bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular allergology and its impact in specific allergy diagnosis and therapy
Authors: Barber Domingo , Diaz‐Perales Araceli , Escribese Maria M. , Kleine‐Tebbe Jörg , Matricardi Paolo M. , Ollert Markus , Santos Alexandra F. , Sastre Joaquin 
Published: May 2021

AbstractProgressive knowledge of allergenic structures resulted in a broad availability of allergenic molecules for diagnosis. Component‐resolved diagnosis allowed a better understanding of patient sensitization patterns, facilitating allergen immunotherapy decisions. In parallel to the discovery of allergenic molecules, there was a progressive development of a regulation framework that affected both in vitro diagnostics and Allergen Immunotherapy products. With a progressive understanding of underlying mechanisms associated to Allergen immunotherapy and an increasing experience of application of molecular diagnosis in daily life, we focus in analyzing the evidences of the value provided by molecular allergology in daily clinical practice, with a focus on Allergen Immunotherapy decisions.
Increased risk of complications in smokers undergoing reversal of diverting ileostomy
Authors: Cribb Benjamin , Kollias Victoria , Hawkins Rosalyn , Ganguly Timothy , Edwards Suzanne , Hewett Peter 
Published: May 2021

AbstractBackgroundDiverting ileostomy (DI) is utilised in rectal cancer surgery to mitigate the effects of anastomotic leak. The aim of this study was to assess the clinical risk factors associated with post‐operative complications of DI reversal.MethodsA single‐centre retrospective analysis of patients who underwent surgical resection for rectal cancer and subsequent DI reversal between January 2012 and December 2020 was undertaken. Medical records were reviewed to extract clinical, operative and pathologic details and post‐operative complications according to the Clavien‐Dindo classification. Univariate and multivariable analyses were undertaken to assess risk factors associated with post‐operative complications of DI reversal.ResultsOne hundred and twenty‐six adult patients who underwent DI reversal were included of which 49 had a post‐operative complication (39%). The most common complication was prolonged post‐operative ileus, which occurred in 24 patients (19%). On multivariable analysis smoking was significantly associated with overall complications (odds ratio [OR] = 5.60, 95% confidence interval [CI] 1.90–16.52, p = 0.0018), and high Clavien‐Dindo (2–5) category complications (OR = 4.60, 95% CI 1.81–11.68, p = 0.0013). In addition, patients who received adjuvant chemotherapy were less likely to have a reversal of DI complication (OR = 0.43, 95% CI 0.19–0.94, p = 0.0342) and less likely to have a high Clavien‐Dindo (2–5) category complication (OR = 0.44, 95% CI 0.20–0.93, p = 0.0311).ConclusionSmokers who have undergone surgical resection of rectal cancer have a significantly increased risk of post‐operative complications after DI reversal. In these patients, the importance of smoking cessation must be emphasised. The decreased complication rate observed in patients who received adjuvant chemotherapy was an unexpected finding.
Protein O‐GlcNAcylation in the heart
Authors: Ng Yann Huey , Okolo Chidinma A. , Erickson Jeffrey R. , Baldi James C. , Jones Peter P. 
Published: May 2021

AbstractO‐GlcNAcylation is a ubiquitous post‐translational modification that is extremely labile and plays a significant role in physiology, including the heart. Sustained activation of cardiac O‐GlcNAcylation is frequently associated with alterations in cellular metabolism, leading to detrimental effects on cardiovascular function. This is particularly true during conditions such as diabetes, hypertension, cardiac remodelling, heart failure and arrhythmogenesis. Paradoxically, transient elevation of cardiac protein O‐GlcNAcylation can also exert beneficial effects in the heart. There is compelling evidence to suggest that a complex interaction between O‐GlcNAcylation and phosphorylation also exists in the heart. Beyond direct functional consequences on cardiomyocytes, O‐GlcNAcylation also acts indirectly by altering the function of transcription factors that affect downstream signalling. This review focuses on the potential cardioprotective role of protein O‐GlcNAcylation during ischaemia‐reperfusion injury, the deleterious consequences of chronically elevated O‐GlcNAc levels, the interplay between O‐GlcNAcylation and phosphorylation in the cardiomyocytes and the effects of O‐GlcNAcylation on other major non‐myocyte cell types in the heart.
Soil phosphorus availability determines the contribution of small, individual grassland remnants to the conservation of landscape‐scale biodiversity
Authors: Plue Jan , Baeten Lander 
Published: May 2021

