cssi/SciSciGPT-SciSciNet huggingface dataset:
Fractionation of human serum lipoproteins by single-spin gradient ultracentrifugation: quantification of apolipoproteins B and A-I and lipid components

A sensitive and reproducible method has been developed for separation of the major serum lipoproteins from 1 ml or less of human serum by isopycnic density gradient ultracentrifugation. The serum, applied to a step gradient (total volume 12.8 ml), was spun for 48 hr at 38,000 rpm at 10°C and, in each of the fractions, apoli- poproteins B and A-I were quantified by the respective radioimmunoassays. The markers for lipid distribution used were (4-I4C )cholesterol and (U-'4C)lecithin, each in- cubated with an aliquot of serum at 20°C for 75 min prior to ultracentrifugation. In control sera, three main frac- tions, very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins were clearly separated from a bottom fraction. Their flotational, electrophoretic, and chemical properties were in good agreement with those reported for the corresponding lipoproteins separated by conventional ultracentrifugation. Both apo B and apo A-I were fully recovered. Essentially all of the apo B was found in VLDL (9.3 2 3.5%) and LDL (87 & 4.6%); of the apo A-I, 81.0 rt 5.7% was in HDL and the remainder (17.0 +- 5.8%) was in the bottom fraction. The peak activities of (14C)cholesterol coincided with the peak of apo B in both LDL and VLDL, and with the peak of apo A-I in HDL. The results with the radiolabeled cholesterol were in good agreement with those obtained by chemical analyses. Carbon 14-labeled lecithin, although fully recovered, was not an accurate marker of phospholipid distribution be- cause, under our experimental conditions, a significant amount of the lecithin was converted into its lyso deriva- tive. The mechanism of the conversion was not established; it appeared to be unrelated to the activities of either lecithin-cholesterol acyl transferase or a Caz+-dependent phospholipase. Besides its validity in the study of control sera, our method also proved successful in the separation of the serum lipoproteins of the few patients with dyslipo- proteinemia (abetalipoproteinemia and familial hyper- cholesterolemia) who were examined. However, the ap- plicability of the method to all dyslipoproteinemias was not assessed. Taken together, the results indicate that the single-spin method could be useful in clinical studies as a complement to other established techniques.
Manipulating and probing the spatio-temporal dynamics of nanoparticles near surfaces

In this report, we combine total internal reflection-fluorescence correlation spectroscopy (TIR-FCS) with a single optical trap to simultaneously manipulate and measure the dynamics of individual molecules near the substrate-solution interface. As a proof of principle, polystyrene particles (84 nm in diameter) are used as a model system to test our approach in studying their diffusion properties near surfaces, which are treated with polyethylene glycol 8000, bovine serum albumin or sodium hydroxide. The evanescent field of 543 nm excitation propagates ~100 nm into the solution, and the fluorescence detection is spatially confined by a 25 or 50 μm pinhole that is parfocal with the specimen plane. The optical trap is generated using a cw Ti:sapphire laser at 780 nm. Our results indicate that the particles' diffusion is influenced by surface interactions, which might have further implications on biomembrane studies. Furthermore, the observed translational diffusion of individual particles can be manipulated using an optical trap. By combining the single molecule sensitivity of TIR-FCS with a noninvasive manipulation method, such as optical trapping, we will be able to probe molecular dynamics in biomimetic systems and living cells.
Can Cheap Talk Deter? An Experimental Analysis

What effect does cheap talk have on behavior in an entry-deterrence game? We shed light on this question using incentivized laboratory experiments of the strategic interaction between defenders and potential entrants. Our results suggest that cheap talk can have a substantial impact on the behavior of both the target and the speaker. By sending costless threats to potential entrants, defenders are able to deter opponents in early periods of play. Moreover, after issuing threats, defenders become more eager to fight. We offer a number of different explanations for this behavior. These results bring fresh evidence about the potential importance of costless verbal communication to the field of international relations.
Oxidized Metal Powders for Mechanical Shock and Crush Safety Enhancers

The use of oxidized metal powders in mechanical shock or crush safety enhancers in nuclear weapons has been investigated. The functioning of these devices is based on the remarkable electrical behavior of compacts of certain oxidized metal powders when subjected to compressive stress. For example, the low voltage resistivity of a compact of oxidized tantalum powder was found to decrease by over six orders of magnitude during compaction between 1 MPa, where the thin, insulating oxide coatings on the particles are intact, to 10 MPa, where the oxide coatings have broken down along a chain of particles spanning the electrodes. In this work, the behavior of tantalum and aluminum powders was investigated. The low voltage resistivity during compaction of powders oxidized under various conditions was measured and compared. In addition, the resistivity at higher voltages and the dielectric breakdown strength during compaction were also measured. A key finding was that significant changes in the electrical properties persist after the removal of the stress so that a mechanical shock enhancer is feasible. This was verified by preliminary shock experiments. Finally, conceptual designs for both types of enhancers are presented.
Exafs Studies of Semiconductors

