cssi/SciSciGPT-SciSciNet huggingface dataset:
Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes

Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.
Fast and slow effects of medial olivocochlear efferent activity in humans.

Background The medial olivocochlear (MOC) pathway modulates basilar membrane motion and auditory nerve activity on both a fast (10–100 ms) and a slow (10–100 s) time scale in guinea pigs. The slow MOC modulation of cochlear activity is postulated to aide in protection against acoustic trauma. However in humans, the existence and functional roles of slow MOC effects remain unexplored. Methodology/Principal Findings By employing contralateral noise at moderate to high levels (68 and 83 dB SPL) as an MOC reflex elicitor, and spontaneous otoacoustic emissions (SOAEs) as a non-invasive probe of the cochlea, we demonstrated MOC modulation of human cochlear output both on a fast and a slow time scale, analogous to the fast and slow MOC efferent effects observed on basilar membrane vibration and auditory nerve activity in guinea pigs. The magnitude of slow effects was minimal compared with that of fast effects. Consistent with basilar membrane and auditory nerve activity data, SOAE level was reduced by both fast and slow MOC effects, whereas SOAE frequency was elevated by fast and reduced by slow MOC effects. The magnitudes of fast and slow effects on SOAE level were positively correlated. Conclusions/Significance Contralateral noise up to 83 dB SPL elicited minimal yet significant changes in both SOAE level and frequency on a slow time scale, consistent with a high threshold or small magnitude of slow MOC effects in humans.
How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature

Sleep disturbance is perhaps one of the most prevalent complaints of patients with chronically painful conditions. Experimental studies of healthy subjects and cross-sectional research in clinical populations suggest the possibility that the relationship between sleep disturbance and pain might be reciprocal, such that pain disturbs sleep continuity/quality and poor sleep further exacerbates pain. This suggests that aggressive management of sleep disturbance may be an important treatment objective with possible benefits beyond the improvement in sleep. Little is known, however, about how to effectively treat sleep disturbance associated with pain or whether such treatment might have beneficial effects on reducing pain. A small, but growing literature has applied cognitive-behavioral therapies (CBT) for either pain management or insomnia to patients with chronic pain. In this article, we review the longitudinal literature on sleep disturbance associated with chronic pain and clinical trial literatures of cognitive-behavior therapy for pain management and insomnia secondary to chronic pain with the aim of evaluating whether the relationship between clinical pain and insomnia is reciprocal. While methodological problems are common, the literature suggests that the relationship is reciprocal and CBT treatments for pain or insomnia hold promise in reducing pain severity and improving sleep quality. Directions for future research include the use of validated measures of sleep, longitudinal studies, and larger randomized clinical trials incorporating appropriate attentional controls and longer periods of follow-up.
Computer-aided design for DNA self-assembly: process and applications

CAD plays a fundamental role in both top-down and bottom-up system fabrication. This paper presents a bottom-up circuit patterning process based on DNA self-assembly. The process is described in terms of the design tool requirements and the new opportunities that self-assembly creates for circuit designers. The paper also connects recent demonstrations of addressable self-assembly to applications in computer architecture and system design.
β-Adrenergic Regulation of Cardiac Progenitor Cell Death Versus Survival and Proliferation

Rationale:Short-term β-adrenergic stimulation promotes contractility in response to stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death. Endogenous cardiac progenitor cell (CPC) activation may partially offset cardiomyocyte losses, but consequences of long-term β-adrenergic drive on CPC survival and proliferation are unknown. Objective:We sought to determine the relationship between β-adrenergic activity and regulation of CPC function. Methods and Results:Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased AKT, extracellular signal-regulated kinase 1/2, and endothelial NO synthase phosphorylation, upregulation of cyclin D1, and decreased levels of G protein–coupled receptor kinase 2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs CPC proliferation and survival. β1-AR expression...
PMD, a Registered Botanical Mosquito Repellent with Deet-Like Efficacy

para-Menthane-3,8-diol(PMD) is a monoterpene spent product of the distillation of leaves of the Australian lemon-scented gum tree (updated nomenclature Corymbia citriodora ssp. citriodora). In April 2005, the U.S. Centers for Disease Control and Prevention (CDC) endorsed two non-deet mosquito repellents, including PMD. However, few mosquito professionals have in-depth familiarity with the history and efficacy of PMD. In this article, we describe the origin and development of PMD as a repellent and offer a comprehensive review of its performance against Aedes, Anopheles, Culex, and Ochlerotatus. In addition, we present original data from field and laboratory studies involving large numbers of subjects and comparisons with high-concentration deet and other repellents. We conclude that not only is the CDC endorsement warranted but also that it probably underestimates the value of PMD as a deet alternative for public health applications.
Design and Application of the Series 60 Engine, Truck Applications