AbstractQuestionsSmall, remnant habitats embedded in degraded, human‐dominated landscapes are generally not a priority in conservation, despite their potential role in supporting landscape‐scale biodiversity. To warrant their inclusion in conservation management and policy, we question under which conditions they may exhibit the largest conservation value.LocationNine landscapes spread across the counties of Stockholm and Södermanland, Sweden.MethodsPer landscape, plant communities were surveyed in 6 and 12 1 × 1 m2plots across large, intact semi‐natural grasslands and small remnant grasslands, respectively. These two contrasting grassland types served as a model system. A topsoil sample was taken in each plot to determine habitat quality in terms of soil pH, plant‐available P, and C:N ratio. We used a joint species distribution model to analyse the extent to which grassland type and habitat quality define and predict resident community diversity and composition, including whether they support grassland specialists.ResultsAt the landscape scale, the combined remnant grasslands sustained diverse plant communities which did include a significant subset of habitat specialists. Yet, the contribution of individual remnants clearly varied with local‐scale habitat quality; soil phosphorus availability lowered plot‐level species richness, mostly by constraining the occurrence of grassland specialists. Semi‐natural grassland communities were comparatively insensitive to variation in soil phosphorus availability.ConclusionsThe combined habitat amount and the significant number of habitat specialists sustained by remnant grasslands with high habitat quality, shows they can represent a valuable resource to support landscape‐scale biodiversity conservation. This offers no wildcard to neglect the continued biotic and abiotic threats on semi‐natural grassland plant diversity such as chronic and accumulating P eutrophication, discontinuation of management or poor matrix permeability, as semi‐natural grasslands harbour the majority of habitat specialists, while sourcing surrounding remnant grassland communities.
Rent sharing in China: Magnitude, heterogeneity and drivers
Authors: Duan Wenjing , Martins Pedro S. 
Published: May 2021

AbstractDo firms in China share rents with their workers? We address this question by examining firm‐level panel data covering virtually all manufacturing firms over the period 2000–2007, representing an average of 52 million workers per year. We find evidence of rent sharing (RS), with wage–profit elasticities of between 4% and 6%. These results are based on multiple instrumental variables, including firm‐specific international trade shocks. We also present a number of complementary findings to understand better the nature of RS in the country: it involves an element of risk sharing, as wages also decrease when profits fall; RS is lower in regions with more latent competition from rural workers; higher minimum wages tend to reduce RS; and, while employer labour market power reduces wages, it increases RS. Overall, despite its importance, RS in China is smaller and more symmetric than in developed economies, which reflects the weaker bargaining power of its workers and the earlier stage of development of its labour market institutions.
Methodological advances for hypothesis‐driven ethnobiology
Authors: Gaoue Orou G. , Moutouama Jacob K. , Coe Michael A. , Bond Matthew O. , Green Elizabeth , Sero Nadejda B. , Bezeng Bezeng S. , Yessoufou Kowiyou 
Published: May 2021

ABSTRACTEthnobiology as a discipline has evolved increasingly to embrace theory‐inspired and hypothesis‐driven approaches to study why and how local people choose plants and animals they interact with and use for their livelihood. However, testing complex hypotheses or a network of ethnobiological hypotheses is challenging, particularly for data sets with non‐independent observations due to species phylogenetic relatedness or socio‐relational links between participants. Further, to account fully for the dynamics of local ecological knowledge, it is important to include the spatially explicit distribution of knowledge, changes in knowledge, and knowledge transmission and use. To promote the use of advanced statistical modelling approaches that address these limitations, we synthesize methodological advances for hypothesis‐driven research in ethnobiology while highlighting the need for more figures than tables and more tables than text in ethnobiological literature. We present the ethnobiological motivations for conducting generalized linear mixed‐effect modelling, structural equation modelling, phylogenetic generalized least squares, social network analysis, species distribution modelling, and predictive modelling. For each element of the proposed ethnobiologists quantitative toolbox, we present practical applications along with scripts for a widespread implementation. Because these statistical modelling approaches are rarely taught in most ethnobiological programs but are essential for careers in academia or industry, it is critical to promote workshops and short courses focused on these advanced methods. By embracing these quantitative modelling techniques without sacrificing qualitative approaches which provide essential context, ethnobiology will progress further towards an expansive interaction with other disciplines.
Metacarpophalangeal profile pattern analysis in a further patient with a novel ARID1B variant
Authors: Pascolini Giulia 
Published: May 2021