Recent results from EXAFS spectroscopy are discussed, including (i) the determination of the site and local bond lengths of Fe impurities implanted into Si, (ii) the determination of the ferroelectric phase transition in Pb1−x Gex Te as order-disorder rather than displacive, and (iii) the nondestructive measurement of Al diffusion into GaAs at an Al/GaAs Interface.
A few comments on ‘Sustainability and the measurement of wealth’

You have to admire the courage exhibited in going out on a limb like this, especially because the acrobats are sophisticated and understand how many chances to go wrong they have. Of course one can stand back and admire courage and dexterity without actually believing in the results, and without any feeling that one could do better.
Empirical Orthogonal Representation of Time Series in the Frequency Domain. Part I: Theoretical Considerations

Abstract Difficulties in using conventional cross-spectrum analysis to explore atmospheric wave disturbances have indicated the need for some extension of the usual technique. It is suggested here that the eigenvectors of the cross-spectrum matrix be used for interpreting such data. The method is analogous to the use of empirical orthogonal functions applied to band-pass filtered time series. However, the eigenvectors of the cross-spectrum matrix contain additional information concerning phase which is not available from the eigenvectors of the covariance matrix. It is possible to generate a new set of time series which are mutually uncorrelated within a pre-selected frequency interval and which have the same combined variance in the frequency interval as the original set of time series. These new series are obtained by applying the eigenvectors of the cross-spectrum matrix to a set of complex time series involving the original time series and their time derivatives. The application and physical interpret...
Calculating risks and benefits to help guide revascularization decisions: turning all available data into useful information.

We are in the era of “big data” in cardiovascular medicine [(1)][1]. This brings both excitement and challenges to the clinician who is making dozens, if not hundreds, of clinical decisions every day in the care of individual patients. Enormous amounts of data are available on each patient, much
The History of Metabolic Surgery

This chapter recognizes the struggles of the small band of surgeons who had the sensitivity to recognize that severe obesity was a disease. These surgeons, frustrated with the toll of this progressive illness, determined that the severely obese deserved better care and who, over the objections of their colleagues and society, managed not only to devise operations that led to durable loss of about one-third of the patients’ original weights but also produced full and long term remission of type 2 diabetes, hypertension, hyperlipidemias, polycystic ovary disease, and nonalcoholic steatotic hepatitis among other chronic diseases previously considered incurable. In addition, surprisingly, these operations also led to reductions not only in long-term mortality but even the prevalence of solid cancers within 5 years. Even more important, these pioneers provided a framework for basic science and the study of mechanisms that should lead to long-term control with medications and without surgery.
What Does the Narcissistic Personality Inventory Measure Across the Total Score Continuum

The Narcissistic Personality Inventory (NPI) is the most widely used measure of narcissism in the social-personality psychology literature. It contains 40 items that tap into a variety of traits that theoretically comprise narcissism, such as feelings of superiority and willingness to exploit others. Most researchers focus on the total score produced by the NPI and may logically assume that increments in total NPI score correspond with similar increments in underlying narcissism traits. However, research presented in this article suggests that the traits measured by the NPI do not increment at the same rate. Traits reflecting intrapersonally healthy qualities (e.g., leadership, superiority) increment most rapidly within the lower portions of the NPI total score continuum, whereas traits reflecting interpersonally harmful qualities (e.g., entitlement, exploitativeness) increment most rapidly within the upper portions of the NPI continuum. These differences have implications for the meaning of scores on the NPI and how they correlate with other variables. For example, we demonstrate that lower NPI scores best predict self-esteem and higher NPI scores best predict psychopathy.
SEA-Modellierung zur Schallpaket-entwicklung unter Einbeziehung simulierter Luftschallanregung

In den vergangenen Jahren wurde die statistische Energieanalyse (SEA) vermehrt von Fahrzeugherstellern und -zulieferern eingesetzt, um den Luftschall in Strasenfahrzeugen zu analysieren. Wahrend der Aufbau eines SEA-Fahrzeugmodells weithin umgesetzt wird, fehlt es jedoch an einer durchweg anerkannten Methode, Luftschall-anregungen in diesen Modellen adaquat zu berucksichtigen. Im Rahmen eines gemeinsamen Projekts von Rieter Automotive und Volkswagen wurde ein Hybridverfahren zur Auswertung derartiger Anregungen genutzt und validiert. Dieses Verfahren kombiniert die gewohnliche Finite-Elemente-Methode (FEM) mit der jungst entwickelten energetischen Randelemente-Methode (Energy Boundary Element Analysis, EBEA).
Prostacyclin-producing human mesenchymal cells target H19 lncRNA to augment endogenous progenitor function in hindlimb ischaemia

