bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Model Evaluation Tools (MET): More than a Decade of Community-Supported Forecast Verification
Authors: Brown Barbara , Jensen Tara , Gotway John Halley , Bullock Randy , Gilleland Eric , Fowler Tressa , Newman Kathryn , Adriaansen Dan , Blank Lindsay , Burek Tatiana , Harrold Michelle , Hertneky Tracy , Kalb Christina , Kucera Paul , Nance Louisa , Opatz John , Vigh Jonathan , Wolff Jamie 
Published: October 2020

AbstractForecast verification and evaluation is a critical aspect of forecast development and improvement, day-to-day forecasting, and the interpretation and application of forecasts. In recent decades, the verification field has rapidly matured, and many new approaches have been developed. However, until recently, a stable set of modern tools to undertake this important component of forecasting has not been available. The Model Evaluation Tools (MET) was conceived and implemented to fill this gap. MET (https://dtcenter.org/community-code/model-evaluation-tools-met) was developed by the National Center for Atmospheric Research (NCAR), the National Oceanic and Atmospheric Administration (NOAA), and the U.S. Air Force (USAF) and is supported via the Developmental Testbed Center (DTC) and collaborations with operational and research organizations. MET incorporates traditional verification methods, as well as modern verification capabilities developed over the last two decades. MET stands apart from other verification packages due to its inclusion of innovative spatial methods, statistical inference tools, and a wide range of approaches to address the needs of individual users, coupled with strong community engagement and support. In addition, MET is freely available, which ensures that consistent modern verification capabilities can be applied by researchers and operational forecasting practitioners, enabling the use of consistent and scientifically meaningful methods by all users. This article describes MET and the expansion of MET to an umbrella package (METplus) that includes a database and display system and Python wrappers to facilitate the wide use of MET. Examples of MET applications illustrate some of the many ways that the package can be used to evaluate forecasts in a meaningful way.
Anthropogenic Temperature and Salinity Changes in the Southern Ocean
Authors: Hobbs William R. , Roach Christopher , Roy Tilla , Sallée Jean-Baptiste , Bindoff Nathaniel 
Published: October 2020

AbstractIn this study, we compare observed Southern Ocean temperature and salinity changes with the historical simulations from 13 models from phase 5 of the Coupled Model Intercomparison Project (CMIP5), using an optimal fingerprinting framework. We show that there is an unequivocal greenhouse gas–forced warming in the Southern Ocean. This warming is strongest in the Subantarctic Mode Waters but is also detectable in denser water masses, which has not been shown in previous studies. We also find greenhouse gas–forced salinity changes, most notably a freshening of Antarctic Intermediate Waters. Our analysis also shows that non–greenhouse gas anthropogenic forcings—anthropogenic aerosols and stratospheric ozone depletion—have played an important role in mitigating the Southern Ocean’s warming. However, the detectability of these responses using optimal fingerprinting is model dependent, and this result is therefore not as robust as for the greenhouse gas response.
Mixing of Subtropical, Central, and Intermediate Waters Driven by Shifting and Pulsing of the Agulhas Current
Authors: Gunn Kathryn L. , Beal Lisa M. , Elipot Shane , McMonigal K. , Houk Adam 
Published: October 2020

