bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging Efficacy of Tofacitinib Immediate‐Release to Extended‐Release Formulations for Treatment of Ulcerative Colitis: Application of a Model‐Informed Drug Development Approach
Authors: Mukherjee Arnab , Tsuchiwata Shinichi , Chang Cheng , Nicholas Timothy , Su Chinyu , Le Vu H. , Kushner Joseph , Kulisek Nicole 
Published: May 2022

AbstractTofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report a model‐informed drug development approach for bridging efficacy from immediate‐release (IR) to extended‐release (XR) tofacitinib formulations in patients with UC. IR‐XR efficacy bridging was supported by exposure‐response analysis of phase 3 induction/maintenance studies of the IR formulation in UC to identify exposure metrics relevant for efficacy. Pharmacokinetic studies in healthy subjects were used to confirm similarity of relevant exposure metrics of tofacitinib IR 5 mg twice daily to XR 11 mg once daily, and tofacitinib IR 10 mg twice daily to XR 22 mg once daily, thereby bridging efficacy between IR and XR formulations. Food effect was evaluated at both XR formulation dose levels. Exposure‐response analysis demonstrated that area under the plasma concentration–time curve (average plasma concentration) was a relevant predictor of efficacy. Pharmacokinetic studies demonstrated that area under the plasma concentration–time curve was equivalent between formulations under single‐dose and steady‐state conditions, and other exposure metrics were also similar. These results also supported bridging of safety data for IR‐XR formulations. Food had no impact on tofacitinib XR exposure. These data support efficacy/safety bridging of IR‐XR formulations in patients with UC.
Detection of diabetic retinopathy and related retinal disorders using fundus images based on deep learning and image processing techniques: A comprehensive review
Authors: Lalithadevi Balakrishnan , Krishnaveni Sivamohan 
Published: May 2022

AbstractDiabetes mellitus is a chronic disorder disease in which a person's body fails to adhere insulin produced by their pancreas or unable to segregate enough insulin due to harmonic imbalance. Diabetic people are suffering from eye disorders like diabetic retinopathy (DR), glaucoma and various diseases such as neuropathy, nephropathy, cardiomyopathy over long intervals. One of the most prevalent diabetic consequence is DR. Detecting the morphological variations in retina is difficult and requires an effective automated detection system. DR can be predicted in earlier stage using tremendous development of deep learning models and image processing techniques. Recently, many research articles have been published in DR diagnosis system. This article shows a comprehensive review of automated diagnostic methods for DR detection and other related eye disorders from several points: Causes for DR, publicly available datasets, image preprocessing, segmentation of various DR lesions, feature optimization, various deep learning models, and open research challenges. The study offers a thorough overview of DR detection techniques, which delivers valuable information for researchers, medical professionals, and DR affected patients.
A top‐down enriching approach for ontology learning from text
Authors: Tissaoui Anis , Sassi Salma , Chbeir Richard , Mechergui Ameni 
Published: May 2022

SummaryTo allow better communications between computers and people, ontologies have been adopted in several application domains (web, medicine, industry, etc.). Ontology building exhibits a structural and logical complexity. To the end of making high quality domain ontologies, effective and usable methodologies are needed to facilitate their building process. In this article, we propose to extend the classical methods of ontology construction to design semantically richer ontologies. The objective of this article is to study the relevance of the latent Dirichlet allocation model that generates probabilistic topic models for each enrichment proposal by adopting a domain independent core ontology model. The fitted model can be used to estimate the similarity between documents as well as between a set of specified words/terms using an additional layer of latent variables which are referred to as topics. Experiments were conducted to measure the quality of our proposal against other solutions. Obtained results discussed here are satisfactory.
Pleural fluid metastasis of plasmacytoid urothelial carcinoma in comparison to micropapillary and conventional high‐grade urothelial carcinoma: Cytologic and immuonohistochemical findings
Authors: Wang Brant G. , Woodward Kimberly , Menezes Geetha , Wang Zoe Q. , He Rui , Li Wenping 
Published: May 2022

AbstractPlasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high‐grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA‐3, uroplakin II, and CD138, diminished or loss of E‐cadherin membranous expression, negative expression for p63, p53, Epicam‐BerEP4, Epicam‐MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E‐cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA‐3, uroplakin II, p63, Epicam‐BerEP4 (focal weak), and Epicam‐MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.
Cannabinoid receptor activation potential of the next generation, generic ban evading OXIZID synthetic cannabinoid receptor agonists
Authors: Deventer Marie H. , Van Uytfanghe Katleen , Vinckier Inge M. J. , Reniero Fabiano , Guillou Claude , Stove Christophe P. 
Published: May 2022