Promoting the paracrine effects of human mesenchymal stem cell (hMSC) therapy may contribute to improvements in patient outcomes. Here we develop an innovative strategy to enhance the paracrine effects of hMSCs. In a mouse hindlimb ischaemia model, we examine the effects of hMSCs in which a novel triple-catalytic enzyme is introduced to stably produce prostacyclin (PGI2-hMSCs). We show that PGI2-hMSCs facilitate perfusion recovery and enhance running capability as compared with control hMSCs or iloprost (a stable PGI2 analogue). Transplanted PGI2-hMSCs do not incorporate long term into host tissue, but rather they mediate host regeneration and muscle mass gain in a paracrine manner. Mechanistically, this involves long noncoding RNA H19 in promoting PGI2-hMSC-associated survival and proliferation of host progenitor cells under hypoxic conditions. Together, our data reveal the novel ability of PGI2-hMSCs to stimulate host regenerative processes and improve physical function by regulating long noncoding RNA in resident progenitor cells.
An Examination of a Multitiered System of Language Support for Culturally and Linguistically Diverse Preschoolers: Implications for Early and Accurate Identification

Abstract A disproportionate percentage of culturally and linguistically diverse students have difficulties with language-related skills that affect their academic success. Early and intensive langu...
The experimentally Research for Antibacterial Disinfection of Cleaning Type Wet Wipes

Objective: Because common market wet tissue are different in santibacterial effects,this paper is a research for the common commercially wet tissue,airport wet tissues and student wet tissues in order to evaluate the antibacterial performance. Method: Acute diarrhea due to Escherichia coli,Staphylococcus aureus is the most common pathogen in human pyogenic infection,we chose this two strains as type strain and conduct series of experiments. Result: Evaluation of the record and analysis of results for the selection of paper towels,and wet tissues purchase raised some opinions and suggestions.
Antidepressants: effects on histaminic and muscarinic receptors

Antidepressant drugs of many chemical classes are antagonists of several different types of neurotransmitter receptors. Among the first known of these receptor interactions were the antagonisms of histamine H1 and muscarinic acetylcholine receptors. In fact, the first antidepressant, imipramine hydrochloride, was originally synthesized for use as an antihistamine (Kuhn, 1970). More recently, antidepressants have been shown, in addition, to be antagonists in vitro of histamine H2, α1-adrenergic, α2-adrenergic and serotonergic receptors. This paper will present the evidence that antidepressants antagonize histamine H1, histamine H2 and muscarinic acetylcholine receptors in brain and elsewhere. In addition the relevance of these data for the treatment of depression and other diseases will be discussed.
Properties of the principal anion-exchange mechanism in human neutrophils.

As part of our ongoing studies aimed at understanding the physiology of human neutrophil function, we have been investigating the nature of the principal anion-exchange mechanism in these cells. This countertransport system functions physiologically as a Cl-/HCO3- exchanger in intracellular pH regulation from alkalinization (Simchowitz and Roos, 1985). In summarizing the results of our work, it is worthwhile to keep in mind the well-defined properties of the classic inorganic anion-exchange carrier of red blood cells, as important differences between the two are evident. Inhibitor Profile In our original articles on Cl- movements (Simchowitz and De Weer, 1986; Simchowitz et al., 1986), we had identified CHC, which suppresses monocarboxylate transport in mitochondria (Halestrap and Denton, 1975), as a relatively weak inhibitor. Several structural analogues, including alpha-methylcinnamate and alpha-phenylcinnamate, exhibited enhanced activity against anion exchange. The most potent compound thus far identified was UK-5099, which was approximately 300-fold more active than CHC. The inhibitory effect of each member of this series of compounds was strictly competitive in nature: both the drug and Cl ions appeared to bind to the same external translocation site on the exchange carrier. The inhibition by several other unrelated agents (e.g., MK-473, niflumate, flufenamate, and NAP-taurine), all weak organic acids, was also of the competitive type, which suggests that these compounds bind to the carrier by virtue of their negatively charged carboxyl or sulfonic groups. In marked contrast to erythrocytes, the anion-exchange carrier of neutrophils is rather insensitive to the disulfonic stilbenes SITS and DIDS (Simchowitz and De Weer, 1986): little or no effect can be detected in 148 mM Cl-. However, under conditions of low external Cl- (5-35 mM), SITS can in fact be shown to interact weakly with the anion binding site of the exchange carrier. In a comparable vein, several other drugs, all of which have been reported to suppress Cl- fluxes in red cells (for reviews, see Sachs et al., 1975; Gunn, 1979; Knauf, 1979; Lowe and Lambert, 1983), were either completely inactive against anion exchange in neutrophils at a concentration of 1 mM or only marginally effective at doses several orders of magnitude greater than those required in red blood cells. This list included furosemide, picrylsulfonate, maleic anhydride, 5,5'-dithio-bis(2-nitrobenzoate), salicylate, 2-methoxy-5-nitrotropone, and aldrithiol.4+he external
Sintering of multiple Cu–Ag core–shell nanoparticles and properties of nanoparticle-sintered structures

