bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID‐19‐related medicine utilization study in pregnancy: The COVI‐PREG cohort
Authors: Favre Guillaume , Gerbier Eva , Maisonneuve Emeline , Pomar Léo , Winterfeld Ursula , Lepigeon Karine , Bloemenkamp Kitty W. M. , de Bruin Odette , Hurley Eimir , Nordeng Hedvig , Siiskonen Satu J. , Sturkenboom Miriam C. J. M. , Baud David , Panchaud Alice ,   the COVI‐PREG and CONSIGN group
Published: November 2022

AimThe objective of this study was to describe the use of COVID‐19‐related medicines during pregnancy and their evolution between the early/late periods of the pandemic.MethodsPregnant women who tested positive for SARS‐CoV‐2 from March 2020 to July 2021 were included using the COVI‐PREG registry. Exposure to the following COVID‐19‐related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti‐interleukin‐6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID‐19 severity level and early/late period of the pandemic (before and after 1 July 2020).FindingsWe included 1964 pregnant patients who tested positive for SARS‐CoV‐2. Overall, 10.4% (205/1964) received at least one COVID‐19‐related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti‐interleukin‐6 (0.3%; 5/1964). The use of at least one COVID‐19‐related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID‐19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period.ConclusionMedicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID‐19‐related medicines in pregnancy.
Pharmacokinetic and pharmacodynamic interaction between DWP16001, an sodium–glucose cotransporter 2 inhibitor and metformin in healthy subjects
Authors: Kim Byungwook , Huh Ki Young , Hwang Jun Gi , Nah JaeJin , Huh Wan , Cho Jae Min , Jang In‐Jin , Yu Kyung‐Sang , Kim Yun , Lee SeungHwan 
Published: November 2022

AimsDWP16001 is a novel sodium–glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes with selective and sustained sodium–glucose cotransporter 2 inhibition. We aimed to evaluate whether the coadministration of DWP16001 and metformin causes any changes in pharmacokinetics (PK) or pharmacodynamics (PD).MethodsA randomized, open‐label, single‐ and multiple‐dose, 2‐sequence, crossover study was conducted in healthy male subjects. Subjects received the following treatments: a single oral dose of DWP16001 (DWP) 2 mg, metformin immediate release 1000 mg (MET) twice daily for 7 days and a single oral dose of DWP and MET at steady‐state for metformin (DWP+MET). Serial blood and interval urine were collected for PK and PD analyses. Safety and tolerability profiles were assessed throughout the study.ResultsDWP+MET displayed increased peak concentration and area under the concentration–time curve from time 0 to time of the last quantifiable concentration compared with DWP (per standard bioequivalence boundaries, 0.8–1.25); the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) were 1.22 (1.13–1.31) and 1.09 (1.05–1.14), respectively. DWP+MET and MET showed similar peak concentration and area under the concentration–time curve within a dosing interval at steady state for metformin; the GMRs and 90% CIs were 0.98 (0.90–1.06) and 1.05 (0.98–1.13), respectively. The amount of urinary glucose excretion from time 0 to 144 h was also comparable between DWP+MET and DWP (GMR and 90% CI; 0.99, 0.94–1.05).ConclusionThe results suggest that DWP16001 and metformin could be coadministered without clinically relevant PK and PD interactions.
In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review
Authors: Drennan Philip G. , Karponis Dimitrios , Richards Duncan , Coles Mark , Fullerton James N. 
Published: November 2022

