bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I, first‐in‐human, randomized dose‐escalation study of anti‐activated factor XII monoclonal antibody garadacimab
Authors: McKenzie Andrew , Roberts Anthony , Malandkar Sourabh , Feuersenger Henrike , Panousis Con , Pawaskar Dipti 
Published: December 2021

AbstractFactor XII (FXII) is the principal initiator of the plasma contact system and has proinflammatory and prothrombotic activities. This single‐center, first‐in‐human phase I study aimed to assess the safety and tolerability of single escalating doses of garadacimab, a monoclonal antibody that specifically inhibits activated FXII (FXIIa), in healthy male volunteers. Volunteers were randomized to eight cohorts, with intravenous (i.v.) doses of 0.1, 0.3, 1, 3, and 10 mg/kg and subcutaneous (s.c.) doses of 1, 3, and 10 mg/kg. Six volunteers in each cohort received garadacimab or placebo in a ratio of 2:1. Follow‐up for safety lasted 85 days after dosing. Blood samples were collected throughout for pharmacokinetic/pharmacodynamic analysis. Forty‐eight volunteers were enrolled: 32 received garadacimab and 16 received placebo. Most volunteers experienced at least one treatment‐emergent adverse event (TEAE), predominantly grade 1. No serious TEAEs, deaths, or TEAEs leading to discontinuation were reported. No volunteers tested positive for garadacimab antidrug antibodies. Garadacimab plasma concentrations increased in a dose‐dependent manner. Sustained inhibition of FXIIa‐mediated kallikrein activity beyond day 28 resulted from 3 and 10 mg/kg garadacimab (i.v. and s.c.). A dose‐dependent increase in activated partial thromboplastin time with no change in prothrombin time was demonstrated. Garadacimab (single‐dose i.v. and s.c.) was well‐tolerated in healthy volunteers. Dose‐dependent increases in plasma concentration and pharmacodynamic effects in relevant kinin and coagulation pathways were observed. These results support the clinical development of garadacimab, including in phase II studies in hereditary angioedema and coronavirus disease 2019 (COVID‐19).
A case of cutaneous syncytial myoepithelioma with extensive adipocytic metaplasia: Usefulness of EWSR1‐PBX3 gene fusion analysis
Authors: Shimada Kanade , Ansai Osamu , Katsumi Tatsuya , Deguchi Tokiko , Hayashi Ryota , Yuki Akihiko , Nakamura Mai , Umezu Hajime , Fukumoto Takaya , Ansai Shin‐Ichi , Abe Riichiro 
Published: December 2021

AbstractCutaneous syncytial myoepithelioma (CSM) is a recently recognized variant of myoepithelioma characterized by an intradermal syncytial proliferation of spindled, ovoid, and histiocytoid cells. Immunohistochemically, tumor cells usually show strong expression of S‐100 protein and epithelial membrane antigen (EMA). Here we report a case of CSM in the thigh of a 51‐year‐old Japanese woman. Histopathological findings showed a sheet‐like growth of ovoid cells and histiocytoid cells with an eosinophilic syncytial cytoplasm, and adipocytic metaplasia was widely observed in the tumor. Immunohistochemical staining revealed a diffuse, strong pattern for EMA, smooth muscle actin (SMA), and HHF35, and variable expression of S‐100 protein and p63 in ovoid and histiocytoid cells without significant mitotic figures or pleomorphism. In addition, EWSR1‐PBX3 gene fusion, which is characteristic of CSM, was observed in the tumor. Based on these findings, we diagnosed the patient as having CSM. Our case shows that CSM can exhibit extensive adipocytic metaplasia, which could make its histopathological diagnosis challenging.
Legislative, delegated acts, comitology and interinstitutional conundrum in EU law – configuring EU normative spaces
Authors: Türk Alexander H. 
Published: December 2021

