bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine Profile Distinguishes Children With Plasmodium falciparum Malaria From Those With Bacterial Blood Stream Infections
Authors: Struck Nicole S , Zimmermann Marlow , Krumkamp Ralf , Lorenz Eva , Jacobs Thomas , Rieger Toni , Wurr Stephanie , Günther Stephan , Gyau Boahen Kennedy , Marks Florian , Sarpong Nimako , Owusu-Dabo Ellis , May Jürgen , Eibach Daniel
Published: November 2019

Background

Malaria presents with unspecific clinical symptoms that frequently overlap with other infectious diseases and is also a risk factor for coinfections, such as non-Typhi Salmonella. Malaria rapid diagnostic tests are sensitive but unable to distinguish between an acute infection requiring treatment and asymptomatic malaria with a concomitant infection. We set out to test whether cytokine profiles could predict disease status and allow the differentiation between malaria and a bacterial bloodstream infection.

Methods

We created a classification model based on cytokine concentration levels of pediatric inpatients with either Plasmodium falciparum malaria or a bacterial bloodstream infection using the Luminex platform. Candidate markers were preselected using classification and regression trees, and the predictive strength was calculated through random forest modeling.

Results

Analyses revealed that a combination of 7–15 cytokines exhibited a median disease prediction accuracy of 88% (95th percentile interval, 73%–100%). Haptoglobin, soluble Fas-Ligand, and complement component C2 were the strongest single markers with median prediction accuracies of 82% (with 95th percentile intervals of 71%–94%, 62%–94%, and 62%–94%, respectively).

Conclusions

Cytokine profiles possess good median disease prediction accuracy and offer new possibilities for the development of innovative point-of-care tests to guide treatment decisions in malaria-endemic regions.
Reactive oxygen species play a dominant role in all pathways of rapid quinolone-mediated killing
Authors: Hong Yuzhi , Li Qiming , Gao Qiong , Xie Jianping , Huang Haihui , Drlica Karl , Zhao Xilin
Published: November 2019

Background

Quinolones have been thought to rapidly kill bacteria in two ways: (i) quinolone-topoisomerase-DNA lesions stimulate the accumulation of toxic reactive oxygen species (ROS); and (ii) the lesions directly cause lethal DNA breaks. Traditional killing assays may have underestimated the ROS contribution by overlooking the possibility that ROS continue to accumulate and kill cells on drug-free agar after quinolone removal.

Methods

Quinolone-induced, ROS-mediated killing of Escherichia coli was measured by plating post-treatment samples on agar with/without anti-ROS agents.

Results

When E. coli cultures were treated with ciprofloxacin or moxifloxacin in the presence of chloramphenicol (to accentuate DNA-break-mediated killing), lethal activity, revealed by plating on quinolone-free agar, was inhibited by supplementing agar with ROS-mitigating agents. Moreover, norfloxacin-mediated lethality, observed with cells suspended in saline, was blocked by inhibitors of ROS accumulation and exacerbated by a katG catalase deficiency that impairs peroxide detoxification. Unlike WT cells, the katG mutant was killed by nalidixic acid or norfloxacin with chloramphenicol present and by nalidixic or oxolinic acid with cells suspended in saline. ROS accumulated after quinolone removal with cultures either co-treated with chloramphenicol or suspended in saline. Deficiencies in recA or recB reduced the protective effects of ROS-mitigating agents, supporting the idea that repair of quinolone-mediated DNA lesions suppresses the direct lethal effects of such lesions.

Conclusions

ROS are the dominant factor in all modes of quinolone-mediated lethality, as quinolone-mediated primary DNA lesions are insufficient to kill without triggering ROS accumulation. ROS-stimulating adjuvants may enhance the lethality of quinolones and perhaps other antimicrobials.
Phenology of Emerald Ash Borer (Coleoptera: Buprestidae) and Its Introduced Larval Parasitoids in the Northeastern United States
Authors: Jones Michael I , Gould Juli R , Mahon Hope J , Fierke Melissa K
Published: November 2019

Biological control offers a long-term and sustainable option for controlling the destructive forest pest emerald ash borer (EAB), Agrilus planipennis Fairmaire, in North America. Three larval parasitoids, Spathius agrili Yang (Hymenoptera: Braconidae), Tetrastichus planipennisi Yang (Eulophidae), and Spathius galinae Belokobylskij & Strazanac, have been introduced to North America from the native range of EAB (northeastern Asia). While T. planipennisi appears to be persisting where it has been introduced in northern United States, S. agrili failed to establish in northeastern states. The more recently identified parasitoid S. galinae was recovered from the Russian Far East and climate matching suggests it should be suited for release in colder climates. We collected data on the phenology of EAB and its introduced larval parasitoids from colonies established in an insectary, growth chambers, and field-caged trees in Syracuse, New York to determine whether asynchrony between parasitoids and EAB or climate could impact establishment and persistence. Phenological data indicated EAB has one and 2-yr life cycles in New York, with parasitoid-susceptible EAB larvae available spring to fall for parasitism. Insectary and growth chamber studies indicated S. galinae and T. planipennisi were synchronous with EAB phenology, and field studies suggested both species could overwinter in northeastern climates. Spathius agrili was asynchronous with EAB phenology and climate, emerging when fewer parasitoid-susceptible EAB larvae were available and temperatures were not optimal for survival. Our results suggest S. galinae and T. planipennisi are suited for biological control of EAB at the northern limits of its range in North America.
Minimal Duration of Tick Attachment Sufficient for Transmission of Infectious Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) by Its Primary Vector Dermacentor variabilis (Acari: Ixodidae): Duration of Rickettsial Reactivation in the Vector Revisited
Authors: Levin Michael L , Ford Shelby L , Hartzer Kris , Krapiunaya Lnna , Stanley Hannah , Snellgrove Alyssa N
Published: November 2019

