bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRR11 unveiled as a top candidate biomarker within the RBM3‐regulated transcriptome in pancreatic cancer
Authors: Olsson Hau Sofie , Wahlin Sara , Cervin Sophie , Falk Vilgot , Nodin Björn , Elebro Jacob , Eberhard Jakob , Moran Bruce , Gallagher William M , Karnevi Emelie , Jirström Karin 
Published: August 2021

AbstractThe outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers. RNA‐binding motif protein 3 (RBM3) has emerged as a promising biomarker of disease severity and chemotherapy response in several types of cancer, including pancreatic cancer. The aim of this study was to unearth RBM3‐regulated genes and proteins in pancreatic cancer cells in vitro, and to examine their expression and prognostic significance in human tumours. Next‐generation RNA sequencing was applied to compare transcriptomes of MIAPaCa‐2 cells with and without RBM3 knockdown. The prognostic value of differentially expressed genes (DEGs) was examined in The Cancer Genome Atlas (TCGA). Top deregulated genes were selected for further studies in vitro and for immunohistochemical analysis of corresponding protein expression in tumours from a clinically well‐annotated consecutive cohort of 46 patients with resected pancreatic cancer. In total, 19 DEGs (p < 0.01) were revealed, among which some with functions in cell cycle and cell division stood out; PDS5A (PDS cohesin associated factor A) as the top downregulated gene, CCND3 (cyclin D3) as the top upregulated gene, and PRR11 (proline rich 11) as being highly prognostic in TCGA. Silencing of RBM3 in MiaPaCa‐2 cells led to congruent alterations of PDS5A, cyclin D3, and PRR11 levels. High protein expression of PRR11 was associated with adverse clinicopathological features and shorter overall survival. Neither PDS5A nor cyclin D3 protein expression was prognostic. This study unveils several RBM3‐regulated genes with potential clinical relevance in pancreatic cancer, among which PRR11 shows the most consistent association with disease severity, at both transcriptome and protein levels.
Phase 1 trial of adavosertib (AZD1775) in combination with concurrent radiation and cisplatin for intermediate‐risk and high‐risk head and neck squamous cell carcinoma
Authors: Chera Bhishamjit S. , Sheth Siddharth H. , Patel Shetal A. , Goldin Dan , Douglas Kathe E. , Green Rebecca L. , Shen Colette J. , Gupta Gaorav P. , Moore Dominic T. , Grilley Olson Juneko E. , Weiss Jared M. 
Published: August 2021

BackgroundAdavosertib (AZD1775) is an inhibitor of the Wee1 kinase. The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate‐risk/high‐risk, locally advanced head and neck squamous cell carcinoma (HNSCC).MethodsTwelve patients with intermediate‐risk/high‐risk HNSCC were enrolled, including those with p16‐negative tumors of the oropharynx, p16‐positive tumors of the oropharynx with ≥10 tobacco pack‐years, and tumors of the larynx/hypopharynx regardless of p16 status. All patients were treated with an 8‐week course of concurrent intensity‐modulated radiotherapy at 70 grays (Gy) (2 Gy daily in weeks 1‐7), cisplatin 30 mg/m2 weekly (in weeks 1‐7), and adavosertib (twice daily on Monday, Tuesday, and Wednesday of weeks 1, 2, 4, 5, 7, and 8). The primary objective was to determine the maximum tolerated dose and the recommended phase 2 dose of adavosertib given concurrently with radiation and cisplatin. Secondary objectives were to determine the 12‐week objective response rate and progression‐free and overall survival.ResultsThree patients (25%) experienced a dose‐limiting toxicity, including febrile neutropenia (n = 2) and grade 4 thromboembolism (n = 1). Two dose‐limiting toxicities occurred with adavosertib at 150 mg. The median follow‐up was 14.7 months. The 12‐week posttreatment objective response rate determined by positron emission tomography/computed tomography was 100%. The 1‐year progression‐free and overall survival rates were both 90%. The maximum tolerated dose of adavosertib was 100 mg.ConclusionsAdavosertib 100 mg (twice daily on Monday, Tuesday, and Wednesday of weeks 1, 2, 4, 5, 7, and 8), in combination with 70 Gy of intensity‐modulated radiotherapy and cisplatin 30 mg/m2, is the recommended phase 2 dose for patients with HNSCC.
Contrasting genomic profiles from metastatic sites, primary tumors, and liquid biopsies of advanced prostate cancer
Authors: Necchi Andrea , Cucchiara Vito , Grivas Petros , Bratslavsky Gennady , Jacob Joseph , Spiess Philippe E. , Sokol Ethan S. , Killian Jonathan Keith , Lin Douglas , Ramkissoon Shakti , Huang Richard S. P. , Madison Russell W. , Venstrom Jeffrey M. , Schrock Alexa B. , Danziger Natalie , Decker Brennan , Gjoerup Ole , Graf Ryon P. , Oxnard Geoffrey R. , Tukachinsky Hanna , Ross Jeffrey S. 
Published: August 2021

