bluuebunny/crossref_metadata_2025_split huggingface dataset:
A radiomics platform for computing imaging features from µCT images of Thoroughbred racehorse proximal sesamoid bones: Benchmark performance and evaluation
Authors: Basran Parminder S. , Gao Jonathan , Palmer Scott , Reesink Heidi L. 
Published: July 2020

AbstractBackgroundProximal sesamoid bone (PSB) fractures are the most common fatal musculoskeletal injury in North American racehorses. Computed tomography has the potential to detect morphological changes in bone structure but can be challenging to analyse reliably and quantitatively.ObjectivesTo develop a radiomics platform that allows the comparison of features from micro‐CTs (µCT) of PSBs in horses that sustained catastrophic fractures with horses that did not. To compare features calculated with a radiomics approach with features calculated from a previously published study that used quantitative µCT in the same specimens.Study designRetrospective study of cadaver specimens of µCT images of PSBs using prospectively applied radiomics.MethodsRadiomics features were computed on standardised CT datasets to benchmark the software. Features from µCT images of PSBs from eight horses that sustained PSB fracture and eight controls were computed using the contralateral, intact forelimb from horses sustaining PSB fracture (cases, n = 19) and all available forelimbs for controls (n = 30). Two‐hundred and fifteen radiomic features were calculated, and similar or comparable features were compared with those reported in a previous study that used the same specimens.ResultsMorphologic features computed with the radiomics approach, such as volume, minor axis dimensions and anisotropy were highly correlated with previously published data. A high number of imperceptible radiomic features, such as entropy, coarseness and histogram features were also found to be significantly different (P < .01). The extent of the differences in image features for the cases and controls PSBs depends on radiomic calculation settings.Main limitationsOnly datasets obtained from cadaver specimens were included in the study.ConclusionsA radiomics approach for analysing µCT images of PSBs was able to identify and reproduce differences in image features in cases and controls. Furthermore, radiomics revealed many more imperceptible image features between cases and control PSBs.
Molecular approaches to equine sarcoids
Authors: Semik‐Gurgul Ewelina 
Published: July 2020

AbstractSarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto‐oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA differential expression and DNA methylation status. This review focuses on selected groups of genes that contribute to the molecular mechanisms of sarcoid formation. These genes have the potential to complement current clinical examinations of equine sarcoid disease in diagnosis, prognosis, therapeutic response and screening.
Vitamin D receptor(s): In the nucleus but also at membranes?
Authors: Zmijewski Michal A. , Carlberg Carsten 
Published: July 2020

AbstractThe genomic actions of the vitamin D are mediated via its biologically most potent metabolite 1α,25‐dihydroxyvitamin D3 (1,25(OH)2D3) and the transcription factor vitamin D receptor (VDR). Activation of VDR by 1,25(OH)2D3 leads to change in the expression of more 1000 genes in various human tissues. Based on (epi)genome, transcriptome and crystal structure data the molecular details of this nuclear vitamin D signalling pathway are well understood. Vitamin D is known for its role on calcium homeostasis and bone formation, but it also modulates energy metabolism, innate and adaptive immunity as well as cellular growth, differentiation and apoptosis. The observation of rapid, non‐genomic effects of 1,25(OH)2D3 at cellular membranes and in the cytosol initiated the question, whether there are alternative vitamin D‐binding proteins in these cellular compartments. So far, the best candidate is the enzyme PDIA3 (protein disulphide isomerase family A member 3), which is found at various subcellular locations. Furthermore, also VDR seems to play a role in membrane‐based responses to vitamin D. In this viewpoint, we will dispute whether these rapid, non‐genomic pathways are a meaningful addition to the genome‐wide effects of vitamin D.
Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis
Authors: Luengas‐Martinez Andrea , Hardman‐Smart Jonathan , Paus Ralf , Young Helen S. 
Published: July 2020