Conception et utilisation des moteurs General Motors Corporation Serie 60 (principale application pour les camions)
Is Your Refrigerator Running? Intent-To-Own Customers and How Rent-To-Own Transactions Catch Them

The Rent to Own "RTO" industry is accessible to all consumers regardless of financial background. There are no credit checks or price variances based on the customer's credit score. Some RTO customers are more valuable than others and give RTOs significant incentives to pursue customers who intend to own rather than rent.Advertisements reveal RTO desire for a specified class of customers. There are many factions of RTO customers: some with a short term need, some who are unsure of their need, and some who intend to own items. It is the latter that pays the price. They are the "intent-to-own" customers.
Nonce functions

Data, functions, and operators exist in divers current APL systems in primitive, derived, and defined forms. Only data primitives occur in an extended literal form, which can be quite complex. This paper introduces a form of function literal, subsequently extended to include operators. Lexical scope is restricted to the minimum to achieve perspicuousness and syntactic predictability. The short expressions which result form convenient, explicit representations of some common trivial functions. They can indirectly simulate trivial operators. Nonce operators can simulate syntactic entities, which have been called transforms, that produce operators. The trade-offs between extra key strokes and symbol clutter are discussed.
Operationalizing Strategy Content: An Example from the Transit Industry

ABSTRACTWhile models of organizational strategy saturate private sector research, public sector research lags behind. The model created by Boyne and Walker (2004) is an exception. The main objective of this study is to operationalize this model using a unique data set from the US transit industry. Through a survey of 103 local transit agencies, we developed separate strategy profiles for each agency that help us answer important questions about organizational strategy. We find that not only do the organizations adopt a mix of strategic stances through the action areas; they also have distinct profiles, which vary greatly between agencies.
Art and Toil in Hamlin Garland's UP THE COULEE

In Hamlin Garland's short story “Up the Coulee,” from his collection Main Travelled Roads (1891), the reunion of two brothers turns into a strained and troubled process of reconciliation. Their con...
Review: Brutalism: Post-war British Architecture by Alexander Clement; Neo-avant-garde and Postmodern: Postwar Architecture in Britain and Beyond by Mark Crinson and Claire Zimmerman, editors; A Guide to the New Ruins of Great Britain by Owen Hatherley

Alexander Clement. Brutalism: Post-war British Architecture . Wiltshire, England: The Crowood Press, 2011, 160 pp., 150 color illus. £19.95 (cloth), ISBN 9781847972309 Mark Crinson and Claire Zimmerman, editors. Neo-avant-garde and Postmodern: Postwar Architecture in Britain and Beyond . New Haven: Yale University Press, 2010, 420 pp., 103 illus. incl. 76 in color. $65 (cloth), ISBN 9780300166187 Owen Hatherley. A Guide to the New Ruins of Great Britain . London and New York: Verso Books, 2010, 369 pp., $29.95 (cloth), ISBN 9781844676514 “For many years since the war we have continued in our habit of debasing the coinage of M. le Corbusier and have created a style—‘Contemporary’—easily recognizable by its misuse of traditional materials and its veneer of ‘modern’ details, frames, recessed plinths, decorative piloti,” Theo Crosby wrote in a 1955 editorial on the New Brutalism.1 For Crosby, “contemporary” functioned as shorthand for a bastardized version of modernism—a modernism that had already been liquidated of its ideals and reduced to nothing more than a style for up-to-date living. As an antidote to such degradation, Crosby positioned New Brutalism as an archaeology of the modern movement that would include a rigorous reevaluation of its key architects—Le Corbusier and Mies van der Rohe in particular—as well as a thorough reexamination of its programs and intents. New Brutalism, for example, would push modernism’s truth-to-materials rhetoric to its limit with its interest in the “as found” just as it would reaffirm the earlier movement’s commitment to housing and the social. Though Alison and Peter Smithson, the figureheads of New Brutalism along with the critic-historian Reyner Banham, first used the phrase in conjunction with their design for a single-family warehouse-like house for Soho, in the following years the term became most closely identified with institutional building, giving rise to schools, council flats, and city halls frequently cast of rough concrete. In an age of postwar reconstruction, Brutalism positioned itself as a new kind of civic language—more vernacular slang than received pronunciation—and in time more and more architects came to speak its language. As the word spread, however, the critical contours of Brutalism often lost their shape, and the term quickly transformed into yet another style. Indeed, Brutalism is often employed today as nothing more than a vague epithet lobbed at vast expanses of postwar institutional building—a …
Young Black Gay/Bisexual and Other Men Who Have Sex With Men: A Review and Content Analysis of Health-Focused Research Between 1988 and 2013

