cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparison of the effects of zinc delivered in a fortified food or a liquid supplement on the growth, morbidity, and plasma zinc concentrations of young Peruvian children

Background: Zinc supplementation decreases morbidity from infections and increases growth of stunted children, but there is little information on functional responses to zinc delivered in fortified foods. Objective: The aim was to examine the effects of zinc fortification on the growth, morbidity from infections, and plasma zinc concentrations of young children. Design: We compared the physical growth, morbidity, and micronutrient status of 6–8-mo-old Peruvian children with initial lengthfor-age z score (LAZ) 0.50 who were randomly assigned to receive one of the following treatments daily for 6 mo: 1 )3 0 gd ry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin (MV) supplement between meals (control group), 2) the same porridge and MV with 3 mg Zn added to the supplementdose(ZnSupplgroup),or3)theporridgewithaddedzinc (150 mg/kg dry weight) and MV without zinc (ZnFort group). Results: The children consumed a mean of 22–26 g dry porridge/d and 96% of the possible MV doses. After adjustment for small baseline differences in socioeconomic status and morbidity, no significant differences in weight or length increments were observed between the groups, even among the subset with an initial LAZ 1.5,andnosignificantdifferencesintheratesofcommonillnesses were observed. Mean plasma zinc concentrations decreased in the control group (3.9 g/dL), increased in the ZnSuppl group (4.3 g/dL), and did not change significantly in the ZnFort group (1.5 g/dL; P 0.001 for group-wise comparison). Conclusions: Provision of additional zinc, either in an aqueous supplement or a fortified porridge, did not significantly affect the children’s physical growth or morbidity from infections, possibly because they were not sufficiently growth-restricted or zincdeficient initially or because the level of zinc intake or absorption was inadequate. Additional studies of the functional effect of zincfortified foods are needed in populations that are known to respond to zinc supplements. Am J Clin Nutr 2007;85:538–47.
Phosphodiesterase activity as a mediator of renal resistance to ANP in pathological salt retention.

Resistance to the natriuretic action of atrial natriuretic peptide (ANP) is a hallmark of states of pathological sodium retention including congestive heart failure, cirrhosis of the liver, and nep...
Genetic variants in cell cycle control pathway confer susceptibility to aggressive prostate carcinoma

Background Because a significant number of patients with prostate cancer (PCa) are diagnosed with disease unlikely to cause harm, genetic markers associated with clinically aggressive PCa have potential clinical utility. Since cell cycle checkpoint dysregulation is crucial for the development and progression of cancer, we tested the hypothesis that common germ-line variants within cell cycle genes were associated with aggressive PCa. Methods Via a two-stage design, 364 common sequence variants in 88 genes were tested. The initial stage consisted of 258 aggressive PCa patients and 442 controls, and the second stage added 384 aggressive PCa Patients and 463 controls. European-American and African-American samples were analyzed separately. In the first stage, SNPs were typed by Illumina Goldengate assay while in the second stage SNPs were typed by Pyrosequencing assays. Genotype frequencies between cases and controls were compared using logistical regression analysis with additive, dominant and recessive models. Results Eleven variants within 10 genes (CCNC, CCND3, CCNG1, CCNT2, CDK6, MDM2, SKP2, WEE1, YWHAB, YWHAH) in the European-American population and nine variants in 7 genes (CCNG1, CDK2, CDK5, MDM2, RB1, SMAD3, TERF2) in the African-American population were found to be associated with aggressive PCa using at least one model. Of particular interest, CCNC (rs3380812) was associated with risk in European-American cohorts from both institutions. CDK2 (rs1045435) and CDK5 (rs2069459) were associated with risk in the African-American cohorts from both institutions. Lastly, variants within MDM2 and CCNG1 were protective for aggressive PCa in both ethnic groups. Conclusions This study confirms that polymorphisms within cell cycle genes are associated with clinically aggressive PCa. Validation of these markers in additional populations is necessary, but these markers may help identify patients at risk for potentially lethal carcinoma. Prostate © 2015 Wiley Periodicals, Inc.
Non-Lagrangian Models of Current Algebra

An alternative is proposed to specific Lagrangian models of current algebra. In this alternative there are no explicit canonical fields, and operator products at the same point [say, ${j}_{\ensuremath{\mu}}(x){j}_{\ensuremath{\mu}}(x)$] have no meaning. Instead, it is assumed that scale invariance is a broken symmetry of strong interactions, as proposed by Kastrup and Mack. Also, a generalization of equal-time commutators is assumed: Operator products at short distances have expansions involving local fields multiplying singular functions. It is assumed that the dominant fields are the $\mathrm{SU}(3)\ifmmode\times\else\texttimes\fi{}\mathrm{SU}(3)$ currents and the $\mathrm{SU}(3)\ifmmode\times\else\texttimes\fi{}\mathrm{SU}(3)$ multiplet containing the pion field. It is assumed that the pion field scales like a field of dimension $\ensuremath{\Delta}$, where $\ensuremath{\Delta}$ is unspecified within the range $1\ensuremath{\le}\ensuremath{\Delta}l4$; the value of $\ensuremath{\Delta}$ is a consequence of renormalization. These hypotheses imply several qualitative predictions: The second Weinberg sum rule does not hold for the difference of the ${K}^{*}$ and axial-${K}^{*}$ propagators, even for exact $\mathrm{SU}(2)\ifmmode\times\else\texttimes\fi{}\mathrm{SU}(2)$; electromagnetic corrections require one subtraction proportional to the $I=1$, ${I}_{z}=0\ensuremath{\sigma}$ field; $\ensuremath{\eta}\ensuremath{\rightarrow}3\ensuremath{\pi}$ and ${\ensuremath{\pi}}_{0}\ensuremath{\rightarrow}2\ensuremath{\gamma}$ are allowed by current algebra. Octet dominance of nonleptonic weak processes can be understood, and a new form of superconvergence relation is deduced as a consequence. A generalization of the Bjorken limit is proposed.
Thrombocytopenia and platelet transfusions in patients with cancer.