AbstractThe Agulhas Current, like all western boundary currents, transports salt from the subtropics toward the poles and, on average, acts as a barrier to exchange between the open ocean and continental seas. Uniquely, the Agulhas jet also feeds a leakage of relatively salty waters from the Indian Ocean into the Atlantic Ocean. Despite its significance, the signals and drivers of water mass variability within the Agulhas Current are not well known. To bridge this gap, we use 26 months of moored observations to determine how and why salinity—a water mass tracer—varies across the Agulhas Current. We find that salinity variability is driven by both shifting (i.e., changes in location) and pulsing (i.e., changes in strength) of the current. Shifting of the current causes heave and diapycnal mixing of subtropical, central, and intermediate waters. Diapycnal mixing between central and intermediate waters explains most of the variability, creating salinity anomalies between −0.4 and +0.1 psu. Pulsing of the current drives heave and, to a lesser extent, along-isopycnal mixing within the halocline. This cross-stream mixing results in salinity anomalies of up to 0.3 psu. The mean and standard deviation of Agulhas Current volume and salt transports are −76 and 22 Sv (1 Sv ≡ 106 m3 s−1) and −2650 and 770 Sv psu. Transport-weighted salinity has a standard deviation of 0.05 psu. We estimate that O(1013) kg yr−1 of the salt transported southwestward leaks into the fresher Atlantic Ocean. On the basis of our observations, the variability of the Agulhas Current could alter this salt leakage by an order of magnitude.
Deficits in higher visual area representations in a mouse model of Angelman syndrome
Authors: Townsend Leah B. , Jones Kelly A. , Dorsett Christopher R. , Philpot Benjamin D. , Smith Spencer L. 
Published: October 2020

Abstract
Background
Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, “higher” sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs).

Methods
Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli.

Results
We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS.

Conclusion
Assaying downstream, or “higher” circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders.

Trial registration
Not applicable.
Divergent genes in gerbils: prevalence, relation to GC-biased substitution, and phenotypic relevance
Authors: Dai Yichen , Pracana Rodrigo , Holland Peter W. H. 
Published: October 2020

Abstract
Background
Two gerbil species, sand rat (Psammomys obesus) and Mongolian jird (Meriones unguiculatus), can become obese and show signs of metabolic dysregulation when maintained on standard laboratory diets. The genetic basis of this phenotype is unknown. Recently, genome sequencing has uncovered very unusual regions of high guanine and cytosine (GC) content scattered across the sand rat genome, most likely generated by extreme and localized biased gene conversion. A key pancreatic transcription factor PDX1 is encoded by a gene in the most extreme GC-rich region, is remarkably divergent and exhibits altered biochemical properties. Here, we ask if gerbils have proteins in addition to PDX1 that are aberrantly divergent in amino acid sequence, whether they have also become divergent due to GC-biased nucleotide changes, and whether these proteins could plausibly be connected to metabolic dysfunction exhibited by gerbils.

Results
We analyzed ~ 10,000 proteins with 1-to-1 orthologues in human and rodents and identified 50 proteins that accumulated unusually high levels of amino acid change in the sand rat and 41 in Mongolian jird. We show that more than half of the aberrantly divergent proteins are associated with GC biased nucleotide change and many are in previously defined high GC regions. We highlight four aberrantly divergent gerbil proteins, PDX1, INSR, MEDAG and SPP1, that may plausibly be associated with dietary metabolism.

Conclusions
We show that through the course of gerbil evolution, many aberrantly divergent proteins have accumulated in the gerbil lineage, and GC-biased nucleotide substitution rather than positive selection is the likely cause of extreme divergence in more than half of these. Some proteins carry putatively deleterious changes that could be associated with metabolic and physiological phenotypes observed in some gerbil species. We propose that these animals provide a useful model to study the ‘tug-of-war’ between natural selection and the excessive accumulation of deleterious substitutions mutations through biased gene conversion.
Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle
Authors: Dorji Jigme , Vander Jagt Christy J. , Garner Josie B. , Marett Leah C. , Mason Brett A. , Reich Coralie M. , Xiang Ruidong , Clark Emily L. , Cocks Benjamin G. , Chamberlain Amanda J. , MacLeod Iona M. , Daetwyler Hans D. 
Published: October 2020

AbstractBackgroundMutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterized by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MP) from both the nuclear (NuMP) and mitochondrial (MtMP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses.ResultsMP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DENuMP genes in varying proportions of over-expression and under-expression. On the other hand, DE ofMtMP genes was observed in < 50% of tissues and notablyMtMP genes within a tissue was either all over-expressed or all under-expressed. A high proportion ofNuMP (up to 60%) andMtMP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% ofNuMP, 77% ofMtMP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of allMtMP genes in the direction of dominantNuMP genes expression. TheNuMP andMtMP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathway. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets.ConclusionsThe results of this study support the concept that there are biological interaction of MP genes from the mitochondrial and nuclear genomes given their over-expression in tissues with high energy demand and co-expression in tissues. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism.
Temporal proteomic profiling reveals insight into critical developmental processes and temperature-influenced physiological response differences in a bivalve mollusc
Authors: Wanamaker Shelly A. , Mitchell Kaitlyn R. , Thompson Rhonda Elliott , Eudeline Benoit , Vadopalas Brent , Timmins-Schiffman Emma B. , Roberts Steven B. 
Published: October 2020