Black young gay, bisexual, and other men who have sex with men (YGBMSM) are at high risk for negative health outcomes, though this population is underrepresented in the health literature. An extensive literature review and content analysis of health-related peer-reviewed articles (1988-2013) was conducted that targeted Black YGBMSM, examining five content areas: sexual health, health care, substance use, psychosocial functioning, and sociostructural factors. A coding sheet was created to collect information on all content areas and related subtopics and computed descriptive statistics. Out of 54 articles, most were published after 2004 ( N = 49; 90.7%) and addressed some aspect of sexual health ( N = 50; 92.6%). Few articles included content on psychosocial functioning, including bullying/harassment, suicide, and racial/ethnic identity. Data on health care delivery/receipt and health insurance were underrepresented; tobacco use and substance abuse were seldom addressed. Important sociostructural factors, including sexual networks and race-based discrimination, were poorly represented. Last, there was a noteworthy deficit of qualitative studies and research exploring intersectional identity and health. This review concludes that studies on Black YGBMSM health places sex at the forefront to the neglect of other critical health domains. More research is needed on the diverse health issues of a vulnerable and underexamined population.
A Design of the Numerical Controi Process Imitate System Bases on PRO/E

Imatate system that suitable for NC process practice was designed.Composition,basical structure and function principle of NC process imitate system were expounded. It has actuality significance that application NC process imitate system, to train handy ability of students, prevent injury and raise quality of practice in NC process practice. [
Investigation on Occupational Hazards in A Silicone Products Enterprise

[Objective]To investigate the occupational hazardous factors and degree of occupational hazard.Propose control of occupational hazards and protection requirements,Make the concentration(intensity) of occupational hazardous factors and protective facilities comply with occupational hygienic requirements.[Methods]On-site occupational hygienic investigation has been carried out on the occupational hygienic protection facilities[detection has been made on the toxicants,dust,noise.[Results]The position(detection spots) toxicants,dust and noise of the concentration(intensity) accorded with the national standards.During Occupational Health Surveillance for workers,One has been found occupational contraindication and none has occupational diseases.[Conclusion]In general,Protective measures against occupational diseases adopt by enterprise is effective.The occupational hazards actors during production can be prevented and controlled.
Effect of hematocrit on wall shear rate in oscillatory flow : do the elastic properties of blood play a role ?

Porcine blood was used to examine the relationship between hematocrit levels and wall shear rate patterns in straight and curved artery models under fixed oscillatory flow conditions characteristic of larger arteries. It is demonstrated that porcine blood models both the viscous and elastic components of the 2 Hz complex viscosity of human blood quite accurately over a broad range of shear rates (1-1000 s-1) and hematocrits (20%-80%). For a fixed oscillatory flow waveform (Poiseuille peak shear rate = 168 s-1; mean shear rate 84 s-1), increases in hematocrit produced a decrease in the peak wall shear rate in both the straight and curved artery models and a corresponding decrease in wall shear rate reversal on the inside wall of the curved artery model. The same trends were also observed for oscillatory flows of aqueous glycerin solutions of increasing viscosity in the range of viscosity of the blood samples tested. Aqueous glycerin solutions produced wall shear rate waveforms of the same magnitude and shape as the porcine blood. This indicates that variations in the shear rate, and therefore the shear stress, were caused primarily by changes in the viscous and not the elastic properties of blood. The results suggest that simple Newtonian fluids may be sufficient for in vitro determination of the first order effects to be expected of human blood flow in large vessels having complex geometries and shear rates in or above the range of the present study.
Resolution of Oculomotor Nerve Palsy Secondary to Posterior Communicating Artery Aneurysms: Comparison of Clipping and Coiling.