It has been reported that starving ticks do not transmit spotted fever group Rickettsia immediately upon attachment because pathogenic bacteria exist in a dormant, uninfectious state and require time for ‘reactivation’ before transmission to a susceptible host. To clarify the length of reactivation period, we exposed guinea pigs to bites of Rickettsia rickettsii-infected Dermacentor variabilis (Say) and allowed ticks to remain attached for predetermined time periods from 0 to 48 h. Following removal of attached ticks, salivary glands were immediately tested by PCR, while guinea pigs were observed for 10–12 d post-exposure. Guinea pigs in a control group were subcutaneously inoculated with salivary glands from unfed D. variabilis from the same cohort. In a parallel experiment, skin at the location of tick bite was also excised at the time of tick removal to ascertain dissemination of pathogen from the inoculation site. Animals in every exposure group developed clinical and pathological signs of infection. The severity of rickettsial infection in animals increased with the length of tick attachment, but even attachments for less than 8 h resulted in clinically identifiable infection in some guinea pigs. Guinea pigs inoculated with salivary glands from unfed ticks also became severely ill. Results of our study indicate that R. rickettsii residing in salivary glands of unfed questing ticks does not necessarily require a period of reactivation to precede the salivary transmission and ticks can transmit infectious Rickettsia virtually as soon as they attach to the host.
Recent Trends in Squamous Cell Carcinoma of the Anus Incidence and Mortality in the United States, 2001–2015
Authors: Deshmukh Ashish A , Suk Ryan , Shiels Meredith S , Sonawane Kalyani , Nyitray Alan G , Liu Yuxin , Gaisa Michael M , Palefsky Joel M , Sigel Keith
Published: November 2019

Background

Squamous cell carcinoma of the anus (SCCA) incidence is rising in the United States. Study of incidence trends by stage at diagnosis, age-specific and birth cohort patterns, and trends in mortality could provide evidence for a true increase and etiological clues for the increase in incidence.

Methods

Using the US Cancer Statistics dataset, we examined trends in SCCA incidence (2001–2015) and mortality (2001–2016) rates. Join-point regression was used to compute annual and average annual percentage change (AAPC). Incidence patterns by 5-year age group and birth cohort were evaluated using incidence rate ratios (IRRs) and age-period-cohort modeling.

Results

SCCA incidence increased 2.7% per year (95% confidence interval [CI] = 2.1% to 3.3%), with pronounced increases in age groups 50 years and older. Distant-stage SCCA incidence tripled (AAPC = 8.6%, 95% CI = 5.4% to 12.0%, among men and AAPC = 7.5%, 95% CI = 4.8% to 10.2%, among women) and regional-stage SCCA incidence nearly doubled (AAPC = 4.7% for men and women) in both sexes; the AAPC for localized stage was 1.3% (95% CI = 0.6% to 2.0%) in men and 2.3% (95% CI = 1.8% to 2.8%) in women. Compared with adults born circa 1946, recently born black men (born circa 1986) had a nearly fivefold higher risk (IRR = 4.7, 95% CI = 2.1 to 10.2) of SCCA, and the risk doubled among white men (IRR = 2.0, 95% CI = 1.7 to 2.2) and white women (IRR = 2.1, 95% CI = 1.9 to 2.3) born after circa 1960. Anal cancer mortality rates increased 3.1% per year (95% CI = 2.6% to 3.5%) with statistically significant increases in age groups 50 years and older. SCCA incidence-based mortality increased 1.9% annually (95% CI = 0.5% to 3.4%), with a notable (4.9%, 95% CI = 2.4% to 7.3%, per year) rise in adults ages 60–69 years.

Conclusion

The increase in SCCA incidence, particularly advanced-stage disease, and a similar increase in mortality suggest a true increase in the occurrence of SCCA. Future research and improved prevention are urgently needed to mitigate the increasing disease burden.
Efficacy of the AS04-Adjuvanted HPV16/18 Vaccine: Pooled Analysis of the Costa Rica Vaccine and PATRICIA Randomized Controlled Trials
Authors: Tota Joseph E , Struyf Frank , Sampson Joshua N , Gonzalez Paula , Ryser Martin , Herrero Rolando , Schussler John , Karkada Naveen , Rodriguez Ana Cecilia , Folschweiller Nicolas , Porras Carolina , Schiffman Mark , Schiller John T , Quint Wim , Kreimer Aimée R , Wheeler Cosette M , Hildesheim Allan ,   for the Costa Rica Vaccine Trial and PATRICIA Study
Published: November 2019

Background

The AS04-adjuvanted HPV16/18 (AS04-HPV16/18) vaccine provides excellent protection against targeted human papillomavirus (HPV) types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests that lower levels of protection may exist for a wide range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials, we aimed to evaluate AS04-HPV16/18 vaccine efficacy against incident HPV infections and cervical abnormalities .