Abstract
Background
Protein expression patterns underlie physiological processes and phenotypic differences including those occurring during early development. The Pacific oyster (Crassostrea gigas) undergoes a major phenotypic change in early development from free-swimming larval form to sessile benthic dweller while proliferating in environments with broad temperature ranges. Despite the economic and ecological importance of the species, physiological processes occurring throughout metamorphosis and the impact of temperature on these processes have not yet been mapped out.

Results
Towards this, we comprehensively characterized protein abundance patterns for 7978 proteins throughout metamorphosis in the Pacific oyster at different temperature regimes. We used a multi-statistical approach including principal component analysis, ANOVA-simultaneous component analysis, and hierarchical clustering coupled with functional enrichment analysis to characterize these data. We identified distinct sets of proteins with time-dependent abundances generally not affected by temperature. Over 12 days, adhesion and calcification related proteins acutely decreased, organogenesis and extracellular matrix related proteins gradually decreased, proteins related to signaling showed sinusoidal abundance patterns, and proteins related to metabolic and growth processes gradually increased. Contrastingly, different sets of proteins showed temperature-dependent abundance patterns with proteins related to immune response showing lower abundance and catabolic pro-growth processes showing higher abundance in animals reared at 29 °C relative to 23 °C.

Conclusion
Although time was a stronger driver than temperature of metamorphic proteome changes, temperature-induced proteome differences led to pro-growth physiology corresponding to larger oyster size at 29 °C, and to altered specific metamorphic processes and possible pathogen presence at 23 °C. These findings offer high resolution insight into why oysters may experience high mortality rates during this life transition in both field and culture settings. The proteome resource generated by this study provides data-driven guidance for future work on developmental changes in molluscs. Furthermore, the analytical approach taken here provides a foundation for effective shotgun proteomic analyses across a variety of taxa.
Genome-wide analysis of differentially expressed mRNAs, lncRNAs, and circRNAs in chicken bursae of Fabricius during infection with very virulent infectious bursal disease virus
Authors: Huang Xuewei , Zhang Junyan , Liu Zengsu , Wang Meng , Fan Xiaolong , Wang Li , Zhou Han , Jiang Yanping , Cui Wen , Qiao Xinyuan , Xu Yigang , Li Yijing , Tang Lijie 
Published: October 2020

Abstract
Background
Infectious bursal disease virus (IBDV) causes acute, highly contagious, immunosuppressive, and lethal infectious disease in young chickens and mainly infects the bursa of Fabricius (BF). To investigate interactions between IBDV and its host, RNA sequencing was applied to analyze the responses of the differentially expressed transcriptional profiles of BF infected by very virulent IBDV (vvIBDV).

Results
In total, 317 upregulated and 94 downregulated mRNAs were found to be significantly differentially expressed in infected chickens, compared to controls. Long non-coding RNA (lncRNA) and circular RNA (circRNA) alterations were identified in IBDV-infected chickens, and significantly different expression was observed in 272 lncRNAs and 143 circRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the functions of significantly dysregulated genes, which showed that the JAK-STAT signaling pathway, the NOD-like receptor signaling pathway, and apoptosis may be activated by IBDV infection. We predicted interactions between differentially expressed genes and produced lncRNA-mRNA and circRNA-miRNA-mRNA regulator network.

