rate of the chronic diseases in the elderly residents is high in Zhongshan Community. It should take the effective intervention measures.
Fine-granularity tile-level parallelism in non-volatile memory architecture with two-dimensional bank subdivision

Emerging memory technologies such as phase-change memory (PCM) and resistive RAMs (RRAM) have been proposed as promising candidates for future DRAM replacements. Due to the nature of how these memories operate, unique properties (such as non-destructive read and current-sensing) can be exploited to further subdivide memory and provide increasing parallelism with negligible overhead. In this work, we leverage these properties to design a finegrained non-volatile memory (FgNVM), featuring two-dimensional bank subdivision for tile-level parallelism (TLP) in a NVM memory bank, with much finer-granularity and increased parallelism than the one-dimensional bank subdivision for subarray-level parallelism (SALP) in a DRAM memory bank. With such new tile-level parallelism, three new memory access modes are proposed for further performance improvement and energy reduction: Partial-Activation, Multi-Activation, and Background Writes. Our experimental results show that the new architecture is highly effective in boosting non-volatile memory performance with significant energy reduction. To the best of our knowledge, this is the first work to study fine-granularity memory access in emerging non-volatile memory architectures.
Prevention and treatment of nonpostmenopausal osteoporosis.

PURPOSE: The causes, prevention, and treatment of osteoporosis in specific populations are discussed. SUMMARY: Osteoporosis and osteopenia affect 44 million women and men ages 50 years or older. Fractures are the most devastating consequence of this disease and significantly affect quality of life, activities of daily living, survival, and health care costs. Most osteoporosis research has focused on postmenopausal women, but several other populations are at risk for osteoporosis, such as patients taking certain medications that affect bone health and those with various health conditions that cause bone loss, including anorexia nervosa, hyperthyroidism, organ transplantation, chronic obstructive pulmonary disease, and inflammatory bowel disease. Glucocorticoids are the most common secondary cause of osteoporosis. Other medications that have been implicated as secondary causes include anticonvulsants, heparin, warfarin, and methotrexate. Preventing osteoporosis may be even more important in adolescence than after menopause. CONCLUSION: Osteoporosis needs to be recognized, monitored, and appropriately treated in patients taking medications that affect bone health and in patients with conditions that increase the risk of osteoporosis.
Perspectives on International Crisis

Scholars of international politics and foreign policy are often preoccupied with the development of empirical theory consisting of a set of interrelated propositions (confirmed hypotheses) about how, why, and when states in the international system are likely to act and interact. For the most part, those who seek this kind of theory are relatively unconcerned with the potential for actual application of their work. This is usually as much a function of available time and energy as it is of preference.. Others, however,. are concerned primarily with the policy implications of theoretical work and, in some cases, with the development of solutions to specific policy problems. Thiis special issue on international crisis forecasting and management is comprised of articles we believe to be representative of the la-test and best efforts in both communities.. It does. not contain articles devoted-or in any way hostile-to the development of theory for its own sake; indeed, it could not have been written but for the efforts of basic researchers. Nor is it prescriptive in nature. Instead, the issue seeks to present the international studies community with a set of papers designed to stimulate thought and discussion regarding the prospects for applied crisis forecasting and management and to apprise them of recent progress in this area along
Display of Passion

In very formal settings, displays of passion are strongly constrained by ritual proprieties. Roll calls in a convention, for example, are thoroughly structured by parliamentary rules. These rules identify who can vote, when they can vote, and what will be the relative weight assigned to their vote. Once delegates have voted, the rules apply an exact calculus that determines the outcome. In other settings, people display sentiment much more spontaneously, as in the collective displays created by mass demonstrations and riots. Such displays are not formally recognized or structured by an institution. For convenience, let us agree to call displays of sentiment that are strongly constrained by formal ritual institutionally recognized preferences and label displays that lay outside institutional forms demonstrative acts . Institutionally recognized preferences are usually “flat” in that the way in which an individual or group displays sentiment does not affect the manner in which the institution calculates the outcome. For example, in a legislative roll call members may stand perfectly still or wildly gesticulate as they cast their vote. However they cast their vote, the calculus will treat it as the same act. There are thus three characteristics associated with the display of institutionally recognized preferences: they are strongly constrained by ritual formalities; they enter into a calculus that processes them into a collectively recognized decision; and the intensity with which they are displayed has no effect on how the calculus processes the response.
ILC3s and the Willow Tree of Voices