AbstractVascular endothelial growth factor‐A (VEGF‐A), the main angiogenic mediator, plays a critical role in the pathogenesis of several inflammatory immune‐mediated diseases, including psoriasis. Even though anti‐angiogenic therapies, such as VEGF inhibitors, are licensed for the treatment of various cancers and eye disease, VEGF‐targeting interventions are not part of current psoriasis therapy. In this viewpoint essay, we argue that the existing preclinical research evidence on the role of VEGF‐A in the pathogenesis of psoriasis as well as clinical observations in patients who have experienced psoriasis remission during oncological anti‐VEGF‐A therapy strongly suggests to systematically explore angiogenesis targeting also in the management of psoriasis. We also point out that some psoriasis therapies decrease circulating levels of VEGF‐A and normalise the psoriasis‐associated vascular pathology in the papillary dermis of plaques of psoriasis and that a subset of patients with constitutionally high levels of VEGF‐A may benefit most from the anti‐angiogenic therapy we advocate here. Given that novel, well‐targeted personalised medicine therapies for the development of psoriasis need to be developed, we explore the hypothesis that VEGF‐A and signalling through its receptors constitute a promising target for therapeutic intervention in the future management of psoriasis.
Climatic breadth of calling behaviour in two widespread Neotropical frogs: Insights from humidity extremes
Authors: Bonnefond Anaïs , Courtois Elodie A. , Sueur Jérôme , Sugai Larissa Sayuri M. , Llusia Diego 
Published: July 2020

AbstractClimate change is severely altering precipitation regimes at local and global scales, yet the capacity of species to cope with these changes has been insufficiently examined. Amphibians are globally endangered and particularly sensitive to moisture conditions. For mating, most amphibian species rely on calling behaviour, which is a key weather‐dependent trait. Using passive acoustics, we monitored the calling behaviour of two widespread Neotropical frogs in 12 populations located at the humidity extremes but thermal mean of the species distribution. Based on 2,554 hr of recordings over a breeding season, we found that both the aquatic speciesPseudis paradoxaand the arboreal speciesBoana ranicepsexhibited calling behaviour at a wide range of relative humidity. Calling humidity was significantly lower in conspecific populations subjected to drier conditions, while calling temperature did not differ between populations or species. Overall, no variation in climatic breadth was observed between large and small choruses, and calling behaviour was scarcely detected during the driest, hottest and coldest potential periods of breeding. Our results showed that calling humidity of the studied species varies according to the precipitation regime, suggesting that widespread Neotropical anurans may have the capacity to exhibit sexual displays in different climatic environments. Regardless of the underlying mechanism (plasticity or local adaptation), which should be determined by common garden experiments, a wide and population‐specific climatic breadth of calling behaviour may assist species to deal with changing humidity conditions. To our knowledge, this is the first study to explore the response capacity of anurans to perform calling behaviour under contrasting precipitation regimes.
Spruce beetle outbreak was not driven by drought stress: Evidence from a tree‐ring iso‐demographic approach indicates temperatures were more important
Authors: Pettit Jessika M. , Voelker Steve L. , DeRose R. Justin , Burton Julia I. 
Published: July 2020

AbstractClimate change has amplified eruptive bark beetle outbreaks over recent decades, including spruce beetle (Dendroctonus rufipennis). However, for projecting future bark beetle dynamics there is a critical lack of evidence to differentiate how outbreaks have been promoted by direct effects of warmer temperatures on beetle life cycles versus indirect effects of drought on host susceptibility. To diagnose whether drought‐induced host‐weakening was important to beetle attack success we used an iso‐demographic approach in Engelmann spruce (Picea engelmannii) forests that experienced widespread mortality caused by spruce beetle outbreaks in the 1990s, during a prolonged drought across the central and southern Rocky Mountain region. We determined tree death date demography during this outbreak to differentiate early‐ and late‐dying trees in stands distributed across a landscape within this larger regional mortality event. To directly test for a role of drought stress during outbreak initiation we determined whether early‐dying trees had greater sensitivity of tree‐ring carbon isotope discrimination (∆13C) to drought compared to late‐dying trees. Rather, evidence indicated the abundance and size of host trees may have modified ∆13C responses to drought. ∆13C sensitivity to drought did not differ among early‐ versus late‐dying trees, which runs contrary to previously proposed links between spruce beetle outbreaks and drought. Overall, our results provide strong support for the view that irruptive spruce beetle outbreaks across North America have primarily been driven by warming‐amplified beetle life cycles whereas drought‐weakened host defenses appear to have been a distant secondary driver of these major disturbance events.
Global declines in human‐driven mangrove loss
Authors: Goldberg Liza , Lagomasino David , Thomas Nathan , Fatoyinbo Temilola 
Published: July 2020