Methods

Data were available from the Costa Rica Vaccine Trial (NCT00128661) and Papilloma Trial Against Cancer in Young Adults trial (NCT00122681), two large-scale, double-blind randomized controlled trials of the AS04-HPV16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline.

Results

A total of 12 550 women were included in our primary analyses (HPV arm = 6271, control arm = 6279). Incidence of 6-month persistent oncogenic and nononcogenic infections, excluding known and accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy = 9.9%, 95% confidence interval [CI] = 1.7% to 17.4%). Statistically significant efficacy (P < .05) was observed for individual oncogenic types 16/18/31/33/45/52 and nononcogenic types 6/11/53/74. Efficacy against cervical abnormalities (all types) increased with severity, ranging from 27.7% (95% CI = 21.7% to 33.3%) to 58.7% (95% CI = 34.1% to 74.7%) for cytologic outcomes (low-grade squamous intraepithelial neoplasia lesion or greater, and high-grade squamous intraepithelial neoplasia lesion or greater, respectively) and 66.0% (95% CI = 54.4% to 74.9%) to 87.8% (95% CI = 71.1% to 95.7%) for histologic outcomes (CIN2+ and CIN3+, respectively). Comparing Costa Rica Vaccine Trial and Papilloma Trial Against Cancer in Young Adults results, there was no evidence of heterogeneity, except for type 51 (efficacy = −28.6% and 20.7%, respectively; two-sided P = .03).

Conclusions

The AS04-HPV16/18 vaccine provides some additional cross-protection beyond established protected types, which partially explains the high efficacy against CIN3+.
Two SLENDER AND CRINKLY LEAF dioxygenases play an essential role in rice shoot development
Authors: Liu Xiong , Cai Wen-Jing , Yin Xiaoming , Yang Di , Dong Tian , Feng Yu-Qi , Wu Yan
Published: November 2019

It is clear that 2-oxoglutarate-dependent dioxygenases have critical functions in salicylic acid (SA) metabolism in plants, yet their role in SA biosynthesis is poorly understood. Here, we report that two dioxygenase-encoding genes, SLENDER AND CRINKLY LEAF1 (SLC1) and SLC2, play essential roles in shoot development and SA production in rice. Overexpression of SLC1 (SLC1-OE) or SLC2 (SLC2-OE) in rice produced infertile plants with slender and crinkly leaves. Disruption of SLC1 or SLC2 led to dwarf plants, while simultaneous down-regulation of SLC1 and SLC2 resulted in a severe defect in early leaf development. Enhanced SA levels in SLC1-OE plants and decreased SA levels in slc1 and slc2 mutants were observed. Accordingly, these lines all showed altered expression of a set of SA-related genes. We demonstrated that SLC1 interacts with homeobox1 (OSH1), and that either the knotted1-like homeobox (KNOX1) or glutamate, leucine, and lysine (ELK) domain of OSH1 is sufficient for accomplishing this interaction. Collectively, our data reveal the importance of SLC1 and SLC2 in rice shoot development.
A role for Arabidopsis growth-regulating factors 1 and 3 in growth–stress antagonism
Authors: Piya Sarbottam , Liu Jinyi , Burch-Smith Tessa , Baum Thomas J , Hewezi Tarek
Published: November 2019

Growth-regulating factors (GRFs) belong to a small family of transcription factors that are highly conserved in plants. GRFs regulate many developmental processes and plant responses to biotic and abiotic stimuli. Despite the importance of GRFs, a detailed mechanistic understanding of their regulatory functions is still lacking. In this study, we used ChIP sequencing (ChIP-seq) to identify genome-wide binding sites of Arabidopsis GRF1 and GRF3, and correspondingly their direct downstream target genes. RNA-sequencing (RNA-seq) analysis revealed that GRF1 and GRF3 regulate the expression of a significant number of the identified direct targets. The target genes unveiled broad regulatory functions of GRF1 and GRF3 in plant growth and development, phytohormone biosynthesis and signaling, and the cell cycle. Our analyses also revealed that clock core genes and genes with stress- and defense-related functions are most predominant among the GRF1- and GRF3-bound targets, providing insights into a possible role for these transcription factors in mediating growth–defense antagonism and integrating environmental stimuli into developmental programs. Additionally, GRF1 and GRF3 target molecular nodes of growth–defense antagonism and modulate the levels of defense- and development-related hormones in opposite directions. Taken together, our results point to GRF1 and GRF3 as potential key determinants of plant fitness under stress conditions.
Star formation and gas flow history of a dwarf irregular galaxy traced by gas-phase and stellar metallicities
Authors: Fukagawa Nao
Published: November 2019