Type 3 innate lymphoid cells (ILC3s) and enteric glia, an essential structural component of gut innervation, are well-known regulators of intestinal homeostasis. Ibiza et al. (2016) uncover a new link between commensal bacteria, enteric glial cells, and ILC3s that is required for intestinal homeostasis and defense.
Microscopic Damage Traces And Manufacture Process: The Denali Complex Example

(1980). Microscopic Damage Traces And Manufacture Process: The Denali Complex Example. Lithic Technology: Vol. 9, Edge Damage, pp. 34-35.
Using Digital Resources for Motivation and Engagement in Learning Mathematics: Reflections from Teachers and Students

Students’ motivation to learn mathematics often declines during the middle grades. How do we keep students engaged with learning mathematics as it gets more complex? One way is through the use of technology, such as computer games, interactive lessons, or on-line videos. Yet evidence from creating technology-based tasks and resources to motivate students to learn mathematics is mixed, partially because most interventions only loosely incorporate motivational constructs. This article is part of a larger research project examining the impact of three digital resources on students’ motivation and learning in mathematics. In it, we provided resources tightly aligned to motivational constructs from research: self-efficacy, implicit theories of ability, and interest and enjoyment. Students then engaged with these resources before and after a 2-day mathematical patterns lesson. We present results from interviews and observations with eighty-eight fifth- to eighth-grade students and their ten teachers. Findings suggest that, even with a minimal encounter over 1 or 2 days, students were able to notice the motivational constructs present within these digital resources.
Adult congenital heart disease: right ventricular outflow tract lesions.

It has variably been estimated that between 800 000 and 1 million patients with congenital heart disease are now adults and that by 2010 more patients older than 16 years will undergo surgery for congenital heart disease than those younger than 16 years.1 This review will focus on the clinical aspects of identifying and caring for the portion of the unique population that have right ventricular (RV) outflow tract lesions. The left ventricle (LV) and RV both have inlet, apical, and outlet portions, although they differ considerably.2 The inlet of the RV includes the tricuspid valve, and it is separated from the pulmonary valve (PV) by the crista supraventricularis. This structure results in the PV being raised upward. The apical portion of the RV has coarse trabeculations. As shown in Figure 1, the septum is home to a large septomarginal (septal) trabeculation that divides into the anterior and posterior limbs in the outflow tract. A series of septoparietal trabeculations arise along the free wall. The crista supraventricularis inserts between these limbs and is made up of 3 components: the muscular outlet septum, the ventriculoinfundibular fold, and the inner curvature of the RV.3 The small part that separates the RV and LV cavities is the outlet or conal septum. A loop including the septal trabeculation, the moderator band, septoparietal trabeculations, and the outlet septum can be conceptualized as circling the RV outflow tract. The PV is supported by the circular muscular infundibulum rising outside the RV proper. Abnormalities involving the RV outflow tract involve malpositioning of 1 or more of these structures. Figure 1. The anatomy of the RV outflow tract.2 There is a large septomarginal (septal) trabeculation that divides into 2 limbs. The anterior limb supports the leaflets of the PV, and the posterior limb …
Driving force of globalization: A multi- paradigmatic look

Abstract Any explanation of the driving force of globalization is based on a worldview. The premise of this paper is that any worldview can be associated with one of the four broad paradigms: functionalist, interpretive, radical humanist, and radical structuralist. This paper takes the case of the driving force of globalization and discusses it from the four different viewpoints. It emphasizes that the four views expressed are equally scientific and informative; they look at the phenomenon from their certain paradigmatic viewpoint; and together they provide a more balanced understanding of the phenomenon under consideration. This approach is applicable to any phenomena, including financial phenomena.
Curious partner: an autonomous system that proactively dialogues with human teammates