AbstractAcral clinical and radiographic characteristics of a further patient with Coffin‐Siris syndrome (CSS), which is caused by mutations in the ARID1B gene, encoding a subunit of the BAF‐complex, are here described. Metacarpophalangeal profile pattern analysis (MCPPPA) of the present proband and other two known ARID1B mutated individuals has been performed for the first time, demonstrating hands brachydactyly. In this novel study, the utility of an accurate appendicular radiographic examination and MCPPPA in this congenital condition is highlighted. The MCPPPA could be considered in the clinical practice, to better study the hand skeletal morphology in patients with a syndrome characterized by limb defects, including CSS.
Normalization of non‐canonical Wnt signalings does not compromise blood‐brain barrier protection conferred by upregulating endothelial Wnt/β‐catenin signaling following ischemic stroke
Authors: Ji Ya‐bin , Wang Tian‐xi , Gao Qiang , Huang Xiao‐wen , Chang Junlei 
Published: May 2021

AbstractBackgroundEndothelial canonical (Wnt/β‐catenin) and non‐canonical Wnt signalings (Wnt/PCP and Wnt/Ca2+) promote blood‐brain barrier (BBB) development and antagonize each other. However, the effects of ischemic stroke on endothelial canonical and non‐canonical Wnt signalings are unclear. Further, how non‐canonical Wnt signalings are influenced by upregulation of endothelial Wnt/β‐catenin signaling and subsequently affect BBB function following ischemic stroke have not been studied.MethodsFirst, we determined the levels of Wnt signaling markers including TCF/LEF1 transcription activity, Axin2 mRNA, phospho‐JNKThr183/Tyr185, and NFAT in brain endothelial cells (ECs) with the deletion of Wnt receptor Frizzled (Fzd)4 or Fzd6, the two most abundant Fzds in brain ECs. Next, we observed the effect of ischemia/reperfusion injury on Wnt signalings in brain ECs and adult mice. Last, we assessed the changes of non‐canonical Wnt signalings and BBB injury in the early stage of ischemic stroke in mice with endothelial β‐catenin activation (β‐cat mice).ResultsFzd4 or Fzd6 deletion dampened both Wnt/β‐catenin and Wnt/PCP signalings but enhanced Wnt/Ca2+ signaling in brain ECs. Both canonical and non‐canonical Wnt signalings in brain ECs were downregulated after ischemia/reperfusion injury in vitro and in vivo. Upregulating endothelial Wnt/β‐catenin signaling in β‐cat mice normalized the downregulated non‐canonical Wnt signalings, which did not compromise its protective effects on BBB integrity and endothelial tight junction following ischemic stroke.ConclusionsThe BBB protection induced by upregulation of endothelial Wnt/β‐catenin signaling may be not interfered by the normalization of non‐canonical Wnt signalings in the early stage of ischemic stroke.
Pharmacokinetic, pharmacodynamic, and immunogenic rationale for optimal dosing of pegvaliase, a PEGylated bacterial enzyme, in adult patients with phenylketonuria
Authors: Qi Yulan , Patel Gina , Henshaw Joshua , Gupta Soumi , Olbertz Joy , Larimore Kevin , Harding Cary O. , Merilainen Markus , Zori Roberto , Longo Nicola , Burton Barbara K. , Li Mingjin , Gu Zhonghua , Zoog Stephen J. , Weng Haoling H. , Schweighardt Becky 
Published: May 2021

