bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of ryanodine receptor target‐site mutations in diamide insecticide‐resistant Spodoptera frugiperda in China
Authors: Lv Sheng‐Lan , Shi Yang , Zhang Jia‐Cheng , Liang Pei , Zhang Lei , Gao Xi‐Wu 
Published: January 2021

AbstractSpodoptera frugiperda (Lepidoptera: Noctuidae) is a widely distributed pest of corn. Since it invaded China in 2018, it has caused serious damage to local corn production. Chlorantraniliprole, an anthranilic diamide insecticide, has been widely used to control lepidopteran pests. Tetrachloropyramid is a new allosteric modulator insecticide developed based on chlorantraniliprole, so it has a similar mechanism and insecticidal effect. In this study, we investigated resistance levels to chlorantraniliprole and tetrachloropyramid in S. frugiperda from 13 populations in China. Among the populations tested, the relative highest resistance to chlorantraniliprole occurred in the Guangzhou population, and the most susceptible to chlorantraniliprole was found in the Wuhan population. The lethal dosage LD50 value of the Guangzhou population against chlorantraniliprole was 27.8‐fold higher than that of the Wuhan population. Minimal differences were observed among S. frugiperda populations in terms of sensitivity to tetrachloropyramid. Heterozygous mutations at the I4734 site of the ryanodine receptor (RyR) were found, while no mutations were found in the G4891 site. The mutations were detected in only two of the 786 individuals analyzed, one from the Qinzhou population and other from the Anshun population (frequency below 2% in both cases). There were no significant differences in the expression levels of RyR between Guangzhou and Wuhan populations. In summary, our results indicate that: (i) S. frugiperda has low resistance levels to diamide insecticides in China; and (ii) the differences in relative resistance among the 13 populations analyzed are not caused by the mutations in RyR or the expression of RyR.
Pedigree reconstruction and distant pairwise relatedness estimation from genome sequence data: A demonstration in a population of rhesus macaques (Macaca mulatta)
Authors: Petty Lauren E. , Phillippi‐Falkenstein Kathrine , Kubisch H. Michael , Raveendran Muthuswamy , Harris R. Alan , Vallender Eric J. , Huff Chad D. , Bohm Rudolf P. , Rogers Jeffrey , Below Jennifer E. 
Published: January 2021

AbstractA primary challenge in the analysis of free‐ranging animal populations is the accurate estimation of relatedness among individuals. Many aspects of population analysis rely on knowledge of relatedness patterns, including socioecology, demography, heritability and gene mapping analyses, wildlife conservation and the management of breeding colonies. Methods for determining relatedness using genome‐wide data have improved our ability to determine kinship and reconstruct pedigrees in humans. However, methods for reconstructing complex pedigree structures and estimating distant relatedness (beyond third‐degree) have not been widely applied to other species. We sequenced the genomes of 150 male rhesus macaques from the Tulane National Primate Research Center colony to estimate pairwise relatedness, reconstruct closely related pedigrees, estimate more distant relationships and augment colony records. Methods for determining relatedness developed for human genetic data were applied and evaluated in the analysis of nonhuman primates, including identity‐by‐descent‐based methods for pedigree reconstruction and shared segment‐based inference of more distant relatedness. We compared the genotype‐based pedigrees and estimated relationships to available colony pedigree records and found high concordance (95.5% agreement) between expected and identified relationships for close relatives. In addition, we detected distant relationships not captured in colony records, including some as distant as twelfth‐degree. Furthermore, while deep sequence coverage is preferable, we show that this approach can also provide valuable information when only low‐coverage (5×) sequence data is available. Our findings demonstrate the value of these methods for determination of relatedness in various animal populations, with diverse applications to conservation biology, evolutionary and ecological research and biomedical studies.
Resistance in wild macadamia germplasm to Phytophthora cinnamomi and Phytophthora multivora
Authors: Jeff‐Ego Olumide S. , Topp Bruce , Drenth Andre , Henderson Julianne , Akinsanmi Olufemi A. 
Published: January 2021