AbstractThis article seeks to contribute to The Conference on the Future of Europe by arguing that its debates on substantive policies and democratic foundations cannot be detached from consideration being given to the configuration of the Union's normative spaces in which those policies will be developed and implemented. In its current stage of development, we can find in the Union legal system two competing conceptions for the configuration of its different normative spaces, one that relies on the Member States for resources and legitimacy and another that intends to free itself from those constraints. This article will argue that a uniquely European model of governance will benefit from the integration of both conceptions in the configuration of its normative spaces, not only where they are provided for by the Union Treaties but also where they have developed in the shadow of those official spaces, which they complement and increasingly supplant.
Gross primary productivity and water use efficiency are increasing in a high rainfall tropical savanna
Authors: Hutley Lindsay B. , Beringer Jason , Fatichi Simone , Schymanski Stanislaus J. , Northwood Matthew 
Published: December 2021

AbstractDespite their size and contribution to the global carbon cycle, we have limited understanding of tropical savannas and their current trajectory with climate change and anthropogenic pressures. Here we examined interannual variability and externally forced long‐term changes in carbon and water exchange from a high rainfall savanna site in the seasonal tropics of north Australia. We used an 18‐year flux data time series (2001–2019) to detect trends and drivers of fluxes of carbon and water. Significant positive trends in gross primary productivity (GPP, 15.4 g C m2 year−2), ecosystem respiration (Reco, 8.0 g C m2 year−2), net ecosystem productivity (NEE, 7.4 g C m2 year−2) and ecosystem water use efficiency (WUE, 0.0077 g C kg H2O−1 year−1) were computed. There was a weaker, non‐significant trend in latent energy exchange (LE, 0.34 W m−2 year−1). Rainfall from a nearby site increased statistically over a 45‐year period during the observation period. To examine the dominant drivers of changes in GPP and WUE, we used a random forest approach and a terrestrial biosphere model to conduct an attribution experiment. Radiant energy was the dominant driver of wet season fluxes, whereas soil water content dominated dry season fluxes. The model attribution suggested that [CO2], precipitation and Tair accounting for 90% of the modelled trend in GPP and WUE. Positive trends in fluxes were largest in the dry season implying tree components were a larger contributor than the grassy understorey. Fluxes and environmental drivers were not significant during the wet season, the period when grasses are active. The site is potentially still recovering from a cyclone 45 years ago and regrowth from this event may also be contributing to the observed trends in sequestration, highlighting the need to understand fluxes and their drivers from sub‐diurnal to decadal scales.
Cross‐sector partnerships: Mapping the field and advancing an institutional approach
Authors: Vogel Rick , Göbel Markus , Grewe‐Salfeld Marit , Herbert Barbara , Matsuo Yuka , Weber Christiana 
Published: December 2021

AbstractCross‐sector partnerships (CSPs) addressing economic, social, and environmental issues continue to be a vibrant topic in management research and beyond. However, compared to the exogenous factors that drive collaborative advantage through structures and governance, the endogenous problems of collaborating across different institutional logics, residing at the micro‐level of interactions among partners from the business, government, and nonprofit sectors, have received scant attention. The preoccupation with success factors often leads to a bias toward the problem‐solving capacities of CSPs at the neglect of the considerable barriers to successful collaboration across sectors. This study addresses this shortcoming and extracts an institutional approach of CSPs from an integrative review of the literature combining bibliometric methods with qualitative reviewing. A bibliometric map shows how the literature is divided into several clusters, each addressing a specific type of CSP but not engaging much in exchange with other clusters. Zooming in on the clusters provides a more nuanced picture of how institutional theory has hitherto been applied to CSPs. We build on these pieces of the puzzle and assemble them into a preliminary framework that accounts for inter‐institutional conflicts in CSPs and actor‐level responses to these conflicts. Our framework introduces a new analytical platform that facilitates multi‐level research, bringing the micro‐level of individual actors back in and connecting it with institutional frames at the macro‐level.
Trois mécanismes de gouvernance pour remédier aux déficits de travail décent dans les chaînes de valeur mondiales
Authors: ANNER Mark 
Published: December 2021

