bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacometabolomics with a combination of PLS‐DA and random forest algorithm analyses reveal meloxicam alters feline plasma metabolite profiles
Authors: Broughton‐Neiswanger Liam E. , Rivera‐Velez Sol M. , Suarez Martin A. , Slovak Jennifer E. , Hwang Julianne K. , Villarino Nicolas F. 
Published: June 2020

AbstractRepeated administration of meloxicam to cats is often limited by the potential damage to multiple organ systems. Identifying molecules that predict the adverse effects of meloxicam would help to monitor and individualize its administration, maximizing meloxicam's beneficial effects. The objectives of this study were to (a) determine if the repeated administration of meloxicam to cats alters the plasma metabolome and (b) identify plasma metabolites that may serve to monitor during the administration of meloxicam in cats. Purpose bred young adult cats (n = 12) were treated with meloxicam at 0.3 mg/kg or saline subcutaneously once daily for up to 17 days. An untargeted metabolomics approach was applied to plasma samples collected prior to and at designated time points after meloxicam or saline administration. To refine the discovery of biomarkers, the machine‐learning algorithms, partial least squares discriminant analysis (PLS‐DA) and random forest (RF), were trained and validated using a separate unrelated group of meloxicam‐ and saline‐treated cats (n = 8). A total of 74 metabolites were included in the statistical analysis. Metabolomic analysis shows that the repeated administration of meloxicam alters multiple substances in plasma, including nonvolatile organic acids, aromatic amino acids, monosaccharides, and inorganic compounds as early as four days following administration of meloxicam. Seventeen plasma molecules were able to distinguish meloxicam‐treated from saline‐treated cats. The metabolomic changes discovered in this study may help to unveil unknown mechanisms of NSAID‐induced side effects. In addition, some metabolites could be valuable for individualizing the administration of meloxicam to cats to mitigate adverse effects.
Lymphocyte‐C‐reactive protein ratio as a novel prognostic index in intrahepatic cholangiocarcinoma: A multicentre cohort study
Authors: Lu Liang‐He , Zhong Chong , Wei Wei , Li Shao‐Hua , Mei Jie , Zou Jing‐wen , Guo Rong‐Ping , Zhang Yong‐Fa 
Published: June 2020

AbstractBackground & AimsThe lymphocyte‐C‐reactive protein ratio (LCR) is a novel inflammatory‐based score, based solely on the lymphocyte and C‐reactive protein. We aimed to clarify the prognostic value of the LCR score in intrahepatic cholangiocarcinoma (ICC) patients after resection.MethodsWe compared the prognostic accuracy of the LCR score with other inflammatory‐based scores in this large, multicentre cohort study. The independent variables associated with overall survival (OS) were explored in both the primary (n = 228) and validation cohorts (n = 135). Harrell's concordance index (C‐index) was used to compare the predictive ability of all the assessed inflammatory‐based scores.ResultsThe LCR score was differentiated two groups of ICC patients with distinct prognoses (1‐, 3‐, and 5‐year OS rates: 94.4%, 66.3%, and 59.3%; and 66.6%, 45.6%, and 32.7%, respectively) (P < .001). Multivariate analysis showed that the LCR score, as well as the TNM stage and preoperative CA19‐9 level, were independently associated with OS. The predictive accuracy of the LCR score (c score: 0.634) was superior to that of the other inflammatory‐based scores (c scores: 0.508‐0.615). These findings were supported by the external validation cohort.ConclusionThe LCR score is stable and consistently the best prognostic score and may offer as a simple, objective and discriminatory method in facilitating the risk stratification of ICC patients.
Choledochal malformations in adults in the Netherlands: Results from a nationwide retrospective cohort study
Authors: de Kleine Ruben H. , Schreuder A. Marthe , ten Hove Anneke , Hulscher Jan B. F. , Borel Rinkes Inne H. M. , Dejong Cornelis H. C. , de Jonge Jeroen , de Reuver Philip , Erdmann Joris , Kazemier Geert ,   the PALGA Foundation, van Gulik Thomas M. , Gouw Annette S. H. , Porte Robert J. 
Published: June 2020

