bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time loop gain and bandwidth measurement of phase-locked loop
Authors: Tian Jie , Li Kai , Cheng Yongsheng , Xie Nan , Hou Dong
Published: December 2018

We propose herein a simple and reliable technique to directly measure in real time the loop gain and bandwidth of a phase-locked loop (PLL). This technique can be used to make direct real-time measurements of the closed-loop gain of a PLL without breaking the locking state. We show the validity of the technique by demonstrating that the theoretical analysis is consistent to the experimental results with an actual PLL system. This simple technique with a systematic experimental configuration may easily be extended to the other PLL systems that require precise loop gain and bandwidth measurements.
Asymmetric velocity and tilt angle of domain walls induced by spin-orbit torques
Authors: Baumgartner Manuel , Gambardella Pietro
Published: December 2018

We present a micromagnetic study of the current-induced domain wall motion in perpendicularly magnetized Pt/Co/AlOx racetracks. We show that the domain wall velocity depends critically on the tilt angle of the wall relative to the current direction, which is determined by the combined action of the Dzyaloshinskii-Moriya interaction, damping-like, and field-like spin-orbit torques. The asymmetry of the domain wall velocity can be controlled by applying a bias-field perpendicular to the current direction and by the current amplitude. As the faster domain walls are expelled rapidly from the racetrack boundaries, we argue that the domain wall velocity and tilt measured experimentally depend on the timescale of the observations. Our findings reconcile the discrepancy between time-resolved and quasi-static domain wall measurements in which domain walls with opposite tilts were observed and are relevant to tune the velocity of domain walls in racetrack structures.
Corrigendum 1 (published 19 Sep 2018) and Corrigendum 2 (published 11 Dec 2018) to: Wildland fires behaviour: wind effect versus Byram’s convective number and consequences upon the regime of propagation
Authors: Morvan D. , Frangieh N.
Published: December 2018

With fuel moisture content and slope, wind velocity (UW) is one of the major physical parameters that most affects the behaviour of wildland fires. The aim of this short paper was to revisit the relationship between the rate of spread (ROS) and the wind velocity, through the role played by the two forces governing the trajectory of the flame front and the plume, i.e. the buoyancy of the plume and the inertia due to wind. A large set of experimental data (at field and laboratory scale) from the literature was analysed, by introducing the ratio between these two forces, namely Byram's convective number NC and considering the relationship between the fire ROS/wind speed ratio and Byram's number. This short note was also an opportunity to make a point on particular issues, such as the existence of two regimes of propagation of surface fires (wind-driven fire vs plume-dominated fire), the relative importance of the two modes of heat transfer (by convection and radiation) on the propagation of a fire front, and others scientific debates animating the wildland fire community.
The chaperone effect in scientific publishing
Authors: Sekara Vedran , Deville Pierre , Ahnert Sebastian E. , Barabási Albert-László , Sinatra Roberta , Lehmann Sune
Published: December 2018

Experience plays a critical role in crafting high-impact scientific work. This is particularly evident in top multidisciplinary journals, where a scientist is unlikely to appear as senior author if he or she has not previously published within the same journal. Here, we develop a quantitative understanding of author order by quantifying this “chaperone effect,” capturing how scientists transition into senior status within a particular publication venue. We illustrate that the chaperone effect has a different magnitude for journals in different branches of science, being more pronounced in medical and biological sciences and weaker in natural sciences. Finally, we show that in the case of high-impact venues, the chaperone effect has significant implications, specifically resulting in a higher average impact relative to papers authored by new principal investigators (PIs). Our findings shed light on the role played by experience in publishing within specific scientific journals, on the paths toward acquiring the necessary experience and expertise, and on the skills required to publish in prestigious venues.
Changing demographics of scientific careers: The rise of the temporary workforce
Authors: Milojević Staša , Radicchi Filippo , Walsh John P.
Published: December 2018

Contemporary science has been characterized by an exponential growth in publications and a rise of team science. At the same time, there has been an increase in the number of awarded PhD degrees, which has not been accompanied by a similar expansion in the number of academic positions. In such a competitive environment, an important measure of academic success is the ability to maintain a long active career in science. In this paper, we study workforce trends in three scientific disciplines over half a century. We find dramatic shortening of careers of scientists across all three disciplines. The time over which half of the cohort has left the field has shortened from 35 y in the 1960s to only 5 y in the 2010s. In addition, we find a rapid rise (from 25 to 60% since the 1960s) of a group of scientists who spend their entire career only as supporting authors without having led a publication. Altogether, the fraction of entering researchers who achieve full careers has diminished, while the class of temporary scientists has escalated. We provide an interpretation of our empirical results in terms of a survival model from which we infer potential factors of success in scientific career survivability. Cohort attrition can be successfully modeled by a relatively simple hazard probability function. Although we find statistically significant trends between survivability and an author’s early productivity, neither productivity nor the citation impact of early work or the level of initial collaboration can serve as a reliable predictor of ultimate survivability.
Different iron storage strategies among bloom-forming diatoms
Authors: Lampe Robert H. , Mann Elizabeth L. , Cohen Natalie R. , Till Claire P. , Thamatrakoln Kimberlee , Brzezinski Mark A. , Bruland Kenneth W. , Twining Benjamin S. , Marchetti Adrian
Published: December 2018

