bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria
Authors: Stefanova Veselina , Ngai Michelle , Weckman Andrea M , Wright Julie K , Zhong Kathleen , Richard-Greenblatt Melissa , McDonald Chloe R , Conroy Andrea L , Namasopo Sophie , Opoka Robert O , Hawkes Michael , Kain Kevin C 
Published: June 2022

Abstract

Background
Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria.

Methods
Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]).

Results
Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P &lt; .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P &lt; .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P &lt; .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96–.98]; P &lt; .0001).

Conclusions
Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.
The Lanzhou Brucella Leak: The Largest Laboratory Accident in the History of Infectious Diseases?
Authors: Pappas Georgios 
Published: June 2022

Abstract
An inadequacy in sanitizing processes in a biopharmaceutical plant in Lanzhou, China, during July and August 2019, led to the aerosolization of Brucella that was subsequently spread through wind to nearby settlements and academic institutes, resulting in &gt;10 000 human brucellosis cases, as of November 2020. The leak, possibly the largest laboratory accident in the history of infectious diseases, underlines the particular characteristics of Brucella that have made the pathogen a historical entity in biodefense research and a major cause of laboratory-associated infections. It further underlines the need for enhanced vigilance and strict regulatory interventions in similar facilities.
Direct and cross-generational effects of reproduction on fitness and behavioral variability in male-biased environments
Authors: Sanmartín-Villar Iago , Yu Xin , Cordero-Rivera Adolfo 
Published: June 2022

AbstractPopulation structure determines individuals’ interactions and trade-offs with evolutionary consequences. Male-biased populations increase intrasexual competition and intersexual harassment, reducing female resource acquisition, and thus, resources availability for the following generation. We analyzed direct and cross-generational effects of male harassment in two generations of damselflies (Odonata). We exposed adult females to treatments with different sex-ratio and density (balanced and male-biased) to modify the male harassment level. We analyzed female fecundity, fertility, and number of faecal deposits as an indirect measure of resources acquisition. We studied female flight performance after repeated exposures to males. We analyzed survivorship, development, exploration, thigmotaxis, and feeding latency of larvae produced by the experimental females. In both generations, we analyzed four metrics of behavior: mean value, interindividual differences in plasticity, intra-individual unpredictability, and repeatability. Mating duration increased in male-biased treatment, whereas female resources acquisition and fertility decreased. Females that mated longer showed higher fecundity when they were exposed to balanced treatment, but not if they were exposed to male-biased treatment. Females from the male-biased treatment showed interindividual differences in plasticity and no repeatability in flight performance. Offspring showed balanced sex-ratio and similar survivorship, development, and feeding latency independently of the parental treatment; however, females exposed to male-biased treatment produced offspring with higher differences in exploration plasticity and daughters less explorative and with higher unpredictable thigmotaxis. We propose prolonged copulation as courtship at balanced sex-ratio but a cost to females under male-biased sex-ratio. Cross-generational effects in behavioral variability may be a mechanism to cope with predicted future environments.
Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial
Authors: Metra Marco , Pagnesi Matteo , Claggett Brian L , Díaz Rafael , Felker G Michael , McMurray John J V , Solomon Scott D , Bonderman Diana , Fang James C , Fonseca Cândida , Goncalvesova Eva , Howlett Jonathan G , Li Jing , O’Meara Eileen , Miao Zi Michael , Abbasi Siddique A , Heitner Stephen B , Kupfer Stuart , Malik Fady I , Teerlink John R 
Published: June 2022

Abstract

Aim
Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF).