AbstractBackground and AimsPatients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome.MethodsIn a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity.ResultsA total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18‐70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30‐day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later.ConclusionsIn a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%).
Regorafenib in patients with advanced Child‐Pugh B hepatocellular carcinoma: A multicentre retrospective study
Authors: Kim Hyung‐Don , Bang Yeonghak , Lee Myung Ah , Kim Jin Won , Kim Jee Hyun , Chon Hong Jae , Kang Beodeul , Kang Myoung Joo , Kim Ilhwan , Cheon Jaekyung , Hwang Jun‐Eul , Kang Jung Hun , Byeon Seonggyu , Hong Jung Yong , Ryoo Baek‐Yeol , Lim Ho Yeong , Yoo Changhoon 
Published: June 2020

AbstractIntroductionRegorafenib is an approved agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib, but little is known about its clinical outcomes in Child‐Pugh B patients. We aimed to investigate the safety and effectiveness of regorafenib in Child‐Pugh B HCC patients.MethodsThis multicentre retrospective study included 59 patients with Child‐Pugh B HCC who received regorafenib. Comparative analyses were performed with an independent cohort of Child‐Pugh class A patients from the same registry (n = 440).ResultsThe median age was 58 years (range, 19‐83). All patients had progression on prior sorafenib. Regorafenib was given as 2nd line, and 3rd‐4th line systemic therapy in 37 (62.7%) and 22 (37.3%) patients respectively. Compared to Child‐Pugh A cohort, grade 3‐4 AEs were more common in the Child‐Pugh B cohort (27.1% vs 14.1%, P = .017). The median progression‐free survival (PFS) and overall survival (OS) were 1.8 and 4.6 months, respectively, and these were significantly poorer than the Child‐Pugh A cohort (P = .008 and P < .001 respectively). Child‐Pugh B patients with albumin‐bilirubin (ALBI) grade 3 had a significantly higher frequency of increased bilirubin (P = .01 for any grade and P = .01 for grade 3‐4) and showed significantly poorer OS (P = .021), compared to those with ALBI grade 1 or 2.ConclusionRegorafenib's poor clinical outcomes and increased frequency of severe adverse events lead us to discourage its use in the Child‐Pugh B population. In particular, regorafenib should not be used in Child‐Pugh B patients with ALBI grade 3.
Accounting for environmental variation in co‐occurrence modelling reveals the importance of positive interactions in root‐associated fungal communities
Authors: Abrego Nerea , Roslin Tomas , Huotari Tea , Tack Ayco J. M. , Lindahl Björn D. , Tikhonov Gleb , Somervuo Panu , Schmidt Niels Martin , Ovaskainen Otso 
Published: June 2020

AbstractUnderstanding the role of interspecific interactions in shaping ecological communities is one of the central goals in community ecology. In fungal communities, measuring interspecific interactions directly is challenging because these communities are composed of large numbers of species, many of which are unculturable. An indirect way of assessing the role of interspecific interactions in determining community structure is to identify the species co‐occurrences that are not constrained by environmental conditions. In this study, we investigated co‐occurrences among root‐associated fungi, asking whether fungi co‐occur more or less strongly than expected based on the environmental conditions and the host plant species examined. We generated molecular data on root‐associated fungi of five plant species evenly sampled along an elevational gradient at a high arctic site. We analysed the data using a joint species distribution modelling approach that allowed us to identify those co‐occurrences that could be explained by the environmental conditions and the host plant species, as well as those co‐occurrences that remained unexplained and thus more probably reflect interactive associations. Our results indicate that not only negative but also positive interactions play an important role in shaping microbial communities in arctic plant roots. In particular, we found that mycorrhizal fungi are especially prone to positively co‐occur with other fungal species. Our results bring new understanding to the structure of arctic interaction networks by suggesting that interactions among root‐associated fungi are predominantly positive.
Seeing but not believing: Insights into the intractability of failure to fail
Authors: Gingerich Andrea , Sebok‐Syer Stefanie S. , Larstone Roseann , Watling Christopher J. , Lingard Lorelei 
Published: June 2020