Diatoms are prominent eukaryotic phytoplankton despite being limited by the micronutrient iron in vast expanses of the ocean. As iron inputs are often sporadic, diatoms have evolved mechanisms such as the ability to store iron that enable them to bloom when iron is resupplied and then persist when low iron levels are reinstated. Two iron storage mechanisms have been previously described: the protein ferritin and vacuolar storage. To investigate the ecological role of these mechanisms among diatoms, iron addition and removal incubations were conducted using natural phytoplankton communities from varying iron environments. We show that among the predominant diatoms,
Pseudo-nitzschia
were favored by iron removal and displayed unique ferritin expression consistent with a long-term storage function. Meanwhile,
Chaetoceros
and
Thalassiosira
gene expression aligned with vacuolar storage mechanisms.
Pseudo-nitzschia
also showed exceptionally high iron storage under steady-state high and low iron conditions, as well as following iron resupply to iron-limited cells. We propose that bloom-forming diatoms use different iron storage mechanisms and that ferritin utilization may provide an advantage in areas of prolonged iron limitation with pulsed iron inputs. As iron distributions and availability change, this speculated ferritin-linked advantage may result in shifts in diatom community composition that can alter marine ecosystems and biogeochemical cycles.
Ubiquitin-dependent switch during assembly of the proteasomal ATPases mediated by Not4 ubiquitin ligase
Authors: Fu Xinyi , Sokolova Vladyslava , Webb Kristofor J. , Old William , Park Soyeon
Published: December 2018

Significance

In the proteasome, an essential protease of eukaryotes, the hexameric ATPases (Rpt1-Rpt6) inject ubiquitinated proteins into the proteolytic core particle. Individual Rpt proteins assemble into the hexameric Rpt ring through binding to specific chaperones: Nas2, Hsm3, Rpn14, and Nas6. Here, we show that Rpt ring assembly uses a ubiquitination-mediated control. Not4 ubiquitinates Rpt5 by competing against Nas2 first and then Hsm3 throughout Rpt ring assembly. Thus, Not4 selectively recognizes a Rpt ring that matures without these chaperones. Rpt5 ubiquitination blocks recruitment of Rpn1 ubiquitin receptor and Ubp6 deubiquitinase, halting proteasome assembly and its recognition of ubiquitinated substrates. Our findings reveal an assembly checkpoint where Not4 monitors chaperone actions during hexameric ATPase ring assembly, ensuring the accuracy of proteasome holoenzyme maturation.
Newcomb–Benford law and the detection of frauds in international trade
Authors: Cerioli Andrea , Barabesi Lucio , Cerasa Andrea , Menegatti Mario , Perrotta Domenico
Published: December 2018

The contrast of fraud in international trade is a crucial task of modern economic regulations. We develop statistical tools for the detection of frauds in customs declarations that rely on the Newcomb–Benford law for significant digits. Our first contribution is to show the features, in the context of a European Union market, of the traders for which the law should hold in the absence of fraudulent data manipulation. Our results shed light on a relevant and debated question, since no general known theory can exactly predict validity of the law for genuine empirical data. We also provide approximations to the distribution of test statistics when the Newcomb–Benford law does not hold. These approximations open the door to the development of modified goodness-of-fit procedures with wide applicability and good inferential properties.
MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat
Authors: Purdy Michael D. , Shi Dan , Chrustowicz Jakub , Hattne Johan , Gonen Tamir , Yeager Mark
Published: December 2018

HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-Å MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring. These results provide insight into the mechanism of action of BVM and related maturation inhibitors that will inform further drug discovery efforts. This study also demonstrates the capabilities of MicroED for structure-based drug design.
Mitotic antipairing of homologous and sex chromosomes via spatial restriction of two haploid sets
Authors: Hua Lisa L. , Mikawa Takashi
Published: December 2018

Significance

Mitotic recombination must be prevented to maintain genetic stability across daughter cells, but the underlying mechanism remains elusive. We report that mammalian cells impede homologous chromosome pairing during mitosis by keeping the two haploid chromosome sets apart, positioning them to either side of a meridional plane defined by the centrosomes. Chromosome oscillation analysis revealed collective genome behavior of noninteracting chromosome sets. Male translocation mice with a maternal-derived supernumerary chromosome display the tracer chromosome exclusively to the haploid set containing the X chromosome. This haploid set-based antipairing motif is shared by multiple cell types, is doubled in tetraploid cells, and is lost in carcinoma cells. The data provide a model of nuclear polarity through the antipairing of homologous chromosomes during mitosis.
Electrostatic effects, band distortions, and superconductivity in twisted graphene bilayers
Authors: Guinea Francisco , Walet Niels R.
Published: December 2018