Platelet transfusions are a critical component of the supportive care for patients receiving intensive therapy for hematologic malignancies. The platelet count “triggering” prophylactic transfusion has decreased over the years, and studies comparing a prophylactic versus a therapeutic transfusion approach are in progress. The evidence supporting the need for platelet transfusions prior to different invasive procedures is reviewed. Lastly, studies evaluating the use of thrombopoietic stimulating agents to reduce hemorrhage and decrease the need for platelet transfusions are discussed. To date, there is no evidence that this approach is of clinical utility.
Empire of Difference: Emergence: Brokerage across Networks

The Turkish raiders are called in their language akandye [sic. akinci ], which means “those who flow,” and they are like torrential rains that fall from the clouds. From these storms come great floods until the streams leave their banks and overflow, and everything this water strikes, it takes, carries away, and moreover, destroys, so that in some places they cannot quickly make repairs. But such sudden downpours do not last long. Thus also the Turkish raiders, or “those who flow” like rainstorms, do not linger long, but whatever they strike they burn, plunder, kill, and destroy everything so that for many years the cock will not crow there. This chilling description of Turkish cavalrymen descending on villages in northwestern Anatolia at the frontiers of the Byzantine Empire was reproduced many times by numerous fifteenth-century chroniclers of various origins; this particular one is from the pen of Konstantin Mihailovic, a Serb who served in the Janissary army. These authors reflect a certain reality of the frontier zones, where boundaries between fractured and decaying empires and past kingdoms were eroding, where the further one got from centers of authority, the further removed from law and order, the lower the stakes, the greater the thrills, and the more the expectation of “chaos.” Yet, in many ways it was from the disorder and uncertainty of the frontier that a world-class empire was born at the twilight of the thirteenth century.
Donepezil’s Effect on Cardiac Function in Patients with Alzheimer’s Disease through an In Vivo, Non Invasive Measure of Cardiac Autonomic Function

The aim of the current study was to explore the effects of the medication Donepezil (Aricept®) on cardiac autonomic function for individuals diagnosed with mild to moderate (probable) Alzheimer’s disease (AD). Using age (± 3 years) and gender matched controls, differences in heart rate variability (HRV) among individuals with Alzheimer’s disease were compared to healthy controls over a period of six months (session 1 [baseline], session 2 [3 months], and session 3 [6 months]) in both supine and standing positions. HRV was obtained through frequency-domain (Low Frequency Power, High Frequency Power, RMSSD, LF/HF Ratio) and time-domain (six minutes) measures using ECG technology. Data were analyzed using 2x2x2 (AD group n= 12; HC group n= 12) and 2x2x3 (AD group n= 8; HC group n= 8) repeated measures ANCOVA’s while controlling for age, gender, body mass index (BMI), blood pressure, medications, dose of Donepezil (Aricept®), alcohol use, caffeine use, and physical activity. Results from the ANCOVA did not reveal statistically significant between group differences for the HRV frequency-domain measures. However, data indicated a trend towards greater reductions in normalized high frequency power (parasympathetic depression) and greater increases in normalized low frequency power (sympathetic exacerbation) among the AD group versus healthy controls at all three time points despite the use of Donepezil (Aricept®).
Ireland in the Virginian Sea: Colonialism in the British Atlantic. By Audrey Horning. (Chapel Hill, NC: University of North Carolina Press, 2013. Pp. xiii, 385. $49.95.)

In her comparison of English colonization in early modern Ireland and the Albemarle Sound/Chesapeake Bay region of North America, the author of this volume challenges the standard textbook assertio...
Abstract 4533: Interaction between androgen receptor and its corepressor SLIRP is regulated by Ack1 tyrosine kinase