AbstractExperimental exposure of healthy volunteers to the T‐cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational medicinal product (IMP) pharmacology prior to the recruitment of patient populations. Despite widespread use, no standardized approach to the design and conduct of such studies has been agreed. The objective of this systematic review was to survey the published literature where KLH was used as a challenge agent, describing methodology, therapeutic targets addressed, and pharmacodynamic outcome measures. We searched MEDLINE, EMBASE, clinicaltrials.gov, and Cochrane CENTRAL for studies using KLH challenge in humans between January 1, 1994, and April 1, 2022. We described key study features, including KLH formulation, dose, use of adjuvants, route of administration, co‐administered IMPs, and end points. Of 2421 titles and abstracts screened, 46 met the inclusion criteria, including 14 (31%) early phase trials of IMP, of which 10 (71%) targeted T‐cell co‐stimulation. IMPs with diverse mechanisms demonstrated modulation of the humoral response to KLH, suggesting limited specificity of this end point. Two early phase IMP studies (14%) described the response to intradermal re‐challenge (delayed type hypersensitivity). Challenge regimens for IMP assessment were often incompletely described, and exhibited marked heterogeneity, including primary KLH dose (25‐fold variation: 100–2500 mcg), KLH formulation, and co‐administration with adjuvants. Methodological heterogeneity and failure to exploit the access to tissue‐level mechanism‐relevant end points afforded by KLH challenge has impaired the translational utility of this paradigm to date. Future standardization, characterization, and methodological development is required to permit tailored, appropriately powered, mechanism‐dependent study design to optimize drug development decisions.
Developmental changes in the categorization of speech and song
Authors: Vanden Bosch der Nederlanden Christina M. , Qi Xin , Sequeira Sarah , Seth Prakhar , Grahn Jessica A. , Joanisse Marc F. , Hannon Erin E. 
Published: November 2022

AbstractMusic and language are two fundamental forms of human communication. Many studies examine the development of music‐ and language‐specific knowledge, but few studies compare how listeners know they are listening to music or language. Although we readily differentiate these domains, how we distinguish music and language—and especially speech and song— is not obvious. In two studies, we asked how listeners categorize speech and song. Study 1 used online survey data to illustrate that 4‐ to 17‐year‐olds and adults have verbalizable distinctions for speech and song. At all ages, listeners described speech and song differences based on acoustic features, but compared with older children, 4‐ to 7‐year‐olds more often used volume to describe differences, suggesting that they are still learning to identify the features most useful for differentiating speech from song. Study 2 used a perceptual categorization task to demonstrate that 4–8‐year‐olds and adults readily categorize speech and song, but this ability improves with age especially for identifying song. Despite generally rating song as more speech‐like, 4‐ and 6‐year‐olds rated ambiguous speech–song stimuli as more song‐like than 8‐year‐olds and adults. Four acoustic features predicted song ratings: F0 instability, utterance duration, harmonicity, and spectral flux. However, 4‐ and 6‐year‐olds’ song ratings were better predicted by F0 instability than by harmonicity and utterance duration. These studies characterize how children develop conceptual and perceptual understandings of speech and song and suggest that children under age 8 are still learning what features are important for categorizing utterances as speech or song.Research Highlights
Children and adults conceptually and perceptually categorize speech and song from age 4.
Listeners use F0 instability, harmonicity, spectral flux, and utterance duration to determine whether vocal stimuli sound like song.
Acoustic cue weighting changes with age, becoming adult‐like at age 8 for perceptual categorization and at age 12 for conceptual differentiation.
Young children are still learning to categorize speech and song, which leaves open the possibility that music‐ and language‐specific skills are not so domain‐specific.
Public governance and firm total factor productivity: Evidence from a quasi‐natural event in China
Authors: Cheng Maoyong , Li Zhenjun 
Published: November 2022

AbstractEmploying a quasi‐natural event, that is, gangdom and evil forces (GEs) elimination in China, we examine how public governance proxied by GEs elimination affects firm total factor productivity (TFP) using data on Chinese‐listed firms between 2009 and 2020. Our findings show that GEs elimination significantly reduces firm TFP through two complementary channels: increase in environmental uncertainty and the weakening of the protective umbrella. We also reveal that the effects of GEs elimination on firm TFP are more prominent in SOEs and in firms exposed to weaker media attention. Our main results pass a series of robustness and endogeneity checks. We provide clear policy implications to regulators by identifying firm‐level evidence.
Soil fertility shifts the relative importance of saprotrophic and mycorrhizal fungi for maintaining ecosystem stability
Authors: Zhang Hongjin , Dong Lizheng , Yao Xiaodong , Wang Wei 
Published: November 2022