AbstractContextInadequate documentation of observed trainee incompetence persists despite research‐informed solutions targeting this failure to fail phenomenon. Documentation could be impeded if assessment language is misaligned with how supervisors conceptualise incompetence. Because frameworks tend to itemise competence as well as being vague about incompetence, assessment design may be improved by better understanding and describing of how supervisors experience being confronted with a potentially incompetent trainee.MethodsFollowing constructivist grounded theory methodology, analysis using a constant comparison approach was iterative and informed data collection. We interviewed 22 physicians about their experiences supervising trainees who demonstrate incompetence; we quickly found that they bristled at the term ‘incompetence,’ so we began to use ‘underperformance’ in its place.ResultsPhysicians began with a belief and an expectation: all trainees should be capable of learning and progressing by applying what they learn to subsequent clinical experiences. Underperformance was therefore unexpected and evoked disbelief in supervisors, who sought alternate explanations for the surprising evidence. Supervisors conceptualised underperformance as: an inability to engage with learning due to illness, a life event or learning disorders, so that progression was stalled, or an unwillingness to engage with learning due to lack of interest, insight or humility.ConclusionPhysicians conceptualise underperformance as problematic progression due to insufficient engagement with learning that is unresponsive to intensified supervision. Although failure to fail tends to be framed as a reluctance to document underperformance, the prior phase of disbelief prevents confident documentation of performance and delays identification of underperformance. The findings offer further insight and possible new solutions to address under‐documentation of underperformance.
Rhizosphere control of soil nitrogen cycling: a key component of plant economic strategies
Authors: Henneron Ludovic , Kardol Paul , Wardle David A. , Cros Camille , Fontaine Sébastien 
Published: June 2020

Summary

Understanding how plant species influence soil nutrient cycling is a major theme in terrestrial ecosystem ecology. However, the prevailing paradigm has mostly focused on litter decomposition, while rhizosphere effects on soil organic matter (SOM) decomposition have attracted little attention.

Using a dual 13C/15N labeling approach in a ‘common garden’ glasshouse experiment, we investigated how the economic strategies of 12 grassland plant species (graminoids, forbs and legumes) drive soil nitrogen (N) cycling via rhizosphere processes, and how this in turn affects plant N acquisition and growth.

Acquisitive species with higher photosynthesis, carbon rhizodeposition and N uptake than conservative species induced a stronger acceleration of soil N cycling through rhizosphere priming of SOM decomposition. This allowed them to take up larger amounts of N and allocate it above ground to promote photosynthesis, thereby sustaining their faster growth. The N2‐fixation ability of legumes enhanced rhizosphere priming by promoting photosynthesis and rhizodeposition.

Our study demonstrates that the economic strategies of plant species regulate a plant–soil carbon–nitrogen feedback operating through the rhizosphere. These findings provide novel mechanistic insights into how plant species with contrasting economic strategies sustain their nutrition and growth through regulating the cycling of nutrients by soil microbes in their rhizosphere.
Modeling the impact of social network measures on institutional adaptive capacity needed for sustainable governance of water resources
Authors: Salajegheh Sosan , Jafari Hamid R. , Pourebrahim Sharareh 
Published: June 2020