In this paper, a human-autonomy interaction approach is presented that enables autonomy to proactively dialogue with human teammates to maintain common understanding of the underlying processes. A class of human-autonomy systems where the role of the autonomy is to assist a human teammate in decision making tasks is considered. The autonomy maintains its knowledge of the processes and the environment in a Bayesian engine, and uses a Bayesian inference framework to provide decision support. Any discrepancy in the knowledge of the process between the autonomy and the human teammate may lead to inefficient decision support. The presented curious partner interaction framework uses a dialogue-based approach to resolve differences between the human and the autonomy. The dialog acts as a feedback mechanism to revise the Bayesian engine representation of the autonomy’s knowledge to establish common ground. An application to military operations is considered where a digital assistant uses the curious partner framework to provide decision support to a commander.
Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

ABSTRACTIntroduction: Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration.Areas covered: This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery.Expert opinion: Further research is necessary to elucidate the dynam...
Envisioning the Library-Centric First-Year Experience: A Case Study about Mississippi State University Libraries' Course Proposal Process

ABSTRACTFirst-Year experience (FYE) courses have become increasingly implemented in higher education institutions in recent years to help drive student retention. Although many of these FYE courses...
Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn.

Abstract Evidence is reviewed that behavioral training and neural injury can engage metaplastic processes that regulate adaptive potential. This issue is explored within a model system that examines how training affects the capacity to learn within the lower (lumbosacral) spinal cord. Response-contingent (controllable) stimulation applied caudal to a spinal transection induces a behavioral modification indicative of learning. This behavioral change is not observed in animals that receive stimulation in an uncontrollable manner. Exposure to uncontrollable stimulation also engages a process that disables spinal learning for 24–48 h. Controllable stimulation has the opposite effect; it engages a process that enables learning and prevents/reverses the learning deficit induced by uncontrollable stimulation. These observations suggest that a learning episode can impact the capacity to learn in future situations, providing an example of behavioral metaplasticity. The protective/restorative effect of controllable stimulation has been linked to an up-regulation of brain-derived neurotrophic factor (BDNF). The disruption of learning has been linked to the sensitization of pain (nociceptive) circuits, which is enabled by a reduction in GABA-dependent inhibition. After spinal cord injury (SCI), the co-transporter (KCC2) that regulates the outward flow of Cl− is down-regulated. This causes the intracellular concentration of Cl− to increase, reducing (and potentially reversing) the inward flow of Cl− through the GABA-A receptor. The shift in GABA function (ionic plasticity) increases neural excitability caudal to injury and sets the stage for nociceptive sensitization. The injury-induced shift in KCC2 is related to the loss of descending serotonergic (5HT) fibers that regulate plasticity within the spinal cord dorsal horn through the 5HT-1A receptor. Evidence is presented that these alterations in spinal plasticity impact pain in a brain-dependent task (place conditioning). The findings suggest that ionic plasticity can affect learning potential, shifting a neural circuit from dampened/hard-wired to excitable/plastic.
THE SEVEN VEILS OF DIPICOLINIC ACID

Publisher Summary This chapter describes the composition of dipicolinic acid. Many articles that deal with dipicolinic acid (pyridine 2, 6 dicarboxylate) (DPA), at some point, are sure to mention that this single substance constitutes 10–15% of the dry weight of the bacterial endospore. This is an arresting fact that immediately draws one's attention to an exceptional aspect of what is already an unusual biological material. Bacterial endospores are indeed a dramatic representative of the cryptobiotic state. As one surveys the literature, there is a definite feeling that there is an analogy to be drawn between the multilayered ultrastructure of the spore and the successive veils of secrecy that have enshrouded the mysteries of dipicolinate. It is clear that the involvement of B. natto in the fermentation of the soy beans is the reason that DPA occurs in the condiment.
CONNECTIVITY AND SEPARATION IN AUTOMATA

Publisher Summary This chapter presents several characteristics of connectedness and of separation in automata and discusses their relationships to other connectivity properties and to the basic structure of automata. An automaton is finite only if its set of states is finite. A primary of a nonempty finite automaton is a maximal singly generated subautomaton. The union and the intersection of subautomata of A are themselves subautomata of A. The chapter illustrates a method for finding the minimal separated subautomata of a finite automaton and explains its use in determining the homomorphisms, endomorphisms, isomorphisms, and automorphisms of finite automata. The separated parts of an automaton can be regarded as unrelated automata with the same input alphabet. Every nonempty automaton is made entirely of blocks. Many problems are profitably reducible to the natural building blocks. Two blocks of a nonempty automaton are either identical or disjoint. A nonempty subautomaton C of A is separated only if C is the union of blocks of A.
Stress Analysis of a Duplex Structure in a High Heat Flux Fusion Environment