Significance

For small twist angles, bilayer graphene forms long-wavelength Moiré patterns. For specific, so-called magic, angles of the order of 1 degree, very narrow bands have been seen that lead to superconductivity. The underlying mechanisms have since been discussed in a variety of theoretical approaches. We show that the modulation of the charge density significantly modifies the electronic structure. These changes can make an important contribution to superconductivity through electron-assisted hopping.
Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques
Authors: Snyder-Mackler Noah , Sanz Joaquín , Kohn Jordan N. , Voyles Tawni , Pique-Regi Roger , Wilson Mark E. , Barreiro Luis B. , Tung Jenny
Published: December 2018

Low social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used an in vitro GC challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We show that social status not only influences immune cell gene expression but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression after GC exposure. Regions that were more accessible in high-status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including motifs for the GC receptor cofactor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation and identify chromatin accessibility as a mechanism involved in social stress-driven GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor.
Human cytomegalovirus US21 protein is a viroporin that modulates calcium homeostasis and protects cells against apoptosis
Authors: Luganini Anna , Di Nardo Giovanna , Munaron Luca , Gilardi Gianfranco , Fiorio Pla Alessandra , Gribaudo Giorgio
Published: December 2018

Significance

During coevolution with its host, human cytomegalovirus (HCMV) has invested a large part of its protein coding potential to ensure the dysregulation of the majority of cellular homeostatic circuits. Defining the role of these HCMV proteins is important to understand viral pathogenesis and to design new antiviral strategies able to exploit their functions. Here, we report on the functional characterization of the protein encoded by the US21 gene, the founding member of the HCMV US12 gene family. The pUS21 acts as a calcium-permeable multitransmembrane channel able to reduce the calcium content of intracellular stores; pUS21-mediated tampering with intracellular calcium homeostasis, in turn, decreases the cells’ susceptibility to apoptosis, thus contributing to the overall HCMV protein toolbox evolved to blunt apoptosis in infected cells.
Quantifying single-cell secretion in real time using resonant hyperspectral imaging
Authors: Juan-Colás José , Hitchcock Ian S. , Coles Mark , Johnson Steven , Krauss Thomas F.
Published: December 2018

Cell communication is primarily regulated by secreted proteins, whose inhomogeneous secretion often indicates physiological disorder. Parallel monitoring of innate protein-secretion kinetics from individual cells is thus crucial to unravel systemic malfunctions. Here, we report a label-free, high-throughput method for parallel, in vitro, and real-time analysis of specific single-cell signaling using hyperspectral photonic crystal resonant technology. Heterogeneity in physiological thrombopoietin expression from individual HepG2 liver cells in response to platelet desialylation was quantified demonstrating how mapping real-time protein secretion can provide a simple, yet powerful approach for studying complex physiological systems regulating protein production at single-cell resolution.
Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in
Drosophila
Authors: Copur Ömer , Gorchakov Andrey , Finkl Katja , Kuroda Mitzi I. , Müller Jürg
Published: December 2018

Significance

The posttranslational modification of nucleosomes is implicated in the regulation of gene expression and chromatin packaging in all eukaryotes. In this study, we investigate the function of histone H4 lysine 16 (H4K16) and its acetylation in
Drosophila
by generating strains in which lysine 16 is mutated to arginine, glutamine, or alanine. The main conclusion of our paper is that even though H4K16 acetylation was reported to be a critical regulator of chromatin folding in vitro and has therefore been assumed to affect many different nuclear processes, its essential function in
Drosophila
is in one process: X-chromosome dosage compensation in males.
University environment and entrepreneurial intention: the mediating role of the components of the theory of planned behaviour / El entorno universitario y la intención emprendedora: el papel mediador de los componentes de la teoría de la acción planificada
Authors: Laguía González Ana , Jaén Inmaculada , Topa Gabriela , Moriano Juan
Published: December 2018