Studying the evolution of dwarf galaxies can provide insights into the characteristics of systems that can act as building blocks of massive galaxies. This paper discusses the history of star formation and gas flows (inflow and outflow) of a dwarf irregular galaxy in the Local Group, NGC 6822, from the viewpoint of gas-phase and stellar chemical abundance. Gas-phase oxygen abundance, stellar metallicity distribution, and gas fraction data are compared to chemical evolution models in which continuous star formation and gas flows are assumed. If the galaxy is assumed to be a closed or an accretion-dominated system where steeper stellar initial mass functions are allowed, the observed gas-phase oxygen abundance and gas fraction can be explained simultaneously; however, metallicity distributions predicted by the models seem to be inconsistent with the observed distribution, which suggests that the star formation, gas flows, and/or chemical enrichment are more complex than assumed by the models. When NGC 6822 is assumed to be a system dominated by outflow, the observed values of gas-phase oxygen abundance and gas fraction can be explained, and the metallicity distributions predicted by some of the models are also roughly consistent with the observed distribution in the metallicity range of −2.0 ≲ [Fe/H] ≲ −0.5. It should be noted that this result does not necessarily mean that the accretion of gas is completely ruled out. More observables, such as chemical abundance ratios, and detailed modelling may provide deeper insight into the evolution of the system.
The Sloan Digital Sky Survey extended point spread functions
Authors: Infante-Sainz Raúl , Trujillo Ignacio , Román Javier
Published: November 2019

A robust and extended characterization of the point spread function (PSF) is crucial to extract the photometric information produced by deep imaging surveys. Here, we present the extended PSFs of the Sloan Digital Sky Survey (SDSS), one of the most productive astronomical surveys of all time. By stacking ∼1000 images of individual stars with different brightness, we obtain the bidimensional SDSS PSFs extending over 8 arcmin in radius for all the SDSS filters (u, g, r, i, z). This new characterization of the SDSS PSFs is near a factor of 10 larger in extension than previous PSFs characterizations of the same survey. We found asymmetries in the shape of the PSFs caused by the drift scanning observing mode. The flux of the PSFs is larger along the drift scanning direction. Finally, we illustrate with an example how the PSF models can be used to remove the scattered light field produced by the brightest stars in the central region of the Coma cluster field. This particular example shows the huge importance of PSFs in the study of the low-surface brightness Universe, especially with the upcoming of ultradeep surveys, such as the Large Synoptic Survey Telescope (LSST). Following a reproducible science philosophy, we make all the PSF models and the scripts used to do the analysis of this paper publicly available (snapshot v0.4-0-gd966ad0).
New constraints on the HR 8799 planetary system from mid-infrared direct imaging
Authors: Petit dit de la Roche D J M , van den Ancker M E , Kissler-Patig M , Ivanov V D , Fedele D
Published: November 2019

Direct imaging is a tried and tested method of detecting exoplanets in the near-infrared (IR), but has so far not been extended to longer wavelengths. New data at mid-IR wavelengths (8–20 μm) can provide additional constraints on planetary atmospheric models. We use the VLT Imager and Spectrometer for the mid-IR (VISIR) instrument on the VLT to detect or set stringent limits on the 8.7 μm flux of the four planets surrounding HR 8799, and to search for additional companions. We use a novel circularized point spread function subtraction technique to reduce the stellar signal and obtain instrument limited background levels and obtain optimal flux limits. The BT SETTL isochrones are then used to determine the resulting mass limits. We find flux limits between 0.7 and 3.3 mJy for the J8.9 flux of the different planets at better than 5σ level and derive a new mass limit of 30 MJup for any objects beyond 40 au. While this work has not detected planets in the HR 8799 system at 8.7 μm, it has found that an instrument with the sensitivity of VISIR is sufficient to detect at least four known hot planets around close stars, including β Pictoris b (1700 K, 19 pc), with more than 5σ certainty in 10 h of observing time in the mid-IR.
In situ scattering of warm Jupiters and implications for dynamical histories
Authors: Anderson Kassandra R , Lai Dong , Pu Bonan
Published: November 2019

Many warm Jupiters (WJs) have substantial eccentricities, which are linked to their formation and migration histories. This paper explores eccentricity excitation of WJs due to planet–planet scattering, beginning with three to four planets in unstable orbits, with the innermost planet placed in the range (0.1−1) au. Such a setup is consistent with either in situ formation or arrival at sub-au orbits due to disc migration. Most previous N-body experiments have focused on ‘cold’ Jupiters at several au, where scattering results in planet ejections, efficiently exciting the eccentricities of surviving planets. In contrast, scattering at sub-au distances results in a mixture of collisions and ejections, and the final eccentricities of surviving planets are unclear. We conduct scattering experiments for a range of planet masses and initial spacings, including the effect of general relativistic apsidal precession, and systematically catalogue the scattering outcomes and properties of surviving planets. A comparable number of one-planet and two-planet systems are produced. Two-planet systems arise exclusively through planet–planet collisions, and tend to have low eccentricities/mutual inclinations and compact configurations. One-planet systems arise through a combination of ejections and collisions, resulting in higher eccentricities. The observed eccentricity distribution of solitary WJs (lacking detection of a giant planet companion) is consistent with roughly $60 {{\ \rm per\ cent}}$ of the systems having undergone in situ scattering, and the remaining experiencing a quiescent history.
A double-stranded RNA platform is required for the interaction between a host restriction factor and the NS1 protein of influenza A virus
Authors: Chen Guifang , Ma Li-Chung , Wang Shanshan , Woltz Ryan L , Grasso Emily M , Montelione Gaetano T , Krug Robert M
Published: November 2019