Background Previous studies have attempted to determine the best treatment for oculomotor nerve palsy (ONP) secondary to posterior communicating artery (PCoA) aneurysms, but have been limited by small sample sizes and limited treatment. Objective To analyze the treatment of ONP secondary to PCoA with both coiling and clipping in ruptured and unruptured aneurysms. Methods Data from 2 large academic centers was retrospectively collected over 22 years, yielding a total of 93 patients with ONP secondary to PCoA aneurysms. These patients were combined with 321 patients from the literature review for large data analyses. Onset symptoms, recovery, and time to resolution were evaluated with respect to treatment and aneurysm rupture status. Results For all patients presenting with ONP (n = 414) 56.6% of those treated with microsurgical clipping made a full recovery vs 41.5% of those treated with endovascular coil embolization (P = .02). Of patients with a complete ONP (n = 229), full recovery occurred in 47.3% of those treated with clipping but in only 20% of those undergoing coiling (P = .01). For patients presenting with ruptured aneurysms (n = 130), full recovery occurred in 70.9% compared with 49.3% coiled patients (P = .01). Additionally, although patients with full ONP recovery had a median time to treatment of 4 days, those without full ONP recovery had a median time to treatment of 7 days (P = .01). Conclusion Patients with ONP secondary to PCoA aneurysms treated with clipping showed higher rates of full ONP resolution than patients treated with coil embolization. Larger prospective studies are needed to determine the true potential of recovery associated with each treatment. Abbreviations EUH, Emory University HospitalIQR, interquartile rangeJHU, Johns Hopkins UniversitymRS, modified Rankin ScaleONP, oculomotor nerve palsyPCoA, posterior communicating arterySAH, subarachnoid hemorrhage.
Nutrition in Inflammatory Bowel Disease

It is estimated that as many as 75 % of hospitalized patients with Crohn’s disease are malnourished [1]. The prevalence of malnutrition is significant even for patients considered to be in clinical remission. Bin et al. observed decreased handgrip strength of 73 % of subjects who had been in remission at least 3 months [2]. Similar observations were made by Valentini et al. despite the presence of normal body mass index (BMI) and serum albumin concentration [3]. In general, the likelihood of nutritional deficiencies is greater in patients with Crohn’s disease than in those with ulcerative colitis. Reduced intake of food because of abdominal cramping, nausea, and nutrient loss in diarrhea are prominent causes of weight loss in patients with IBD. Intestinal malabsorption also contributes to malnutrition in patients with active IBD, primarily those with Crohn’s disease involving the small intestine in whom entero-enteric fistulas that bypass large segments of the proximal intestine may also result in substantial nutrient malabsorption. Extensive mucosal disease, bacterial overgrowth proximal to strictures, and surgical resection all contribute to malabsorption and subsequent weight loss. Increased energy expenditure, as seen with fever, abscess or sepsis, or systemic inflammation, can also result in weight loss. Nutrient deficiency can result in altered cellular immunity with increased risk of infection, delayed wound healing, and in children, growth retardation. Therefore, it is important to identify those patients that are at potential risk of malnutrition. Medical and surgical management plans should then include prevention of, and correction of, nutritional deficits.
Immunoreactive β-endorphin in human ovaries

Beta-endorphin ( β -EP) immunostainable cells were demonstrated in human ovarian tissue using a non-cross-reacting anti- β -EP serum and the avidin-biotin-peroxidase detection technique. In ovaries from ovulating and premenopausal women, β -EP immunoreactivity was localized in the luteinized cells of theca interna of maturing follicles with almost negligible staining in granulosa cells; cells of primary follicles did not stain. In corpora lutea, luteinized cells in both theca interna and granulosa, layers were equally positive. In postmenopausal ovaries, staining was detectable only in scattered luteinized stromal cells. This is the first report on the presence of immunoreactive β -EP in human ovaries, in which β -EP seems to be produced by the same sex cord cells engaged in active steroidogenesis and may be under gonadotropin central regulation. The significance of this finding is discussed.
The Safety of Pyrantel, Oxantel, and Morantel

This discussion covers the safety and clinical toxicity of three anthelmintics of the tetrahydropyrimidine class of neuroactive agents, compounds that are primarily active against a range of nematodes affecting humans and animals. These agents act by selectively targeting the nervous system of the worms by inhibiting the neurotransmitter acetylcholine system, and thus interfering with the worms’ ability to remain in the host. Side effects and intoxication, when they result, are most commonly due to the direct effect of these agents on this nervous system in the host. Nevertheless, in general, these agents remain amongst the safest of anthelminthic drugs in use today. The clinical changes related to toxicity with all three drugs include effects on the intestinal physiology and function (nausea, abdominal discomfort, and diarrhea), CNS changes (dizziness and nausea), and less commonly, changes in other body systems. These agents are commonly used in both veterinary and human medicine successfully and safely, and often in combination with other anthelmintics.
Numerical simulations and kinetic theory for simple shear motion of bubbly suspensions

Simple shear flows of dilute suspensions of spherical bubbles at large Reynolds numbers are studied using numerical simulations and kinetic theory. It is shown that the mean-square bubble velocity is very sensitive to the volume fraction and Reynolds number of the bubbles as well as on initial conditions. The balance of energy contained in bubble velocity fluctuations plays an important role in the rheology of the dispersed phase, which is generally non-Newtonian.
ROLE OF STRIATONIGRAL PATHWAY AND GABA SYSTEMS IN METHAMPHETAMINE-INDUCED DEPRESSION OF STRIATAL TYROSINE HYDROXYLASE ACTIVITY