AbstractSoil microbial communities are essential for regulating the dynamics of plant productivity. However, how soil microbes mediate temporal stability of plant productivity at large scales across various soil fertility conditions remains unclear. Here, we combined a regional survey of 51 sites in the temperate grasslands of northern China with a global grassland survey of 120 sites to assess the potential roles of soil microbial diversity in regulating ecosystem stability. The temporal stability of plant productivity was quantified as the ratio of the mean normalized difference vegetation index to its standard deviation. Soil fungal diversity, but not bacterial diversity, was positively associated with ecosystem stability, and particular fungal functional groups determined ecosystem stability under contrasting conditions of soil fertility. The richness of soil fungal saprobes was positively correlated with ecosystem stability under high‐fertility conditions, while a positive relationship was observed with the richness of mycorrhizal fungi under low‐fertility conditions. These relationships were maintained after accounting for plant diversity and environmental factors. Our findings highlight the essential role of fungal diversity in maintaining stable grassland productivity, and suggest that future studies incorporating fungal functional groups into biodiversity–stability relationships will advance our understanding of their linkages under different fertility conditions.
Stress rupture of SiC/SiC composite tubes under high‐temperature steam
Authors: Koyanagi Takaaki , Karakoc Omer , Hawkins Charles , Lara‐Curzio Edgar , Deck Christian , Katoh Yutai 
Published: November 2022

AbstractSiC‐fiber–reinforced SiC matrix composite cladding for light water reactor fuel elements must withstand high‐temperature steam oxidation in a loss‐of‐coolant accident scenario (LOCA). Current composite designs include an outer monolithic SiC layer, in part, to increase steam oxidation resistance. However, it is not clear how such a structure would behave under high‐temperature steam in the case when the monolithic layer cracks and carbon interphases and SiC fibers are exposed to the environment. To fill this knowledge gap, stress‐rupture tests of prototypic SiC composite cladding at 1000°C under steam and inert environments were conducted. The applied stress was ∼120 MPa, which was beyond the initial cracking stress. The failure lifetime under steam was 400–1300 s, while 75% of the composite specimens did not fail after 3 h of total exposure under inert gases. Microstructural observations suggest that steam oxidation activated slow crack growth in the fibers, which led to failure of the composite. The results from this study suggest that stress rupture in steam environments could be a limiting factor of the cladding under reactor LOCA conditions.
ARID1A downregulation promotes cell proliferation and migration of colon cancer via VIM activation and CDH1 suppression
Authors: Baldi Salem , Zhang Qianshi , Zhang Zhenyu , Safi Mohammed , Khamgan Hassan , Wu Han , Zhang Mengyan , Qian Yuanyuan , Gao Yina , Shopit Abdullah , Al‐Danakh Abdullah , Alradhi Mohammed , Al‐Nusaif Murad , Zuo Yunfei 
Published: November 2022

AbstractAccording to our prior findings, ARID1A expression is decreased in colon cancer, which has a poor prognosis. In this study, we investigated the ARID1A‐VIM/CDH1 signalling axis's role in colon cancer proliferation and migration. The differentially expressed genes in cells that might be controlled by ARID1A were discovered by a database screening for ARID1A knockout. qPCR was used to analyse ARID1A and EMT markers expression levels in colon cancer. We utilized siRNA RID1A to explore the influence of ARID1A silencing on EMT in CRC cells. The function of ARID1A in the colon was investigated utilizing the wound healing, transwell and CCK‐8 WST‐ assays. The molecular mechanism by which ARID1A regulates VIM and CDH1 was elucidated using chip‐qPCR. Numerous genes involved in EMT were dysregulated in the absence of ARID1A. VIM expression increased in cells lacking ARID1A expression and vice versa. Many COAD samples with high ARID1A mRNA expression had low VIM mRNA expression, despite the relevance. CDH1 gene was positively correlated with ARID1A. Moreover, siRNA‐ARID1A‐transfected cells accelerated cell migration and invasion and increased cell proliferation rate in vitro. Chip‐qPCR analysis showed that ARID1A binds to the promoters of both genes and changes their expression in colon cancer. ARID1A inactivation is associated with VIM activation and CDH1 suppression, which might serve as crucial molecules influencing COAD prognosis, accelerate tumour progression, and shorten patients' survival time, and promote metastases of COAD. Thus, depletion of ARID1A can be therapeutically exploited by targeting downstream effects to improve cancer treatment‐related outcomes.
A ‘Geopolitical Commission’: Supranationalism Meets Global Power Competition
Authors: Haroche Pierre 
Published: November 2022