RésuméGereffi et Lee (2016) distinguent six mécanismes de gouvernance susceptibles de remédier aux déficits de travail décent dans les chaînes de valeur mondiales. En s'appuyant sur des travaux relatifs au Viet Nam, au Honduras et au Bangladesh, l'auteur affirme que, pour être véritablement efficace, la gouvernance en question doit permettre de rééquilibrer le rapport de force entre les partenaires en présence. Trois mécanismes remplissent cette condition: la gouvernance publique, les conventions collectives de large portée et les accords multipartites globaux contraignants. L'option la plus adaptée dépend du régime de relations professionnelles et des caractéristiques et stratégies du mouvement ouvrier dans le pays.
Development of structural descriptors to predict dissolution rate of volcanic glasses: Molecular dynamic simulations
Authors: Gong Kai , Olivetti Elsa A. 
Published: December 2021

AbstractEstablishing the composition–structure–property relationships for amorphous materials is critical for many important natural and engineering processes, including the dissolution of highly complex volcanic glasses. In this investigation, we performed force field molecular dynamics (MD) simulations to generate detailed structural representations for 10 natural CaO–MgO–Al2O3–SiO2–TiO2–FeO–Fe2O3–Na2O–K2O glasses with compositions ranging from rhyolitic to basaltic. Based on the resulting atomic structural representations at 300 K, we have calculated the partial radial distribution functions, nearest interatomic distances and coordination number, which are consistent with the literature data on silicate‐based glasses. Based on these structural attributes and classical bond valence models, we have introduced a novel structural descriptor, that is, average metal–oxygen (M–O) bond strength parameter, which has captured the log dissolution rates of the 10 glasses at both acidic and basic conditions (based on literature data) with R2 values of ∼0.80–0.92 based on linear regression. This structural descriptor is seen to outperform several other structural descriptors also derived from MD simulation results, including the average metal oxide dissociation energy, the average self‐diffusion coefficient of all the atoms at 2000 K, and the energy barrier of self‐diffusion. Furthermore, we showed that the MD‐derived descriptors generally exhibit better predictive performance than the degree of depolymerization parameter commonly used to describe glass and mineral reactivity. The results suggest that the structural descriptors derived from MD simulations, especially the average M–O bond strength parameter, are promising structural descriptors for connecting composition with dissolution rates of highly complex natural glasses.
Production and characterization of naturally occurring antibacterial magnetite nanoparticles from magnetotactic Bacillus sp. MTB17
Authors: Rajalakshmi Arumugam , Ramesh Manickam , Divya Ellappan , Kavitha Kuppuswamy , Puvanakrishnan Rengarajulu , Ramesh Balasubramanian 
Published: December 2021

Abstract

Aims
This study envisaged the isolation and characterization of magnetite nanoparticles (MNPs) from magnetotactic bacteria (MTB) and the evaluation of their antibacterial efficacy.

Methods and Results
MNPs were extracted from 20 motile but morphologically different MTB, and they were subjected to antibacterial activity assay. These MNPs were found to be highly effective against Vibrio cholerae. MTB17 was considered as the potent MTB strain based on the antibacterial activity. The MNPs of MTB17 were isolated and validated by UV-Visible spectroscopy, particle size analysis, FTIR analysis, and PXRD.

Conclusions
Isolation and characterization of ~85 nm MNPs from MTB is reported, and it is highly active against all the gram-positive and gram-negative strains tested.

Significance and Impact of the Study
This study focuses on a novel use of biogenic magnetite MNPs as an antibacterial agent, which can be further explored using in vivo studies.
Effects of water activity, ammonia and Corynebacterium urealyticum on the survival of Salmonella Typhimurium in sterile poultry litter
Authors: Gutierrez Alan , Schneider Keith R. 
Published: December 2021

Abstract

Aims
This study examined the effects of water activity (aw), ammonia and Corynebacterium urealyticum on the survival of Salmonella Typhimurium in sterile poultry litter.

Methods and Results
Sterile poultry litter inoculated with S. Typhimurium was adjusted to pH 9.0, various aw levels (0.84, 0.92 and 0.96), and total ammonia nitrogen levels were increased either by the addition of ammonium sulphate or C. urealyticum inoculation with 1% urea added. All litter treatments were incubated at 30°C and sampled daily for five days. Similar results were observed at each aw level in both experiments. At 0.84 and 0.92 aw, S. Typhimurium populations in litter fell below 1 log CFU g−1 within 5 days, with no significant differences between the controls and increased ammonia treatments. At 0.96 aw, Salmonella populations treated with increased ammonia levels were significantly lower than control treatments on days 1–5.

