bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introducing the Escalation Antibiogram: A Simple Tool to Inform Changes in Empiric Antimicrobials in the Nonresponding Patient
Authors: Teitelbaum Daniel , Elligsen Marion , Katz Kevin , Lam Philip W , Lo Jennifer , MacFadden Derek , Vermeiren Christie , Daneman Nick 
Published: April 2022

Abstract

Background
Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients.

Methods
Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type.

Results
Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P &lt; .0001), ciprofloxacin (63.0%, P &lt; .0001), ertapenem (73.4%, P &lt; .0001), tobramycin (80.1%, P &lt; .0001), gentamicin (82.8%, P &lt; .0001), meropenem (94.3%, P &lt; .0001), and amikacin (97.1%, P &lt; .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals.

Conclusions
Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study
Authors: Gazit Sivan , Shlezinger Roei , Perez Galit , Lotan Roni , Peretz Asaf , Ben-Tov Amir , Herzel Esma , Alapi Hillel , Cohen Dani , Muhsen Khitam , Chodick Gabriel , Patalon Tal 
Published: April 2022

Abstract

Background
Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity.

Methods
A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel.

Results
SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease.

Conclusions
Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.
The chromosome-level genome assembly of Gentiana dahurica (Gentianaceae) provides insights into gentiopicroside biosynthesis
Authors: Li Ting , Yu Xi , Ren Yumeng , Kang Minghui , Yang Wenjie , Feng Landi , Hu Quanjun 
Published: April 2022

Abstract
Gentiana dahurica Fisch. is a perennial herb of the family Gentianaceae. This species is used as a traditional Tibetan medicine because of its rich gentiopicroside constituents. Here, we generate a high-quality, chromosome-level genome of G. dahurica with a total length of 1,416.54 Mb. Comparative genomic analyses showed that G. dahurica shared one whole-genome duplication (WGD) event with Gelsemium sempervirens of the family Gelsemiaceaei and had one additional species-specific WGD after the ancient whole-genome triplication with other eudicots. Further transcriptome analyses identified numerous enzyme coding genes and the transcription factors related to gentiopicroside biosynthesis. A set of candidate cytochrome P450 genes were identified for being involved in biosynthetic shifts from swertiamarin to gentiopicroside. Both gene expressions and the contents measured by high-performance liquid chromatography indicated that the gentiopicrosides were mainly synthesized in the rhizomes with the highest contents. In addition, we found that two above-mentioned WGDs, contributed greatly to the identified candidate genes involving in gentiopicroside biosynthesis. The first reference genome of Gentianaceae we generated here will definitely accelerate evolutionary, ecological, and pharmaceutical studies of this family.
Frontiering International Relations: Narrating US Policy in the Asia Pacific
Authors: Turner Oliver 
Published: April 2022

Abstract
This article reintegrates the frontier into debates about contemporary global affairs. Its analytical focus is the United States, because despite widespread agreement that it constitutes a “frontier nation,” we lack clear explanations of what the American frontier is today and what role(s) it occupies in US politics and foreign policy. To resolve this, the article ontologically reconceptualizes the frontier, arguing that it first constitutes a narrative, rather than a spatial, construct. Instead of conquering a once self-evident frontier, the United States has a long-standing tradition of narrative “frontiering” as the ideational (re)production of frontiers. The frontier has been most consistently understood not in terms of territory but ideas, with Washington's modern-day “frontiers of freedom”—notably in the Asia Pacific—as real and consequential as those of the past. The frontier-as-narrative represents a performative act about what the United States is and how it should engage at peripheral borderlands of its identity. Beyond the United States, frontiers are created and actioned anew to reshape international affairs.
Gene Regulatory Evolution in Cold-Adapted Fly Populations Neutralizes Plasticity and May Undermine Genetic Canalization
Authors: Huang Yuheng , Lack Justin B. , Hoppel Grant T. , Pool John E. 
Published: April 2022