AbstractThis article examines the origins and operationalisation of the concept of a ‘geopolitical Commission’, which has been promoted by President of the European Commission Ursula von der Leyen since 2019. This concept has been used to guide the stronger co‐ordination of the external aspects of the Commission's work. It is also symptomatic of the growing role of strategic considerations in the Commission's recent initiatives, particularly through the objective of strengthening the EU's ‘open strategic autonomy’. To explain this phenomenon, I combine three different theoretical perspectives: neorealism, neofunctionalism, and geoeconomics. I conclude that the geopolitical Commission should be understood as the result of the interactions between exogenous factors – the intensification of global power competition and the rise of geoeconomic strategies – and endogenous factors, such as the rivalry between the Commission and the European External Action Service and the functional link between the Commission's economic powers and international security issues.
Shared decision‐making in the realm of uncertainty: The example of coronary artery disease through an EBM and complexity science lens
Authors: Sturmberg Joachim P. , Kissling Bruno , Kühlein Thomas 
Published: November 2022

AbstractPatients look to their clinicians for explanations and treatments that achieve predictable cures with certainty. Clinicians usually respond accordingly. Acknowledging uncertainty, while necessary, is difficult, anxiety‐provoking and at times overwhelming for patients and clinicians alike. We here present three case studies to illustrate the uncertainties of managing patients with potentially life‐threatening illnesses. Research aims to provide answers to clinical problems. But, conducting research almost inevitably entails a reduction of real‐world complexities. Research ultimately can only provide ‘partial or in general answers’ mostly revealing new questions. Due to the complexity of clinical care, research cannot really achieve certainty and predictability for an individual within his specific living context and values. In an unavoidably uncertain environment, instead of oversimplifying, clinicians like patients—as far as possible—ought to better embrace a complexity thinking frame. This provides a deeper understanding how living bodies function as‐a‐whole within their living contexts. Uncertainty and unpredictability, being inherent elements of complexity thinking, cannot be overcome. However, it may be made easier to cope with uncertainty by at least adopting the thinking in probabilities for benefits and harms of patient related outcomes as introduced in Sackett's Evidence‐Based Medicine framework. Through the lenses of evidence‐based medicine and complexity sciences this paper critically explores the clinical management of three patients diagnosed as having coronary artery disease. They all received the same treatment even though they presented with very different clinical complaints arising from different disease manifestations. Looking at these case studies the authors reflect on the reasons behind this astonishing, but widely seen medical behaviour of ‘one size fits all’. They critically reflect the importance of research and evidence in view of a person‐centred solution.
A recombinant baculovirus vector vaccine (BacMCP) against the infectious spleen and kidney necrosis virus (ISKNV)
Authors: Zhu Min , Shen Zeen , Gu Yuchao , Tong Xinyu , Zhang Yaxin , Pan Jun , Feng Yongjie , Hu Xiaolong , Wang Yujun , Cao Guangli , Xue Renyu , Gong Chengliang 
Published: November 2022