Reactivation of androgen receptor (AR) is critical to castration resistant progression of prostate cancer. We previously demonstrated that Ack1 (activated cdc42-associated kinase) promotes growth of prostate xenograft tumors in castrated animals by activation of AR through phosphorylation of the Tyr-267 site. However, the molecular mechanisms underlying activation of AR by Ack1 need to be fully elucidated. Using the proteomics-based approach of Differential In-Gel Electrophoresis, we searched for proteins whose interaction with AR was regulated by Ack1 by characterizing proteins coimmunoprecipitating with AR in transfected 293T cells in the absence or in the presence of activated Ack1 kinase. SLIRP (SRA stem-loop interacting RNA binding protein) was identified as a candidate protein. We confirmed that the interaction between AR and SLIRP is abrogated by Ack1 expression and dihydrotestosterone (DHT) in 293T cells and in LNCaP prostate cancer cells. Additionally, treatment with heregulin, a ligand activating HER-2/HER-3 and Ack1 downstream, also led to dissociation of AR and SLIRP in LNCaP cells. Tyrosine kinase activity of Ack1 was shown to be required for its ability to dissociate AR and SLIRP through the use of a kinase-dead mutant in 293T cells and the use of an Ack1 inhibitor dasatinib in LNCaP cells treated with heregulin. However, disruption of interaction between AR and SLIRP by Ack1 cannot be attributed to any known AR tyrosine phosphorylation sites since Ack1 expression led to disruption of binding between SLIRP and AR Y267F, Y363F, and Y534F mutants. Since SLIRP does not contain tyrosine residues, the substrate of Ack1 involved in AR-SLIRP dissociation is not known yet. We showed that SLIRP functions as a physiologically relevant corepressor of AR in prostate cancer cells. Chromatin immunoprecipitation analysis demonstrated that SLIRP was bound to the androgen regulated enhancers of AR target genes in the absence of androgen and that androgen or heregulin treatment led to loss of SLIRP binding at the androgen regulated enhancers. AR-dependent reporter activity was inhibited by overexpression of SLIRP and was increased by SLIRP knockdown. SLIRP knockdown also increased the expression of endogenous AR target mRNA levels of PSA and hK2. In summary, our data suggest that Ack1 kinase inhibits the interaction between AR and the SLIRP corepressor and causes dissociation of SLIRP from the AR target gene enhancers and thereby enhance AR transcriptional activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4533. doi:10.1158/1538-7445.AM2011-4533
SELECTIVE LEACHING OF CADMIUM IN SPENT CADMIUM-NICKEL BATTERIES

This paper studied the leaching kinetics of Ni and Co in spent cadmium - nickel batteries. The spent batteries were first crushed and roasted to convert nickel and cadmium into their oxides. The effects of H2SO4 concentrations, leaching temperature, roasting parameters and oxidant of leaching processes were investigated. Experiment results show that leaching process of Ni and Co is controlled by surface chemical reaction, the leaching percentage can markedly increase through roasting in oxygen, and addition of oxidant during leaching can enhance leaching of nickel but decrease the leaching percentage of cobalt.
Anankastic conditionals are just conditionals

This paper presents a relative theory of tense which accounts for tense behaviors in English in both matrix and embedded contexts. Crucial to this proposal is novel data which shows that the temporal orientation of finite embedded clauses is constrained by the attitude verbs which embed them. While such constraints have been observed in modal auxiliaries and non-finite-embedding attitude verbs, finite-embedding-attitudes present an important new perspective because they show that whatever constraints are introduced by the modal must be able to coexist with a tensed prejacent. This proposal is compositional, and a formal analysis is given, by which modals, including attitude verbs, may constrain the temporal possibilities of an embedded clause, without themselves introducing a reference time argument. The constraining effect of attitude verbs also eliminates the need to stipulate a general Upper Limit Constraint, and allows for a means to capture correspondences between modal flavor and temporal orientation. The result is an elegant accounting of embedded tense with empirical coverage superior to previous proposals. http://dx.doi.org/10.3765/sp.9.9 BibTeX info
Is Plutocracy Sinful

Confronting extreme inequality requires disrupting the ways that cultures legitimate concentrations of wealth and curtailing the political advantages that wealth confers. Can theology do that? Beli...
Capitalizing Resolving Power of Density Gradient Ultracentrifugation by Freezing and Precisely Slicing Centrifuged Solution: Enabling Identification of Complex Proteins from Mitochondria by Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

Density gradient centrifugation is widely utilized for various high purity sample preparations, and density gradient ultracentrifugation (DGU) is often used for more resolution-demanding purification of organelles and protein complexes. Accurately locating different isopycnic layers and precisely extracting solutions from these layers play a critical role in achieving high-resolution DGU separations. In this technique note, we develop a DGU procedure by freezing the solution rapidly (but gently) after centrifugation to fix the resolved layers and by slicing the frozen solution to fractionate the sample. Because the thickness of each slice can be controlled to be as thin as 10 micrometers, we retain virtually all the resolution produced by DGU. To demonstrate the effectiveness of this method, we fractionate complex V from HeLa mitochondria using a conventional technique and this freezing-slicing (F-S) method. The comparison indicates that our F-S method can reduce complex V layer thicknesses by ~40%. After fractionation, we analyze complex V proteins directly on a matrix assisted laser desorption/ionization, time-of-flight mass spectrometer. Twelve out of fifteen subunits of complex V are positively identified. Our method provides a practical protocol to identify proteins from complexes, which is useful to investigate biomolecular complexes and pathways in various conditions and cell types.
Knee arthrodesis: procedures and perspectives in the US from 1993 to 2011.