Entrepreneurship contributes to job creation and economic development. Thus, it is important to promote entrepreneurial initiatives; universities play a key role in this regard. The psychosocial perspective can contribute a great deal to studying the antecedents that lead a person to become an entrepreneur, with the theory of planned behaviour (TPB) being the theoretical framework used the most to predict entrepreneurial intention. Based on the data collected in Spain as part of the international GUESSS project (Global University Entrepreneurial Spirit Students’ Survey) with a sample of 9,753 students, the influence of the university environment, the entrepreneurial environment and the perceived risk of entrepreneurship on entrepreneurial intention are analysed, both directly and as mediated by the three components of the TPB (attitudes towards entrepreneurship, subjective norms and entrepreneurial self-efficacy). The results show that the university environment is the antecedent with the greatest effect on entrepreneurial intention; therefore, it is recommended that entrepreneurship be promoted through initiatives and educational programmes in the university environment.
Gene expression models based on transcription factor binding events confer insight into functional cis-regulatory variants
Authors: Shi Wenqiang , Fornes Oriol , Wasserman Wyeth W
Published: December 2018

Motivation

Deciphering the functional roles of cis-regulatory variants is a critical challenge in genome analysis and interpretation. It has been hypothesized that altered transcription factor (TF) binding events are a central mechanism by which cis-regulatory variants impact gene expression levels. However, we lack a computational framework to understand and quantify such mechanistic contributions.

Results

We present TF2Exp, a gene-based framework to predict the impact of altered TF-binding events on gene expression levels. Using data from lymphoblastoid cell lines, TF2Exp models were applied successfully to predict the expression levels of 3196 genes. Alterations within DNase I hypersensitive, CTCF-bound and tissue-specific TF-bound regions were the greatest contributing features to the models. TF2Exp models performed as well as models based on common variants, both in cross-validation and external validation. Combining TF alteration and common variant features can further improve model performance. Unlike variant-based models, TF2Exp models have the unique advantage to evaluate the functional impact of variants in linkage disequilibrium and uncommon variants. We find that adding TF-binding events altered only by uncommon variants could increase the number of predictable genes (R2 > 0.05). Taken together, TF2Exp represents a key step towards interpreting the functional roles of cis-regulatory variants in the human genome.

Availability and implementation

The code and model training results are publicly available at https://github.com/wqshi/TF2Exp.

Supplementary information

Supplementary data are available at Bioinformatics online.
Menthol Cigarettes, Tobacco Dependence, and Smoking Persistence: The Need to Examine Enhanced Cognitive Functioning as a Neuropsychological Mechanism
Authors: Jao Nancy C , Tan Marcia M , Matthews Phoenix A , Simon Melissa A , Schnoll Robert , Hitsman Brian
Published: December 2018

Introduction

Despite the overall decline in the prevalence of cigarette use in the United States, menthol cigarette use among smokers is rising, and evidence shows that it may lead to more detrimental effects on public health than regular cigarette use. One of the mechanisms by which nicotine sustains tobacco use and dependence is due to its cognitive enhancing properties, and basic science literature suggests that menthol may also enhance nicotine’s acute effect on cognition.

Aims and Methods

The purpose of this review is to suggest that the cognitive enhancing effects of menthol may be a potentially important neuropsychological mechanism that has yet to be examined. In this narrative review, we provide an overview of basic science studies examining neurobiological and cognitive effects of menthol and menthol cigarette smoking. We also review studies examining menthol essential oils among humans that indicate menthol alone has acute cognitive enhancing properties. Finally, we present factors influencing the rising prevalence of menthol cigarette use among smokers and the importance of this gap in the literature to improve public health and smoking cessation treatment.

Conclusions

Despite the compelling evidence for menthol’s acute cognitive enhancing and reinforcing effects, this mechanism for sustaining tobacco dependence and cigarette use has yet to be examined and validated among humans. On the basis of the basic science evidence for menthol’s neurobiological effects on nicotinic receptors and neurotransmitters, perhaps clarifying menthol’s effect on cognitive performance can help to elucidate the complicated literature examining menthol and tobacco dependence.

Implications

Menthol cigarette use has continued to be a topic of debate among researchers and policy makers, because of its implications for understanding menthol’s contribution to nicotine dependence and smoking persistence, as well as its continued use as a prevalent flavoring in tobacco and nicotine products in the United States and internationally. As international tobacco regulation policies have begun to target menthol cigarettes, research studies need to examine how flavoring additives, specifically menthol, may acutely influence neurobiological and cognitive functioning as a potential mechanism of sustained smoking behavior to develop more effective treatments.
Antibody Responses in HIV-Infected Patients With Advanced Immunosuppression and Asymptomatic Cryptococcal Antigenemia
Authors: Hlupeni Admire , Nakouzi Antonio , Wang Tao , Boyd Kathryn F , Makadzange Tariro A , Ndhlovu Chiratidzo E , Pirofski Liise-anne
Published: December 2018

Background

There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/µL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg- patients.

Methods

We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/µL; 125 CrAg- and CrAg+ but cerebrospinal fluid CrAg- by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1–3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay.

Results

GXM-IgG, -IgM, and -IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg- patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG, -IgG2, and -IgM, this model had an 80.4% probability (95% confidence interval, 0.75–0.86) of predicting CrAg+ status.