AbstractIn recent years, several nations have implemented various measures to control the surge of new synthetic cannabinoid receptor agonists (SCRAs) entering the recreational drug market. In July 2021, China put into effect a new generic legislation, banning SCRAs containing one of seven general core scaffolds. However, this has driven manufacturers towards the synthesis of SCRAs with alternative core structures, exemplified by the recent emergence of “OXIZID SCRAs.” Here, using in vitro β‐arrestin2 recruitment assays, we report on the CB1 and CB2 potency and efficacy of five members of this new class of SCRAs: BZO‐HEXOXIZID, BZO‐POXIZID, 5‐fluoro BZO‐POXIZID, BZO‐4en‐POXIZID, and BZO‐CHMOXIZID. All compounds behaved as full agonists at CB1 and partial agonists at CB2. Potencies ranged from 84.6 to 721 nM at CB1 and 2.21 to 25.9 nM at CB2. Shortening the n‐hexyl tail to a pentyl tail enhanced activity at both receptors. Fluorination of this pentyl analog did not yield a higher receptor activation potential, whereas an unsaturated tail resulted in decreased potency and efficacy at CB1. The cyclohexyl methyl analog BZO‐CHMOXIZID was the most potent compound at both receptors, with EC50 values of 84.6 and 2.21 nM at CB1 and CB2, respectively. Evaluation of the activity of a seized powder containing BZO‐4en‐POXIZID suggested a high purity, in line with high‐performance liquid chromatography coupled to diode‐array detection (HPLC‐DAD), gas chromatography coupled to mass spectrometry (GC–MS), liquid chromatography coupled to time‐of‐flight mass spectrometry (LC‐QTOF‐MS), and Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analysis. Furthermore, all tested compounds showed a preference for CB2, except for BZO‐POXIZID. Overall, these findings inform public health officials, law enforcement agencies, and clinicians on these newly emerging SCRAs.
Application of modern coexistence theory to rare plant restoration provides early indication of restoration trajectories
Authors: Aoyama Lina , Shoemaker Lauren G. , Gilbert Benjamin , Collinge Sharon K. , Faist Akasha M. , Shackelford Nancy , Temperton Vicky M. , Barabás György , Larios Loralee , Ladouceur Emma , Godoy Oscar , Bowler Catherine , Hallett Lauren M. 
Published: May 2022

AbstractRestoration ecology commonly seeks to re‐establish species of interest in degraded habitats. Despite a rich understanding of how succession influences re‐establishment, there are several outstanding questions that remain unaddressed: are short‐term abundances sufficient to determine long‐term re‐establishment success, and what factors contribute to unpredictable restorations outcomes? In other words, when restoration fails, is it because the restored habitat is substandard, because of strong competition with invasive species, or alternatively due to changing environmental conditions that would equally impact established populations? Here, we re‐purpose tools developed from modern coexistence theory to address these questions, and apply them to an effort to restore the endangered Contra Costa goldfields (Lasthenia conjugens) in constructed (“restored”) California vernal pools. Using 16 years of data, we construct a population model of L. conjugens, a species of conservation concern due primarily to habitat loss and invasion of exotic grasses. We show that initial, short‐term appearances of restoration success from population abundances is misleading, as year‐to‐year fluctuations cause long‐term population growth rates to fall below zero. The failure of constructed pools is driven by lower maximum growth rates compared with reference (“natural”) pools, coupled with a stronger negative sensitivity to annual fluctuations in abiotic conditions that yield decreased maximum growth rates. Nonetheless, our modeling shows that fluctuations in competition (mainly with exotic grasses) benefit L. conjugens through periods of competitive release, especially in constructed pools of intermediate pool depth. We therefore show how reductions in invasives and seed addition in pools of particular depths could change the outcome of restoration for L. conjugens. By applying a largely theoretical framework to the urgent goal of ecological restoration, our study provides a blueprint for predicting restoration success, and identifies future actions to reverse species loss.
Impacts of seasonality on gene expression in the Chinese horseshoe bat
Authors: Chen Wenli , Mao Xiuguang 
Published: May 2022