Background The incidence and prevalence of knee arthrodesis (fusion) in the United States is largely unknown, in spite of numerous case reports and review articles that have called attention to this life altering procedure.
Error Entropy, Correntropy and M-Estimation

Minimization of the error entropy (MEE) cost function was introduced for nonlinear and non-Gaussian signal processing. In this paper, we show that this cost function has a close relation to a recently introduced correntropy criterion and M-estimation, thus it also theoretically explains the robustness of MEE to outliers. Based on this understanding, we propose a modification to the MEE cost function named minimization of error entropy with fiducial points, which sets the bias for MEE in an elegant and robust way. The performance of this new criterion is compared with the original MEE and the mean square error criterion (MSE) in robust regression and short-term prediction of a chaotic time series.
Higher order absorbing boundary conditions using reverse operation self-consistent evaluation

A higher order absorbing boundary construction scheme using Reverse Operation Self-consistent Evaluation (R.O.S.E.) for vector finite element method (FEM) is presented in this paper. With the addition of higher order absorbing truncation, the accuracy of the full-wave simulation can be adjusted to the desired level while keeping the numerical calculations at minimum. This feature of the proposed method creates the bridge between First Order ABC and its more accurate but numerically expensive counterpart Boundary Element Method (BEM). The numerical examples validate the improved accuracy compared to First Order ABC at a lower cost than BEM.
Negotiating Cultural Boundaries Through Collaboration: The Roles of Motivation, Advocacy and Process

This case study investigated the roles of organizational culture and the individual in collaborative processes at a large, public university. Results indicate that individuals who are motivated by a belief in shared mission use their awareness of the collaborative process to advocate for themselves and others, leading to stronger and more cognitively complex collaborations across organizational cultural differences. These findings provide insight into the individual’s role in the collaborative process and are the foundation for recommendations for ways to bridge the loosely-coupled and diverse components of higher education.
Impact of wind turbine modeling on a renewable energy system

This paper investigates the influence of the wind turbine (WT) modeling on an on-grid wind energy system installed in Ibrahimyya, a city in Jordan. A closer look is taken at parameters affecting the output power for correctly modeling the system. This helps in monitoring the turbine performance, sizing of the wind farm and the entire system, which significantly affect the energy extracted per year (EEPY) from the wind turbines (WTs) and the entire system. The net present cost (NPC), grid operating cost (GOC), initial capital cost (ICC) and the cost of energy (COE) are affected. As the WT model changes from the linear to quadratic and on to the cubic model the system has progressively more percentage error in the estimation of the cost as well as EEPY, which cannot be neglected. In fact, the EEPY difference has to be supplied by the conventional generation of the utility grid, which is more expensive than wind energy. However, this is the result of imprecise sizing solutions, which result in error estimates for the project investment. So, an improved cubic model (ICM) is suggested to model the WT precisely by considering more parameters such as the air density. The WT model designed at sea level, shows error estimates in cost and EEPY compared with the ICM. This paper investigates the effects of elevation above sea level (a.s.l) and temperature to model the WT in addition to wind speed and WT power coefficient. Therefore, the simplified WT models will not deliver the EEPY that is theoretically possible. The more costly utility conventional fuel plants will have to replace this energy deficit. In other words, to solve a real-world problem, the real values for parameters affecting the WT model must be considered. This same procedure can be applied in any location worldwide.
Immigration and housing: A spatial econometric analysis

In this paper we examine the effect of immigration into the U.S. on the U.S. housing market, both in terms of rents and single family house prices. We model the housing market in a spatial econometrics context using the spatial Durbin model. This approach helps us exploit and capture both the direct and indirect effects of immigration inflows on the U.S. housing market. We find that an increase in immigration inflows into a particular MSA is associated with increases in rents and with house prices in that MSA while also seeming to drive up rents and prices in neighboring MSAs. The patterns observed in the rental and house price markets, along with the larger spillover effects, are consistent with native-flight from immigrant receiving areas.
Addressing information gaps in wild-caught foods in the US: Brook trout nutritional analysis for inclusion into the USDA national nutrient database for standard reference

Abstract Motivations for seeking local food include eating foods for quality, nutritional value, ethics and environmental concerns. Wild foods, such as wild game and fish, are increasingly included as a local food source, yet many legally procured species of wild game and fish lack knownnutrition information in the USDA National Nutrient Database for Standard Reference (SR). Among those species that lack nutrition information are brook trout. The research team worked with the Nutrient Data Laboratory (NDL) within USDA to develop a collection protocol for brook trout. Using legal angling techniques, samples were collected in the Adirondack region of New York State during the months of May and June 2012 by members of the research team. The trout were processed according to USDA determined dissection protocols to attain edible meat portions. Nutrient analysis was conducted on raw brook trout meat samples at USDA appointed commercial laboratories for proximates, calcium, iron, magnesium, phosphorus, potassium, sodium, zinc, riboflavin, niacin, thiamin, Vitamin B6, Vitamin B12, individual fatty acids, and cholesterol. Analytical data was sent to NDL at USDA, where it was reviewed, compiled and published in SR. Nutrient values were determined by validated laboratories using quality assurance procedures. Full nutrient profiles were made available in SR.
The Cardiovascular Pharmacology of Nonsteroidal Anti-inflammatory Drugs