Influenza A viruses cause widespread human respiratory disease. The viral multifunctional NS1 protein inhibits host antiviral responses. This inhibition results from the binding of specific cellular antiviral proteins at various positions on the NS1 protein. Remarkably, binding of several proteins also requires the two amino-acid residues in the NS1 N-terminal RNA-binding domain (RBD) that are required for binding double-stranded RNA (dsRNA). Here we focus on the host restriction factor DHX30 helicase that is countered by the NS1 protein, and establish why the dsRNA-binding activity of NS1 is required for its binding to DHX30. We show that the N-terminal 152 amino-acid residue segment of DHX30, denoted DHX30N, possesses all the antiviral activity of DHX30 and contains a dsRNA-binding domain, and that the NS1-DHX30 interaction in vivo requires the dsRNA-binding activity of both DHX30N and the NS1 RBD. We demonstrate why this is the case using bacteria-expressed proteins: the DHX30N-NS1 RBD interaction in vitro requires the presence of a dsRNA platform that binds both NS1 RBD and DHX30N. We propose that a similar dsRNA platform functions in interactions of the NS1 protein with other proteins that requires these same two amino-acid residues required for NS1 RBD dsRNA-binding activity.
Geospatial Analyses of Pain Intensity and Opioid Unit Doses Prescribed on the Day of Discharge Following Orthopedic Surgery
Authors: Tighe Patrick , Modave François , Horodyski MaryBeth , Marsik Matthew , Lipori G , Fillingim Roger , Hu Hui , Hagen Jennifer
Published: November 2019

Objective

Inappropriate opioid prescribing after surgery contributes to opioid use disorder and risk of opioid overdose. In this cross-sectional analysis of orthopedic surgical patients, we examined the role of patient location on postoperative pain intensity and opioids prescribed on hospital discharge.

Methods

We used geospatial analyses to characterize spatial patterns of mean pain intensity on the day of discharge (PiDoD) and opioid units prescribed on the day of discharge (OuPoD), as well as the effect of regional social deprivation on these outcomes.

Results

At a 500-km radius from the surgery site, the Global Moran’s I for PiDoD (2.71 × 10−3, variance = 1.67 × 10−6, P = 0.012) and OuPoD (2.19 × 10−3, SD = 1.87, variance = 1.66 × 10−6, P = 0.03) suggested significant spatial autocorrelation within each outcome. Local indicators of spatial autocorrelation, including local Moran’s I, Local Indicator of Spatial Autocorrelation cluster maps, and Getis-Ord Gi* statistics, further demonstrated significant, specific regions of clustering both OuPoD and PiDoD. These spatial patterns were associated with spatial regions of area deprivation.

Conclusions

Our results suggest that the outcomes of pain intensity and opioid doses prescribed exhibit varying degrees of clustering of patient locations of residence, at both global and local levels. This indicates that a given patient’s pain intensity on discharge is related to the pain intensity of nearby individuals. Similar interpretations exist for OuPoD, although the relative locations of hot spots of opioids dispensed in a geographic area appear to differ from those of hot spots of pain intensity on discharge.
Maximal efficiency of the collisional Penrose process with a spinning particle. II. Collision with a particle on the innermost stable circular orbit
Authors: Okabayashi Kazumasa , Maeda Kei-ichi
Published: November 2019

We analyze the collisional Penrose process between a particle on the innermost stable circular orbit (ISCO) orbit around an extreme Kerr black hole and a particle impinging from infinity. We consider both cases with non-spinning and spinning particles. We evaluate the maximal efficiency, $\eta_{\text{max}}=(\text{extracted energy})/(\text{input energy})$, for the elastic collision of two massive particles and for the photoemission process, in which the ISCO particle will escape to infinity after a collision with a massless impinging particle. For non-spinning particles, the maximum efficiency is $\eta_{\text{max}} \approx 2.562$ for the elastic collision and $\eta_{\text{max}} \approx 7$ for the photoemission process. For spinning particles we obtain the maximal efficiency $\eta_{\text{max}} \approx 8.442$ for the elastic collision and $\eta_{\text{max}} \approx 12.54$ for the photoemission process.
Representation of Partisan, Territorial, and Institutional Interests in Second Chambers: Evidence from the German Bundesrat and its Committees
Authors: Finke Patrick , Müller Markus M , Souris Antonios , Sturm Roland
Published: November 2019

Revisiting the longstanding debate on interest representation in federal second chambers, this article investigates the influence of partisanship vis-à-vis territorial and other interests such as institutional concerns on deliberations. We argue that committees as the actual place of policy- and decision-making provide an instructive approach to understand interest representation in second chambers, just as in first chambers. For the empirical part of our study, we focus on the German Bundesrat and its committees. Based on the protocols of their meetings, we developed a new dataset that contains information on more than 51,000 roll call votes, the largest-ever empirical basis to study interest representation and decision-making in the Bundesrat. Above all, we find that partisanship plays a role, yet a minor one. The representatives prioritize individual or joint sub-state interests over their political party affiliations, just like the founding fathers of the Federal Republic have envisaged it in the German constitution.
MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis
Authors: Barendregt Anouk M , Veldkamp Saskia R , Hissink Muller Petra C E , van de Geer Annemarie , Aarts Cathelijn , van Gulik E Charlotte , Schilham Marco W , Kessel Christoph , Keizer Mischa P , Hemke Robert , Nassar-Sheikh Rashid Amara , Dolman Koert M , Schonenberg-Meinema Dieneke , ten Cate Rebecca , van den Berg J Merlijn , Maas Mario , Kuijpers Taco W
Published: November 2019

Objective

To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA.