Conclusions

Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.
AKARI NEP field: Point source catalogs from GALEX and Herschel observations and selection of candidate lensed sub-millimeter galaxies
Authors: Burgarella Denis , Mazyed Firas , Oi Nagisa , Goto Tomotsugu , Buat Veronique , Malkan Matt , Lee Hyung Mok , Matsuhara Hideo , Pearson Chris , Serjeant Stephen , White Glenn J , Barrufet de Soto Laia
Published: December 2018

The AKARI Wide North Ecliptic field is one of the most important cosmological fields because it lies in the continuous viewing zones for many space telescopes, e.g., Herschel, HST, and JWST, and it is also a natural high-visibility field from the L2 halo orbit. The field will be also the location of the deep survey for the Euclid mission. Finally, AKARI has made deep mid-IR observations using its nine continuous band filters in the North Ecliptic Pole (NEP) field. We analyzed GALEX and Herschel observations in the NEP field to build catalogs in seven bands: GALEX far UV and near UV, Herschel PACS 100 μm and 250 μm, and SPIRE 250 μm, 350 μm, and 500 μm with quality checks. The SPIRE catalogs are used to identify 61 (6 in a main list and 55 in a supplementary list) candidate lensed galaxies through red 350 μm to 500 μm colors. For the brightest of these candidates with 500 μm flux densities >100 mJy, follow-up observations in millimeter wavelengths have been carried out with the NOEMA interferometer. The high quality of these observations has allowed us to study and compare their morphology beyond that possible using Herschel data alone. We find that the majority of them appear as multiple objects. The redshift distribution of the sources in the main list is found to be in the range 1.5 < $z$ < 2.3. Their IR luminosities confirm that these sources are very likely strongly lensed galaxies.
Neutrophils in lupus nephritis
Authors: Nishi Hiroshi , Mayadas Tanya N.
Published: December 2018

Purpose of review

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease characterized by IgG-autoantibodies to nuclear antigens that can deposit in the kidney and trigger lupus nephritis. Neutrophils accumulate in the kidneys of patients with proliferative LUPUS NEPHRITIS and neutrophil products and a subset of granulocytes, called low-density granulocytes (LDG) may contribute to lupus nephritis pathogenesis. Here, we will discuss recent studies implicating neutrophils in the pathogenesis of human SLE nephritis and then examine studies that provide mechanistic insights into how these cells are recruited to the glomerulus following immune complex deposition and how their products may promote lupus nephritis.

Recent findings

SLE patients display unique blood transcriptional signatures linked to Type I interferon and myeloblast differentiation, which could help stratify lupus nephritis progression. Multiphoton intravital microscopy of kidney glomerular capillaries revealed a role for neutrophil FcγRs in the rapid capture of neutrophils following immune complex deposition. The view that reduced degradation of neutrophil extracellular traps (NETS) contributes to lupus nephritis progression, is now challenged by experimental data in lupus-prone mice that genetically fail to produce NETS but still are afflicted.

A greater understanding of the neutrophil dependent mechanisms that promote lupus nephritis may potentially inform on newer therapeutic options that target neutrophil accumulation and reactivity in the nephritic kidney.
Secreted Factors From Intervertebral Disc Cells and Infiltrating Macrophages Promote Degenerated Intervertebral Disc Catabolism
Authors: Yang Hao , Liu Bo , Liu Yajun , He Da , Xing Yonggang , An Yan , Tian Wei
Published: December 2018

Study Design.

Rat nucleus pulposus (NP) cells or annulus fibrosus (AF) cells were stimulated with conditioned media of RAW 264.7 macrophages and vice versa under healthy culture conditions and in the presence of pro-inflammatory mediators. The gene expression of pro-inflammatory mediators, extracellular matrix (ECM)-modifying enzymes, and chemokines, which play important roles in intervertebral disc degeneration (IDD), was determined.

Objective.

To test whether the interaction between native disc cells and infiltrating macrophages accelerates inflammation state, disrupts matrix homeostasis, and promotes inflammatory cells infiltration.

Summary of Background Data.

With macrophages infiltration, the disc resident cells would be inevitably exposed to macrophages. Macrophages have been shown to play pro-inflammatory role in the cellular interactions with disc cells under healthy culture conditions. However, the biologic interactions between macrophages and disc cells under degenerated disc inflammatory environment remain unknown.

Methods.

Murine Macrophages RAW 264.7 were cultured in the conditioned media of Rat AF or NP cells culture in the presence or absence of IL-1β stimulation. Similarly, Rat AF or NP cells were also cultured in the conditioned media of Murine Macrophages RAW 264.7 culture in the presence or absence of IFN-γ stimulation. The mRNA levels difference of pro-inflammatory genes, catabolic genes and chemokines genes for AF cells, NP cells and Macrophages RAW 264.7 were analyzed by qRT-PCR, respectively.