Cu–Ag core–shell (CS) nanoparticles (NP) have been synthesized to replace pure Ag NP paste in order to lower the cost while maintaining excellent thermal and electrical conductivities for electronic applications. In this study, a multiple-CS-NP sintering model with molecular dynamics is employed to investigate the NP size and temperature dependency of the sintering process, as well as mechanical and thermodynamic properties of the sintered structures. Porosity and multiple particle effects are included, which allow for more accurate analysis than the conventional two- or three-NP sintering model. We unravelled the sintering mechanism at room temperature, and the interplay of liquid and solid surface diffusion during sintering at higher temperatures. Interfacial atoms have a higher mobility than surface atoms and contribute to a higher densification in the multiple-CS-NP model. A more densified structure yields higher Young's modulus, yield strength and Poisson's ratio, while lowering isothermal compressibility. The coefficient of thermal expansion and specific heat capacity exhibit grain-size and porosity independence. This multiple-CS-NP model provides a theoretical basis for determining NP configuration and sintering conditions for desirable properties.
Complement Dependence of Murine Costimulatory Blockade-Resistant Cellular Cardiac Allograft Rejection.

Building on studies showing that ischemia–reperfusion-(I/R)-injury is complement dependent, we tested links among complement activation, transplantation-associated I/R injury, and murine cardiac allograft rejection. We transplanted BALB/c hearts subjected to 8-h cold ischemic storage (CIS) into cytotoxic T-lymphocyte associated protein 4 (CTLA4)Ig-treated wild-type (WT) or c3−/− B6 recipients. Whereas allografts subjected to 8-h CIS rejected in WT recipients with a median survival time (MST) of 37 days, identically treated hearts survived >60 days in c3−/− mice (p 60 days in mannose binding lectin (mbl1−/−mbl2−/−) recipients and 42 days in factor B (cfb−/−) recipients (n = 4–6/group, p 60 days, p < 0.05 vs. controls, n = 6) and prevented CI-induced increases in donor-reactive, IFNγ-producing spleen cells (p < 0.05). These new findings link donor I/R injury to T cell–mediated rejection through MBL-initiated, complement activation and support testing C1-INH administration to prevent CTLA4Ig-resistant rejection of deceased donor allografts in human transplant patients.
Abstract 1819: Reprogramming the tumor microenvironment by targeting endothelial DNA repair

The tumor microenvironment (TME) plays a critical role in orchestrating immune infiltration, tumor progression and response to therapeutics. Therefore, strategies to manipulate the TME including cytokine gene therapy, antibodies to reverse macrophage polarization etc are under active investigation. We have identified an alternative approach to target the TME by disrupting DNA repair in the tumor endothelial cells (ECs). We discovered a seven-microRNA (miR) signature induced in ECs in in vitro and in vivo by oxidative stress and DNA damage. The top miR candidate in this signature, miR-103 altered the TME by inducing DNA damage in ECs, eliciting type I interferons, upregulating immune costimulatory receptors and decreasing PD-L1 expressing tumor associated macrophages and granulocytes. Moreover, miR-103 treatment had a paracrine effect on the tumors and upregulated Fas and TRAIL receptors. Mechanistically, these functions of miR-103 were largely due to its downregulation of the three prime exonuclease TREX1. Local, systemic or vascular targeted delivery of miR-103 decreased both angiogenesis and tumor burden in multiple mouse tumor models. Complementary to the role of miR-103, two additional miRs in the miR signature, miRs 494 and 99b each induced senescence in the vasculature by downregulating the Mre11a-Rad50-NBN (MRN) complex. Ectopic expression of miRs 494 or 99b decreased telomerase activity, increase p21 levels with a concomitant decrease in pRb levels. Vascular targeted delivery of miR-494 decreased angiogenesis in vivo whereas systemic delivery decreased tumor growth. Interestingly, both miR mimics and the MRN knockdowns induced the transcription of a number of senescence associated genes including CD44. Taken together these data suggest that miRs 494 and 99b targeting of the MRN complex induces senescence. The MRN complex interacts with the ATM kinase, histone H2AX and TREX1 suggesting that the miRs we identified disrupt critical nodes of a DNA Damage Response (DDR) network. Our findings reveal a complex, miR mediated cross talk between EC DNA damage pathways, the TME and tumor cells. These interactions can be exploited for designing therapies that synergize with tumor cell killing to enhance host anti-tumor responses. Citation Format: Cristina Espinosa-Diez, RaeAnna Wilson, Rebecca Ruhl, Nathan Kanner, Namita Chatterjee, Clay Hudson, Sudarshan Anand, Shushan Rana. Reprogramming the tumor microenvironment by targeting endothelial DNA repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1819. doi:10.1158/1538-7445.AM2017-1819
Recent advances in modeling of interfaces and mechanical behavior of multilayer metallic/ceramic composites