AbstractPhenylketonuria (PKU), a deficiency in the activity of the enzyme phenylalanine hydroxylase, leads to toxic levels of phenylalanine (Phe) in the blood and brain. Pegvaliase (recombinant Anabaena variabilis phenylalanine ammonia lyase conjugated with polyethylene glycol) is approved to manage PKU in patients aged greater than or equal to 18 years in the United States and in patients aged greater than or equal to 16 years in the European Union. Pharmacokinetic, pharmacodynamic, and immunogenicity results from five open‐label pegvaliase trials were assessed. Studies with induction/titration/maintenance (I/T/M) dosing regimens demonstrated pharmacokinetic stabilization and sustained efficacy associated with maintenance doses (20, 40, or 60 mg/day). Immune‐mediated pegvaliase clearance was high during induction/titration phases when the early immune response was peaking. The combination of low drug dosage and high drug clearance led to low drug exposure and minimal decreases in blood Phe levels during induction/titration. Higher drug exposure and substantial reductions in blood Phe levels were observed later in treatment as drug clearance was reduced due to the maturation of the immune response, which allowed for increased dosing to target levels. The incidence of hypersensitivity reactions was temporally associated with the peaking of the early antidrug immune response and decreased with time as immune response matured after the first 6 months of treatment. These results support an I/T/M dosing regimen and suggest a strategy for administration of other nonhuman biologics to achieve efficacy and improve tolerability.
Potential benefit of vitamin D supplementation in people with respiratory illnesses, during the COVID‐19 pandemic
Authors: Chetty Vasudevan V. , Chetty Manoranjenni 
Published: May 2021

AbstractThis review describes the evidence for the potential benefit of vitamin D supplementation in people with respiratory diseases who may have a higher susceptibility to coronavirus disease 2019 (COVID‐19) infection and its consequences. Clinical evidence indicates that vitamin D may reduce the risk of both upper and lower respiratory tract infections and offers benefit particularly in people with vitamin D deficiency. Some evidence exists for a higher incidence of active tuberculosis (TB) in patients who are deficient in vitamin D. An association between low levels of 25(OH)D (the active form of vitamin D) and COVID‐19 severity of illness and mortality has also been reported. In addition, low 25(OH)D levels are associated with poor outcomes in acute respiratory distress syndrome (ARDS). The cytokine storm experienced in severe COVID‐19 infections results from excessive release of pro‐inflammatory cytokines. Due to its immunomodulatory effects, adequate vitamin D levels may cause a decrease in the pro‐inflammatory cytokines and an increase in the anti‐inflammatory cytokines during COVID‐19 infections. Vitamin D deficiency was found in 82.2% of hospitalized COVID‐19 cases and 47.2% of population‐based controls (p < 0.0001). The available evidence warrants an evaluation of vitamin D supplementation in susceptible populations with respiratory diseases, such as TB, and particularly in those who are deficient in vitamin D. This may mitigate against serious complications of COVID‐19 infections or reduce the impact of ARDS in those who have been infected.
Translational and pharmacokinetic‐pharmacodynamic application for the clinical development of GDC‐0334, a novel TRPA1 inhibitor
Authors: Chan Phyllis , Ding Han Ting , Liederer Bianca M. , Mao Jialin , Belloni Paula , Chen Liuxi , Gao Simon S. , Joseph Victory , Yang Xiaoying , Lin Joseph S. , Mitra Mayur S. , Putnam Wendy S. , Quartino Angelica , Bauer Rebecca N. , Pan Lin 
Published: May 2021

AbstractGDC‐0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC‐0334 were evaluated in this first‐in‐human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC‐0334 in guinea pigs, rats, dogs, and monkeys. Human PK and PK‐PD of GDC‐0334 were characterized after single and multiple oral dosing using a population modeling approach. The ability of GDC‐0334 to inhibit dermal blood flow (DBF) induced by topical administration of allyl isothiocyanate (AITC) was evaluated as a target‐engagement biomarker. Quantitative models were developed iteratively to refine the parameter estimates of the dose‐concentration‐effect relationships through stepwise estimation and extrapolation. Human PK analyses revealed that bioavailability, absorption rate constant, and lag time increase when GDC‐0334 was administered with food. The inhibitory effect of GDC‐0334 on the AITC‐induced DBF biomarker exhibited a clear sigmoid‐Emax relationship with GDC‐0334 plasma concentrations in humans. This study leveraged emerging preclinical and clinical data to enable iterative refinement of GDC‐0334 mathematical models throughout the FIH study for dose selection in subsequent cohorts throughout the study.
Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

GDC‐0334 is a novel, small molecule TRPA1 inhibitor and a pharmacokinetic‐pharmacodynamic (PK‐PD) modeling strategy could be implemented in a systematic and step‐wise manner to build and learn from emerging data for early clinical development.