Methods

Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months. Receiver operating characteristic analyses were carried out to study the predictive value of MRP8/14 and NE for treatment response and flare.

Results

For both cohorts, baseline MRP8/14 and NE levels for patients who did or did not respond to treatment were not different. Also, MRP8/14 and NE levels were not different in patients who did or did not flare. Receiver operating characteristic analysis of MRP8/14 and NE demonstrated areas under the curve <0.7 in both cohorts.

Conclusion

In our cohorts, MRP8/14 and NE could not predict treatment response. Also, when patients had inactive disease, neither marker could predict flares.
Sex differences in obstructive sleep apnea phenotypes, the multi-ethnic study of atherosclerosis
Authors: Won Christine H J , Reid Michelle , Sofer Tamar , Azarbarzin Ali , Purcell Shaun , White David , Wellman Andrew , Sands Scott , Redline Susan
Published: November 2019

Study Objectives

The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea–hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes.

Methods

Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI.

Results

The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%–10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P.

Conclusions

There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.
Analyzing State Action on Women’s Rights: Institutions, Actors, and Issues
Authors: Waylen Georgina
Published: November 2019

Htun and Weldon’s thought-provoking book The Logics of Gender Justice makes an important contribution to gender and politics scholarship in three areas: its methods and scope; its analytical framing; and its empirical findings. It significantly advances our understanding in these key areas. In this commentary, I outline the numerous positive aspects of the book before discussing some of the research’s potential limitations, primarily from an institutionalist perspective; and I conclude by asking how this book might serve as a jumping-off point for further research that will help us better understand the current conjuncture, particularly backlash and retrenchment.
Minimum Age Regulation and Child Labor: New Evidence from Brazil
Authors: Bargain Olivier , Boutin Delphine
Published: November 2019

This study presents new evidence on the effects of minimum age regulations obtained from a natural experiment. In 1998, a constitutional reform in Brazil changed the minimum working age from 14 to 16. The reform was the legislative counterpart of a broad set of measures taken by a government strongly committed to eliminating child labor. This article investigates the role of the minimum working age in this context. The setting allows for improvements upon past approaches based on comparing employment rates of children at different ages. A discontinuity in treatment is exploited, namely the fact that only children who turned 14 after the enactment date (mid-December 1998) are banned from work. According to regression discontinuity and difference-in-discontinuity designs, the null hypothesis of no overall effect of the ban cannot be rejected. Throughout the methods and specifications, an employment effect in a confidence interval of $[-0.06, \, 0.03]$ (in percentage points) is found. A detailed heterogeneity analysis is performed and provides suggestive evidence of diminishing child labor trends in regions characterized by higher labor inspection intensity, which is interpreted as a trace of there being a law. However, contrary to what has been claimed in recent studies, the law seems not to have produced sizeable effects overall, at least in the short run. Power calculations and extensive sensitivity checks support these conclusions.
Transgenic Wheat Harboring an RNAi Element Confers Dual Resistance Against Synergistically Interacting Wheat Streak Mosaic Virus and Triticum Mosaic Virus
Authors: Tatineni Satyanarayana , Sato Shirley , Nersesian Natalya , Alexander Jeff , Quach Truyen , Graybosch Robert A , Clemente Tom Elmo
Published: November 2019

Wheat streak mosaic virus (WSMV) and triticum mosaic virus (TriMV) are economically important viruses of wheat (Triticum aestivum L.), causing significant yield losses in the Great Plains region of the United States. These two viruses are transmitted by wheat curl mites, which often leads to mixed infections with synergistic interaction in grower fields that exacerbates yield losses. Development of dual-resistant wheat lines would provide effective control of these two viruses. In this study, a genetic resistance strategy employing an RNA interference (RNAi) approach was implemented by assembling a hairpin element composed of a 202-bp (404-bp in total) stem sequence of the NIb (replicase) gene from each of WSMV and TriMV in tandem and of an intron sequence in the loop. The derived RNAi element was cloned into a binary vector and was used to transform spring wheat genotype CB037. Phenotyping of T1 lineages across eight independent transgenic events for resistance revealed that i) two of the transgenic events provided resistance to WSMV and TriMV, ii) four events provided resistance to either WSMV or TriMV, and iii) no resistance was found in two other events. T2 populations derived from the two events classified as dual-resistant were subsequently monitored for stability of the resistance phenotype through the T4 generation. The resistance phenotype in these events was temperature-dependent, with a complete dual resistance at temperatures ≥25°C and an increasingly susceptible response at temperatures below 25°C. Northern blot hybridization of total RNA from transgenic wheat revealed that virus-specific small RNAs (vsRNAs) accumulated progressively with an increase in temperature, with no detectable levels of vsRNA accumulation at 20°C. Thus, the resistance phenotype of wheat harboring an RNAi element was correlated with accumulation of vsRNAs, and the generation of vsRNAs can be used as a molecular marker for the prediction of resistant phenotypes of transgenic plants at a specific temperature.
Serelaxin inhibits the profibrotic TGF‐β1/IL‐1β axis by targeting TLR‐4 and the NLRP3 inflammasome in cardiac myofibroblasts
Authors: Cáceres Felipe Tapia , Gaspari Tracey A. , Samuel Chrishan S. , Pinar Anita A.
Published: November 2019