Conclusions
The present study identified the expression profiles of mRNAs, lncRNAs, and circRNAs during vvIBDV infection and provides new insights into the pathogenesis of IBDV and antiviral immunity of the host.
Orbital mucormycosis in immunocompetent children; review of risk factors, diagnosis, and treatment approach
Authors: Amanati Ali , Barzegar Hamide , Pouladfar Gholamreza , Sanaei Dashti Anahita , Abtahi Mohamad Bagher , Khademi Bijan , Ashraf Mohammad Javad , Badiee Parisa , Hamzavi Seyedeh Sedigheh , Kashkooe Ali 
Published: October 2020

Abstract
Background
Orbital mucormycosis is a rare but potentially severe and troublesome invasive fungal infection that could be occurred even in healthy individuals. The initial clinical presentation is similar to bacterial pre-septal or septal cellulitis, especially in early stages.

Case presentation
Herein, we describe the successful management of a series of five cases presenting with orbital mucormycosis in previously healthy children.

Conclusions
Orbital mucormycosis is extremely rare in healthy children and maybe life-threatening when diagnosis delayed given a similar clinical presentation with bacterial septal cellulitis. Intravenous antifungal therapy with amphotericin B and timely surgical drainage is live-saving.
Risk conditions in children hospitalized with influenza in Norway, 2017–2019
Authors: Hauge Siri Helene , Bakken Inger Johanne , de Blasio Birgitte Freiesleben , Håberg Siri Eldevik 
Published: October 2020

Abstract
Background
Norwegian children are more frequently hospitalized with influenza than adults. Little is known about the characteristics of these children. Our aim was to investigate the presence of pre-existing risk conditions and to determine the duration of influenza hospitalizations in children during two influenza seasons.

Methods
The Norwegian Patient Registry holds data on all hospitalized patients in Norway. We included all patients younger than 18 years hospitalized with a diagnosis of influenza during the influenza seasons 2017–18 and 2018–19. Pre-existing risk conditions for influenza were identified by ICD-10 diagnoses in the Norwegian Patient Registry. In addition, information on asthma diagnoses were also retrieved from the Norwegian Registry for Primary Health Care. To estimate the prevalence of risk conditions in the child population, we obtained diagnoses on all Norwegian children in a two-year period prior to each influenza season. We calculated age-specific rates for hospitalization and risk for being hospitalized with influenza in children with risk conditions.

Results
In total, 1013 children were hospitalized with influenza during the two influenza seasons. Children younger than 6 months had the highest rate of hospitalization, accounting for 13.5% of all admissions (137 children). Hospitalization rates decreased with increasing age. Among children hospitalized with influenza, 25% had one or more pre-existing risk conditions for severe influenza, compared to 5% in the general population under 18 years. Having one or more risk conditions significantly increased the risk of hospitalization, (Odds Ratio (OR) 6.1, 95% confidence interval (CI) 5.0–7.4 in the 2017–18 season, and OR 6.8, 95% CI 5.4–8.4 in the 2018–19 season). Immunocompromised children and children with epilepsy had the highest risk of hospitalization with influenza, followed by children with heart disease and lung disease. The average length of stay in hospital were 4.6 days, and this did not differ with age.

Conclusion
Children with pre-existing risk conditions for influenza had a higher risk of hospitalization for influenza. However, most children (75%) admitted to hospital with influenza in Norway during 2017–2019 did not have pre-existing risk conditions. Influenza vaccination should be promoted in particular for children with risk conditions and pregnant women to protect new-borns.
Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania
Authors: Brown Jennifer Anne , Ringera Isaac , Luoga Ezekiel , Cheleboi Molisana , Kimera Namvua , Muhairwe Josephine , Kayembe Buntshi Paulin , Molapo Hlasoa Mosa , Kabundi Lorraine , Yav Ching Wey David , Mothobi Buoang , Thahane Lineo , Amstutz Alain , Bachmann Nadine , Mollel Getrud Joseph , Bresser Moniek , Glass Tracy Renée , Paris Daniel Henry , Klimkait Thomas , Weisser Maja , Labhardt Niklaus Daniel 
Published: October 2020

Abstract
Background
Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART).

Methods
GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up.

Discussion
This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART.

Trial registration
This trial is registered with ClinicalTrials.gov (NCT04233242; registered 18.01.2020). More information: www.givemove.org.