AbstractThe relationships between adaptive evolution, phenotypic plasticity, and canalization remain incompletely understood. Theoretical and empirical studies have made conflicting arguments on whether adaptive evolution may enhance or oppose the plastic response. Gene regulatory traits offer excellent potential to study the relationship between plasticity and adaptation, and they can now be studied at the transcriptomic level. Here, we take advantage of three closely related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. We measure the transcriptome-wide plasticity in gene expression levels and alternative splicing (intron usage) between warm and cold laboratory environments. We find that suspected adaptive changes in both gene expression and alternative splicing tend to neutralize the ancestral plastic response. Further, we investigate the hypothesis that adaptive evolution can lead to decanalization of selected gene regulatory traits. We find strong evidence that suspected adaptive gene expression (but not splicing) changes in cold-adapted populations are more vulnerable to the genetic perturbation of inbreeding than putatively neutral changes. We find some evidence that these patterns may reflect a loss of genetic canalization accompanying adaptation, although other processes including hitchhiking recessive deleterious variants may contribute as well. Our findings augment our understanding of genetic and environmental effects on gene regulation in the context of adaptive evolution.
Race, Childhood Socioeconomic Status, and Region of Childhood Residence as Intersectional Life-Course Predictors of Cognitive Aging in the United States
Authors: Reynolds Addam , Greenfield Emily A , Moorman Sara , Reyes Laurent 
Published: April 2022

Abstract

Background and Objectives
Race, childhood socioeconomic status (cSES), and region of childhood residence are each associated with later-life cognition, but no studies have examined how the confluence of these factors influences later-life cognitive performance. Guided by intersectionality theory, we examined individuals’ social positionality across these dimensions as a predictor of cognitive performance in later life among non-Hispanic White (NHW) and non-Hispanic Black (NHB) older adults.

Research Design and Methods
We used data from the 2010–2016 waves of the Health and Retirement Study with participants aged 65 and older in 2010. We employed growth curve modeling to estimate associations among race, cSES, and region of childhood residence, as well as their interactions, and cognitive performance at baseline and over time.

Results
Identifying as NHB, residing in the South, and having lower cSES each were associated with poorer later-life cognition at baseline. Childhood residence in the South was an especially strong risk factor for poorer cognition among NHBs. Among NHWs, higher cSES was associated with better baseline cognitive performance, especially among those from the South. NHBs from the South demonstrated a small advantage of higher cSES, but regardless of cSES, NHBs from the South had lower levels of baseline cognitive scores compared to all other subgroups. We observed steeper declines in cognitive performance over the 6-year study period among participants who lived in the South as children.

Discussion and Implications
Our findings suggest that intersectional social positions across race, cSES, and region of childhood residence primarily influence baseline cognition in later life. Results implicate the importance of attention to multiple life-course social positions in the context of racism within social policies and other initiatives to promote equity in later-life brain health.
Peach fruit PpNAC1 activates PpFAD3-1 transcription to provide ω-3 fatty acids for the synthesis of short-chain flavor volatiles
Authors: Jin Zhengnan , Wang Jiaojiao , Cao Xiangmei , Wei Chunyan , Kuang Jianfei , Chen Kunsong , Zhang Bo 
Published: April 2022

Abstract
Volatile organic compounds (VOCs) derived from fatty acids are major contributors to fruit flavor and affect human preferences. The ω-3 fatty acid linolenic acid 3 (18:3) serves as an important precursor for synthesis of (E)-2-hexenal and (Z)-3-hexenol. These short-chain C6 VOCs provide unique fresh notes in multiple fruit species. Metabolic engineering to improve fruit aroma requires knowledge of the regulation of fatty acid-derived VOCs. Here, we determined that ripe fruit-specific expression of PpFAD3-1 contributes to 18:3 synthesis in peach fruit. However, no significant increases in (E)-2-hexenal and (Z)-3-hexenol were detected after overexpressing PpFAD3-1. Interestingly, overexpressing the PpNAC1 transcription factor increased the content of 18:3 and enhanced the production of its derived volatiles. Moreover, induced expression of genes responsible for downstream VOC synthesis was observed for transgenic tomato fruit overexpressing PpNAC1, but not for transgenic fruit overexpressing PpFAD3-1. Electrophoretic mobility shift and ChIP-Seq assays showed that PpNAC1 activated PpFAD3-1 expression via binding to its promoter. Therefore, PpNAC1 plays an important role in modulating fatty acid flux to produce fruit flavor-related VOCs. In addition to PpNAC1, PpFAD3-1 expression was also associated with epigenetic modifications during peach fruit ripening. Taken together, our results provide new insights into the molecular mechanisms regulating biosynthesis of fatty acid and short-chain VOCs in fruit.
Is Salt at Fault? Dietary Salt Consumption and Inflammatory Bowel Disease
Authors: Kuang Rebecca , O’Keefe Stephen J D , Ramos del Aguila de Rivers Claudia , Koutroumpakis Filippos , Binion David G 
Published: April 2022