High heat flux components in fusion reactors will experience inelastic strains resulting from swelling, creep, and thermal expansion. Additionally, because of thermal and irradiation creep, the stresses will redistribute during the lifetime of the component. Current proposals for fusion first walls and divertors include structures fabricated by bonding two different metals together. The plasma-side material is chosen to minimize sputtering; the coolant-side material is chosen to maximize heat transfer. The structural response of such a design is not well known. Accordingly, a one dimensional inelastic stress analysis of a thin walled shell element has been performed. The stress analysis can include temperature-dependent material properties, radiation-induced swelling, thermal and irradiation creep, and thermal expansion. Furthermore, a simple equation has been derived for the case of a duplex plate constrained from bending. The stress distribution through the plate is followed with time. It is shown that the initial stress distribution evolves with time until some near-steady-state distribution is approached. The evolution is dependent on swelling and particularly on creep.
Immune Responses of Hamsters and Humans with Antibiotic-Associated Colitis

The Golden Syrian hamster has served as a model for antibiotic-associated colitis of humans and has been instrumental in discovering its pathogenesis (4,18). Toxigenic Clostridium difficile have been implicated as the major cause of antibiotic-associated colitis (AAC) in both hamsters and humans (5,10,20). While clindamycin first focused attention on this lesion, many other antibiotics have been implicated subsequently following either parenteral or oral administrations. AAC also varies greatly in its clinical presentation in humans and in its geographic distribution (17,23).
Deciphering cancer fibroblasts

In this issue of JEM, Raz et al. (https://doi.org/10.1084/jem.20180818) identify a subset of bone marrow-derived cells that uniquely promotes breast cancer angiogenesis and tumor growth. The existence of functional heterogeneity among stromal populations motivates further fundamental and therapeutic inquiries.
Optimal Needle Diameter, Shape, and Path in Autonomous Suturing.

Needle shape, diameter, and path are critical parameters that directly affect suture depth and tissue trauma in autonomous suturing. This paper presents an optimization-based approach to specify these parameters. Given clinical suturing guidelines, a kinematic model of needle-tissue interaction was developed to quantify suture parameters and constraints. The model was further used to formulate constant curvature needle path planning as a nonlinear optimization problem. The optimization results were confirmed experimentally with the Raven II surgical system. The proposed needle path planning algorithm guarantees minimal tissue trauma and complies with a wide range of suturing requirements.
LEFT VENTRICULAR SUPPORT IN VA-ECMO: NATIONAL TRENDS AND OUTCOMES (2007-2014)

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides cardiopulmonary support in cardiogenic shock (CS) as a bridge to recovery, durable left ventricular assist device (LVAD) or orthotopic heart transplant (OHT). Over the past decade, there has been an increase in the use of VA-ECMO in
Characterization of a Mouse Model of Hypereosinophilic Syndrome