Methamphetamine (METH), given in repeated, toxic doses, decreased tyrosine hydroxylase (TH) activity in the corpus striatum. Three GABA transaminase inhibitors, aminooxyacetic acid, γ-acetylenic GABA and ethanolamine O-sulfate inhibited the METH-induced decline in enzyme activity. Striatal injection of kainic acid did not prevent the above responses which would suggest that striatal interneurons and the striatonigral pathway are not involved in the alteration of striatal TH activity by METH.
Assessing the effort associated with teaching residents

Summary Background Intraoperative resident education is an integral mission of academic medical centers and serves as the basis for training the next generation of surgeons. The actual effort associated with teaching residents is unknown as it pertains to additional operative time. Using a large validated multi-institutional dataset, this study aims to quantify the effect of having a resident present in common plastic surgery procedures on operative time. Future directions for developing standardized methods to record and report teaching time are proposed, which can help inform prospective studies. Study design The 2006–2012 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify seven isolated plastic surgical procedures that were categorized based on resident involvement and supervision. Linear regression models were used to calculate the difference in operative time with respect to resident participation while controlling for patient and operative factors. Results Resident involvement was associated with longer operative times for muscle flap trunk procedures (53 min, 95% CI = [25, 80], p-value = 0.0002) and breast reconstruction procedures with a latissimus dorsi flap (55 min, 95% CI = [22, 88], p-value = 0.001). For six of the seven surgeries evaluated, resident involvement was associated with longer operative times, as compared to no resident involvement. Conclusion Resident involvement is associated with an increase in operative time for certain plastic surgery procedures. This finding underscores the need for a mechanism to quantify the time and effort that the attending surgeons allocate toward intraoperative resident education. Further study is also necessary to determine the causal impact on patient care.
Sirens song or a bugle call to charge

Radial access for catheterization is associated with reduced bleeding and mortality across a spectrum of clinical conditions compared to femoral. Transradial technique is associated with a higher rate of access site failure but this is in those most likely to have a femoral-based complication. Improved outcomes will come with further radial technique refinement and not with a retreat to legacy femoral approaches.
Challenge with Staphylococcus aureus induces a lipid response in newborn piglets

The innate immune system provides the first line of defense against microbes. Epithelial cells recognize pathogen-associated molecular patterns and detection leads to induction of antimicrobial peptides, proinflammatory cytokines, and chemokines. Recent evidence suggests that antimicrobial lipids, including fatty acids and cholesteryl esters, are also important effectors in the innate mucosal defense of the airways. We have previously shown that cholesteryl linoleate and cholesteryl arachidonate are active against Pseudomonas aeruginosa and other bacteria, and that the expression of SOAT1, a key enzyme for cholesteryl ester biosynthesis, is increased in sinus mucosa of patients with chronic rhinosinusitis. The objective of this study was to further elucidate the regulation of antimicrobial lipid production by assessing the gene expression of enzymes involved in lipid biosynthesis in an in vivo pig infection model. Newborn pigs were challenged intratracheally with aerosolized heat-killed Staphylococcus aureus (n = 7) or saline (n = 5) and RNA was extracted from trachea tissues 4 h later. Gene expression of the enzymes SOAT1, FADS2, FASN and ACSL1 was statistically significantly increased (p S. aureus an increased staining with Oil Red O consistent with increased lipid accumulation. These data provide evidence that infection leads to increased lipid biosynthesis further supporting the concept of lipid-mediated innate mucosal defense.
Nutritional Anemias Overview; Megaloblastic Anemias

Nutritional anemia is defined as a condition in which the hemoglobin content of the blood is lower than normal as a result of deficiency of one or more essential nutrients, regardless of the cause of such deficiency (WHO Scientific Group on Nutritional Anemias, 1968). To delineate that a given anemia is due to deficiency of a nutrient, two criteria must be met: First, it must be demonstrated that lack of the nutrient will produce the anemia, and second, that providing the nutrient will correct the anemia (Herbert, 1970). By these two criteria, there are only three unequivocal true nutritional anemias: those due to lack of the mineral iron and those due to lack of the vitamins folate (folic acid) and vitamin B12.
Osteoarthritis and risk of mortality in the USA: a population-based cohort study.