AbstractThe four Macadamia species (M. integrifolia, M. tetraphylla, M. ternifolia and M. jansenii) occur naturally in the wild in fragmented habitats in Australia and there is limited information on their vulnerability to pathogens including species of the genus Phytophthora. Macadamias in commercial orchards are affected by Phytophthora cinnamomi and Phytophthora multivora causing stem canker and root rot. Wild germplasm is often regarded as sources of resistance in macadamia breeding programme. We assessed the performance of 152 trees of wild macadamia genotypes in the field using a Phytophthora disease severity rating scale and used in vivo leaf assay to examine their susceptibility to P. cinnamomi and P. multivora. Macadamia ternifolia trees showed the highest Phytophthora disease severity compared with the other species. In the in vivo trial, there were significant variations in disease severity among the genotypes within each Macadamia species. Comparison of the mean leaf lesion area of the Macadamia spp. showed that M. tetraphylla and M. jansenii were the most resistant to P. cinnamomi, whereas M. ternifolia and M. jansenii followed by M. tetraphylla had the least disease severity to P. multivora. The quantitative variations among the genotypes with strong differential effects resulted in demarcation of the wild genotypes into three resistance groups. Overall, a total of 14 M. tetraphylla and 2 M. integrifolia genotypes were identified as resistant to both P. cinnamomi and P. multivora in the in vivo assay.
Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ
Authors: Webb Louise M. C. , Fra‐Bido Sigrid , Innocentin Silvia , Matheson Louise S. , Attaf Noudjoud , Bignon Alexandre , Novarino Julien , Fazilleau Nicolas , Linterman Michelle A. 
Published: January 2021

AbstractAgeing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre‐Tfh) but no associated increase in germinal centre (GC)‐Tfh cells in aged mice, suggesting age‐driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age‐associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age‐induced changes in T‐cell activation that affects the differentiation and ultimately the function of effector T cells.
Effect of prehospital workflow optimization on treatment delays and clinical outcomes in acute ischemic stroke: A systematic review and meta‐analysis
Authors: Chowdhury Seemub Zaman , Baskar Prithvi Santana , Bhaskar Sonu 
Published: January 2021

AbstractBackgroundThe prehospital phase is critical in ensuring that stroke treatment is delivered quickly and is a major source of time delay. This study sought to identify and examine prehospital stroke workflow optimizations (PSWOs) and their impact on improving health systems, reperfusion rates, treatment delays, and clinical outcomes.MethodsThe authors conducted a systematic literature review and meta‐analysis by extracting data from several research databases (PubMed, Cochrane, Medline, and Embase) published since 2005. We used appropriate key search terms to identify clinical studies concerning prehospital workflow optimization, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines.ResultsThe authors identified 27 articles that looked at the impact of prehospital workflow optimizations on time and treatment parameters; 26 were included in the meta‐analysis. The PSWO were subgrouped into three categories: improved intravenous thrombolysis (IVT) triage, large‐vessel occlusion (LVO) bypass, and mobile stroke unit (MSU). The salient findings are as follows: improved IVT triage led to significantly improved rates of IVT (relative risk [RR] = 1.80, 95% confidence interval [CI] = 1.18 to 2.75); however, MSU did not (RR = 1.22, 95% CI = 0.98 to 1.52). Improved IVT triage (standard mean difference [SMD] = –0.82, 95% CI = –1.32 to –0.32), LVO bypass (SMD = –0.80, 95% CI = –1.13 to –0.47), and MSU (SMD = –0.87, 95% CI = –1.57 to –0.17) were found to significantly reduce door‐to‐needle time for IVT. MSU was found to significantly reduce call‐to‐needle (SMD = –1.41, 95% CI = –1.94 to –0.88) and onset‐to‐needle (SMD = –1.15, 95% CI = –1.74 to –0.56) times for IVT. MSU additionally demonstrated significant reduction in door‐to‐perfusion (SMD = –0.72, 95% CI = –1.32 to –0.12) as well as call‐to‐perfusion (SMD = –0.73, 95% CI = –1.08 to –0.38) times for EVT. Finally, PSWO did not demonstrate significant improvements in rates of good functional outcome (RR = 1.04, 95% CI = 0.97 to 1.12) or mortality at 90 days (RR = 1.00, 95% CI = 0.76 to 1.31).ConclusionsThis systematic review and meta‐analysis found that PSWO significantly improves several time metrics related to stroke treatment leading to improvement in IVT reperfusion rates. Thus, the implementation of these measures in stroke networks is a promising avenue to improve an often‐neglected aspect of the stroke response. However, the limited available data suggest functional outcomes and mortality are not significantly improved by PSWO; hence, further studies and improvement strategies vis‐à‐vis PSWOs are warranted.
The management and course of eosinophilic oesophagitis in Israeli children
Authors: Rosen Irit , Mahamed Aos , Garah Jamal , Magen‐Rimon Ramit , Shaoul Ron 
Published: January 2021