Abstract Introduction: Hypereosinophilic syndrome is characterized by sustained blood and/or tissue hypereosinophilia leading to tissue damage and organ dysfunction. Nearly half the cases are classified as idiopathic, since no known cause is identified and there is no evidence of a clonal disorder. In such cases, nonspecific treatment approaches, including corticosteroids, hydroxyurea and interferon-alpha, are used aimed at mitigating eosinophil-mediated organ damage. However, mortality occurs primarily due to cardiac and thromboembolic complications. Understanding the cause and mechanism of disease would aid in the development of targeted therapies with greater efficacy and fewer side effects. For instance, while the traditional view is that eosinophils are detrimental via toxicity of their granule proteins, recent studies suggest other mechanisms including non-canonical cell death subroutines, such as regulated necrosis, release of pro-thrombotic DNA “traps” and others. Lack of a mouse model hinders testing such hypotheses in vivo. We have developed a mouse model of eosinophil-associated hypereosinophilic syndrome characterized by multi-organ involvement including lethal prothrombotic myocardial damage. Results: We discovered a spontaneous mouse mutant in our colony with a hypereosinophilic phenotype. Mice develop peripheral blood eosinophilia, infiltration of lungs, spleen and heart by eosinophils, and extensive myocardial damage and remodeling. This ultimately leads to heart failure and premature death, often by 14 weeks of age. Histopathologic assessment of the hearts from affected mice (Fig. 1) revealed a robust inflammatory infiltrate of the ventricular myocardium. Immunohistochemistry demonstrated that this infiltrate is composed primarily of eosinophils (MBP) and B lymphocytes (B220), leading to myocardial damage and replacement fibrosis. In some cases, hearts showed dilatation and thinning of the right ventricular wall, suggestive of an inflammatory dilated cardiomyopathy. An exam of most mice revealed primarily atrial thrombi, which often filled the entire/majority of the chamber. Expression analysis by protein multiplex assay in heart homogenates revealed overexpression of Th1 and Th2 cytokines and chemokines, including IL-4, IL-6, LIF, IL-16, IP-10/Cxcl10, MIG/Cxcl9, Eotaxin-1/Ccl11, RANTES/Ccl5, MIP-1β/Ccl4, MIP-3β/Ccl19, MCP-1/Ccl2, MCP-3/Ccl7, MDC/Ccl22 and TARC/Ccl17. Conclusion: The pathologies observed in the mutant line are reminiscent of those seen in patients with hypereosinophilia, where cardiac-related morbidities, like congestive heart failure and thrombi, are the most common causes of death. As such, our model provides an opportunity to test mechanistic hypotheses and develop targeted therapies. Download : Download high-res image (595KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
What (Quilting) Circles Can Be Squared

SummaryIn a certain type of round robin quilting circle, each person starts their own quilt by making a square of some color or design. Everybody in the circle then passes their quilt to someone el...
Impact of Extracorporeal Membrane Oxygenation on Mortality in Adults With Cardiac Arrest.

Previous studies regarding benefit of extracorporeal membrane oxygenation (ECMO) in adults with cardiac arrest have yielded conflicting results. We aimed to determine whether ECMO in adults hospitalized with cardiac arrest is associated with improved survival compared with conventional cardiopulmonary resuscitation in a nationally representative sample. The U.S. Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (2006 to 2014) was utilized to identify a cohort of adults hospitalized with cardiac arrest at ECMO-capable facilities (defined by the presence of at least 1 ECMO procedure at the facility during the study period of 2006 to 2014). In-hospital mortality was compared between the ECMO and non-ECMO groups using generalized estimating equations with and without coarsened exact matching analysis. Of 273,690 hospitalizations for adults with cardiac arrest, 33,274 occurred at 363 ECMO-capable facilities, of which 775 (2.3%) involved the use of ECMO. There was no significant difference in in-hospital mortality between patients who received ECMO versus those who did not (60.1% vs 57.2%, p = 0.106). In the risk-adjusted analysis, the presence of ECMO was associated with higher rates of in-hospital mortality in the overall sample [odds ratio 1.59, 95% confidence interval 1.37 to 1.85] and the coarsened exact matching sample (n = 1,068 with 534 adults in each group; odds ratio 1.47, 95% confidence interval 1.14 to 1.88). In this cohort of hospitalizations for cardiac arrest at ECMO-capable centers in the U.S., adults who received ECMO had significantly higher mortality than those who did not receive ECMO. Large scale, adequately powered, randomized controlled trials are warranted to assess the benefit of ECMO in cardiac arrest.
Fractals, Intermittency and Morphogenesis

Until recently, there were no satisfactory models to account for complex physiological structures or processes that do not have characteristic scales of length and/or time. The concept of fractal offers new insights into multiple scaled structures such as the bronchial and coronary tree, His-Purkinje system and chordae tendineae as well as into the broadband, inverse power-law spectra associated with normal electrophysiological dynamics. In a broader biological context the notion of a fractal distribution may have implications regarding error-tolerance and evolution. These ideas are discussed and some supporting mathematical analysis and data are presented.
Early Use of Tocilizumab May Prevent Clinical Deterioration in Select COVID-19 Patients: A Case Series