The recombinant form of the peptide hormone relaxin, serelaxin (RLX), mediates its anti‐fibrotic actions by impeding the profibrotic activity of cytokines including TGF‐β1 and IL‐1β. As IL‐1β can be produced by the nucleotide‐binding oligomerization domain, leucine‐rich repeat and pyrin domains‐containing protein 3 (NLRP3) inflammasome, this study determined whether RLX targeted the inflammasome to inhibit the profibrotic TGF‐β1/IL‐1β axis in primary human cardiac myofibroblasts (HCMFs) in vitro and in mice with isoproterenol (ISO)‐induced cardiomyopathy in vivo. HCMFs stimulated with TGF‐β1 (5 ng/ml), LPS (100 ng/ml), and ATP (5 mM) (T+L+A) for 8 h, to induce the NLRP3 inflammasome, demonstrated significantly increased protein expression of markers of NLRP3 priming (NLRP3, apoptosis‐associated speck‐like protein containing a C‐terminal caspase‐recruitment domain, procaspase‐1) and activity (IL‐1β, IL‐18). After 72 h, there was significantly increased neuronal NOS (nNOS), TLR‐4, procaspase‐1, myofibroblast differentiation, and collagen‐I deposition. These measures, along with interstitial TGF‐β1 expression and collagen deposition, were also increased in the left ventricle (LV) of ISO‐injured mice 14 d postinjury. RLX [16.8 nM (100 ng/ml) in vitro; 0.5 mg/kg per day in vivo] inhibited T+L+A‐ and ISO‐induced TLR‐4 expression, NLRP3 priming, IL‐1β, IL‐18, myofibroblast differentiation, and interstitial collagen deposition at the time points studied, via the promotion of nNOS; with the NLRP3‐ and IL‐1β‐inhibitory effects of RLX in HCMFs being abrogated by pharmacological blockade of nNOS or TLR‐4. Comparatively, the small molecule NLRP3 inhibitor, N‐{[(1,2,3,5,6,7‐hexahydro‐s‐indacen‐4‐yl)amino]carbonyl}‐4‐(1‐hydroxy‐1‐methylethyl)‐2‐furansulfonamide (1 μM in vitro, 10 mg/kg/d in vivo), inhibited components of the NLRP3 inflammasome in vitro and in vivo and ISO‐induced interstitial LV fibrosis in vivo but did not affect nNOS, TLR‐4, myofibroblast differentiation, or myofibroblast‐induced collagen deposition. Hence, RLX can inhibit the TGF‐β1/IL‐1β axis via a nNOS‐TLR‐4‐NLRP3 inflammasome‐dependent mechanism on cardiac myofibroblasts.—Cáceres, F. T., Gaspari, T. A., Samuel, C. S., Pinar, A. A. Serelaxin inhibits the profibrotic TGF‐β1/IL‐1β axis by targeting TLR‐4 and the NLRP3 inflammasome in cardiac myofibroblasts. FASEB J. 33, 14717‐14733 (2019). www.fasebj.org
Asthma/obstructive pulmonary disease overlap: update on definition, biomarkers, and therapeutics
Authors: Generoso August , Oppenheimer John
Published: November 2019

Purpose of review

Asthma/chronic obstructive pulmonary disease overlap (ACO) continues to be a poorly understood condition. This review discusses newly proposed criteria and potential biomarkers in ACO, to aid in diagnosis and research studies, and prudent therapeutic approaches.

Recent findings

A global expert panel proposed an operational definition consisting of major and minor criteria as a step toward defining ACO. Serum periostin and YKL-40 may serve as biomarkers for ACO. Clinically, a reasonable therapeutic approach to ACO is the early addition of a long-acting β-agonist (LABA) and/or a long-acting muscarinic antagonist (LAMA) to an inhaled corticosteroid (ICS).

Both the proposed criteria and the described biomarkers for ACO can help guide clinicians in identifying this condition as well as aid researchers in designing much needed future studies. In the meantime, clinicians can treat potential ACO patients using the above approach, until therapeutic studies in clearly defined ACO patients are performed.
Ex-vivo lung perfusion
Authors: Moreno Garijo Jacobo , Roscoe Andrew
Published: November 2019

Purpose of review

Ex-vivo lung perfusion (EVLP) has been developed to expand the donor pool for lung transplantation recipients. The role of EVLP in organ preservation, evaluation and potential reconditioning is reviewed.