Results.

Compared with serum-free media exposure, RAW 264.7 macrophages exposed to AF or NP cells conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of RAW 264.7 macrophages to conditioned media from AF or NP cells with IL-1β stimulation dramatically increased mRNA levels of all the investigated cytokines. Similarly, compared with serum-free media exposure, AF or NP cells exposed to RAW 264.7 macrophages conditioned media selectively modestly upregulated mRNA levels of the aforementioned cytokines. Exposure of AF or NP cells to conditioned media from RAW 264.7 macrophages with IFN-γ stimulation dramatically increased mRNA levels of all the investigated cytokines.

Conclusion.

The biologic interactions between infiltrating macrophages and native disc cells under degenerated disc inflammatory environment lead to an increasingly severe inflammatory conditions, which may be a self-stimulated process from the macrophages infiltration occurrence

Level of Evidence: 5
Vertebral Growth Around Distal Instrumented Vertebra in Patients With Early-Onset Scoliosis Who Underwent Traditional Dual Growing Rod Treatment
Authors: Rong Tianhua , Shen Jianxiong , Kwan Kenny , Zhang Jianguo , Wang Yahan , Li Shugang , Li Zheng , Chen Chong , Lin Youxi , Tan Haining
Published: December 2018

Study Design.

Retrospective radiographic study.

Objective.

To investigate the growth of the vertebrae around distal instrumented vertebra (DIV) in patients with early-onset scoliosis (EOS) who underwent dual growing rod (DGR) treatment.

Summary of Background Data.

Previous studies indicated that DGR was likely to preserve or even stimulate the spinal growth. However, report pertaining to the effect of growing rod on the growth of individual vertebral body is rare.

Methods.

The EOS patients treated with DGR who had at least four lengthenings and 5-year follow-up were enrolled. Spine radiographs at index surgery and final follow-up were reviewed. The height, width, and depth of vertebral body from DIV–2 to DIV+2, and the height of the adjacent intervertebral space (IVS) were measured. The percentage of growth was calculated.

Results.

Thirty-one patients (mean age, 6.2 ± 2.5 years old) met the inclusion criteria, 74.2% (23/31) of whom were female. The average follow-up was 6.2 years (range, 5.0–10.4 yr). The measured vertebrae were divided into DIV group (n = 65), DIV- group (DIV-1 and DIV-2, n = 60), and DIV+ group (DIV+1 and DIV+2, n = 47). There were 33, 90, and 78 measured IVSs in DIV, DIV–, and DIV+ group, respectively. The total percentage growth of vertebral height was significantly higher in DIV– group than that in DIV and DIV+ groups (56.6 ± 20.3% vs. 45.6 ± 18.0% and 42.7 ± 16.2%, respectively, P ≤ 0.001). The vertebrae in DIV– group also had the highest annual height growth rate (8.7 ± 2.6% vs. 7.0 ± 2.4% and 6.6 ± 2.0%, respectively, P ≤ 0.001). A significant decrease of IVS height was observed in DIV– and DIV groups (P ≤ 0.001).

Conclusion.

Traditional DGR with periodical distraction stimulated the longitudinal growth of the two segments immediately above DIV in patients with EOS. DGR technique had a negative effect on the development of intervertebral discs within distracted levels.

Level of Evidence: 3
Poor Baseline Mental Health Does Not Influence Improvement in Patient-reported Outcomes, Satisfaction, and Return to Work Two Years After Single-level Anterior Cervical Discectomy and Fusion
Authors: Goh Graham Seow-Hng , Liow Ming Han Lincoln , Yeo William , Ling Zhixing Marcus , Guo Chang Ming , Yue Wai Mun , Tan Seang Beng , Chen Li Tat John
Published: December 2018

Study Design.

Retrospective study using prospectively collected registry data.

Objective.

The authors examine the influence of preoperative mental health on outcomes after anterior cervical discectomy and fusion (ACDF) and determine the impact of ACDF on postoperative mental health.

Summary of Background Data.

While studies have reported a negative correlation between preoperative mental health and outcomes following lumbar spine surgery, the influence on outcomes following cervical spine surgery remains relatively understudied.

Methods.

Prospectively collected registry data of 104 patients who underwent single-level ACDF for cervical spondylotic myelopathy were reviewed. Patients were dichotomized into top and bottom halves based on preoperative SF-36 MCS (Mental Component Summary) using a cutoff of 48. Outcomes assessed were visual analogue scale for neck pain, arm pain, AAOS Neck Pain and Disability, Neurogenic Symptoms, Neck Disability Index, Short-Form 36, Japanese Orthopaedic Association myelopathy score, return to work, return to function, satisfaction and expectation fulfilment up to 2 years postoperatively.

Results.