Coronavirus disease 2019 (COVID-19) is a respiratory viral illness caused by the novel severe acute respiratory syndrome coronavirus 2. It is known to cause severe illness in certain patients, who develop acute respiratory distress syndrome (ARDS) often requiring intubation and mechanical ventilation adding to significant morbidity and mortality. Tocilizumab is an interleukin-6 inhibitor that has shown promise in improving outcomes in patients with COVID-19. It is usually administered to patients with severe COVID-19 who develop ARDS. We present three cases of COVID-19 where the patients were admitted to the hospital for observation and were found to be worsening clinically. They were believed to be developing ARDS, and intubation and mechanical ventilation were anticipated. Tocilizumab was administered in the early phase of the disease before intubation. Patients improved clinically and ultimately did not require intubation. Our findings suggest that early use of tocilizumab might be beneficial in preventing clinical deterioration and intubation in select COVID-19 patients.
Sort, Assess, Life-Saving Intervention, Triage With Drone Assistance in Mass Casualty Simulation: Analysis of Educational Efficacy.

Introduction Mass casualty incident (MCI) simulation and triage are educational methods used to provide high fidelity training to first response teams. Simulation and triage need to be as effective as possible to train professionals for true emergencies involving mass casualty. Although MCI simulation and triage have been used in the pre-professional setting (i.e. medical school, nursing school, etc.), more data is required regarding quality improvement of these simulations. This study focuses on quality improvement of MCI simulation and triage in the pre-professional training. In order to evaluate simulation quality to optimize future triage simulations, this study had three specific aims: (1) assess participant accuracy of triage after training in Sort, Assess, Life-Saving Interventions, Triage/Transport (SALT); (2) evaluate the role of stress and confidence in participants of triage simulation; (3) determine trainees' perception of unmanned aerial vehicles (drones) in the setting of mass casualty simulation. Methods A total of 44 attendees of the University of Central Florida (UCF) College of Medicine Global Health Conference participated in this study across three groups. Each group was provided a 15-minute lecture on SALT protocol. After the training, the participants continued to a 30-minute simulation in which they were asked to accurately triage up to 46 patient-actors. Each participants' triage designations were compared to the previously assigned designations of each patient-actor. Pre- and post-simulation surveys were collected and analyzed using Statistical Package for the Social Sciences (SPSS) (IBM Corp., Chicago, IL). All other data were analyzed using descriptive statistics. Results Qualitative and Likert data for the simulation were collected from 44 participants. Given a total of 1,113 triage scores (average of 25.29 triage designations per person), there was data to support that novice learners in this study tended to under-triage using the SALT protocol after 15-minute SALT training, with an overall accuracy of 52.43%. Survey data showed that confidence in mass casualty triage improved post-simulation, improving from median 3/10 to 5/10. Most participants were unaware of the use of unmanned aerial vehicles in MCI but most had positive opinions of their usefulness in MCI after the simulation, with a median score of 8/10. Conclusions Participant accuracy of triage after undergoing a 15-minute training in SALT triage was 52.43%, with a non-statistically significant tendency to under-triage. This accuracy level is consistent with other studies of SALT triage in MCI, but the tendency to undertriage requires further study for validation. Stress levels during the simulation were significantly elevated, while post-simulation confidence increased significantly from pre-simulation. The perception of drone utility in MCI was favorable among participants in this study, indicating drones may be useful for first response teams in future mass casualty simulations.
Emerging treatment options for patients with high-risk myelodysplastic syndrome

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis with peripheral blood cytopenias, dysplastic cell morphology, and a variable risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine have been used for over a decade in MDS treatment and lead to a modest survival benefit. However, response rates are only around 40% and responses are mostly transient. For HMA-refractory patients the prognosis is poor and there are no therapies approved by the United States Food and Drug Administration. Combinations of HMAs, especially along with immune checkpoint inhibitors, have shown promising signals in both the frontline and HMA-refractory setting. Several other novel agents including orally available and longer acting HMAs, the BCL-2 inhibitor venetoclax, oral agents targeting driver mutations (IDH1/2, FLT3), immunotherapies, and new options for intensive chemotherapy have been studied with variable success and will be reviewed herein. Except for the minority of patients with targetable driver mutations, HMAs - likely as part of combination therapies - will remain the backbone of frontline MDS treatment. However, the wider use of genetic testing may enable a more targeted and individualized therapy of MDS patients.
yt: A Multi-code Analysis Toolkit for Astrophysical Simulation Data