AbstractGiven the hydrological, social, and economic complexity of water resources, planning for evaluation of such resources is extremely challenging. The vulnerability and limitations of water resources in one hand, and the growing demand on the other hand necessitates integrated planning for resource protection. Accordingly, applying Smart partial least squares software for structural equation modeling using the partial least square path modeling, the impact of social network measures upon the adaptive capacity of organizational stakeholders faced with water scarcity in industries of Kerman Province was scrutinized in the present study. To investigate the structural position of actors (organizational stakeholders) within the social network, relevant data was extracted and thereafter used to estimate the dependent variables of research (dimensions of adaptation). It was found out that there is significant correlation between the measures of stakeholders' network and the adaptive capacity. Closeness centrality (access to information sources related to water) was found to have the strongest effect on fair governance and leadership, necessary for higher adaptive capacity. On the contrary, betweenness centrality (revealing intermediary actors capable of consensus building) was found to have a negative effect on the adaptive capacity. In other words, better access to the flow of information related to water resources enhances the adaptive capacity of stakeholders but the presence of actors of high betweenness centrality, who are reluctant to an adaptive governance system, decreases adaptive capacity.Recommendations for Resource Managers:Establishment of a polycentric governance system that requires power sharing, coordination, and collaboration of all involved actors and stakeholders.Considering water rights in exploiting water resources.Instructing and educating executive managers of water industry projects for increasing adaptive capacity against water scarcity.Creating integrated watershed management.Development of social network analysis knowledge for analyzing the relationships of stakeholders and the governance network of natural resources and environment.
Pyk2 deficiency enhances bone mass during midpalatal suture expansion
Authors: Sun Jun , Eleniste Pierre P. , Utreja Achint , Turkkahraman Hakan , Liu Sean Shih‐Yao , Bruzzaniti Angela 
Published: June 2020

AbstractObjectiveTo determine if Pyk2 deficiency increases midpalatal suture bone mass and preserves sutural integrity after maxillary expansion.Setting and SampleThirty‐six male Pyk2 knockout (KO) and control (WT) mice at 6 weeks of age.Materials and MethodsMice received nickel‐titanium spring expanders delivering 0 g (no intervention control), 10 or 20 g force for 14 days. High‐resolution micro‐CT was used to determine bone volume/tissue volume (BV/TV), sutural width and intermolar width. Effects on osteoclasts, chondrocytes and suture morphology were determined by histomorphometry.ResultsPyk2‐KO controls (0 g) had 7% higher BV/TV compared with WT controls. Expanded Pyk2‐KO maxillae also exhibited 12% (10 g) and 18% (20 g) higher BV/TV than WT mice. Although bone loss following expansion occurred in both genotypes, BV/TV was decreased to a greater extent in WT maxillae (−10% at 10g; −22% at 20 g) compared with Pyk2‐KO maxillae (−11% only at 20 g). Expanded WT maxillae also showed a greater increase in sutural width, intermolar width and fibrous connective tissue width compared with expanded Pyk2‐KO maxillae. Moreover, osteoclast number was increased 77% (10 g) and 132% (20 g) in expanded WT maxillae, but remained unchanged in expanded Pyk2‐KO, compared to their respective controls. Cartilage area and chondrocyte number were increased to the same extent in expanded WT and Pyk2‐KO sutures.ConclusionsThese findings suggest that midpalatal suture expansion increases osteoclast formation in WT but not Pyk2‐KO mice, leading to higher BV/TV in expanded Pyk2‐KO maxillae. These studies suggest Pyk2‐targeted strategies may be beneficial to increase bone density and preserve sutural integrity during maxillary expansion.
The chemokine lymphotactin and its recombinant variants in oral cancer cell regulation
Authors: Abdullah Zubir Amir Zaki , Whawell Simon A. , Wong Tuck Seng , Khurram Syed Ali 
Published: June 2020