BackgroundThis study assessed the contrasting genomic profiles from the primary tumors (PTs), metastatic (MET) sites, and circulating tumor DNA (ctDNA) of patients with prostate cancer (PC).MethodsA total of 1294 PC tissue specimens and 2462 ctDNA specimens underwent hybrid capture–based comprehensive genomic profiling (CGP). Specimens included tissue from PTs; MET biopsies from bone, liver (LIV), lung (LU), brain (BN), lymph node, and soft tissue sites; and ctDNA.ResultsDifferences in alteration frequencies between PT, MET, and ctDNA specimens for selected genes were observed. TMPRSS2:ERG fusion frequencies were similar between PTs and MET sites (35% vs 33%) but varied among MET sites. Genomic alterations (GAs) in AR were lowest in PTs (2%) and highest in MET sites (from 24% in LU to 50% in LIV). BN had the highest genomic alterations/tumor (8) and enrichment for PTEN GAs. The BRCA2 GA frequency varied from 0% in BN to 15% in LIV. ERBB2 amplification was increased in MET sites in comparison with PTs. RB1 GAs were increased in LIV. Biomarkers potentially associated with an anti‐PD(L)1 response included CDK12 GAs (16% in LU) and a microsatellite instability–high status (29% in BN). Analyses of ctDNA featured a broad spectrum of GAs similar to those detected across MET sites.ConclusionsCGP of PTs, MET sites, and ctDNA in PC exhibited differences most likely associated with tumor progression, clonal evolution, and exposure to systemic therapies; ctDNA can also capture a broad range of potential therapeutic opportunities for patients with PC.
A framework for investigating search engines' stemming mechanisms: A case study on Bing
Authors: Şentürk Fatmana , Gunduz Gurhan 
Published: August 2021

SummaryBig data attracts the attention of governments and a lot of companies today. The developments in technology and the Internet make it one of the important sources of big data. It is easy to get lost in the enormous amount of information contained on the Internet if there were no search engines. Knowing how the search engines work will be helpful to access the desired information. This work aims to be a guide for accessing the right information and also to help to understand search engine stemming and indexing algorithm for interested parties. In this article, we have developed a framework that could be used to investigate the stemming mechanisms of search engines. Our framework also uses Word2vec to analyze semantic relations. We have used our framework to investigate the stemming algorithm of the search engine Bing for English language. In order to achieve that we have used this framework to select words, create queries, send them to Bing, and finally analyze the millions of returned results. We have discussed the results in the context of our article. The results indicate that our framework is useful for analyzing the stemming mechanisms of search engines.
Shade and nitrogen fertilization affect forage accumulation and nutritive value of C4 grasses differing in growth habit
Authors: Moreno Leonardo S. B. , Boote Kenneth J. , Sollenberger Lynn E. , Dubeux José C. B. , Kohmann Marta M. , Pequeno Diego Noleto Luz 
Published: August 2021