Abstract
Epidemiological trends have led to a growing consensus that diet plays a central role in the etiopathogenesis of inflammatory bowel diseases (IBD). A Western diet high in ultra-processed foods has been associated with an increased prevalence of IBD worldwide. Much attention has focused on components of the Western diet, including the high fat content, lack of fiber, added sugars, and use of additives, such as carrageenan and other emulsifiers. Less attention has been paid to the impact of high salt intake, an integral component of ultra-processed foods, which has increased dramatically in the US diet over the past 50 years. We review a growing body of literature linking the rise in dietary salt intake with the epidemiology of IBD, increased consumption of salt as a component of ultra-processed foods, high salt intake and imbalances in immune homeostasis, the effects of a high-salt diet on other inflammatory disorders, salt’s impact on animal colitis models, salt as an underrecognized component in diet modification–induced remission of IBD, and directions for future investigation.
Debt Overhang, Rollover Risk, and Corporate Investment: Evidence from the European Crisis
Authors: Kalemli-Özcan Şebnem , Laeven Luc , Moreno David 
Published: April 2022

Abstract
We quantify the role of financial leverage behind the sluggish post-crisis investment performance of European firms. We use a cross-country firm-bank matched database to identify separate roles for firm leverage, bank balance sheet weaknesses arising from sovereign risk, and aggregate demand conditions. We find that firms entering the crisis with higher debt levels reduce their investment more after the crisis. This negative effect is stronger for firms holding short-term debt in countries whose banks are weak due to sovereign stress, consistent with rollover risk being an important channel influencing investment. The negative effect of firm leverage on investment is also persistent for several years after the shock in the countries with sovereign stress. The corporate leverage channel can explain about 20% of the cumulative decline in aggregate private sector investment over the crisis period.
Reevaluation of the Role of Blocked Oropsylla hirsuta Prairie Dog Fleas (Siphonaptera: Ceratophyllidae) in Yersinia pestis (Enterobacterales: Enterobacteriaceae) Transmission
Authors: Miarinjara Adélaïde , Eads David A , Bland David M , Matchett Marc R , Biggins Dean E , Hinnebusch B Joseph 
Published: April 2022

Abstract
Prairie dogs in the western United States experience periodic epizootics of plague, caused by the flea-borne bacterial pathogen Yersinia pestis. An early study indicated that Oropsylla hirsuta (Baker), often the most abundant prairie dog flea vector of plague, seldom transmits Y. pestis by the classic blocked flea mechanism. More recently, an alternative early-phase mode of transmission has been proposed as the driving force behind prairie dog epizootics. In this study, using the same flea infection protocol used previously to evaluate early-phase transmission, we assessed the vector competence of O. hirsuta for both modes of transmission. Proventricular blockage was evident during the first two weeks after infection and transmission during this time was at least as efficient as early-phase transmission 2 d after infection. Thus, both modes of transmission likely contribute to plague epizootics in prairie dogs.
Rotating neutron stars without light cylinders
Authors: Lyutikov Maxim , Sharma Praveen 
Published: April 2022

ABSTRACTWe find a class of twisted and differentially rotating neutron star magnetospheres that do not have a light cylinder, generate no wind, and thus do not spin-down. The magnetosphere is composed of embedded differentially rotating flux surfaces, with the angular velocity decreasing as Ω ∝ 1/r (equivalently, becoming smaller at the foot-points closer to the axis of rotation). For each given North–South self-similar twist profile there is a set of self-similar angular velocity profiles (limited from above) with a ‘smooth’, dipolar-like magnetic field structure extending to infinity. For spin parameters larger than some critical value, the light cylinder appears, magnetosphere opens up, and the wind is generated.
Transient two-pole accretion in the polar V496 UMa
Authors: Kennedy M R , Littlefield C , Garnavich P M 
Published: April 2022

ABSTRACT
We report XMM–Newton and TESS observations of V496 UMa, an AM Herculis-type cataclysmic variable. The XMM–Newton observation reveals that at times, two poles on the white dwarf accrete simultaneously, but accretion on to the secondary magnetic pole is erratic and can nearly cease in less than one binary orbit (1.5 h). Modelling of the X-ray spectrum during the primary maximum reveals no change in the accretion structures on to the primary pole when accretion on to the secondary pole is disrupted, suggesting that the disruption of accretion on to the secondary pole may be caused by mass-transfer variations from the donor star. The TESS observation, which spanned eight weeks at a 2-min cadence, shows a stable, double-humped orbital modulation due to cyclotron emission from the post-shock region, while the observed times of maximum light show a slow systematic drift that does not correlate with the system’s overall brightness.
A mechanism to explain galaxy alignment over a range of scales
Authors: Tiwari Prabhakar , Jain Pankaj 
Published: April 2022