AbstractAimEosinophilic oesophagitis (EoE) is a chronic inflammatory oesophageal disease, which has become more recognised in the past decade. We wanted to characterise our patients and review their course of disease and response to treatment.MethodsWe retrospectively reviewed the medical records of EoE patients from January 2010 to May 2018 in our Gastroenterology Institute. A hundred and two children were included in this study. We investigated the characteristics of patients and the response to three treatment options: proton pump inhibitors, elimination diet and topical steroids. The response to treatment was analysed according to 3 aspects: clinical, endoscopic appearance and histological features.ResultsClinical improvement was noted in 55%, 75% and 87.5% on PPIs, diet and budesonide, respectively. Endoscopic improvement was noted in 38.4%, 51.4% and 65.4% on PPIs, diet and budesonide, respectively. Histological improvement was noted in 43.7%, 62.2% and 88.5% on PPIs, diet and budesonide, respectively.ConclusionOur findings suggest that Israeli paediatric EoE patients have characteristics that resemble previous reports. Although there is a correlation between symptoms, endoscopic and histological appearance, we cannot rely on patients reports alone, and therefore, repeated endoscopy and biopsies are mandated. Topical steroids seem to be the most effective treatment option.
AtFH14 crosslinks actin filaments and microtubules in different manners
Authors: Du Pingzhou , Wang Jiaojiao , He Yunqiu , Zhang Sha , Hu Bailing , Xue Xiuhua , Miao Long , Ren Haiyun 
Published: January 2021

Background InformationIn many cellular processes including cell division, the synergistic dynamics of actin filaments and microtubules play vital roles. However, the regulatory mechanisms of these synergistic dynamics are not fully understood. Proteins such as formins are involved in actin filament–microtubule interactions and Arabidopsis thaliana formin 14 (AtFH14) may function as a crosslinker between actin filaments and microtubules in cell division, but the molecular mechanism underlying such crosslinking remains unclear.ResultsWithout microtubules, formin homology (FH) 1/FH2 of AtFH14 nucleated actin polymerisation from actin monomers and capped the barbed end of actin filaments. However, in the presence of microtubules, quantitative analysis showed that the binding affinity of AtFH14 FH1FH2 to microtubules was higher than that to actin filaments. Moreover, microtubule‐bound AtFH14 FH1FH2 neither nucleated actin polymerisation nor inhibited barbed end elongation. In contrast, tubulin did not affect AtFH14 FH1FH2 to nucleate actin polymerisation and inhibit barbed end elongation. Nevertheless, microtubule‐bound AtFH14 FH1FH2 bound actin filaments and the bound actin filaments slid and elongated along the microtubules or elongated away from the microtubules, which induced bundling or crosslinking of actin filaments and microtubules. Pharmacological analyses indicated that AtFH14 FH1FH2 promoted crosslinking of actin filaments and microtubules in vivo. Additionally, co‐sedimentation and fluorescent dye‐labelling experiments of AtFH14 FH2‐truncated proteins in vitro revealed the essential motifs of bundling actin filaments or microtubules, which were 63–92 aa and 42–62 aa in the AtFH14 FH2 N‐terminal, respectively, and 42–62 aa was the essential motif to crosslink actin filaments and microtubules.Conclusions and SignificanceOur results aid in explaining how AtFH14 functions as a crosslinker between actin filaments and microtubules to regulate their dynamics via different manners during cell division. They also facilitate further understanding of the molecular mechanisms of the interactions between actin filaments and microtubules.
A unique ligand‐steered strategy for CC chemokine receptor 2 homology modeling to facilitate structure‐based virtual screening
Authors: Jin Hongwei , Xia Jie , Liu Zhenming , Wang Xiang Simon , Zhang Liangren 
Published: January 2021