AbstractLight reduction in silvopastoral systems and self‐shading in treeless grasslands can lead to shade‐avoidance responses by tropical grasses. Light environment in association with nitrogen (N) supply influence the growth and nutritive value of forage grasses. This study aimed to quantify forage accumulation (FA) and forage nutritive value of tropical grasses differing in growth habit in environments with contrasting light and N resources. A field study was conducted using ‘Jiggs’ bermudagrass [Cynodon dactylon (L.) Pers.] and ‘Mulato II’ hybrid brachiariagrass (Urochloa spp). Full‐sun environments were compared with shaded environments where shade cloth limited incident radiation to 45% of ambient. Low and high N treatments were imposed (30 and 120 kg N ha−1 after each harvest), resulting in a 2 × 2 × 2 factorial arrangement of treatments in four replicates of a randomized complete block design. Forage was harvested every 28 d from May to September in 2014 and 2015 to determine FA. Herbage crude protein (CP) concentration and in vitro digestible organic matter (IVDOM) were assessed. Annual FA was greater for Mulato II than Jiggs and for high‐N and full‐sun treatments. Species showed similar CP concentrations, but Mulato II had greater IVDOM than Jiggs, likely due to a greater leaf percentage. Shade increased CP concentration of the forages whereas effects on IVDOM were not consistent. Although more productive with greater leaf percentage and nutritive value than decumbent, stoloniferous Jiggs, upright‐growing, bunchgrass Mulato II was not persistent when multiple freeze events occurred during winter, limiting its adoption in cooler subtropical environments.
Heterosis for biomass yield and other traits in ‘Alamo’ × ‘Kanlow’ switchgrass populations
Authors: Shrestha Surya L. , Bhandari Hem S. , Allen Fred L. , Tobias Christian M. , Nayak Santosh , Goddard Ken , Senseman Scott A. 
Published: August 2021

AbstractHeterosis plays an important role in switchgrass (Panicum virgatum L.) breeding. To identify superior clones for hybrid development through seasonal single cut, 10 crosses derived from ‘Alamo’ × ‘Kanlow’ and parents were evaluated. The experiment was planted in 2018 using a randomized complete block design with two replications at two locations in Tennessee: the East Tennessee Research and Education Center (ETREC), Knoxville, and the Plateau Research and Education Center (PREC), Crossville. The crosses and their parents were evaluated for biomass yield, plant height, and clonal mass in the fall of 2019 and 2020. The crosses were significantly different in biomass yield within and across locations (P ≤ .05). Average biomass yield of the crosses ranged from 7.1 to 8.7 Mg ha−1 at ETREC and from 10.0 to 11.8 Mg ha−1 at PREC. The crosses demonstrated an average of 46% mid‐parent heterosis (MPH) and 24% high‐parent heterosis (HPH) for biomass yield across the two locations. The MPH and HPH were 3 and −1.3% for plant height and 12 and 1% for clonal mass, respectively. Moderate to strong positive association was found between clonal mass scores and biomass yield at individual locations across years and across locations and years (r = 0.37–0.79, P ≤ .05). The association between biomass yield and plant height was inconsistent (r = −0.24 to 0.67, P ≤ .05). The findings of biomass yield heterosis in these crosses suggested the potential of hybrid cultivars for biomass yield improvement in lowland switchgrass.
A fast screening method for the detection of CERA in dried blood spots
Authors: Rocca Angela , Martin Laurent , Kuuranne Tiia , Ericsson Magnus , Marchand Alexandre , Leuenberger Nicolas 
Published: August 2021

AbstractContinuous erythropoietin receptor activator (CERA) is a third‐generation erythropoiesis‐stimulating agent that was developed for the treatment of anemia. However, misuse of CERA for doping in endurance sports has been reported. Previous studies have shown blood as the matrix of choice for the detection of CERA, due to its high molecular weight. The use of dried blood spots (DBSs) for anti‐doping purposes constitutes a complementary approach to the standard urine and venous blood matrices and could facilitate sample collection and increase the number of blood samples available for analysis due to reduced costs of sample collection and transport. Here, we investigated whether CERA could be indirectly detected in extracts of single DBSs using an erythropoietin‐specific immunoassay that is capable of providing results within approximately 2 h. Reconstituted DBS samples were prepared from mixtures of red blood cell pellets and serum samples. The samples were collected in a previous clinical study in which six healthy volunteers were injected with a single, 200 μg dose of CERA. Using a commercially available ELISA kit, CERA was detected in the DBSs with a detection window of up to 20 days post‐injection. Furthermore, in order to demonstrate the fitness‐for‐purpose, three authentic doping control serum samples, which were identified as containing CERA, were analyzed by the presented methodological approach on DBS. The testing procedure described here could be used as a fast and cost‐effective method for the detection of CERA abuse in sport.
Drivers of Solidago species invasion in Central Europe—Case study in the landscape of the Carpathian Mountains and their foreground
Authors: Perera Peliyagodage Chathura Dineth , Szymura Tomasz H. , Zając Adam , Chmolowska Dominika , Szymura Magdalena 
Published: August 2021