Since the introduction of the term “nanolaminate” in the mid-1990s, considerable research activities on metallic/ceramic nanolaminates (MCN) have been conducted. Incorporating ceramics with high hardness and high melting point together with high ductile metals can improve their thermomechanical behavior in corrosive environments. A great number of researchers have reported that MCNs exhibit outstanding thermomechanical properties compared with the constituent layers and bulk material, which is attributed to the atomic structure and high density of the interfaces. This article provides a review of recent advances in modeling of the mechanical behavior of MCN composites, with focus on Nb/NbC and Ti/TiN multilayer composites. The main strengthening mechanisms of MCNs, based on the layer thickness, the interface structure, and the interaction of threading dislocations with the interface as well as dislocations nucleation from the interface, are reviewed, and recently, obtained results from molecular dynamics simulations, along with these findings, are presented. Moreover, MD-based flow surfaces for use in large-scale continuum models are reviewed in connection with results from MD of MCNs under various mechanical loading conditions, including uniaxial and biaxial loadings.
Conquering with capital: social, cultural, and economic capital’s role in combating socioeconomic disadvantage and contributing to educational attainment

While socioeconomic barriers to learning have been well-documented by education, sociology, and social policy scholars, further research is needed to understand how students with low-socioeconomic ...
Sexua-romanticised pathways of transmasculine college students in the USA

Much of the expanding literature positions trans college students as an overly homogenous population, lacking agency and wrought with hardship and tragedy. Drawn from a broader study on transmascul...
Increasing Contraceptive Use Among Young Married Couples in Bihar, India: Evidence From a Decade of Implementation of the PRACHAR Project.

Background Evidence on effective behavior change programming for sexual and reproductive health among married youth aged 15-24 in developing countries is lacking. To address this gap, we examined monitoring, evaluation, and special study data from the Promoting Change in Reproductive Behavior of Adolescents (PRACHAR) Project, which was implemented between 2001 and 2012 in Bihar, India, over 3 phases using 2 different implementation models (NGO- and government-led). Methods We conducted a synthesis of evidence from multiple PRACHAR studies to identify key findings on intervention effectiveness, scalability, and sustained effects on behaviors. Data were triangulated from quantitative population-based quasi-experimental evaluations from each project phase; the project's performance monitoring database; and qualitative studies with beneficiaries. Results PRACHAR's original comprehensive NGO-led model, which included behavior change elements and multiple overlapping communication channels (including home visits and small-group meetings), increased contraceptive use among young married couples, and these outcomes were sustained 4-8 years after project interventions ended. Several program elements were critical to the effectiveness of PRACHAR, including use of a socioecological intervention model with emphasis on behavior change efforts; use of a gender-synchronized approach that engages both male and female partners; and intensity of interventions calibrated to different moments in the life cycle of adolescents and youth. While the hybrid government-NGO model of PRACHAR implementation reached greater scale than the original NGO-led model, comparison of results suggests trade-offs in effectiveness of interventions and sustained impacts. Conclusions A decade of learning from the PRACHAR Project in Bihar, India, finds that comprehensive programming with gender-synchronized interventions tailored to specific life stages and aimed at different levels of the socioecological model can effectively increase contraceptive use among married young people in a conservative context. Shifting from a more intensive NGO-led model to less intensive government implementation enhances scalability but may have diminished impact on reach and long-lasting effectiveness.
High-Sensitivity C-Reactive Protein and the Metabolic Syndrome

Elevated levels of C-reactive protein (CRP) well below the conventional clinical upper limit of 10 mg/L (as measured by high-sensitivity CRP) have been shown to be a strong predictor of incident type 2 diabetes and cardiovascular events. Low-grade chronic inflammation, as reflected by elevated high-sensitivity CRP, may be one of the common antecedents underlying the clustering of obesity, impaired glucose tolerance, dyslipidemia, and hypertension, known as the metabolic syndrome. This article aims to summarize epidemiological data on the relation between CRP and features of the conventionally defined metabolic syndrome. The available evidence indicates that CRP levels correlate not only with each of the metabolic syndrome components individually, but also with the metabolic syndrome as an entity. Furthermore, CRP appears to add independent prognostic information across all levels of the metabolic syndrome, indicating the clinical value of CRP for prediction of cardiovascular disease and diabetes. Future studies are warranted to assess the predictive values of combining CRP and the metabolic syndrome in the risk assessment.
Analysis of the Resource Chain Model: the New Peer-to-Peer Reputation-Based Trust Model.

Great attention has recently been shown to computer security. Therefore, many mechanisms have been employed or invented to increase the Peer-to-Peer (P2P) security like encryption, sandboxing, digital rights management, reputation, and firewall. Among those technologies, trust-reputation controlling mechanism, as an active self-controlling method is especially useful to automatically record, analyze and even adjust peers reputation trust credibility among the different peers so that the system can adjust itself according to the credibility changes. This kind of self-adjusting system is suitable for our anonymous, dynamic and variable P2P environment. Using the Resource Chain Model (RCM), the new P2P reputation-based trust model, we can find the best resource location both effectively and efficiently while maintaining the system security. The goal of this paper is to find whether the model can increase the successful download rate when the number of transactions and the number of malicious nodes are increasing. The study’s results show that RCM improved the performance. Thus, this approach enables one to find a better solution to find the best resource chain in a P2P community.
Peripheral Nerve Injuries of the Shoulder and Upper Arm

Nerve injuries about the shoulder and proximal upper limb are uncommon but important causes of pain and dysfunction in athletes. In general, athletes involved in overhead sports appear to be at increased risk for nerve injuries in the shoulder region, which can be challenging for the clinician to identify and treat. This chapter takes a comprehensive look at the peripheral nerves in the upper arm that are susceptible to injury and gives a detailed approach to the evaluation and management of the disorders that result.
Revisiting assumptions about age-based mixing representations in mathematical models of sexually transmitted infections.