Methods and results
The GALACTIC-HF enrolled patients with baseline SBP ≥85 mmHg with a primary outcome of time to cardiovascular death or first heart failure event. In this analysis, patients were divided according to their baseline SBP (≤100 vs. &gt;100 mmHg). Among the 8232 analysed patients, 1473 (17.9%) had baseline SBP ≤100 mmHg and 6759 (82.1%) had SBP &gt;100 mmHg. The primary outcome occurred in 715 (48.5%) and 2415 (35.7%) patients with SBP ≤100 and &gt;100 mmHg, respectively. Patients with lower SBP were at higher risk of adverse outcomes. Omecamtiv mecarbil, compared with placebo, appeared to be more effective in reducing the primary composite endpoint in patients with SBP ≤100 mmHg [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70–0.94] compared with those with SBP &gt;100 mmHg (HR, 0.95; 95% CI, 0.88–1.03; P-value for interaction = 0.051). In both groups, omecamtiv mecarbil did not change SBP values over time and did not increase the risk of adverse events, when compared with placebo.

Conclusion
In GALACTIC-HF, risk reduction of heart failure outcomes with omecamtiv mecarbil compared with placebo was large and significant in patients with low SBP. Omecamtiv mecarbil did not affect SBP and was well tolerated independent of SBP values.
Local adaptation in fungi
Authors: Bazzicalupo Anna 
Published: June 2022

AbstractIn this review, I explore the pervasive but underappreciated role of local adaptation in fungi. It has been difficult historically to study local adaptation in fungi because of the limited understanding of fungal species and their traits, but new hope has been offered with technological advances in sequencing. The filamentous nature of fungi invalidates some assumptions made in evolution because of their ability to exist as multinucleate entities with genetically different nuclei sharing the same cytoplasm. Many insights on local adaptation have come from studying fungi, and much of the empirical evidence gathered about local adaptation in the context of host–pathogen interactions comes from studying fungal virulence genes, drug resistance, and environmental adaptation. Together, these insights paint a picture of the variety of processes involved in fungal local adaptation and their connections to the unusual cell biology of Fungi (multinucleate, filamentous habit), but there is much that remains unknown, with major gaps in our knowledge of fungal species, their phenotypes, and the ways by which they adapt to local conditions.
Chromosomal-level reference genome assembly of the North American wolverine (Gulo gulo luscus): a resource for conservation genomics
Authors: Lok Si , Lau Timothy N H , Trost Brett , Tong Amy H Y , Wintle Richard F , Engstrom Mark D , Stacy Elise , Waits Lisette P , Scrafford Matthew , Scherer Stephen W 
Published: June 2022

Abstract
We report a chromosomal-level genome assembly of a male North American wolverine (Gulo gulo luscus) from the Kugluktuk region of Nunavut, Canada. The genome was assembled directly from long-reads, comprising: 758 contigs with a contig N50 of 36.6 Mb; contig L50 of 20; base count of 2.39 Gb; and a near complete representation (99.98%) of the BUSCO 5.2.2 set of 9,226 genes. A presumptive chromosomal-level assembly was generated by scaffolding against two chromosomal-level Mustelidae reference genomes, the ermine and the Eurasian river otter, to derive a final scaffold N50 of 144.0 Mb and a scaffold L50 of 7. We annotated a comprehensive set of genes that have been associated with models of aggressive behavior, a trait which the wolverine is purported to have in the popular literature. To support an integrated, genomics-based wildlife management strategy at a time of environmental disruption from climate change, we annotated the principal genes of the innate immune system to provide a resource to study the wolverine’s susceptibility to new infectious and parasitic diseases. As a resource, we annotated genes involved in the modality of infection by the coronaviruses, an important class of viral pathogens of growing concern as shown by the recent spillover infections by severe acute respiratory syndrome coronavirus-2 to naïve wildlife. Tabulation of heterozygous single nucleotide variants in our specimen revealed a heterozygosity level of 0.065%, indicating a relatively diverse genetic pool that would serve as a baseline for the genomics-based conservation of the wolverine, a rare cold-adapted carnivore now under threat.
Functional analysis of the N-terminal region of Vibrio FlhG, a MinD-type ATPase in flagellar number control
Authors: Homma Michio , Mizuno Akira , Hao Yuxi , Kojima Seiji 
Published: June 2022