AbstractAimThe invasion process is a complex, context‐dependent phenomenon; nevertheless, it can be described using the PAB framework. This framework encompasses the joint effect of propagule pressure (P), abiotic characteristics of the environment (A), and biotic characteristics of both the invader and recipient vegetation (B). We analyzed the effectiveness of proxies of PAB factors to explain the spatial pattern of Solidago canadensis and S. gigantea invasion using invasive species distribution models.LocationCarpathian Mountains and their foreground, Central Europe.MethodsThe data on species presence or absence were from an atlas of neophyte distribution based on a 2 × 2 km grid, covering approximately 31,200 km2 (7,752 grid cells). Proxies of PAB factors, along with data on historical distribution of invaders, were used as explanatory variables in Boosted Regression Trees models to explain the distribution of invasive Solidago. The areas with potentially lower sampling effort were excluded from analysis based on a target species approach.ResultsProxies of the PAB factors helped to explain the distribution of both S. canadensis and S. gigantea. Distributions of both species were limited climatically because a mountain climate is not conducive to their growth; however, the S. canadensis distribution pattern was correlated with proxies of human pressure, whereas S. gigantea distribution was connected with environmental characteristics. The varied responses of species with regard to distance from their historical distribution sites indicated differences in their invasion drivers.Main conclusionsProxies of PAB are helpful in the choice of explanatory variables as well as the ecological interpretation of species distribution models. The results underline that human activity can cause variation in the invasion of ecologically similar species.
Natal dispersal of Whooping Cranes in the reintroduced Eastern Migratory Population
Authors: Thompson Hillary L. , Caven Andrew J. , Hayes Matthew A. , Lacy Anne E. 
Published: August 2021

AbstractNatal dispersal is a key demographic process for evaluating the population rate of change, especially for long‐lived, highly mobile species. This process is largely unknown for reintroduced populations of endangered avian species. We evaluated natal dispersal distances (NDD) for male and female Whooping Cranes (Grus americana) introduced into two locations in central Wisconsin (Necedah National Wildlife Refuge, or NNWR, and the Eastern Rectangle, or ER) using a series of demographic, spatial, and life history‐related covariates. Data were analyzed using gamma regression models with a log‐link function and compared using Akaike information criterion corrected for small sample sizes (AICc). Whooping Cranes released in the ER dispersed 261% further than those released into NNWR, dispersal distance increased 4% for each additional nesting pair, decreased about 24% for males as compared to females, increased by 21% for inexperienced pairs, and decreased by 3% for each additional year of age. Natal philopatry, habitat availability or suitability, and competition for breeding territories may be influencing observed patterns of NDD. Whooping Cranes released in the ER may exhibit longer NDD due to fragmented habitat or conspecific attraction to established breeding pairs at NNWR. Additionally, sex‐biased dispersal may be increasing in this population as there are more individuals from different natal sites forming breeding pairs. As the population grows and continues to disperse, the drivers of NDD patterns may change based on individual or population behavior.
Delimitation despite discordance: Evaluating the species limits of a confounding species complex in the face of mitonuclear discordance
Authors: Firneno Thomas J. , O’Neill Justin R. , Itgen Michael W. , Kihneman Timothy A. , Townsend Josiah H. , Fujita Matthew K. 
Published: August 2021

AbstractThe delimitation of species is an essential pursuit of biology, and proper taxonomies are crucial for the assessment and conservation management of organismal diversity. However, delimiting species can be hindered by a number of factors including highly conserved morphologies (e.g., cryptic species), differences in criteria of species concepts, lineages being in the early stages of the speciation or divergence process, and discordance between gene topologies (e.g., mitonuclear discordance). Here we use a taxonomically confounded species complex of toads in Central America that exhibits extensive mitonuclear discordance to test delimitation hypotheses. Our investigation integrates mitochondrial sequences, nuclear SNPs, morphology, and macroecological data to determine which taxonomy best explains the divergence and evolutionary relationships among these toads. We found that a three species taxonomy following the distributions of the nuclear SNP haplotypes offers the best explanation of the species in this complex based off of the integrated data types. Due to the taxonomic instability of this group, we also discuss conservation concerns in the face of improper taxonomic delimitation. Our study provides an empirical and integrative hypothesis testing framework to assess species delimitation hypotheses in the face of cryptic morphology and mitonuclear discordance and highlights the importance that a stable taxonomy has over conservation‐related actions.
A model for the relationship between plant biomass and photosynthetic rate based on nutrient effects
Authors: Hu Han‐Jian , Xu Kang , He Ling‐Chao , Wang Gen‐Xuan 
Published: August 2021