AbstractCC chemokine receptor 2 (CCR2) antagonists that disrupt CCR2/MCP‐1 interaction are expected to treat a variety of inflammatory and autoimmune diseases. The lack of CCR2 crystal structure limits the application of structure‐based drug design (SBDD) to this target. Although a few three‐dimensional theoretical models have been reported, their accuracy remains to be improved in terms of templates and modeling approaches. In this study, we developed a unique ligand‐steered strategy for CCR2 homology modeling. It starts with an initial model based on the X‐ray structure of the closest homolog so far, that is, CXCR4. Then, it uses Elastic Network Normal Mode Analysis (EN‐NMA) and flexible docking (FD) by AutoDock Vina software to generate ligand‐induced fit models. It selects optimal model(s) as well as scoring function(s) via extensive evaluation of model performance based on a unique benchmarking set constructed by our in‐house tool, that is, MUBD‐DecoyMaker. The model of 81_04 presents the optimal enrichment when combined with the scoring function of PMF04, and the proposed binding mode between CCR2 and Teijin lead by this model complies with the reported mutagenesis data. To highlight the advantage of our strategy, we compared it with the only reported ligand‐steered strategy for CCR2 homology modeling, that is, Discovery Studio/Ligand Minimization. Lastly, we performed prospective virtual screening based on 81_04 and CCR2 antagonist bioassay. The identification of two hit compounds, that is, E859‐1281 and MolPort‐007‐767‐945, validated the efficacy of our model and the ligand‐steered strategy.
Test‐guided dietary management of eczema in children: A randomized controlled feasibility trial (TEST)
Authors: Ridd Matthew J. , Webb Douglas , Roberts Kirsty , Santer Miriam , Chalmers Joanne R. , Gilbertson Anna , Marriage Deb , Blair Peter S. , Turner Nicholas L. , Garfield Kirsty , Coast Joanna , Selman Lucy E. , Clement Clare , Shaw Alison R.G. , Muller Ingrid , Waddell Lisa , Angier Elizabeth , Taylor Jodi , Kai Joe , Boyle Robert J. 
Published: January 2021

AbstractBackgroundParents commonly ask about food allergy tests, to find a cause for their child's eczema, yet the value of routine testing is uncertain.ObjectiveTo determine whether a clinical trial comparing test‐guided dietary advice versus usual care, for the management of eczema, is feasible.MethodsChildren (>3 months and <5 years) with mild‐to‐severe eczema, recruited via primary care, were individually randomized (1:1) to intervention or usual care. Intervention participants underwent structured allergy history and skin prick tests (SPT) with dietary advice for cow's milk, hen's egg, wheat, peanut, cashew and codfish. All participants were followed up for 24 weeks. A sample of doctors and parents was interviewed. Registration ISRCTN15397185.ResultsFrom 1059 invitation letters sent to carers of potentially eligible children, 84 were randomized (42 per group) with mean age of 32.4 months (SD 13.9) and POEM of 8.7 (4.8). Of the 42, 6 (14%) intervention participants were advised to exclude one or more foods, most commonly egg, peanut or milk. By participant, 1/6 had an oral food challenge (negative); 3/6 were told to exclude until review in allergy clinic; and 6/6 advised a home dietary trial (exclusion and reintroduction of food over 4–6 weeks) – with 1/6 partially completing it. Participant retention (four withdrawals) and data completeness (74%–100%) were acceptable and contamination low (two usual care participants had allergy tests). There were three minor SPT‐related adverse events. During follow‐up, 12 intervention and 8 usual care participants had minor, unrelated adverse events plus one unrelated hospital admission.ConclusionsIt is possible to recruit, randomize and retain children with eczema from primary care into a trial of food allergy screening and to collect the outcomes of interest. Changes to recruitment and inclusion criteria are needed in a definitive trial, to ensure inclusion of younger children from more diverse backgrounds.
Long‐term efficacy and safety of gonadotropin‐releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta‐analysis
Authors: Luo Xiaoping , Liang Yan , Hou Ling , Wu Wei , Ying Yanqin , Ye Feng 
Published: January 2021