Abstract
GTPase FlhF and ATPase FlhG are two key factors involved in regulating the flagellum number in Vibrio alginolyticus. FlhG is a paralogue of the Escherichia coli cell division regulator MinD and has a longer N-terminal region than MinD with a conserved DQAxxLR motif. The deletion of this N-terminal region or a Q9A mutation in the DQAxxLR motif prevents FlhG from activating the GTPase activity of FlhF in vitro and causes a multi-flagellation phenotype. The mutant FlhG proteins, especially the N-terminally deleted variant, were remarkably reduced compared to that of the wild-type protein in vivo. When the mutant FlhG was expressed at the same level as the wild-type FlhG, the number of flagella was restored to the wild-type level. Once synthesized in Vibrio cells, the N-terminal region mutation in FlhG seems not to affect the protein stability. We speculated that the flhG translation efficiency is decreased by N-terminal mutation. Our results suggest that the N-terminal region of FlhG controls the number of flagella by adjusting the FlhF activity and the amount of FlhG in vivo. We speculate that the regulation by FlhG, achieved through transcription by the master regulator FlaK, is affected by the mutations, resulting in reduced flagellar formation by FlhF.
Rapid and Efficient Detection by PCR ofCulicoides insignis(Diptera: Ceratopogonidae), the Main Vector of Bluetongue Virus (BTV) in the Neotropical Region
Authors: Ayala Mahia Mariel , Díaz Florentina , Micieli María Victoria , Spinelli Gustavo Ricardo , Ronderos María Marcela 
Published: June 2022

AbstractBluetongue virus (BTV) causes a viral, non-contagious disease that mainly affects sheep, cattle, and wild and farmed ruminants causing damage to these animals and significant economic losses. Culicoides insignis Lutz, the major BTV vector in South America, is one of the most abundant species in Argentina and commonly associated with cattle farms. The morphological identification of Culicoides spp. is routinely carried out with the aid of morphological keys, which mainly refer to the wing patterns, sensillae of palpi, and antennal flagella. Molecular tools applied to taxonomy provide a rapid and efficient method of identification of vector species. An easy protocol for the extraction of total DNA from single midges is herein described, and a forward primer for rapid and reliably test detection by polymerase chain reaction of C. insignis is developed.
Enzyme activity profiling for physiological phenotyping within functional phenomics: plant growth and stress responses
Authors: Jammer Alexandra , Akhtar Saqib Saleem , Amby Daniel Buchvaldt , Pandey Chandana , Mekureyaw Mengistu F , Bak Frederik , Roth Peter M , Roitsch Thomas 
Published: June 2022

Abstract
High-throughput profiling of key enzyme activities of carbon, nitrogen, and antioxidant metabolism is emerging as a valuable approach to integrate cell physiological phenotyping into a holistic functional phenomics approach. However, the analyses of the large datasets generated by this method represent a bottleneck, often keeping researchers from exploiting the full potential of their studies. We address these limitations through the exemplary application of a set of data evaluation and visualization tools within a case study. This includes the introduction of multivariate statistical analyses that can easily be implemented in similar studies, allowing researchers to extract more valuable information to identify enzymatic biosignatures. Through a literature meta-analysis, we demonstrate how enzyme activity profiling has already provided functional information on the mechanisms regulating plant development and response mechanisms to abiotic stress and pathogen attack. The high robustness of the distinct enzymatic biosignatures observed during developmental processes and under stress conditions underpins the enormous potential of enzyme activity profiling for future applications in both basic and applied research. Enzyme activity profiling will complement molecular -omics approaches to contribute to the mechanistic understanding required to narrow the genotype-to-phenotype knowledge gap and to identify predictive biomarkers for plant breeding to develop climate-resilient crops.
Neutrino observations of LHAASO sources: Present constraints and future prospects
Authors: Huang Tian-Qi , Li Zhuo 
Published: June 2022