The preoperative MCS was 37.5 ± 8.1 and 57.4 ± 6.3 in the Low and High MCS groups respectively (P < 0.001). The Low MCS group had poorer preoperative scores (P < 0.05). There was no significant difference in length of stay or comorbidities (P > 0.05). The High MCS group had less neck pain (P = 0.002) and showed a trend towards lower Neck Disability Index (P = 0.062) at 2 years. The Low MCS group demonstrated greater improvement in Japanese Orthopaedic Association (P = 0.007) and similar improvement in other scores (P > 0.05). There was no significant difference in proportion that achieved minimal clinically important difference for each score (P > 0.05). Both groups had similar rates of return to work, return to function, expectation fulfilment, and satisfaction (P > 0.05). Lower preoperative MCS was predictive of greater improvement in MCS (r = −0.477, P < 0.001).

Conclusion.

Despite relatively greater pain and disability at 2 years, patients with poor baseline mental health experienced similar improvement in clinical outcomes, return to work, and satisfaction rates.

Level of Evidence: 3
Titration and Tolerability of Sacubitril/Valsartan for Patients With Heart Failure in Clinical Practice
Authors: Du Amy X. , Westerhout Cynthia M. , McAlister Finlay A. , Shanks Miriam , Oudit Gavin Y. , Paterson David Ian , Hanninen Mikael , Thomas Jissy , Ezekowitz Justin A.
Published: December 2018

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.
Circulating tumor cells in metastatic breast cancer: clinical relevance and biological potential
Authors: Arkadius Polasik , Volkmar Müller , Jens Huober , Wolfgang Janni , Tanja Fehm
Published: December 2018

Purpose of review

The possibility of tumor dissemination through the blood system has been known for years. Circulating tumor cells (CTCs) are detectable in the peripheral blood of patients with early as well as metastatic breast cancer. The prognostic relevance of this biomarker has already been described. By the use of repeated blood sampling along the course of disease, CTCs can be monitored in terms of a regular ‘liquid biopsy’. This review aims to summarize recent research findings and actual ongoing clinical studies to demonstrate the actual and future relevance of CTCs in daily clinical routine.

Recent findings

Recent research results show that additional molecular analysis of CTCs might be helpful in gaining information about tumor characteristics, tumor heterogeneity and possible therapy resistance. Repetitive invasive core biopsies might be avoided.

The assessment of molecular attributes may be indispensable for obtaining an optimized and personalized therapy aiming at extended survival and/or improved quality of life.
Effect of Mannitol on Intraocular Pressure in Vitrectomized and Nonvitrectomized Eyes: A Prospective Comparative Study
Authors: Ramachandra Varsha , Chandran Premanand , Philip Reji , Arunaachalam Vinoth , Raman Ganesh V.
Published: December 2018

Purpose:

To compare the effect of mannitol in reducing intraocular pressure (IOP) in vitrectomized and nonvitrectomized eyes.

Materials and Methods:

Prospective comparative case study. Eyes with IOP≥40 mm Hg were included. Eyes which are vitrectomized and silicon oil filled were classified as group 1, and nonvitrectomized open-angle eyes were classified as group 2. Mannitol (20%, 1 g/kg) was administered intravenously over 30 minutes, and IOP was recorded at 30 minutes interval till 2 hours and at the third and fourth hour from the start of mannitol.

Results:

Thirty eyes (patients) were recruited in each group. Mean (SD) IOP reduced from 48.5±5.2 to 43.7±8 at 30 minutes, 40.7±8.4 at 60 minutes, 37.3±9.6 at 90 minutes, 35.6±10.4 at 2 hours, 34±10.7 at 3 hours, and 33±11.2 mm Hg at 4 hours in group 1, and from 48.9±6.5 to 43.2±8.6 at 30 minutes, 40.2±7.8 at 60 minutes, 36.7±7.3 at 90 minutes, 35.1±7.7 at 2 hours, 34.2±8.8 at 3 hours, and 35.7±9.4 mm Hg at 4 hours in group 2. There was a significant reduction in IOP at each time point compared with baseline in both the groups (P<0.001). There was no significant difference in IOP between the 2 groups at each time point.