The principal molecular mechanisms underlying the cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and their relative predisposition to complications. In review article, we discuss how heterogeneity in the pharmacokinetics and pharmacodynamics of distinct NSAIDs may be expected to affect their CV risk profile. We consider evidence afforded by studies in model systems, mechanistic clinical trials, a meta-analysis of randomized controlled trials, and two recent large clinical trials, Standard Care vs. Celecoxib Outcome Trial (SCOT) and Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION), designed specifically to compare the CV safety of the cyclooxygenase-2-selective NSAID, celecoxib, with traditional NSAIDs. We conclude that SCOT and PRECISION have apparently not compared equipotent doses and have other limitations that bias them toward underestimation of the relative risk of celecoxib.
Particle Radiation Therapy for Liver Tumors: Simulation and Treatment Planning

Throughout this chapter, the methods utilized to provide clinical proton treatment delivery will be reviewed. This will begin with the historical rationale for use of particle therapy followed by particle-specific issues in patient selection, patient setup and immobilization, proton treatment planning and delivery, dose constraints, and carbon therapy. The discussion will primarily focus on proton therapy with some discussion of the utility of carbon therapy. Clinical outcomes of particle therapy will be discussed in separate chapters of this text. The final section of this chapter will be devoted to the future direction of particle therapy.
On the Mechanism and Kinetics of the Scaling of Iron

The transport mechanisms previously proposed in wustite and hematite have been confirmed by movement of inert markers during the growth of these phases. By similar measurements the mechanism for magnetite has been determined. The rates of growth of multilayer scales on iron, magnetite and hematite on wustite, and hematite on magnetite have been measured. All rates are found to be diffusion controlled under the conditions of the experiments.
The Ups and Downs of α2β1-Integrin Expression: Contributions to Epithelial Cell Differentiation and the Malignant Phenotype

The integrins are a family of cell surface adhesion receptors that mediate adhesion to either components of the extracellular matrix or to other cells. The integrins are noncovalently associated, heterodimeric glycoproteins composed of distinct α and β subunits of which at least 14 α and nine β subunits have been identified (Ruoslahti 1991; Hynes 1992; Albelda 1993). The β1 family of integrins represent the major class of cell substrate receptors with specificities primarily for collagens, laminins, and fibronectins. Ligand specificity is a function of the particular α-β combination with a great deal of apparent redundancy within the system. For example, many integrins may bind a given extracellular matrix molecule and a single integrin may bind more than one matrix molecule. Recent evidence from several laboratories suggests that some of the apparent redundancy observed at the level of adhesion is not at all redundancy since each receptor may mediate distinct post-receptor occupancy events such as cell differentiation (Dedhar et al. 1987; Reichardt and Tomaselli 1991), alteration in gene expression (Werb et al. 1989; Damsky and Werb 1992), ion fluxes through membrane channels (Schwartz and Denninghoff 1994), and regulation of tumor progression, invasion and metastasis.
Older Families and Issues of Alcohol Misuse

Summary This article addresses some of the recent information that has been collected on the issues of alcohol misuse in later stages of the life span. It discusses the risks to both long-term alcoholics who have grown old with their drinking problem and the issues facing those persons for whom the risks of alcohol become apparent in later life. Three cases are included to illustrate the different consequences of alcoholism in the family as it impacts on separate members and generations within the family system. Authors discuss some principles of intervention and prevention that can and should be applied by different mental health and health practitioners that work with older persons and their family groups.
Deciphering T Cell Immunometabolism with Activity-Based Protein Profiling

As a major sentinel of adaptive immunity, T cells seek and destroy diseased cells using antigen recognition to achieve molecular specificity. Strategies to block checkpoint inhibition of T cell activity and thus reawaken the patient's antitumor immune responses are rapidly becoming standard of care for treatment of diverse cancers. Adoptive transfer of patient T cells genetically engineered with tumor-targeting capabilities is redefining the field of personalized medicines. The diverse opportunities for exploiting T cell biology in the clinic have prompted new efforts to expand the scope of targets amenable to immuno-oncology. Given the complex spatiotemporal regulation of T cell function and fate, new technologies capable of global molecular profiling in vivo are needed to guide selection of appropriate T cell targets and subsets. In this chapter, we describe the use of activity-based protein profiling (ABPP) to illuminate different aspects of T cell metabolism and signaling as fertile starting points for investigation. We highlight the merits of ABPP methods to enable target, inhibitor, and biochemical pathway discovery of T cells in the burgeoning field of immuno-oncology.
Use of veno-venous extracorporeal membrane oxygenation to treat severe combined calcium channel blocker and angiotensin converting enzyme inhibitor overdose:

Introduction:Calcium channel blockers (CCBs) are a commonly prescribed medication that, at toxic levels, are capable of causing severe refractory hypotension, hypoxic respiratory failure and cardio...
Transformation kinetics of cyclophosphamide and ifosfamide by ozone and hydroxyl radicals using continuous oxidant addition reactors.