Background Osteoarthritis (OA) is the most common joint disease, but its association with mortality is unclear. Methods We analysed data on adult participants in the 1988-94 and 1999-2010 National Health and Nutrition Examination Surveys, followed for mortality through 2011. OA was defined by self-report, and in a subset of participants 60 years or older with knee X-rays, radiographic knee OA (RKOA) was defined as Kellgren-Lawrence score ≥2. Cox proportional hazards were used to determine the mortality hazard ratio (HR) associated with self-reported OA and RKOA, adjusting for covariates. Results The sample included 51 938 participants followed for a median 8.9 years; 2589 of them had knee X-rays and were followed for a median of 13.6 years. Self-reported OA and RKOA prevalences were 6.6% and 40.6%, respectively. Self-reported OA was not associated with mortality. RKOA was associated with an increased risk of mortality from cardiovascular diseases (CVD) {HR 1.43 [95% confidence interval (CI): 1.32, 1.64]}, diabetes [HR 2.04 (1.87, 2.23)] and renal diseases [HR 1.14 (1.04, 1.25)], but with a reduced risk of cancer mortality [HR 0.88 (0.80, 0.96)]. Participants with early RKOA onset (diagnosed before age 40) had a higher risk of mortality from all causes [HR 1.53 (1.43, 1.65)] and from diabetes [HR 7.18 (5.45, 9.45)]. Obese participants with RKOA were at increased risk of mortality from CVD [HR 1.89 (1.56, 2.29)] and from diabetes [HR: 3.42 (3.01, 3.88)]. Conclusions Self-reported OA was not associated with mortality. RKOA was associated with higher CVD, diabetes and renal mortality, especially in people with early onset of the disease or with obesity.
Severe immune-related adverse effects (irAE) requiring hospital admission in patients treated with immune checkpoint inhibitors for advanced malignancy: Temporal trends and clinical significance.

3096Background: Disruption of the immune system using immune checkpoint inhibitors can result in a multitude of immune-related adverse effects (irAE). While irAEs have been well-reported in clinica...
Using technology-enhanced cases in teacher education: An exploratory study in a social studies methods course

Abstract The purpose of this case study was to gain insight into pre-service teachers' and an instructor's perceptions and experiences on their uses of technology-enhanced cases in a teaching methods course. Findings demonstrate two different reactions from pre-service teachers. The majority of them valued case discussions with co-construction of knowledge as useful and meaningful, but a few also perceived the cases as meaningless and disengaged from the discussions. The study also provides insight into how the instructor's case-based instruction mediated such differences and used the cases as a means of closing the gap between the methods course and field experience.
Do certain subpopulations of adults with drug-resistant epilepsy respond better to modified ketogenic diet treatments? Evaluation based on prior resective surgery, type of epilepsy, imaging abnormalities, and vagal nerve stimulation.

Abstract Objective Adults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. Methods Changes in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥ 17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. Results Responder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p Conclusions Modified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.
Nanoparticle contrast-enhanced micro-CT: A preclinical tool for the 3D imaging of liver and spleen in longitudinal mouse studies

Abstract In drug discovery and development, X-ray micro-computed tomography (micro-CT) has gained increasing importance over the past decades. In recent years, micro-CT imaging of soft tissues has become popular due to the introduction of a variety of radiopaque contrast agents. More recently, nanoparticle-based ExiTron nano 12,000 has become commercially available for the nonclinical micro-CT imaging of soft tissues in rodents. Phagocytosis and accumulation of the contrast agent by Kupffer cells in the liver, as well as macrophages in the spleen, increase the soft tissue X-ray attenuation for up to 6 months. Therefore, it is essential to understand the potential toxicity of this nanomaterial in micro-CT imaging prior to its application in pharmacology and/or toxicology studies. Herein, we describe the time-course and distribution of the contrast in the liver, spleen and blood after a single intravenous injection (IV) of this nanoparticle contrast agent at 0.1 ml/mouse. Thoracic images of male adult C57BL/6 mice were acquired using a Bruker SkyScan 1276 micro-CT over a period of 29 days. The stability of X-ray attenuation enhancement in the above tissues was also tested after a single dose of Kupffer cell toxicant gadolinium chloride (GdCl3) at 15 mg/kg on day 2. The liver, spleen and kidney were examined microscopically on days 15 and 29 post treatment. Serum and liver cytokines (IL-1β, IL-2, IL-6, IL-10, IL-12p70, IFN-γ, IP-10, MIP1-α, MIP1-β and TNF-α) were quantified on days 15 and 29 as indicators of a pro-inflammatory response to treatment. This study determined that there was an accumulation of amphophilic granular material in the cells of the mononuclear phagocyte system in the liver and spleen following a single dose of ExiTron nano 12,000 and a second dose of GdCl3 or its vehicle. However, ExiTron nano12000 contrast administration did not cause any hepatotoxicity in the liver, nor did pro-inflammatory cytokines release in the liver or serum. Similarly, there were no adverse pathologies in the spleen or kidneys. In summary, ExiTron nano12000 contrast agent-enhanced micro-CT could be used as a safe method in up to 29-day longitudinal efficacy and toxicology mouse studies for the non-invasive assessment of the liver and spleen.
Neurophysiological evidence of impaired attention and working memory in untreated hematologic cancer patients.