ABSTRACT
The Large High Altitude Air Shower Observatory (LHAASO) observed a dozen gamma-ray sources with significant emission above 100 TeV that may be strong candidates for PeVatrons. Neutrino observations are crucial for diagnosing whether the gamma-ray radiative process is hadronic or leptonic. We use the Bayesian method to analyse the 10-yr (2008–2018) IceCube data, and hence constrain the hadronic gamma-ray emission in the LHAASO sources. The present neutrino data show that the hadronic gamma-ray flux from the Crab Nebula is lower than the observed gamma-ray flux at the 90 per cent confidence level and contributes less than 86 per cent, which disfavours the hadronic origin of gamma-rays below tens of TeV. For the other LHAASO sources, the present neutrino observations cannot put useful constraints on the gamma-ray radiative process. We consider the uncertainty of the source extension: the upper limits on the hadronic gamma-ray flux tend to increase with the extension; and some sources, namely LHAASO J2032+4102, LHAASO J1929+1745, and LHAASO J1908+0621, show a relatively high statistical significance of neutrino signals if the extension is ≲ 0.°6. Finally, we estimate the future observational results of LHAASO sources by proposed neutrino telescopes. If the LHAASO-observed PeV gamma-rays are of hadronic origin, the Crab Nebula may be detected at &gt;100 TeV at the 3σ confidence level within 20 years by a neutrino detector with an effective area 30 times that of IceCube.
Zeaxanthin Epoxidase Activity Is Downregulated by Hydrogen Peroxide
Authors: Holzmann Dimitrij , Bethmann Stephanie , Jahns Peter 
Published: June 2022

AbstractThe xanthophyll zeaxanthin (Zx) serves important photoprotective functions in chloroplasts and is particularly involved in the dissipation of excess light energy as heat in the antenna of photosystem II (PSII). Zx accumulates under high-light (HL) conditions in thylakoid membranes and is reconverted to violaxanthin by Zx epoxidase (ZEP) in low light or darkness. ZEP activity is completely inhibited under long-lasting HL stress, and the ZEP protein becomes degraded along with the PSII subunit D1 during photoinhibition of PSII. This ZEP inactivation ensures that high levels of Zx are maintained under harsh HL stress. The mechanism of ZEP inactivation is unknown. Here, we investigated ZEP inactivation by reactive oxygen species (ROS) under in vitro conditions. Our results show that ZEP activity is completely inhibited by hydrogen peroxide (H2O2), whereas inhibition by singlet oxygen or superoxide seems rather unlikely. Due to the limited information about the amount of singlet oxygen and superoxide accumulating under the applied experimental conditions, however, a possible inhibition of ZEP activity by these two ROS cannot be generally excluded. Despite this limitation, our data support the hypothesis that the accumulation of ROS, in particular H2O2, might be responsible for HL-induced inactivation of ZEP under in vivo conditions.
Core circadian clock and light signaling genes brought into genetic linkage across the green lineage
Authors: Michael Todd P 
Published: June 2022

AbstractThe circadian clock is conserved at both the level of transcriptional networks as well as core genes in plants, ensuring that biological processes are phased to the correct time of day. In the model plant Arabidopsis (Arabidopsis thaliana), the core circadian SHAQKYF-type-MYB (sMYB) genes CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and REVEILLE (RVE4) show genetic linkage with PSEUDO-RESPONSE REGULATOR 9 (PRR9) and PRR7, respectively. Leveraging chromosome-resolved plant genomes and syntenic ortholog analysis enabled tracing this genetic linkage back to Amborella trichopoda, a sister lineage to the angiosperm, and identifying an additional evolutionarily conserved genetic linkage in light signaling genes. The LHY/CCA1–PRR5/9, RVE4/8–PRR3/7, and PIF3–PHYA genetic linkages emerged in the bryophyte lineage and progressively moved within several genes of each other across an array of angiosperm families representing distinct whole-genome duplication and fractionation events. Soybean (Glycine max) maintained all but two genetic linkages, and expression analysis revealed the PIF3–PHYA linkage overlapping with the E4 maturity group locus was the only pair to robustly cycle with an evening phase, in contrast to the sMYB–PRR morning and midday phase. While most monocots maintain the genetic linkages, they have been lost in the economically important grasses (Poaceae), such as maize (Zea mays), where the genes have been fractionated to separate chromosomes and presence/absence variation results in the segregation of PRR7 paralogs across heterotic groups. The environmental robustness model is put forward, suggesting that evolutionarily conserved genetic linkages ensure superior microhabitat pollinator synchrony, while wide-hybrids or unlinking the genes, as seen in the grasses, result in heterosis, adaptation, and colonization of new ecological niches.
CYSTEINE-RICH RECEPTOR-LIKE KINASE5 (CRK5) and CRK22 regulate the response to Verticillium dahliae toxins
Authors: Zhao Jun , Sun Yuhui , Li Xinyue , Li Yingzhang 
Published: June 2022