AbstractThe photosynthetic rate is considered to be affected by individual biomass and limited by nutrients. Metabolic scaling models are often utilized to predict photosynthetic rates based on plant size and other factors, such as temperature and plant nutrient composition. However, the intrinsic regulatory mechanisms of the combined factors that affect the photosynthetic rates of living organisms are subject to debate. Here, we present a model developed from the metabolic scaling model, the Michaelis‐Menten equation and elemental stoichiometric models to precisely predict the relationship between plant photosynthetic rate and biomass. The developed model was verified against data for small woody and nonwoody plants, and in comparison with the typical metabolic scaling model, this model was shown to be more capable of explaining the photosynthesis‐biomass relationship. Moreover, the results showed that the combined factors affected photosynthesis via the regulatory effect of nutrients on photosynthesis‐biomass allometry. We highlight that nutrients have direct effects on the allocation of plant biomass and photosynthetic investment under stable and balanced growth states.
Carboxylic Acid Promoted, Redox‐Neutral Ru‐Catalyzed C−H Allylation of Aromatic Ketones
Authors: Dethe Dattatraya H. , Beeralingappa Nagabhushana C. , Dherange Balu D. 
Published: August 2021

AbstractA redox‐neutral, carboxylic acid promoted, [RuCl2(p‐cymene)]2 catalyzed, weakly coordinating, carbonyl assisted C−H allylation of aromatic ketones has been developed. The beneficial effect of carboxylic acid on the ruthenium catalyst towards C−H allylation of aromatic ketones has been further explored, using commercially available allyl acetate under mild reaction conditions. In addition, this method requires redox‐neutral reaction conditions, easily accessible starting materials, and shows excellent functional group compatibility.
Synthesis of Pyrrolo[2,1‐a]isoquinoline Class of Natural Product Crispine A
Authors: Mohan Chithra , Krishna R. Bharath , Sivanandan Sudheesh T. , Ibnusaud Ibrahim 
Published: August 2021

AbstractAs a naturally occurring small‐molecule, various optical isomers of chiral pyrrolo[2,1‐a]isoquinoline alkaloid crispine A represent a potential class of chiral molecules in contemporary organic chemistry, and possess diverse biological activities. The range of pharmacological activities include antidepressant, antiplatelet, antileukemic, and anticancer activities. This review provides an overview of the literature on the strategies, employed in the synthesis of crispine A in their racemic and enantiopure forms via Bischler‐Napieralski cyclization, Pictet‐Spengler cyclization, N‐Alkylation/Acylation‐cyclization, Oxidative cyclization, and Asymmetric hydrogenation in the period of 1931–2021. This study accentuates the need for the developing more effective synthesis, and search for involved biological applications for the pyrroloisoquinoline class of natural product. Attention has been drawn towards the use of relatively less documented but easily accessible naturally occurring diastereomeric scaffolds namely, garcinia and hibiscus acids. These lactones obtained from (+)‐ and (−)‐2‐hydroxycitric acids bearing chemically amenable functional groups are investigated as an ideal choice for the enantiopure synthesis of the (−)‐(R)‐ and (+)‐(S)‐Crispine A structural frame work.
Ferric Sulphate/Potassium Bisulfate Promoted Facile Synthesis of N‐Sulfonylimidates from a Multi‐Component Reaction
Authors: Li Jingjing , Zhao Yanwei , Yang Jinwei , Li Ruyi , Cao Zhiyu , Wan Xiaobing 
Published: August 2021

AbstractThe highly efficient Fe2(SO4)3/KHSO4 promoted synthesis of N‐sulfonylimidates from amides, sulfonamides and ethyl diazoacetate is reported. This transformation is compatible with a wide range of substrates and exhibits good functional group tolerance. This multi‐component reaction can be useful for synthesizing a variety of drugs and bioactive molecules with satisfactory yields.