Abstract Objective Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment. Methods Hematologic cancer patients (19–80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance. Results Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen’s d = 1.1) but not controls (p = .64). Conclusions Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity. Significance Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors.
A History of Past Prostate Cancer Still Carries Risk After Total Knee Arthroplasty.

Prostate cancer (PCa) is one of the most prevalent diseases in the North American elderly population. Moreover, many patients undergo prostate resection without further treatment and are often considered cured. As such, it is expected that many undergo total knee arthroplasty (TKA) for osteoarthritis while having a history of PCa. Nonetheless, limited research is available on this topic, and without it, surgeons may not be aware of increased complication rates. Therefore, the purpose of this study was to evaluate whether patients at a national level with a history of PCa are at increased risk for complications after TKA. A retrospective case–control, comorbidity matched paired analysis was performed. Patients were identified based on International Classification of Diseases, Ninth Revision codes and matched 1:1 ratio to age, smoker status, chronic kidney disease, diabetes, chronic lung disease, smoking status, and obesity. Patients with active disease were excluded. The 90-day outcomes of TKA were compared through univariate regressions (odds ratios [ORs] and 95% confidence intervals). A total of 2,381,706 TKA patients were identified, and after matching, each comprised 113,365 patients with the same prevalence of the matched comorbidities and demographic characteristics. A significant increase in thromboembolic events that was clinically relevant was found in pulmonary embolisms (PEs) (1.44 vs. 0.4%, OR: 3.04, p
Morphological Control of Chromophore Spin State in Zinc Porphyrin–Peptide Assemblies

Self-assembled peptide micelles and fibers demonstrate unique control over the photophysical properties of the bound, light-activated chromophore, zinc protoporphyrin IX, (PPIX)Zn. Micelles encapsu...
Analysis of 1478 Cases of Hypospadias Repair: The Incidence of Requiring Repeated Anesthetic Exposure as Well as Exploration of the Involvement of Trainees on Case Duration.

BACKGROUND Recently, there has been significant focus on the effects of anesthesia on the developing brain. Concern is heightened in children 3 hours. METHODS We analyzed all cases of hypospadias repair from December 2011 through December 2018 at Texas Children's Hospital. In all, 1326 patients undergoing isolated hypospadias repair were analyzed for anesthesia time, surgical time, provider types involved, AE, caudal block, and additional AE related/unrelated to hypospadias. RESULTS For the primary aim, a total of 1573 anesthetics were performed in children <3 years of age, including 1241 hypospadias repairs of which 1104 (89%) were completed with <3 hours of AE. For patients with <3 hours of AE, 86.1% had a single surgical intervention for hypospadias. Of patients <3 years of age, 17.3% required additional nonrelated surgeries. There was no difference in anesthesia time in cases performed solely by anesthesia attendings versus those performed with trainees/assistance (16.8 vs 16.8 minutes; P = .98). With regard to surgery, cases performed with surgical trainees were of longer duration than those performed solely by surgical attendings (83.5 vs 98.3 minutes; P < .001). Performance of surgery solely by attending surgeon resulted in a reduced total AE in minimal alveolar concentration (MAC) hours when compared to procedures done with trainees (1.92 vs 2.18; P < .001). Finally, comparison of patients undergoing initial correction of hypospadias with subsequent revisions revealed a longer time (117.7 vs 132.2 minutes; P < .001) and AE during the primary stage. CONCLUSIONS The majority of children with hypospadias were repaired within a single AE. In general, most children did not require repeated AE before age 3. While presence of nonattending surgeons was associated with an increase in AE, this might at least partially be due to differences in case complexity. Moreover, the increase is likely not clinically significant. While it is critical to maintain a training environment, attempts to minimize AE are crucial. This information facilitates parental consent, particularly with regard to anesthesia duration and the need for additional anesthetics in hypospadias and nonhypospadias surgeries.
Characterization of Aerosols in an Underground Mine during a Longwall Move