Abstract Background Sexual mixing between heterogeneous population subgroups is an integral component of mathematical models of sexually transmitted infections (STIs). This study compares the fit of different mixing representations to survey data and the impact of different mixing assumptions on the predicted benefits of hypothetical human papillomavirus (HPV) vaccine strategies. Methods We compared novel empirical (data-driven) age mixing structures with the more commonly-used assortative-proportionate (A-P) mixing structure. The A-P mixing structure assumes that a proportion of sexual contacts – known as the assortativity constant, typically estimated from survey data or calibrated – occur exclusively within one’s own age group and the remainder mixes proportionately among all age groups. The empirical age mixing structure was estimated from the National Survey on Sexual Attitudes and Lifestyles 3 (Natsal-3) using regression methods, and the assortativity constant was estimated from Natsal-3 as well. Using a simplified HPV transmission model under each mixing assumption, we calibrated the model to British HPV16 prevalence data, then estimated the reduction in steady-state prevalence and the number of infections averted due to expanding HPV vaccination from 12- through 26-year-old females alone to 12-year-old males or 27- to 39-year-old females. Results Empirical mixing provided a better fit to the Natsal-3 data than the best-fitting A-P structure. Using the model with empirical mixing as a reference, the model using the A-P structure often under- or over-estimated the benefits of vaccination, in one case overestimating by 2-fold the number of infections prevented due to extended female catch-up in a high vaccine uptake setting. Conclusions An empirical mixing structure more accurately represents sexual mixing survey data, and using the less accurate, yet commonly-used A-P structure has a notable effect on estimates of HPV vaccination benefits. This underscores the need for mixing structures that are less dependent on unverified assumptions and are directly informed by sexual behavior data.
Examination of the enhanced recovery guidelines in thoracic surgery.

Purpose of review Enhanced Recovery After Thoracic Surgery (ERATS) has gained momentum over the past few years, although the evidence base and expert recommendations lag behind other specialties. This review will present and examine key points from the first guidelines for enhanced recovery after lung surgery, released in 2018, jointly sponsored by the European Society of Thoracic Surgeons and the Enhanced Recovery After Surgery Society. Recent findings The recently released guidelines present core components of enhanced recovery as they pertain to lung resection surgery. Although evidence is still sparse in some areas, the guidelines summarize the available literature and incorporate levels of recommendation based upon the strength of available data as well as expert consensus. As of yet, the relative contribution of individual ERATS components to improvement in outcomes is unclear, but overall compliance does seem to be linked to positive results. Since the creation of the guidelines, additional literature related to ERATS has been released, and it will be incorporated and discussed into our review. Summary The creation of guidelines for enhanced recovery after lung resection will provide the thoracic anesthesiologist a framework upon which to build a comprehensive perioperative anesthetic plan.
Predictors and implications of accelerated cognitive aging

Aging is a major risk factor for both normal and pathological cognitive decline. However, individuals vary in their rate of age-related decline. We developed an easily interpretable composite measure of cognitive age, and related both the level of cognitive age and cognitive slope to sociodemographic, genetic, and disease indicators and examine its prediction of dementia transition. Using a sample of 19,594 participants from the Health and Retirement Study, cognitive age was derived from a set of performance tests administered at each wave. Our findings reveal different conclusions as they relate to levels versus slopes of cognitive age, with more pronounced differences by sex and race/ethnicity for absolute levels of cognitive decline rather than for rates of declines. We also find that both level and slope of cognitive age are inversely related to education, as well as increased for persons with APOE e4 and/or diabetes. Finally, results show that the slope in cognitive age predicts subsequent dementia among non-demented older adults. Overall, our study suggests that this measure is applicable to cross-sectional and longitudinal studies on cognitive aging, decline, and dementia with the goal of better understanding individual differences in cognitive decline.
Optical Spectroscopy of Tryptophan Metabolites in Neurodegenerative Disease

Abstract Abnormal metabolism of the essential amino acid, tryptophan, has been associated with many diseases, including cancer, but is also particularly important in the induction of neurodegenerative disease. Neuronal damage results from increased production, through the kynurenine pathway, of neurotoxic compounds, and also from imbalances in neurotransmitters, such as melatonin and serotonin. Optical spectroscopic techniques, such as native fluorescence, Raman spectroscopy, infrared spectroscopy, time-resolved spectroscopy, and fluorescent probes that make use of energy transfer, can be used to measure these compounds, to assess tryptophan to metabolite ratios and thus the degree of neuroinflammation, and to study the kinetics of aggregation of toxic proteins in the brain.
Microchipping the breast: an effective new technology for localizing non-palpable breast lesions for surgery.