Abstract
Cysteine-rich receptor-like kinases (CRKs) play critical roles in responses to biotic and abiotic stresses. However, the molecular mechanisms of CRKs in plant defense responses remain unknown. Here, we demonstrated that two CRKs, CRK5 and CRK22, are involved in regulating defense responses to Verticillium dahliae toxins (Vd-toxins) in Arabidopsis (Arabidopsis thaliana). Biochemical and genetic analyses showed that CRK5 and CRK22 may act upstream of MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6 to regulate the salicylic acid (SA)-signaling pathway in response to Vd-toxins. In addition, MPK3 and MPK6 interact with the transcription factor WRKY70 to modulate defense responses to Vd-toxins. WRKY70 directly binds the promoter domains of the SA-signaling-related transcription factor genes TGACG SEQUENCE-SPECIFIC BINDING PROTEIN (TGA2) and TGA6 to regulate their expression in response to Vd-toxins. Thus, our study reveals a mechanism by which CRK5 and CRK22 regulate SA signaling through the MPK3/6–WRKY70–TGA2/6 pathway in response to Vd-toxins.
Certainty about uncertainty in sleep staging: a theoretical framework
Authors: van Gorp Hans , Huijben Iris A M , Fonseca Pedro , van Sloun Ruud J G , Overeem Sebastiaan , van Gilst Merel M 
Published: June 2022

Abstract
Sleep stage classification is an important tool for the diagnosis of sleep disorders. Because sleep staging has such a high impact on clinical outcome, it is important that it is done reliably. However, it is known that uncertainty exists in both expert scorers and automated models. On average, the agreement between human scorers is only 82.6%. In this study, we provide a theoretical framework to facilitate discussion and further analyses of uncertainty in sleep staging. To this end, we introduce two variants of uncertainty, known from statistics and the machine learning community: aleatoric and epistemic uncertainty. We discuss what these types of uncertainties are, why the distinction is useful, where they arise from in sleep staging, and provide recommendations on how this framework can improve sleep staging in the future.
PAs and NPs improve patient care and productivity in a radiology consult practice
Authors: Virarkar Mayur , Coleman Joseph A. , Siddiqui Zeeshan A. , Leal Viola B. , McClinton Angel E. , Steele Joseph R. , Yang Wei , Bhosale Priya , Klekers Albert R. 
Published: June 2022

ABSTRACT

Objective:
To evaluate the effects on efficiency and patient care of the addition of physician assistants (PAs) and NPs to the abdominal radiology consult service.

Methods:
We obtained radiologist productivity and patient care metrics for 3 months before and 3 months after the integration of PAs and NPs into our consult service.

Results:
Integrating PAs and NPs into the workflow led to a significant increase in mean RVUs/shift (15.2 ± 0.9 versus 6.2 ± 1.8; P = .02), number of studies read per shift (10.1 ± 0.5 versus 4.4 ± 1.5; P = .003), revenue per shift hour ($756.20 ± $55.40 versus $335.40 ± $132.60; P = .007), protocol prescription to patient appointment lead time (39.3 ± 6.7 versus 16.3 ± 2.9 days; P = .005), and significant decreases in mean CT (19.3% ± 0.6 versus 3.3% ± 0.6; P = .001) and MRI (11.7% ± 0.6 versus 8.3% ± 0.12; P = .011) same-day protocol changes as patient appointments.

Conclusions:
PAs and NPs can be effectively integrated into abdominal radiology consult service, increasing the productivity of radiologists, and enhancing clinical care.