A study was conducted in an underground mine with the objective to identify, characterize, and source apportion airborne aerosols at the setup face and recovery room during longwall move operations. The focus was on contributions of diesel- and battery-powered heavy-duty vehicles used to transfer equipment between the depleted and new longwall panels and diesel-powered light-duty vehicles used to transport personnel and materials to various locations within the mine. Aerosols at the setup face were found to be distributed among diesel combustion-generated submicrometer and mechanically generated coarse aerosols. According to the data, the submicrometer aerosols downstream of the setup face were sourced to diesel exhaust emitted by vehicles operated inside and outside of the panel. Depending on the intensity of the activities on the panel, the outby sources contributed between 12.5 and 99.6% to the average elemental carbon mass flow at the setup face and recovery room. Extensively used light-duty vehicles contributed measurably to the elemental carbon concentrations at the setup face. The number concentrations of aerosols downstream of the setup face were associated with aerosols generated by combustion in diesel engines operated in the shield haulage loop and/or outside of the longwall panels. Entrainment of road dust by diesel or battery-powered load-haul-dump vehicles operated near the measurement site appears to be the primary source of mass concentrations of aerosols. The findings of this study should help the underground mining industry in its efforts to reduce exposures of miners to diesel and coarse aerosols.
Embryo, larval, and juvenile staging of Lytechinus pictus from fertilization through sexual maturation.

Background Sea urchin embryos have been used for more than a century in the study of fertilization and early development. However, several of the species used, such as Strongylocentrotus purpuratus, have long generation times making them suboptimal for transgenerational studies. Results Here, we present an overview of the development of a rapidly developing echinoderm species, Lytechinus pictus, from fertilization through sexual maturation. When grown at room temperature (20°C) embryos complete the first cell cycle in 90 minutes, followed by subsequent cleavages every 45 minutes, leading to hatching at 9 hours postfertilization (hpf). The swimming embryos gastrulate from 12 to 36 hpf and produce the cells which subsequently give rise to the larval skeleton and immunocytes. Larvae begin to feed at 2 days and metamorphose by 3 weeks. Juveniles reach sexual maturity at 4 to 6 months of age, depending on individual growth rate. Conclusions This staging scheme lays a foundation for future studies in L. pictus, which share many of the attractive features of other urchins but have the key advantage of rapid development to sexual maturation. This is significant for multigenerational and genetic studies newly enabled by CRISPR-CAS mediated gene editing.
Simulation of Red Blood Cell Migration in Small Arterioles: Effect of Cytoplasmic Viscosity

Abstract The dynamics of red blood cells in small arterioles are important as these dynamics affect many physiological processes such as hemostasis and thrombosis. However, studying red blood cell flows theoretically is challenging due to the complex shapes of red blood cells and the non-trivial viscosity contrast of a red blood cell. To date little progress has been made studying small arteriole flows (20-40µm) with a hematocrit (red blood cell volume fraction) of 10-20% and a physiological viscosity contrast. In this work, we present the results of large-scale simulations that show how the channel size, viscosity contrast of the red blood cells, and hematocrit effect cell distributions and the cell free layer in these systems. We utilize a massively-parallel immersed boundary code coupled to a finite volume solver to capture particle resolved physics in these systems. We show that channel size qualitatively changes how the cells distribute in the channel. Our results also indicate that at a hematocrit of 10% that the viscosity contrast is not negligible when calculating the cell free layer thickness. We explain this result by comparing lift and collision trajectories of cells at different viscosity contrasts.
Visualization as a Service for Scientific Data.

One of the primary challenges facing scientists is extracting understanding from the large amounts of data produced by simulations, experiments, and observational facilities. The use of data across the entire lifetime ranging from real-time to post-hoc analysis is complex and varied, typically requiring a collaborative effort across multiple teams of scientists. Over time, three sets of tools have emerged: one set for analysis, another for visualization, and a final set for orchestrating the tasks. This trifurcated tool set often results in the manual assembly of analysis and visualization workflows, which are one-off solutions that are often fragile and difficult to generalize. To address these challenges, we propose a serviced-based paradigm and a set of abstractions to guide its design. These abstractions allow for the creation of services that can access and interpret data, and enable interoperability for intelligent scheduling of workflow systems. This work results from a codesign process over analysis, visualization, and workflow tools to provide the flexibility required for production use. Finally, this paper describes a forward-looking research and development plan that centers on the concept of visualization and analysis technology as reusable services, and also describes several real-world use cases that implement these concepts.
Recognition Odysseys: Indigeneity, Race and Federal Tribal Recognition Policy in Three Louisiana Indian Communities.

With the publication of Recognition Odysseys: Indigeneity, Race, and Federal Tribal Recognition Policy in Three Louisiana Indian Communities, Brian Klopotek establishes himself as an emerging new star in the field of Native American Studies