WHAT QUESTION DID THIS STUDY ADDRESS?
Can noncompartmental and population‐based analyses be used to describe the PK and PD characteristics of GDC‐0334 in preclinical and clinical studies?

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
GDC‐0334 exposure generally increased with dose in rats, dogs, and monkeys. The starting dose (25 mg) in the clinical study was determined based on the preclinical data. GDC‐0334 exhibited linear PK in humans and the bioavailability was increased with food. The inhibitory effect of GDC‐0334 on dermal blood flow induced by the TRPA1 agonist allyl isothiocyanate in humans indicates a clear PK‐PD relationship.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
The models developed based on TRPA1 agonist‐induced dermal blood flow inhibition data can be used to predict PK‐PD relationships in future preclinical and clinical studies evaluating new drug entities that target TRPA1.
Investigating the Development and Reception of an Art Exhibition on the Theme of Early Modern Representations of Love
Authors: Krause Amanda E. , Davidson Jane W. 
Published: May 2021

AbstractCan the modern‐day art gallery visitor access the historical emotional meaning of what is viewed? The present investigation exploredLove: Art of Emotions, an exhibition curated and shown at the National Gallery of Victoria April–June 2017, which displayed a variety of artworks from the early modern period. The current article aimed to investigate both curator intentions and visitor reception of the exhibition. The project leader and the exhibition curator were interviewed about the aims of the exhibition and the steps implemented to realize its intentions. Materials such as the catalogue and exhibition labels were also subjected to a textual analysis to deepen understanding of the curatorial offerings. Additionally, 80 gallery visitors were asked about their subjective experiences of the exhibition. Thematic analysis of the curatorial team interviews and supporting materials from the exhibition identified how the exhibition was created, including coverage of the presenting the historical meaning of love, the selection of specific artworks to be exhibited, design aesthetics, layout and the additional materials presented to support the viewing experience. Thematic analyses of the impact of the exhibition on visitors highlighted overlap with the curatorial team’s intentions, demonstrating that some curatorial choices were apparent to gallery visitors and were also well received. A major exception was appreciation for a historical understanding of love. This was found to be less striking or memorable than the visitors’ own visceral and personal emotional response, such as an emotional reaction to the ambience, rather than to the historical meanings the work might have generated. These findings challenge curators to devise strategies that can help elicit historical understandings in exhibited art works as well as visceral emotional responses. This will project an understanding of art galleries as multi‐sensorial and also multi‐modal sites in which to experience the emotional impact of artworks through both a visceral and historical frame.
Does the Belt and Road Initiative Increase the Carbon Emission Intensity of Participating Countries?
Authors: Wu Yan , Chen Chunlai , Hu Cong 
Published: May 2021

AbstractThe impact that the Belt and Road Initiative (BRI) has had on carbon emissions is a hotly debated issue. Using a panel dataset of 178 countries from 2002 to 2017, and applying the quantile difference‐in‐difference method in different industries, this study finds that, first, the BRI overall tends to reduce the carbon emission intensity of BRI countries. Second, the impact of BRI on reducing the carbon emission intensity is significant for BRI countries at higher (0.8 and 0.9) and lower (0.2 and 0.3) carbon emission intensity quantiles but it is insignificant for those at medium levels. Third, the BRI has significant impacts on reducing carbon emission intensity in the energy‐intensive industries, and this effect is the highest at the quantile level of 0.9 for all three industries considered here: transportation, electric and heating, and manufacturing and construction. These results indicate that establishing BRI cooperation with China will improve the environment and enhance the sustainable development ability of BRI countries.