Abstract The detection of pharmaceuticals in water and wastewater has triggered human and ecological health concerns. As highly toxic compounds, chemotherapy agents (CAs), such as the cyclophosphamide (CYP) and ifosfamide (IFO) structural isomers, represent a unique threat. This research elucidated the fate of CYP and IFO during ozonation and advanced oxidation by hydroxyl radicals (HO•). Novel semi-batch reactors were used to determine the second-order rate constants for CYP and IFO with O3 and HO•. These reactors provided independent control of the oxidant exposure through continuous and constant aqueous ozone and peroxone (O3-H2O2) addition. The rate constants for transformation of CYP and IFO by ozone were 2.58 ± 0.40 M−1s−1 and 6.95 ± 0.21 M−1s−1, respectively, indicating that ozone alone is not suitable for treating CAs. Transformation of CYP and IFO by hydroxyl radicals was fast, with rate constants of 2.69(±0.17)×109 M−1s−1 and 2.73(±0.16)×109 M−1s−1, respectively. The major transformation products formed by O3 and HO attack consisted of the 4-hydroxy-, 4-keto-, dechloroethyl-, and imino- derivatives of CYP and IFO. Low yields of the active metabolites of the CAs, namely phosphoramide mustard and isophosphoramide mustard, were detected. These findings suggest that treated water may retain the ability to alkylate DNA and confer toxicity.
Tryptophan Metabolism in Caenorhabditis elegans Links Aggregation Behavior to Nutritional Status

Caenorhabditis elegans uses aggregation pheromones to communicate its nutritional status and recruit fellow members of its species to food sources. These aggregation pheromones include the IC-ascarosides, ascarosides modified with an indole-3-carbonyl (IC) group on the 4′-position of the ascarylose sugar. Nothing is known about the biosynthesis of the IC modification beyond the fact that it is derived from tryptophan. Here, we show that C. elegans produces endogenously several indole-containing metabolites, including indole-3-pyruvic acid (IPA), indole-3-acetic acid (IAA; auxin), and indole-3-carboxylic acid, and that these metabolites are intermediates in the biosynthetic pathway from tryptophan to the IC group. Stable isotope-labeled IPA and IAA are incorporated into the IC-ascarosides. Importantly, we show that flux through the biosynthetic pathway is affected by the activity of the pyruvate dehydrogenase complex (PDC). Knockdown of the PDC by RNA interference leads to an accumulation of upstream metab...
Evidence-Based Treatment of Articular Cartilage Lesions in the Knee

Articular cartilage lesions are extremely prevalent in young, athletic patients and are often found during knee arthroscopy. This review analyzes the current treatment methods available for articular cartilage lesions, such as bone marrow stimulation, autologous chondrocyte implantation, particulated juvenile cartilage allograft, osteochondral autograft transfer, and osteochondral allograft transplantation as well as the evidence available for each treatment. While there are a variety of treatments available with promising short-term outcomes, the current literature fails to provide both evidence on the long-term effects of these procedures and evidence of a superior technique for treatment of articular cartilage lesions.
La 2 USe 3 S 2 : A Serendipitously Grown Lanthanide/Actinide Chalcogenide from a Eutectic Halide Flux

La2USe3S2, exact composition La2USe2.96S2.04, crystallized from a reaction between USe2 and La2S3 in a molten CsCl/KCl eutectic flux and was characterized by single crystal X-ray diffraction. La2USe3S2 crystallizes in the orthorhombic space group Pnma in the U3S5 structure type with lattice parameters a = 12.3284(3) A, b = 8.4028(2) A, and c = 7.3452(2) A. In La2USe3S2 all the anion sites have mixed S and Se occupancy and, henceforth, will be simply referred to as Q sites. The compound exhibits sigmoidal sheets built from LaQ8 (Q = S, Se) bicapped trigonal prisms that edge-share down the a-axis forming rectangular-shaped channels or tunnels. These tunnels are occupied by UQ6 (Q = S, Se) octahedra that edge-share to form infinite, one-dimensional chains running down the b-axis. X-ray diffraction quality single crystals of La2USe3S2 were grown from a molten CsCl/KCl eutectic flux at 950 °C and used for structure determination using single crystal X-ray diffraction. The compound crystallizes in the orthorhombic space group Pnma in the U3S5 structure type.
STAT3 Inhibition for Gastroenteropancreatic Neuroendocrine Tumors: Potential for a New Therapeutic Target?

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascular neoplasms treated similarly, irrespective of tumor location. The expression of pro-angiogenic factors (STAT3, VEGF, and HIF-1α) and their association with adverse pathologic factors and disease recurrence following resection remains unclear. All patients with non-metastatic GEP-NETs who underwent curative-intent resection from 2000 to 2013 were included. Immunohistochemistry was performed for pro-angiogenic factors, Ki-67 index, and CD31 using tissue microarrays made in triplicate by a pathologist blinded to other clinicopathologic variables. Primary outcome was a 3-year recurrence-free survival (3-yrRFS); secondary outcomes were correlation of pro-angiogenic factors with Ki-67 index, adverse pathologic factors, and CD31 expression, a marker of microvascular density. Of 144 GEP-NETs resected, STAT3 expression was high in 12 (8%) and low in 132 (92%) pts. High STAT3 expression was associated with worse 3-yrRFS compared to low expression (55% vs 84%; p = 0.003). High VEGF expression had a 3-yrRFS of 76% vs 82% for low expression (p = 0.09). HIF-1α expression was not associated with RFS. Ki-67 ≥ 3% was associated with worse 3-yrRFS (≥ 3%: 51% vs median: 75% vs CD31 < median: 86%; p = 0.04). High STAT3 expressing tumors were more likely to have a Ki-67 ≥ 3% (42% vs 7%; p < 0.001). LVI was present in 82% of high STAT3 tumors compared to only 50% with low STAT3 (p = 0.058). CD31 expression was similar between groups (58% vs 49%; p = 0.5). In resected GEP-NETs, high STAT3 expression is associated with an increased Ki-67 index, presence of lymphovascular invasion and worse 3-yr RFS. STAT3 may be a novel therapeutic target for patients undergoing resection of high-risk tumors.
Oncologic Emergencies: The Fever With Too Few Neutrophils.