AbstractGlobal mangrove loss has been attributed primarily to human activity. Anthropogenic loss hotspots across Southeast Asia and around the world have characterized the ecosystem as highly threatened, though natural processes such as erosion can also play a significant role in forest vulnerability. However, the extent of human and natural threats has not been fully quantified at the global scale. Here, using a Random Forest‐based analysis of over one million Landsat images, we present the first 30 m resolution global maps of the drivers of mangrove loss from 2000 to 2016, capturing both human‐driven and natural stressors. We estimate that 62% of global losses between 2000 and 2016 resulted from land‐use change, primarily through conversion to aquaculture and agriculture. Up to 80% of these human‐driven losses occurred within six Southeast Asian nations, reflecting the regional emphasis on enhancing aquaculture for export to support economic development. Both anthropogenic and natural losses declined between 2000 and 2016, though slower declines in natural loss caused an increase in their relative contribution to total global loss area. We attribute the decline in anthropogenic losses to the regionally dependent combination of increased emphasis on conservation efforts and a lack of remaining mangroves viable for conversion. While efforts to restore and protect mangroves appear to be effective over decadal timescales, the emergence of natural drivers of loss presents an immediate challenge for coastal adaptation. We anticipate that our results will inform decision‐making within conservation and restoration initiatives by providing a locally relevant understanding of the causes of mangrove loss.
An optimality‐based model explains seasonal variation in C3 plant photosynthetic capacity
Authors: Jiang Chongya , Ryu Youngryel , Wang Han , Keenan Trevor F. 
Published: July 2020

AbstractThe maximum rate of carboxylation (Vcmax) is an essential leaf trait determining the photosynthetic capacity of plants. Existing approaches for estimating Vcmax at large scale mainly rely on empirical relationships with proxies such as leaf nitrogen/chlorophyll content or hyperspectral reflectance, or on complicated inverse models from gross primary production or solar‐induced fluorescence. A novel mechanistic approach based on the assumption that plants optimize resource investment coordinating with environment and growth has been shown to accurately predict C3 plant Vcmax based on mean growing season environmental conditions. However, the ability of optimality theory to explain seasonal variation in Vcmax has not been fully investigated. Here, we adapt an optimality‐based model to simulate daily Vcmax,25C (Vcmax at a standardized temperature of 25°C) by incorporating the effects of antecedent environment, which affects current plant functioning, and dynamic light absorption, which coordinates with plant functioning. We then use seasonal Vcmax,25C field measurements from 10 sites across diverse ecosystems to evaluate model performance. Overall, the model explains about 83% of the seasonal variation in C3 plant Vcmax,25C across the 10 sites, with a medium root mean square error of 12.3 μmol m−2 s−1, which suggests that seasonal changes in Vcmax,25C are consistent with optimal plant function. We show that failing to account for acclimation to antecedent environment or coordination with dynamic light absorption dramatically decreases estimation accuracy. Our results show that optimality‐based approach can accurately reproduce seasonal variation in canopy photosynthetic potential, and suggest that incorporating such theory into next‐generation trait‐based terrestrial biosphere models would improve predictions of global photosynthesis.
Low phosphorus supply constrains plant responses to elevated CO2: A meta‐analysis
Authors: Jiang Mingkai , Caldararu Silvia , Zhang Haiyang , Fleischer Katrin , Crous Kristine Y. , Yang Jinyan , De Kauwe Martin G. , Ellsworth David S. , Reich Peter B. , Tissue David T. , Zaehle Sönke , Medlyn Belinda E. 
Published: July 2020