AbstractBackgroundThe expression of XCR1 receptor and its metamorphic ligand lymphotactin (hLtn) has been shown in cancers but their precise role in tumorigenesis is poorly understood including the significance of the physiologically existing hLtn monomeric (CC3) and dimeric (W55D) confirmations where the latter thought to function as the receptor antagonist. The aim of this study was to explore the functional role of bioengineered hLtn variants and the role of fibroblasts in XCR1/hLtn expression regulation in oral cancer cells (OCCL).Material and methodsqRT‐PCR and flow cytometry were performed to evaluate mRNA and protein expression of XCR1 and hLtn. Recombinant hLtn variants (wild‐type, CC3 and W55D mutant) were designed, expressed, purified and evaluated using proliferation, adhesion and chemotaxis assays. XCR1 and hLtn expression regulation by fibroblasts was determined using indirect co‐culture. XCR1 and hLtn expression in primary and metastatic OSCC tissue was assessed using immunohistochemistry.ResultshLtn caused a significant decrease in OCCL XCR1 surface protein expression. hLtn CC3 mutant was highly functional facilitating proliferation and migration. Conditioned media from primary cancer‐associated and senescent fibroblasts significantly upregulated XCR1 and hLtn mRNA expression in OCCL. Immunohistochemistry revealed higher XCR1 and hLtn expression in metastatic tumour deposits and surrounding stroma compared to primary OSCC tissue.ConclusionsThe development of hLtn biological mutants, regulation of XCR1 expression by its ligand hLtn and crosstalk with fibroblasts are novel findings suggesting an important role for the XCR1/hLtn axis within the OSCC tumour microenvironment. These discoveries build upon previous studies and suggest that the hLtn/XCR1 axis has a significant role in stromal crosstalk and OSCC progression.
Functions and regulatory framework of ZmNST3 in maize under lodging and drought stress
Authors: Ren Zhenzhen , Zhang Dongling , Cao Liru , Zhang Weiqiang , Zheng Hongjian , Liu Zhixue , Han Shengbo , Dong Yahui , Zhu Fangfang , Liu Huafeng , Su Huihui , Chen Yanhui , Wu Liancheng , Zhu Yingfang , Ku Lixia 
Published: June 2020

AbstractThe growth and development of maize are negatively affected by various abiotic stresses including drought, high salinity, extreme temperature, and strong wind. Therefore, it is important to understand the molecular mechanisms underlying abiotic stress resistance in maize. In the present work, we identified that a novel NAC transcriptional factor, ZmNST3, enhances maize lodging resistance and drought stress tolerance. ChIP‐Seq and expression of target genes analysis showed that ZmNST3 could directly regulate the expression of genes related to cell wall biosynthesis which could subsequently enhance lodging resistance. Furthermore, we also demonstrated that ZmNST3 affected the expression of genes related to the synthesis of antioxidant enzyme secondary metabolites that could enhance drought resistance. More importantly, we are the first to report that ZmNST3 directly binds to the promoters of CESA5 and Dynamin‐Related Proteins2A (DRP2A) and activates the expression of genes related to secondary cell wall cellulose biosynthesis. Additionally, we revealed that ZmNST3 directly binds to the promoters of GST/GlnRS and activates genes which could enhance the production of antioxidant enzymes in vivo. Overall, our work contributes to a comprehensive understanding of the regulatory network of ZmNST3 in regulating maize lodging and drought stress resistance.
Selective breeding of edible bivalves and its implication of global climate change
Authors: Tan Karsoon , Zhang Hongkuan , Zheng Huaiping 
Published: June 2020

AbstractBivalve molluscs are very nutritious and are an important source of human animal protein. To date, bivalve farming has contributed to about 15% of the mean per capita animal protein intake of approximate 1.5 billion people around the world. Unfortunately, the effects of climate change, mainly global warming and ocean acidification, have had many deleterious effects on bivalve aquaculture, not only leading to mass mortalities of bivalves in farms and hatcheries, but also causing collapse of natural bivalve populations. In response to the recurrent mass mortalities of farmed bivalves, many selective breeding programmes have been launched with the breeding goal of reducing mortality rate caused by disease outbreaks and changing ocean conditions. This article reviews the progress and potential of selective breeding of edible bivalves in the context of global climate change. It is clear from the literature that in terms of environmental sensitivity, and disease resistance and tolerance, selective breeding has great potential for improving the robustness of edible bivalves with significant heritability and genetic gain. Because the robustness of edible bivalves to climate change is a complex trait affected by multiple genes, the application of modern genomic tools in selective breeding is expected to dramatically enhance the accuracy and efficacy of genetic improvements and produce bivalve strains that are robust to climate change. The information in this article is very useful for guidance on adaptation strategies for climate‐smart bivalve aquaculture solutions to be implemented in bivalve hatcheries and farms.