Use of a wire to localize a non-palpable breast lesion for surgery is standard but archaic. We sought to evaluate a new radiofrequency localization system (RFLS) as an effective, non-radioactive alternative to the wire. Patients who required surgical excision of a non-palpable breast lesion were consented for the study. Patients underwent localization with a radiofrequency Tag and surgical removal guided by the handheld LOCalizer probe. The primary study endpoint was successful placement and retrieval of the Tag, and secondary endpoints included marker migration; days prior to surgery of Tag insertion; patient, radiologist, and surgeon experience; distance of Tag from skin; and positive margin and re-excision rates for cancer. Fifty patients had successful placement and retrieval of the radiofrequency Tag. Likert questionnaire data revealed that most patients thought the procedure went smoothly and was easier than expected. Radiologists and surgeons thought that the Tag was as reliable as the wire. Of the 33 patients who had surgery for in situ or invasive cancer, one had a positive margin on final pathology (3%) and two underwent re-excision (6%). Data from this pilot study suggest that the RFLS is an effective localization system for non-palpable breast lesions intended for surgical removal. Unlike most other technologies, the LOCalizer probe detects distance from the Tag, and this unique feature may have contributed to the low positive margin rate seen in this study. The RFLS appears to offer advantages over current localization procedures and should be explored as an alternative to wire. ClinicalTrials.gov Identifier: NCT03202472.
Pharmacologic treatment options for type 1 diabetes: what’s new?

ABSTRACTIntroduction: The expanding variety of insulins, including biosynthetic human insulin and rapid and long-acting insulin analogs, have dramatically transformed the management of type 1 diabe...
Review article: emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications.

Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent disorder associated with obesity and diabetes. Few treatment options are effective for patients with NAFLD, but connections between the gut microbiome and NAFLD and NAFLD-associated conditions suggest that modulation of the gut microbiota could be a novel therapeutic option. Aim To examine the effect of the gut microbiota on pathophysiologic causes of NAFLD and assess the potential of microbiota-targeting therapies for NAFLD. Methods A PubMed search of the literature was performed; relevant articles were included. Results The composition of bacteria in the gastrointestinal tract can enhance fat deposition, modulate energy metabolism and alter inflammatory processes. Emerging evidence suggests a role for the gut microbiome in obesity and metabolic syndrome. NAFLD is often considered the hepatic manifestation of metabolic syndrome, and there has been tremendous progress in understanding the association of gut microbiome composition with NAFLD disease severity. We discuss the role of the gut microbiome in NAFLD pathophysiology and whether the microbiome composition can differentiate the two categories of NAFLD: nonalcoholic fatty liver (NAFL, the non-progressive form) vs nonalcoholic steatohepatitis (NASH, the progressive form). The association between gut microbiome and fibrosis progression in NAFLD is also discussed. Finally, we review whether modulation of the gut microbiome plays a role in improving treatment outcomes for patients with NAFLD. Conclusions Multiple pathophysiologic pathways connect the gut microbiome with the pathophysiology of NAFLD. Therefore, therapeutics that effectively target the gut microbiome may be beneficial for the treatment of patients with NAFLD.
Gallbladder Agenesis: A Case Report

Gallbladder agenesis (GA) is an extremely rare congenital entity. The incidence is around 1 per 6500 live births. The majority of patients, estimated between 50 to 70 percent, remain asymptomatic while those who are symptomatic report symptoms mimicking biliary colic. Initial workup for suspected gallbladder pathology such as right upper quadrant ultrasound (US) can be misleading or inconclusive. Furthermore, advanced diagnostic studies such as hepatobiliary iminodiacetic acid (HIDA) scan and endoscopic retrograde cholangio-pancreatography (ERCP) may report non-visualization of the gallbladder and erroneously lead providers to a diagnosis of cystic duct obstruction rather than GA. Consequently, some GA patients are only finally diagnosed intraoperatively. Surgery can be risky in these patients because unnecessary dissection while looking for the non-existent gallbladder can result in injury of the biliary tree, hepatic vasculature, or small bowel. Therefore, clinicians should keep GA on their differential diagnosis list and imaging modalities such as magnetic resonance cholangiopancreatography (MRCP) should be obtained when other tests prove inconclusive. We report a 35-year-old female presenting with chronic symptoms consistent with biliary colic and an equivocal US reported as cholelithiasis. She underwent laparoscopy during which the absence of the gallbladder was noted. Postoperative MRCP confirmed the diagnosis of GA.
RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling

Within the complex environment of the human cell, the RIG-I innate immune receptor must detect the presence of double-stranded viral RNA molecules and differentiate them from a diversity of host RNA molecules. In an ongoing effort to understand the molecular basis for RIG-I target specificity, here, we evaluate the ability of this sensor to respond to triphosphorylated, double-stranded RNA molecules that contain all possible terminal base pairs and common mismatches. In addition, we test the response to duplexes with various types of 5' and 3' overhangs. We conducted quantitative measurements of RNA ligand affinity, then tested RNA variants for their ability to stimulate the RIG-I-dependent interferon response in cells and in whole animals. The resulting data provide insights into the design of RNA therapeutics that prevent RIG-I activation, and they provide valuable insights into the mechanisms of evasion by deadly pathogens such as the Ebola and Marburg viruses.
Design to Data for mutants of β-glucosidase B from Paenibacillus polymyxa: Q22T, W123R, F155G, Y169M, W438D, V401A

A key goal of protein engineering is to accurately model the stability and catalytic activity of enzymes. However, the limitations of functional predictive abilities pose a major challenge for modeling algorithm design, and can be attributed to the lack of large data sets quantifying the functional properties of enzymes. Here, the thermal stability (TM) and Michaelis-Menten constants (kcat, KM, and kcat/KM) of six new variants of the β-glucosidase B (BglB) protein are quantitatively characterized. Molecular stability of the enzyme variants were hypothesized using the Foldit software and BglB was synthesized in E. coli cells. Testing was done through a colorimetric kinetic assay and thermal stability fluorescence-based protein unfolding assay. Results from the assays suggest that all mutations, with the exception of variant Y169M, all experienced reduced catalytic efficiency compared to the wildtype. Assay results indicate that variant W123R is more thermally stable compared to the wildtype, while the differences in thermal stability between the other variants, and the wildtype are negligible. The collected thermal stability and catalytic efficiency data has been added to a data set with the aim of improving Rosetta algorithms for modeling and predicting the functional interactions between biomolecules through a machine learning algorithm and facilitate the precise engineering of protein catalysts.
Bourbon justice: how whiskey law shaped America

What exactly is bourbon? At its most basic level, bourbon is a type of whiskey made in the United States. Bourbon is defined by American law as a distilled beverage (between 80 and 40% alcohol by v...
Anterior choroidal artery infarct presenting as right hemichoreoathetosis.

A 90-year-old woman presented with choreoathetosis ([video 1][1]) involving her right upper and lower extremities beginning 3 days prior to presentation. Her choreoathetosis worsened with distraction but improved with purposeful movements (eg, writing her name). Further neurological examination
Renewable Rikers: A Plan for Restorative Environmental Justice

This paper makes the case that the City of New York should use the closure of Rikers Island as a moment for restorative environmental justice. The overwhelming majority of the prisoners in the Rikers corrections facility hail from New York City’s environmental justice communities. These communities have been overburdened and under-served by the City on many fronts. They house more than their fair share of polluting activities, including most of the City’s power plants, wastewater treatment plants, bus depots, and municipal waste transfer stations. These communities suffer from under-investment in vital infrastructure like schools and transportation infrastructure. At the same time, the City's policing policies disproportionately sent members from these communities to Rikers Island. As the City plans for a post-prison Rikers Island, it should focus on using the Island to tangibly benefit those communities. Renewable Rikers has three main components: sustainable energy, waste water treatment, and green spaces. By converting part of the island into a wind/solar generating and storage facility and part into a state-of-the-art modern waste water treatment facility, the City could reduce reliance on (and possibly shutter) the old, dirty, peak-load generating facilities that are located in environmental justice communities. Such a step would dramatically improve air quality in those communities and create green jobs; potentially rerouting the school-to-prison pipeline into a school-to-green jobs pipeline. Moreover, the prime waterfront space currently occupied by these noxious uses could be converted into accessible, much-needed green spaces in currently under-served communities — an additional restorative step that would also promote environmental justice.
Clinical utility of echocardiography in secondary ischemic stroke prevention.

Abstract Echocardiography employs ultrasound to evaluate cardiac function, structure and pathology. The clinical value in secondary ischemic stroke prevention depends on identification of associated conditions for which a change in treatment from antiplatelet agents and risk factor intervention leads to improved outcomes. Such therapeutically relevant findings include primarily intracardiac thrombus, valvular heart disease and, in highly selected patients, patent foramen ovale (PFO). Echocardiography in unselected patients with ischemic stroke has a very low yield of therapeutically relevant findings and is not cost-effective. With the exception of PFO, findings on echocardiography that are therapeutically relevant for secondary stroke prevention are almost always associated with history, signs or symptoms of cardiac or systemic disease. Choice of specific echocardiographic modalities should be based on the specific pathology or pathologies that are under consideration for the individual clinical situation. Transthoracic echocardiography (TTE) with agitated saline has comparable accuracy to transesophageal echocardiography (TEE) for PFO detection. For other therapeutically relevant pathologies, with the possible exception of left ventricular thrombus (LVT), TEE is more sensitive than TTE. Professional societies recommend TTE as the initial test but these recommendations do not take cost into account. In contrast, cost-effectiveness studies have determined that the most sensitive echocardiographic modality should be selected as the initial and only test.