AbstractPhosphorus (P) is an essential macro‐nutrient required for plant metabolism and growth. Low P availability could potentially limit plant responses to elevated carbon dioxide (eCO2), but consensus has yet to be reached on the extent of this limitation. Here, based on data from experiments that manipulated both CO2 and P for young individuals of woody and non‐woody species, we present a meta‐analysis of P limitation impacts on plant growth, physiological, and morphological response to eCO2. We show that low P availability attenuated plant photosynthetic response to eCO2 by approximately one‐quarter, leading to a reduced, but still positive photosynthetic response to eCO2 compared to those under high P availability. Furthermore, low P limited plant aboveground, belowground, and total biomass responses to eCO2, by 14.7%, 14.3%, and 12.4%, respectively, equivalent to an approximate halving of the eCO2 responses observed under high P availability. In comparison, low P availability did not significantly alter the eCO2‐induced changes in plant tissue nutrient concentration, suggesting tissue nutrient flexibility is an important mechanism allowing biomass response to eCO2 under low P availability. Low P significantly reduced the eCO2‐induced increase in leaf area by 14.3%, mirroring the aboveground biomass response, but low P did not affect the eCO2‐induced increase in root length. Woody plants exhibited stronger attenuation effect of low P on aboveground biomass response to eCO2 than non‐woody plants, while plants with different mycorrhizal associations showed similar responses to low P and eCO2 interaction. This meta‐analysis highlights crucial data gaps in capturing plant responses to eCO2 and low P availability. Field‐based experiments with longer‐term exposure of both CO2 and P manipulations are critically needed to provide ecosystem‐scale understanding. Taken together, our results provide a quantitative baseline to constrain model‐based hypotheses of plant responses to eCO2 under P limitation, thereby improving projections of future global change impacts.
Types of Triggers in Migraine – Factor Structure of the Headache Triggers Sensitivity and Avoidance Questionnaire and Development of a New Short Form (HTSAQ‐SF)
Authors: Caroli Anna , Klan Timo , Gaul Charly , Kubik Sonja U. , Martin Paul R. , Witthöft Michael 
Published: July 2020

ObjectiveTo examine the factor structure of the Headache Triggers Sensitivity and Avoidance Questionnaire (HTSAQ) and its German version (HTSAQ‐G), in order to identify potential different types of triggers. Furthermore, a short form of the questionnaire was developed.BackgroundThe HTSAQ includes 24 of the most commonly reported headache triggers (eg, stress, odors, lack of sleep). Both the HTSAQ and HTSAQ‐G appeared to be reliable and valid measures of sensitivity to and avoidance of headache triggers.MethodsIn a cross‐country collaboration, data from 2 cross‐sectional studies including N = 391 individuals diagnosed with migraine from Australia (n = 222) and Germany (n = 169) were analyzed. The factor structure of the questionnaire was examined using exploratory and confirmatory factor analysis. Finally, a short form of the HTSAQ was constructed and evaluated regarding psychometric properties.ResultsFactor analytic results showed a differentiation between internal and external headache triggers, and different patterns of strategies in coping with triggers. The scales of both the original questionnaire as well as the developed short form showed good reliability (Cronbach’s α = 0.76 to 0.96). As expected, negative correlations (r = −0.10 to −0.30, P = .006 to .044) with acceptance of pain were observed. Participants with chronic migraine showed significantly higher triggers sensitivity and avoidance of triggers than those with episodic migraine (t(389) = −9.12, P < .001, Cohens d = 0.93).ConclusionsBoth the long and short forms of the questionnaire appear to be reliable and valid measures. The development of the short form of the questionnaire simplifies the use of the HTSAQ in clinical practice. Further research should focus on other primary headache disorders, such as tension‐type headache or cluster headache.
Evaluating the impact of lymph node resampling on colorectal cancer nodal stage
Authors: Tran Christopher , Howlett Christopher , Driman David K 
Published: July 2020