Conclusion:

Mannitol reduces IOP significantly in both vitrectomized and nonvitrectomized eyes.
Safety of Lactobacillus Reuteri DSM 17938 in Healthy Children 2–5 Years of Age
Authors: Kosek Margaret N. , Peñataro-Yori Pablo , Paredes-Olortegui Maribel , Lefante John , Ramal-Asayag Cesar , Zamora-Babilonia Marcelo , Meza-Sanchez Graciela , Oberhelman Richard A.
Published: December 2018

Probiotics are increasingly used for diarrhea, but studies under the Food and Drug Administration and Investigational New Drug program are few. We conducted a phase-one placebo-controlled study of Lactobacillus reuteri DSM 17938 under Investigational New Drug program in 60 children 2–5 years of age (41 L. reuteri, 19 placebos) in a resource-constrained community in Peru. No differences in objective data on adverse events were noted, although some differences based on subjective parental reports for fever and diarrhea were seen.
Refractory Mycobacterium avium Complex Pneumonia and Anti-Interferon-γ Autoantibodies
Authors: Saba Marian , Greene John N.
Published: December 2018

There has been increasing evidence in recent literature of the link between acquired antibodies to cytokines and manifestations of immune deficiency, for example, the emerging association between acquired interferon gamma autoantibody and susceptibility to intracellular organisms, in particular, nontuberculous mycobacterium (NTM). Although the presence of these autoantibodies does not always reflect pathology, their presence in high titers in a healthy individual in the setting of an opportunistic infection necessitates greater research with regard to their role. We report a case of refractory NTM with herpes zoster reactivation in an adult South Asian woman developing in association with acquired interferon gamma autoantibody. Consider testing for this rare adult onset immunodeficiency and similar ones in the setting of severe refractory or disseminated NTM and other opportunistic pathogens in patients without human immunodeficiency virus infection or acquired immunodeficiency syndrome.
Personality traits and styles may affect the reporting of chronic pruritus: a cross-sectional study
Authors: Kini Seema , Chen Kuang-Ho , Chen Suephy C.
Published: December 2018

Introduction:

Chronic pruritus (CP) is a common symptom, but can be a diagnostic and therapeutic challenge. Our objective was to determine how personality traits, and more specifically personality styles, influence quality of life (QoL) impact of CP.

Methods:

Cross-sectional study of patients with CP from 2 main groups: (1) National Eczema Association and (2) US Veterans Health Administration (VHA) National Patient Care Database. Participants (N=483) answered questions regarding demographics, characteristics of CP, personality traits (NEO Five-Factor Model) and pruritus impact (ItchyQoL). A multivariate linear regression was performed to determine which of 15 covariates (age, race, marital status, itch duration, itch frequency, and each of the 10 personality styles) were significantly associated with greater total mean ItchyQoL score (ie, greater burden of CP). Secondary outcome measures included the 3 ItchyQoL subscale scores (symptom, emotion, function).

Results:

The Lethargic personality style (low extraversion, low conscientiousness) was significantly associated with greater total mean ItchyQoL score (β=11.65, P=0.04) while the Overcontrolled (high neuroticism, high conscientiousness) and Undercontrolled (high neuroticism, low conscientiousness) styles were significantly associated with greater symptomatic impact from CP (β=2.76, P=0.01 and β=2.34, P=0.03), respectively. African American race was significantly associated with greater mean ItchyQoL score (β=8.14, P=0.002), ItchyQoL emotional score (β=2.98, P=0.02) and trended to significance for ItchyQoL symptom score (β=1.23, P=0.06). Curiously, white race was associated with higher ItchyQoL scores for the function construct (β=1.2, P=0.04). “Single” marital status trended to significance for higher mean ItchyQoL score (β=3.79, P=0.06).

Discussion:

Our results highlight certain personality styles (Lethargic, Overcontrolled, Undercontrolled) and important demographics (ie, African American race, single marital status) that may influence itch-related QoL impact. In the clinical setting these findings may suggest a role for support structures and other integrative measures (eg, support groups, cognitive and mindfulness based therapies) to augment traditional therapeutics for CP.
Reliability of the Functional Reach Test Using a Mobile Pole Versus the Traditional Fixed Ruler
Authors: Olson Lee , Zareh Ali
Published: December 2018

Background:

The Functional Reach Test (FRT), which uses a ruler fixed to a wall, has been shown to be a reliable and valid method of evaluating fall risk in seniors and persons with various neurological conditions. However, because of various logistical reasons, the FRT may be underused by therapists in some settings. A novel method of performing the FRT has been proposed using a measuring tape attached to the end of a mobile pole.

Purpose:

The purpose was to evaluate and compare the interrater reliability of the FRT using both the traditional ruler and the mobile pole method.

Research Design:

Repeated measures.

Method:

Twenty-one persons ranging from 77 to 92 years of age from an independent living seniors complex completed both the traditional FRT and the mobile pole FRT. Tests were repeated on the same day by 2 different physical therapists.

Result:

The FRT using the mobile pole was shown to have moderate-to-excellent intertester reliability (intraclass correlation coefficient = 0.827; 95% confidence interval, lower bound 0.561, upper bound 0.931). No significant difference was found between scores obtained by the traditional and the mobile pole versions.

Conclusion:

Taking into account a relatively small sample, this study suggests that the mobile pole version is a reliable modification of the FRT. Its portability may make it useful to therapists in settings where a ruler fixed to a wall is unavailable or inconvenient.