AbstractThe infectious spleen and kidney necrosis virus (ISKNV) is a highly lethal virus, which has brought significant losses to aquaculture. Therefore, a new vaccine against ISKNV with high efficiency, safety and convenience must be developed. While baculoviruses are more commonly used as protein expression systems for vaccine antigen production, this paper used baculovirus technology to develop a live‐vector vaccine, BacMCP, which contains the coding sequence of the major capsid protein (MCP) (GenBank accession no. AF371960) of ISKNV and is driven by a CMV promoter. Real‐time PCR and immunofluorescence showed that the MCP gene was successfully delivered to and expressed in fish cells and tissues inoculated with BacMCP. Immune‐related gene (IgM, TGF‐β, IL‐1, IL‐8, TNF‐α) expression was induced in BacMCP‐treated groups of largemouth bass compared with control groups. Specific antibodies could be detected in the serum of BacMCP injection‐vaccinated largemouth bass by ELISA. After injection or immersion vaccination with BacMCP for 21 days, largemouth bass were infected with ISKNV. The immune effect of the injected immunization on fish in different sizes was evaluated. The vaccine efficacy of injection‐vaccinated bass was 100% in small bass and 85.7% in large bass. The vaccine efficacy of immersion‐vaccinated small bass was 77.3%. This study suggested that BacMCP can be used as a vector‐based vaccine candidate to prevent the diseases caused by ISKNV infection.
Lianas rapidly colonize early stages of tropical forests, presumably through leaf trait diversification
Authors: Mumbanza Francis M. , Bauters Marijn , Makelele Isaac , Meunier Félicien , Kearsley Elizabeth , Boeckx Pascal , Verheyen Kris , Ewango Corneille , Mbula Innocent M. , Lubini Constantin A. , Verbeeck Hans 
Published: November 2022

AbstractQuestionsEcological succession is the process during which ecosystems recover after disturbances. Studies investigating community reassembly during tropical forest succession have rarely compared lianas to trees. We addressed two questions: (1) how do changes in stem density, total basal area and species richness of lianas and trees compare throughout a secondary succession, and to what extent does the relative basal area of lianas change along a secondary succession; and (2) how do the successional trajectories of functional community trait values of lianas and trees compare?LocationYoko forest reserve, central Congo basin.MethodsUsing univariate Bayesian modeling techniques, we analyzed differences in successional pathways between lianas and trees in terms of community structure, and functional assembly in a replicated chronosequence spanning from young to old‐growth forests.ResultsWe found divergent structural trajectories between lianas and trees along the forest chronosequence. The stem density of lianas peaked at the intermediate stage, while that of trees almost linearly decreased from early to late stages of succession. The basal area of lianas increased at a higher rate than that of trees, which translated into a marginal increase of liana relative basal area over succession. On the contrary, we observed a lower rate of increase in species richness for lianas than trees over succession. We found a progressive convergence in the responses of lianas and trees to changes with succession in terms of specific leaf area and leaf nitrogen content, but a diverging response in terms of leaf phosphorus content. These functional composition patterns most probably resulted from environmental filtering, induced by a change from nitrogen to phosphorus limitation as the succession progressed to a mature forest.ConclusionsThese findings underscore the rapid colonization of tropical forests by lianas after agricultural abandonment, presumably by deploying a more diverse leaf economic spectrum early in succession.
The Aer2 chemoreceptor from Vibrio vulnificus is a tri‐PAS‐heme oxygen sensor
Authors: Stuffle Erwin C. , Suzuki Tise , Orillard Emilie , Watts Kylie J. 
Published: November 2022

AbstractThe marine pathogen Vibrio vulnificus senses and responds to environmental stimuli via two chemosensory systems and 42–53 chemoreceptors. Here, we present an analysis of the V. vulnificus Aer2 chemoreceptor, VvAer2, which is the first V. vulnificus chemoreceptor to be characterized. VvAer2 is related to the Aer2 receptors of other gammaproteobacteria, but uncharacteristically contains three PAS domains (PAS1‐3), rather than one or two. Using an E. coli chemotaxis hijack assay, we determined that VvAer2, like other Aer2 receptors, senses and responds to O2. All three VvAer2 PAS domains bound pentacoordinate b‐type heme and exhibited similar O2 affinities. PAS2 and PAS3 both stabilized O2 via conserved Iβ‐Trp residues, but PAS1, which was easily oxidized in vitro, was unaffected by Iβ‐Trp replacement. Our results support a model in which PAS1 is largely dispensable for O2‐mediated signaling, whereas PAS2 modulates PAS3 signaling, and PAS3 signals to the downstream domains. Each PAS domain appeared to be positionally optimized, because PAS swapping caused altered signaling properties, and neither PAS1 nor PAS2 could replace PAS3. Our findings strengthen previous conclusions that Aer2 receptors are O2 sensors, but with distinct N‐terminal domain arrangements that facilitate, modulate and tune responses based on environmental signals.