The analysis of complex multiphysics astrophysical simulations presents a unique and rapidly growing set of challenges: reproducibility, parallelization, and vast increases in data size and complexity chief among them. In order to meet these challenges, and in order to open up new avenues for collaboration between users of multiple simulation platforms, we present yt (available at http://yt.enzotools.org/) an open source, community-developed astrophysical analysis and visualization toolkit. Analysis and visualization with yt are oriented around physically relevant quantities rather than quantities native to astrophysical simulation codes. While originally designed for handling Enzo's structure adaptive mesh refinement data, yt has been extended to work with several different simulation methods and simulation codes including Orion, RAMSES, and FLASH. We report on its methods for reading, handling, and visualizing data, including projections, multivariate volume rendering, multi-dimensional histograms, halo finding, light cone generation, and topologically connected isocontour identification. Furthermore, we discuss the underlying algorithms yt uses for processing and visualizing data, and its mechanisms for parallelization of analysis tasks.
Emerging investigator series: immobilization of arsenic in soil by nanoscale zerovalent iron: role of sulfidation and application of machine learning

Despite its widespread success, nanoscale zero-valent iron (nZVI) is ineffective for the remediation of some contaminants, rapidly oxidizes in the natural environment, undergoes side reactions with water, and may be very toxic to organisms. Sulfidated nZVI (SnZVI) overcomes some of the shortcomings of nZVI in aquatic environments but studies in terrestrial systems are rare. Most existing studies either investigated the application of nanoparticles for remediation or their environmental impact, making it challenging to holistically evaluate the sustainability of nanoremediation. In this study, we simultaneously studied the immobilization of 50 ppm arsenic by nZVI and SnZVI in soil for 168 d, as well as their impact on the survival of earthworms (Eisenia fetida) during remediation. Leachable arsenic decreased by 93% and 68% after 7 d when the soil was treated with 0.3% nZVI and SnZVI, respectively. Higher arsenic immobilization was observed at higher nanoparticle dosages and longer treatment times. SnZVI performed better than nZVI when immobilized arsenic was normalized by the surface areas of both nanoparticles. An artificial neural network was successfully used to predict arsenic immobilization over time. The survival of earthworms decreased from 60% in untreated arsenic-contaminated soil to 10% when the soil was treated with 0.3% nZVI, but increased to 73% when the soil was treated with 0.3% SnZVI, showing that sulfidation decreased the toxicity of nZVI. Both nanoparticles decreased the bioaccumulation of arsenic in E. fetida, an important food source in terrestrial systems. This study demonstrates the potential of SnZVI for more sustainable remediation of arsenic in soil.
Point-of-Care Assessment of DCD Livers During Normothermic Machine Perfusion in a Nonhuman Primate Model.

Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5 minutes (DCD-5min, n = 4) or 45 minutes (DCD-45min, n = 4) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow-controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8 hours for analysis. DCD-45min livers had greater terminal portal vein pressure (8.5 vs. 13.3 mm Hg, P = 0.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, P = 0.005). During perfusion, DCD-45min livers had equivalent terminal lactate clearance (93% vs. 96%, P = 0.344), greater terminal alanine aminotransferase (163 vs. 883 U/L, P = 0.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7 U/L, P = 0.002). DCD-45min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250 ng/mL, P = 0.029; and 158 vs. 293 ng/mL, P = 0.003; respectively). DCD-5min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD-45min livers did not. On blinded histologic evaluation, DCD-45min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. Conclusion: Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP.
An Empirical Approach to Identifying Subject Matter Experts for the Development of Situational Judgment Tests

Abstract. The development of a scoring key for the situational judgment test often requires subject matter experts (SMEs) to identify the best responses for a hypothetical situation. And yet, there...