AbstractObjectiveTo investigate the long‐term efficacy and safety of gonadotropin‐releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP).MethodThe protocol was registered with International Prospective Register of Systematic Reviews (CRD42018102792). PubMed, EMBASE and the Cochrane Library were searched for eligible comparative and single‐arm studies.ResultsWe identified a total of 98 studies that included 5475 individuals. The overall risk of bias of the eligible studies ranged from critical to moderate. The overall quality of evidence for each outcome ranged from very low to moderate. Evidence‐based comparative studies showed that GnRHa treatment increase final adult height (FAH, cm; studies = 4, n = 242; mean difference [MD] = 4.83; 95% confidence interval [CI], 2.32 to 7.34; I2 = 49%) and decrease body mass index (BMI, kg/m2; studies = 3, n = 334; MD = −1.01; 95% CI, −1.64 to −0.37; I2 = 0%) in girls with idiopathic CPP compared with no treatment. The incidence of polycystic ovary syndrome (PCOS) did not significantly differ with and without GnRHa treatment (studies = 3, n = 179; risk ratio = 1.21; 95% CI, 0.46 to 3.15; I2 = 48%). The evidence for other long‐term outcomes was very weak to deduce the effects of GnRHa treatment. Further, limited evidence is available on its effects in boys.ConclusionCompared with no treatment, evidence indicates that GnRHa treatment increase FAH and decrease BMI in girls with idiopathic CPP. GnRHa treatment did not evidently increase the risk of PCOS. However, evidence regarding other key long‐term outcomes (such as infertility and malignant or metabolic diseases) was considered very weak to suggest the benefits or side effects of GnRHa treatment. Additional high‐quality evidence is needed before firm conclusions can be drawn.
Country‐, firm‐, and director‐level risk and responsibilities and independent director compensation
Authors: Melis Andrea , Rombi Luigi 
Published: January 2021

AbstractResearch Question/IssueThis study investigates how and to what extent country‐level institutional characteristics and firm‐ and independent director‐level risk and responsibilities are related to independent director compensation, in terms of amount and design.Research Findings/InsightsUsing an international sample of 5,220 independent directors on 727 non‐financial listed firms in 16 countries, this study revealed that both country‐level institutional characteristics and firm‐ and director‐level agency account for the variation of independent director compensation amount. Firm‐level ESG‐related reputational risk and director‐level observable responsibilities on the board are strongly related to independent director compensation amount. These agency relationships vary in the different institutional settings. Country‐level director liability substitutes for firm‐level and director‐level monitoring. Firms conform to institutional pressures for independent director compensation design. Institutional embeddedness comes from the firm's primary institutional environment and its exposure to foreign financial markets.Theoretical/Academic ImplicationsThis study develops a multilevel theory of the antecedents of independent director compensation. Firm‐ and director‐level agency issues are nested in, and interact with, the institutional context in which the agency relationship between shareholders and independent directors is embedded.Practitioner/Policy ImplicationsThis study helps practitioners to understand how director liability regulations, a firm's ESG‐related reputational risk and the specific responsibilities on the board are related to independent director compensation. It helps firms explain to shareholders (and stakeholders) how independent director compensation is determined. Firms should consider that the consequences of their ESG practices extend beyond direct costs. Policymakers can find our results useful when regulating on director liability and developing best practices.
On the ‘Arab Inequality Puzzle’: A Rejoinder
Authors: Achcar Gilbert 
Published: January 2021

ABSTRACTThis rejoinder responds to the Comment by Vladimir Hlasny and Paolo Verme on my article that was recently published in this journal. The acrimonious tone of their Comment is regrettable, and its content reveals a worldview according to which issues such as income inequality and its causal relation to social contention are ‘technical’ in nature and reserved for debate only among ‘apolitical’ econometricians. Beyond that, Hlasny and Verme's Comment adds precious little by way of new argument to the discussion.