AbstractSeasonality can cause changes in many environmental factors which potentially affects gene expression. Here, we used a bat species (Rhinolophus sinicus) from eastern China as a model to explore the molecular mechanisms of seasonal effects, in particular during phenological shifts in the spring and autumn. Based on the analysis of 45 RNA‐seq samples, we found strong seasonal effects on gene expression, with a large number of genes identified as either specific or biased to each season. Weighted gene co‐expression network analysis also identified multiple modules significantly associated with each season. These seasonal genes were further enriched into different functional categories. Consistent with effects of phenological shifts on bats, we found that genes related to promoting food intake were highly expressed in both autumn and spring. In addition, immunity genes were also highly expressed in both seasons although this seasonal immune response had tissue specificity in different seasons. In female bats, genes related to the delay of ovulation (e.g., NPPC, natriuretic peptide precursor type C) were highly expressed in October, while genes associated with the promotion of reproduction (e.g., DIO2, iodothyronine deiodinase 2) were biasedly expressed in April. Lastly, we found multiple known core clock genes in both October‐biased and April‐biased expressed genes, which may be involved in regulating the start and end of hibernation, respectively. Overall, together with studies in other land and aquatic animals, our work supports that seasonal gene expression variations may be a general evolutionary response to environmental changes in wild animals.
Using wildfire as a management strategy to restore resiliency to ponderosa pine forests in the southwestern United States
Authors: Young Jesse D. , Ager Alan A. , Thode Andrea E. 
Published: May 2022

AbstractThe long‐term outcome from accelerated forest restoration using resource objective wildfire in combination with fuel management on fire‐excluded landscapes is not well studied. We used simulation modeling to examine long‐term trade‐offs and synergies of alternative land management strategies by combining two wildfire management alternatives with three levels of contemporary forest restoration treatments on a 778,000‐ha landscape over 56 years. We found that managing wildfires for resource objectives diminished the likelihood of irregular fire events over time by making wildfire activity more predictable. Overall, adding resource objective wildfire reduced the proportion of high‐severity fire in relation to total area burned, but increased total area burned and the area of high‐severity fire. We also found resource objective wildfire changed the distribution of high‐severity burn patches by increasing their total number and range, their likelihood of containing disjunct core areas, and their edge complexity. The results suggested that alongside the current pace of active forest management, expanding the fire footprint to achieve low‐cost restoration carries the potential for increased high‐severity fire and associated impacts to ecological values including old forest structure and wildlife habitat. Concurrently, adding resource objective wildfire expanded the footprint of conventional restoration treatments by fivefold, and restoration objectives were achieved in 25 years when managing resource objective wildfires alongside restoration treatments five times the current pace. This study demonstrates the first fire suppression model to replicate local decision making by fire managers during simulated fire events to manage risk by considering both fire proximity to values at risk, and daily weather conditions. The study paves the way for further investigations of the synergies between wildfires and conventional forest restoration to improve resiliency in fire‐excluded pine forests.
Fuel reduction treatments reduce modeled fire intensity in the sagebrush steppe
Authors: Ellsworth L. M. , Newingham B. A. , Shaff S. E. , Williams C. L. , Strand E. K. , Reeves M. , Pyke D. A. , Schupp E. W. , Chambers J. C. 
Published: May 2022

AbstractIncreased fire size and frequency coupled with annual grass invasion pose major challenges to sagebrush (Artemisia spp.) ecosystem conservation, which is currently focused on protecting sagebrush community composition and structure. A common strategy for mitigating potential fire is to use fuel treatments that alter the structure and amount of burnable material, thus reducing fire behavior and creating access points for fire suppression resources. While there is some recent information on the impacts of fuel treatments on ecological communities, we have little information on fuel treatment effectiveness at modifying fire behavior in sagebrush ecosystems. We present 10 years of data on fuel accumulation and the resultant modeled fire behavior in prescribed fire, mowed, herbicide (tebuthiuron or imazapic), and untreated control plots in the Sagebrush Treatment Evaluation Project (SageSTEP) network in the Great Basin, USA. Fuel data (i.e., aboveground burnable live and dead biomass) were collected in each treatment plot at Years 0 (pretreatment), 1, 2, 3, 6, and 10 posttreatment. We used the Fuel and Fire Tool fire behavior modeling program to test whether treatments impacted potential fire behavior. Prescribed fire initially removed 49% of the total fuel load and 75% of shrubs, and fuel loads remained reduced through Year 10. Mowing shifted fuels from the shrub canopy to the ground surface but did not change the total fuel amount. Prescribed fire and mowing increased herbaceous fuel by the second posttreatment year and that trend persisted through Year 10. Tebuthiuron treatments were ineffective at altering fuel loads. Imazapic suppressed herbaceous vegetation by 30% in Years 2 and 3 following treatment. The modified fuel beds in fire and mow treatments resulted in modeled flame lengths that were significantly lower than untreated control plots for the duration of the study, with shorter term reductions in reaction intensity and rate of spread. Understanding fuel treatment effectiveness will allow natural resource managers to evaluate trade‐offs between protecting wildlife habitat and reducing the potential for high‐intensity wildfire.
Lagged effects of herbivory impact host‐choice but not nymphal survivorship in an ant‐protected treehopper
Authors: Morales Manuel A. , Kirsch Daniel G. , Sanchez Diana S. 
Published: May 2022