Abstract Background Cancer is associated with a variety of complications, including neutropenic fever, which can result in severe morbidity and mortality. This oncologic emergency requires ED management. Objective This narrative review provides focused updates for emergency clinicians regarding neutropenic fever. Discussion Neutropenic fever is defined by fever with oral temperature >38.3°C or temperature >38.0°C for 1 hour with an absolute neutrophil count (ANC) Conclusions Neutropenic fever is an oncologic emergency. Rapid diagnosis and care of patients with neutropenic fever can improve outcomes, along with oncology consultation.
CRT-200.05 Laser Atherectomy for infrapopliteal Lesions in Patients With Critical Limb Ischemia

Infrapopliteal (IP) lesions are difficult to treat and associated with poor prognosis in patients with critical limb ischemia (CLI). Optimal revascularization strategies have the potential to improve the outcomes for these patients. The aim of this study was to compare laser atherectomy (LA) vs no
American Alligator (Alligator mississippiensis) Serum Inhibits Pitviper Venom Metalloproteinases

American Alligators (Alligator mississippiensis) are known to consume venomous Pit Viper snakes, apparently with no ill effects. Alligators handle venomous and nonvenomous snakes similarly during consumption, indicating that alligators may possess a physiological resistance to venom. In our study, we tested the ability of alligator blood sera to inhibit the activity of two of the primary toxins in Eastern Copperhead (Agkistrodon contortrix) venom, hemolytic toxins and snake venom metalloproteinases (SVMP). Specifically, we compared relative venom activity following incubation with alligator sera to a venom-only control as well as venom incubated with serum from a species lacking venom resistance (House Mouse; Mus musculus). In comparison to controls, alligator sera significantly reduced SVMP activity, although we observed no effect of alligator sera on hemolytic activity. Interestingly, we detected individual variation with respect to hemolytic activity such that inhibition was positively related with both alligator length and body condition. Our results provide evidence that alligator serum is capable of inhibiting at least one of the primary toxins present in pit viper venom.
The effects of smoking on adolescent trauma patients: a propensity-score-matched analysis.

Cigarettes have been demonstrated to be toxic to the pulmonary connective tissue by impairing the lung’s ability to clear debris, resulting in infection and acute respiratory distress syndrome (ARDS). Approximately 8% of adolescents are smokers. We hypothesized that adolescent trauma patients who smoke have a higher rate of ARDS and pneumonia when compared to non-smokers. The Trauma Quality Improvement Program (2014–2016) was queried for adolescent trauma patients aged 13–17 years. Adolescent smokers were 1:2 propensity-score-matched to non-smokers based on age, comorbidities, and injury type. Data were analyzed using chi square for categorical data and Mann–Whitney U test for continuous data. From 32,610 adolescent patients, 997 (3.1%) were smokers. After matching, 459 smokers were compared to 918 non-smokers. There were no differences in matched characteristics. Compared to non-smokers, smokers had an increased rate of pneumonia (3.1% vs. 1.1%, p = 0.01) but not ARDS (0.2% vs. 0%, p = 0.16). Compared to the non-smoking group, the smokers had a longer median total hospital length-of-stay (3 vs. 2 days, p = 0.01) and no difference in overall mortality (1.5% vs. 2.4%, p = 0.29). Smoking is associated with an increased rate of pneumonia in adolescent trauma patients. Future research should target smoking cessation and/or interventions to mitigate the deleterious effects of smoking in this population.
Identity Fusion and Adjustment in International Students at U.S. Colleges and Universities

The present study explores how international students’ (IS; N = 169; Mage = 19.81 years, 36% male) identity fusion, the extent to which they feel connected with a particular social group, is concur...
Genomic Landscape of Splicing Factor Mutant Acute Myeloid Leukemia