ABSTRACT
The observed large-scale alignment of polarization angles and galaxy axis have been challenging the fundamental assumption of homogeneity and isotropy in standard cosmology since more than two decades. The intergalactic magnetic field, and its correlations in real space, potentially seems as a viable candidate for explaining this phenomenon. It has been shown earlier that the large-scale intergalactic magnetic-field correlations can explain the alignment signal of quasars over Gpc scale, interestingly, they can also explain the radio polarization alignment observed in JVAS/CLASS data over 100 Mpc. Motivated with recent observations of galaxy axis alignment over several tens of Mpc, and Mpc scale, i.e. the cluster scale, we further explore the correlations of background magnetic field to explain these relatively small-scale alignment observations. In particular, we explore two recently claimed signals of alignment in the radio sources in the FIRST catalogue and in the ACO clusters. We find that the FIRST alignment signal is well-explained in terms of the intergalactic magnetic field with a spectral index of −2.62 ± 0.03. Furthermore, the model also partially explains the very small scale alignment (alignment within clusters). Though the elementary model proposed in this work seems to have its limitations at very small scales, the large-scale magnetic-field correlations potentially seem to explain the polarization and galaxy axis alignment from Gpc to Mpc scales.
Clusters in the disperse cosmic web
Authors: Cohn J D 
Published: April 2022

ABSTRACT
Galaxy cluster mass haloes (‘clusters’) in a dark matter simulation are matched to nodes in several different cosmic webs found using the disperse cosmic web finder. The webs have different simulation smoothings and disperse parameter choices; for each, four methods are considered for matching disperse nodes to clusters. For most of the webs, disperse nodes outnumber clusters, but not every cluster has a disperse node match (and sometimes &gt;1 cluster matches to the same disperse node). The clusters frequently lacking a matching disperse node have a different distribution of local shear trends and perhaps merger histories. It might be interesting to see in what other ways, e.g. observational properties, these clusters differ. For the webs with smoothing ≤ 2.5 Mpc h−1, and all but the most restrictive matching criterion, ∼3/4 of the clusters always have a disperse node counterpart. The nearest cluster to a given disperse node and vice versa, within twice the smoothing length, obey a cluster mass-disperse node density relation. Cluster pairs where both clusters match disperse nodes can also be assigned the filaments between those nodes, but as the web and matching methods are varied most such filaments do not remain. There is an enhancement of subhalo counts and halo mass between cluster pairs, averaging over cluster pairs assigned disperse filaments increases the enhancement. The approach here also lends itself to comparing nodes across many cosmic web constructions, using the fixed underlying cluster distribution to make a correspondence.
Estimation of the masses in the local group by gradient boosted decision trees
Authors: Carlesi Edoardo , Hoffman Yehuda , Libeskind Noam I 
Published: April 2022

ABSTRACT
Our goal is to estimate the mass of the Local Group (LG) and the individual masses of its primary galaxies,the M31 and the Milky Way (MW). We do this by means of a supervised machine learning algorithm, the gradient boosted decision trees (GBDT) and using the observed distance and relative velocity of the two as input parameters. The GBDT is applied to a sample of 2148 mock LGs drawn from a set of 5 dark matter (DM)-only simulations, ran withing the standard ΛCDM cosmological model. The selection of the mock LGs is guided by a LG model, which defines such objects. The role of the observational uncertainties of the input parameters is gauged by applying the model to an ensemble of mock LGs pairs whose observables are these input parameters perturbed by their corresponding observational errors. Finally the observational data of the actual LG is used to infer its relevant masses. Our main results are the sum and the individual masses of the MW and M31: $M_{tot} = 3.31 ^{+0.79}_{-0.67}$, $M_{MW}=1.15^{+0.25}_{-0.22}$ and $M_{M31}=2.01^{+0.65}_{-0.39} \ \ \times 10^{12}M_{\odot }$ (corresponding to the median and the 1st and 3rd quartiles). The ratio of the masses is $M_{M31}/M_{MW}=1.75^{+0.54}_{-0.28}$, where by convention the M31 is defined here to be the more massive of the two haloes.