AbstractTheoretical studies have shown that in protection mutualism, the modification of top‐down control by protectors may be destabilizing. Central to this prediction are the assumptions that (1) protection mutualism increases the abundance of protected partners, (2) this increased abundance generates a lagged effect on partner resources, and (3) spatial dynamics can be ignored. Although a number of studies have confirmed that protection mutualism can increase the abundance of protected herbivores, the evidence for a negative effect of protected herbivores on plant quality is mixed, and we are unaware of any studies that have explored the effect of protected herbivores on plant quality across growing seasons. Here, we use the protection mutualism between ants and the treehopper Publilia concava to evaluate the assumption that treehopper herbivory has a lagged effect on plant quality. We also evaluated whether ant protection exacerbated the negative effect of treehoppers on their host plants. We used a two‐way factorial design that manipulated ant and treehopper presence on goldenrod host plants in 1 year and assessed oviposition and survivorship on those same plants in the subsequent year. Treehopper herbivory was associated with a decrease in the probability of oviposition, and female treehoppers laid significantly fewer egg masses on plants that had been fed on the previous year, regardless of ant tending. In contrast, a prior history of herbivory had no impact on future treehopper performance as measured by nymph survival. Ant tending increased treehopper abundance and exacerbated the risk of plant mortality but otherwise did not significantly modify the negative effect of treehopper herbivory on plant quality or future treehopper performance. Although the increase in treehopper abundance associated with ant tending and the lagged oviposition response of treehoppers is consistent with the core assumptions of a model showing that mutualism can be destabilizing, the avoidance of previously occupied plants for oviposition is not. These results highlight the importance of future modeling studies that explore spatiotemporal dynamics in protection mutualism and long‐term field studies that track the effect of mutualism across years.
Community leaf dry matter content predicts plant production in simple and diverse grassland
Authors: Polley H. Wayne , Collins Harold P. , Fay Philip A. 
Published: May 2022

AbstractPlant growth correlates with values of collinear (covarying) traits from the leaf economics spectrum. Environmental variation and differences in community composition may alter contributions of these traits to plant production and thereby limit the consistency of trait‐based growth predictions among years and plant communities. We tested effects of interannual variation in precipitation and differences in grassland community composition (planted monoculture of switchgrass, Panicum virgatum, and mixture of perennial herbaceous species) on the utility of two traits from the leaf economics spectrum (leaf dry matter content [LDMC] and plant [N]) to predict aboveground net primary production (ANP) during spring of 6 years. Spatial and temporal variation in spring production correlated with community‐scale (species abundance‐weighted) values of both traits, but community LDMC explained 66% of the variance in production and accounted for ≥89% of the variance explained by the two traits combined. The ANP response to trait variation and the variance in ANP explained by trait values differed with precipitation and between communities. Greater precipitation increased the production response to trait variation by increasing slopes of ANP–trait regression relationships and increased the variance in ANP explained by trait values. Communities differed in response to precipitation variation and in the role of annual variation in the [N]–LDMC relationship in explaining variance in ANP. Results indicate that mean trends in grassland production can be predicted using community‐scale values of LDMC. Trait‐based predictions of grassland production could be improved, however, by accommodating precipitation and community effects on production–trait relationships.
Analyzing dynamic species abundance distributions using generalized linear mixed models
Authors: Solbu Erik Blystad , van der Veen Bert , Herfindal Ivar , Hovstad Knut Anders 
Published: May 2022

AbstractUnderstanding the mechanisms of ecological community dynamics and how they could be affected by environmental changes is important. Population dynamic models have well known ecological parameters that describe key characteristics of species such as the effect of environmental noise and demographic variance on the dynamics, the long‐term growth rate, and strength of density regulation. These parameters are also central for detecting and understanding changes in communities of species; however, incorporating such vital parameters into models of community dynamics is challenging. In this paper, we demonstrate how generalized linear mixed models specified as intercept‐only models with different random effects can be used to fit dynamic species abundance distributions. Each random effect has an ecologically meaningful interpretation either describing general and species‐specific responses to environmental stochasticity in time or space, or variation in growth rate and carrying capacity among species. We use simulations to show that the accuracy of the estimation depends on the strength of density regulation in discrete population dynamics. The estimation of different covariance and population dynamic parameters, with corresponding statistical uncertainties, is demonstrated for case studies of fish and bat communities. We find that species heterogeneity is the main factor of spatial and temporal community similarity for both case studies.