AimsNodal staging in colorectal cancer (CRC) informs prognosis and guides adjuvant treatment decisions. A standard minimum of 12 lymph nodes is widely used, with additional sampling being performed as required. However, there are few data on how lymph node resampling in this context has an impact on nodal stage. The aims of this study were to evaluate the effectiveness of resampling in detecting metastases and tumour deposits, and the impact on stage.Methods and resultsA retrospective cohort analysis was performed on CRC resections that underwent resampling because of an initial yield of <12 lymph nodes, from 2008 to 2018. Data relating to patient demographics, specimen, malignancy and prosection were collected. Slides were reviewed to quantify nodal metastases and tumour deposits before and after resampling. Among ≥pN1 cases, logistic regression analysis was performed to evaluate factors that predicted the finding of additional metastases and tumour deposits. The cohort comprised 395 cases: resampling identified nodal metastases and/or tumour deposits in 30 (7.6%) cases; nodal upstaging occurred in 20 (5.1%) cases; and eight (2.0%) cases changed from pN0 to ≥pN1. No factors predicted resampling of positive lymph nodes or tumour deposits, and pN upstaging occurred across a variety of cases. A subgroup analysis was performed to assess the impact of resampling on high‐risk features in stage II cases (n = 117). There were 33 (8.5%) patients who no longer had any high‐risk features after resampling.ConclusionsLymph node resampling has an impact on nodal staging and possible treatment decisions in a considerable proportion of patients, and is recommended in all cases with <12 lymph nodes.
Comprehensive clinicopathological and molecular analysis of primary malignant melanoma of the oesophagus
Authors: Tsuyama Sho , Kohsaka Shinji , Hayashi Takuo , Suehara Yoshiyuki , Hashimoto Takashi , Kajiyama Yoshiaki , Tsurumaru Masahiko , Ueno Toshihide , Mano Hiroyuki , Yao Takashi , Saito Tsuyoshi 
Published: July 2020

AimsThis study was performed to elucidate the clinicopathological characteristics, genetic alterations and therapeutic targets of primary malignant melanoma of the oesophagus (PMME).Methods and ResultsThe clinicopathology and molecular pathology of 13 PMME cases and 10 skin malignant melanoma (SKMM) cases were analysed with next‐generation sequencing (NGS) and immunohistochemistry. The 3‐year overall survival rate and the median survival time for PMME patients were 23.1% and 11.9 months, respectively. Three (23.1%) and eight (61.5%) PMME cases showed a papillary structure and lymph node metastasis, respectively. DNA and RNA hybridization capture‐based NGS analysis revealed that NF1 was the most frequently mutated gene (30%) in 10 of the PMME cases. Other mutations detected in PMME included SF3B1 (20%), KRAS (10%), BRCA2 (10%), KIT (10%) and TP53 (10%) mutations. Commonly detected BRAF mutations in SKMM were not detected in PMME. Immunohistochemistry and mutation status were concordant between p53/c‐Kit and TP53/KIT, respectively. Focal expression of programmed death‐ligand 1 was observed in one PMME sample. The tumour mutation burden in PMME was significantly lower than that in SKMM (P = 0.030). No PMME case showed high microsatellite instability. RNA sequencing revealed a distinctive pattern with respect to RNA expression. T‐cell co‐stimulation differed between PMME and SKMM.ConclusionsThe RAS–mitogen‐activated protein kinase pathway is one of the main pathways involved in PMME. The genetic profile of PMME was similar to that of mucosal/acral melanoma, but differed from the SKMM profile. A subset of PMMEs may contain actionable mutations. Immunotherapy seemed to be less effective for most PMMEs in this series.