Recent findings

EVLP has been shown to significantly increase the utilization of donor lungs for transplantation. Evidence suggests that patient outcomes from EVLP lungs are comparable to standard procurement technique. Novel strategies are being developed to treat and recondition injured donor lungs. EVLP may also prove to be a tool for translational research of lung diseases.

EVLP has been shown to be an effective system to expand donor pool for lung transplantation without detriment to recipients. Future potential ex-vivo developments may further improve patient outcomes as well as increasing availability of donor organs.
A call to action: Building evidence for use of simulation in nurse practitioner education
Authors: Jeffries Pamela R. , Bigley Mary Beth , McNelis Angela M. , Cartier Jeanne M. , Pintz Christine , Slaven-Lee Pamela W. , Zychowicz Michael E.
Published: November 2019

Leaders from national nursing organizations, nursing schools, and health care simulation vendors convened in early 2019 to discuss simulation in nurse practitioner (NP) education. Nurse practitioner clinical education needs a more standardized, efficient, and sustainable model to prepare NPs to provide quality care in complex health care systems. Currently, a major shortage of clinical sites and preceptors to educate students creates challenges for NP programs and nursing faculty. One strategy used by nursing programs to overcome this challenge is using simulation to provide clinical training for NP students in a safe, controlled environment. There remains, however, a lack of evidence linking these simulation experiences with clinical skills acquisition and program outcomes. Implementing competency-based education through standardized simulations has the potential to demonstrate quality, safety, and accountability across NP education programs. Ultimately, the expansion and acceptance of simulation hours in NP education is dependent on strong and favorable evidence from rigorous, high-quality studies.
Platelets as key players in inflammation and infection
Authors: Nicolai Leo , Massberg Steffen
Published: November 2019

Purpose of review

This review highlights recent insights into the role of platelets in acute inflammation and infection.

Recent findings

Platelets exhibit intravascular crawling behavior and can collect and bundle bacteria. In addition, platelets are key in promoting intravascular thrombus formation in infection, a process termed ‘immunothrombosis’, which contributes to pathogen containment, but also potentially damages the host. Platelets are at the nexus of leukocyte recruitment and activation, yet they are at the same time crucial in preventing inflammation-associated hemorrhage and tissue damage. This multitasking requires specific receptors and pathways, depending on stimulus, organ and effector function.

New findings highlight the complex interplay of innate immunity, coagulation and platelets in inflammation and infection, and unravel novel molecular pathways and effector functions. These offer new potential therapeutic approaches, but require further extensive research to distinguish treatable proinflammatory from host–protective pathways.
Transcription factor and cytokine regulation of eosinophil lineage commitment
Authors: Mack Ethan A. , Pear Warren S.
Published: November 2019

Purpose of review

Lineage commitment is governed by instructive and stochastic signals, which drive both active induction of the lineage program and repression of alternative fates. Eosinophil lineage commitment is driven by the ordered interaction of transcription factors, supported by cytokine signals. This review summarizes key findings in the study of eosinophil lineage commitment and examines new data investigating the factors that regulate this process.

Recent findings

Recent and past studies highlight how intrinsic and extrinsic signals modulate transcription factor network and lineage decisions. Early action of the transcription factors C/EBPα and GATA binding protein-1 along with C/EBPε supports lineage commitment and eosinophil differentiation. This process is regulated and enforced by the pseudokinase Trib1, a regulator of C/EBPα levels. The cytokines interleukin (IL)-5 and IL-33 also support early eosinophil development. However, current studies suggest that these cytokines are not specifically required for lineage commitment.

Together, recent evidence suggests a model where early transcription factor activity drives expression of key eosinophil genes and cytokine receptors to prime lineage commitment. Understanding the factors and signals that control eosinophil lineage commitment may guide therapeutic development for eosinophil-mediated diseases and provide examples for fate choices in other lineages.
Genetic and epigenetic factors interacting with clonal hematopoiesis resulting in chronic myelomonocytic leukemia
Authors: Carr Ryan M. , Patnaik Mrinal M.
Published: November 2019

Purpose of review

Since 2016, the WHO has recognized the significant phenotypic heterogeneity of chronic myelomonocytic leukemia (CMML) as a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap disease. Although sharing many somatic mutations with MDS and MPN, the purpose of this review is to put recent biological findings of CMML in the context of evolutionary theory, highlighting it as a distinct evolutionary trajectory occurring in the context of clonal hematopoiesis.

Recent findings

Clonal hematopoiesis of indeterminate potential (CHIP), with a mutational spectrum and prevalence correlated with age, has been defined. Enriched in DNMT3A, TET2, and ASXL1 mutations, clonal evolution can progress into various evolutionary trajectories including CMML. Impact of founder mutations (primarily TET2) on increased hematopoietic stem cell fitness has been well characterized. Epistatic interactions between mutations and epigenetic events have been explored, both in CMML and its pediatric counterpart juvenile myelomonocytic leukemia, including CMML transformation to acute myeloid leukemia. Together, these findings have contributed significantly toward CMML evolutionary dynamics.

Despite relatively few ‘driver’ mutations in CMML, evolutionary development of chronic leukemia remains incompletely understood. Recent studies have shed light on the importance of studying epigenetic consequences of mutations and epistasis between key mutations to better understand clonal architecture and evolutionary dynamics.