Mutations in components of the RNA-splicing machinery are among the most prevalent genomic alterations in myelodysplastic syndromes (MDS, 45-85% based on disease subtype). With the advent of new powered genomic technologies, spliceosomal mutations have been also detected in acute myeloid leukemia (AML). AML cells have shown to express a large number of alternative spliced events with splicing factor (SF) mutations altering pre-mRNA splicing of downstream targets. How these mutations mediate, modify or support leukemogenic transformation is still unknown. One could think that indirectly the targets of SF alterations could be unveiled through detailed analysis of the phenotype of AML patients carrying those events. Therefore, we aimed to describe the frequency of mutations, clinical associations and molecular cooperative lesions of the most common SF genes (SF3B1, SRSF2, U2AF1, ZRSR2) in AML to speculate unique molecular combinations contributing to disease phenotypes. We collected data of targeted deep sequencing and whole exome sequencing of a cohort of 2188 AML cases from the Cleveland Clinic (n=855) and publicly available data. In total, we had 1636 primary (p), 433 secondary (s) and 119 (t) AML. Eighteen% of AML patients (n=388) carried a mutation in SF (SF mutant, SF-MT) while 83% were wild type (SF-WT AML, n=1800). More specifically, the frequency of SF-MT individuals was 14% in pAML (n=234) and tAML (n=17) while a significantly higher frequency was observed in sAML (32%, n=137) as compared to pAML + tAML (P The molecular profile of SF-MT AML was characterized by significantly frequent mutations in ASXL1 (23 vs 5%, P In sum, we described the presence of SF mutations in AML and defined the phenotypic features of this subset and its genomic associations as compared to SF-WT AML. We further highlighted the unique genomic contributors associated with their survival outcomes. Perhaps, future larger scale studies of this AML group will delineate its potential to represent a unique well-defined entity of AML. Disclosures Maciejewski: Alexion, BMS: Speakers Bureau; Novartis, Roche: Consultancy, Honoraria.
Emotion Regulation and Repetitive Negative Thinking Before and After CBT and SSRI Treatment of Internalizing Psychopathologies

Emotion regulation (ER) strategies (i.e., reappraisal, suppression) and repetitive negative thinking (RNT) tendencies (i.e., brooding rumination, worry) are transdiagnostic and contribute to the maintenance of internalizing psychopathologies. Cognitive Behavioral Therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both effective in reducing symptom severity, however, their impact on ER and RNT is unclear. Therefore, the goal of the current study was to examine whether CBT and SSRIs improved ER and RNT in a transdiagnostic sample. The current sample comprised 91 patients with anxiety, depression, and/or posttraumatic stress disorder randomly assigned to receive either CBT (n = 45) or an SSRI (n = 46) and 49 healthy controls as a comparator group. Patients completed measures of clinical symptoms, reappraisal, suppression, brooding rumination, and worry before and after treatment. Controls completed the same measures at baseline. Compared to controls, patients reported greater symptom severity, suppression, brooding, and worry, and less reappraisal. Both treatments improved symptom severity, ER, and RNT. However, patients who completed CBT reported greater improvement in reappraisal than patients who completed treatment with an SSRI. Finally, change in RNT, but not ER, was associated with symptom improvement. Findings suggest treatment improves ER and RNT and provides preliminary evidence of a treatment modality effect on reappraisal.
Time-Domain Loss Modulation Based on Overlap Ratio for Monaural Conversational Speaker Separation

Existing speaker separation methods deliver excellent performance on fully overlapped signal mixtures. To apply these methods in daily conversations that include occasional concurrent speakers, recent studies incorporate both overlapped and non-overlapped segments in the training data. However, such training data can degrade the separation performance due to triviality of non-overlapped segments where the model reflects the input to the output. We propose a new loss function for speaker separation based on permutation invariant training that dynamically reweighs losses using the segment overlap ratio. The new loss function emphasizes overlapped regions while deemphasizing the segments with single speakers. We demonstrate the effectiveness of the proposed loss function on an automatic speech recognition (ASR) task. Experiments on the recently introduced LibriCSS corpus show that our proposed single-channel method produces consistent improvements compared to baseline methods.
De la chorématique. Les dynamiques de l’espace vécu

Plan: Schematismes dynamiques Chorematique sociale Chorematique de la ville Aspect, temps, mode La pensee topologique. Ontologie.
Mortality and readmission in the year following hospitalization for pneumonia among US adults.

Abstract Background Increasing evidence suggests the impact of pneumonia persists beyond hospital discharge and the acute phase of respiratory symptoms. We characterized short-term and long-term risks of mortality and hospital readmission across the adult age span and spectrum of comorbidities. Methods Retrospective cohort design and Optum's de-identified Integrated Claims-Clinical dataset (2012–2018) were employed. Study population comprised adults who had ≥1 pneumonia hospitalization; each hospitalization ≥365 days apart was considered. Cumulative risks of all-cause mortality (from pneumonia hospitalization through 360-day post-discharge period) and all-cause hospital readmission (during 360-day post-discharge period) were summarized on an overall basis as well as by age and comorbidity profile (i.e., healthy, at-risk, high-risk). Results Study population totaled 37,006 patients who contributed 38,809 pneumonia hospitalizations; mean age was 71 years, 51% were female, and 88% had at-risk (33%) or high-risk (55%) conditions. Mortality was 3.5% in hospital, 8.2% from admission to 30 days post-discharge, and 17.7% from admission to 360 days post-discharge. Hospital readmission was 12.5% during the 30-day post-discharge period, and 42.3% during the 360-day post-discharge period. Mortality risk increased with age and severity of comorbidity profile; readmission risk was highest for persons aged 65–74 years and persons with high-risk conditions. Conclusions All-cause mortality up to 1 year following pneumonia hospitalization was substantial, and was associated with increasing age and worsening comorbidity profile. Both readmission and mortality were greater at all ages in at-risk and high-risk subgroups (vs. healthy counterparts). Strategies that prevent pneumonia and/or associated pathophysiologic changes, especially among individuals with comorbidities, have the potential to reduce morbidity and mortality.