Conclusions
This study showed that C. urealyticum can produce ammonia in litter at higher aw levels with sufficient available urea and that the antimicrobial efficacy of ammonia is dependent on high aw (~0.96) in litter.

Significance and Impact of the Study
These results provide insights into the production of ammonia in litter, its antimicrobial efficacy in litter and the importance of aw in this interaction.
Population genomics indicates micro‐refuges and riverine barriers for a southern South American grassland nightshade
Authors: Giudicelli Giovanna C. , Turchetto Caroline , Guzmán‐Rodriguez Sebastián , Teixeira Marcelo C. , Petzold Earl , Bombarely Aureliano , Freitas Loreta B. 
Published: December 2021

AbstractAimPleistocene climate oscillations influenced the species distribution and genetic diversity in grasslands, and such climatic changes promoted expansion and contraction cycles, leading to fragmentation and isolation of evolutionary lineages in refuges. This study aimed to infer the evolutionary processes that most influenced the genetic diversity of a South American nightshade Petunia inhabiting subtropical grasslands under the Pleistocene influence.LocationPampa and Chaco.TaxonThe widely distributed herb Petunia axillaris subsp. parodii (Solanaceae).MethodsWe obtained high‐density genome coverage throughout the geographical distribution of Petunia axillaris subsp. parodii. We estimated the genetic diversity and structure to evaluate population differentiation and applied a model‐based demographic analysis to investigate the scenarios that could have influenced the species' evolutionary history. We evaluated the association between neutral and outlier polymorphisms with environmental variables to distinguish the influence of the geographical distance and environmental differences between populations.ResultsThere are three evolutionary lineages in P. axillaris subsp. parodii. The origin and differentiation of these lineages were related to the Pleistocene refuges and rivers acting as barriers to gene flow. We also identified 496 outlier loci related to adaptation to environmental conditions.Main conclusionThe Pleistocene climate changes drove lineage diversification isolated in micro‐refugia. Rivers and changes in their courses may have also acted on the population divergence, serving as barriers to gene flow or even as corridors for species range expansion. These findings contribute to the knowledge of the evolutionary processes that influenced the lineage diversification of South American subtropical grassland species.
Chlamydia trachomatis induces lncRNA MIAT upregulation to regulate mitochondria‐mediated host cell apoptosis and chlamydial development
Authors: Luo Fangzhen , Wen Yating , Zhao Lanhua , Su Shengmei , Zhao Yuqi , Lei Wenbo , Li Zhongyu 
Published: December 2021

AbstractChlamydia trachomatis persistent infection is the leading cause of male prostatitis and female genital tract diseases. Inhibition of host cell apoptosis is the key to maintaining Chlamydia survival in vivo, and long noncoding RNAs (lncRNAs) play important roles in its developmental cycle and pathogenesis. However, it is not clear how lncRNAs regulate persistent Chlamydia infection. Here, using a microarray method, we identified 1718 lncRNAs and 1741 mRNAs differentially expressed in IFN‐γ‐induced persistent C. trachomatis infection. Subsequently, 10 upregulated and 5 downregulated differentially expressed lncRNAs were verified by qRT–PCR to confirm the reliability of the chip data. The GO and KEGG analyses revealed that differentially regulated transcripts were predominantly involved in various signalling pathways related to host immunity and apoptosis response. Targeted silencing of three lncRNAs (MIAT, ZEB1‐AS1 and IRF1) resulted in increased apoptosis rates. Furthermore, interference with lncRNA MIAT caused not only an obvious downregulation of the Bcl‐2/Bax ratio but also a marked release of cytochrome c, resulting in a significantly elevated level of caspase‐3 activation. Meanwhile, MIAT was involved in the regulation of chlamydial development during the persistent infection. Collectively, these observations shed light on the enormous complex lncRNA regulatory networks involved in mitochondria‐mediated host cell apoptosis and the growth and development of C. trachomatis.
Advances in the study of CDC42 in the female reproductive system
Authors: Mei Qiaojuan , Li Huiying , Liu Yu , Wang Xiaofei , Xiang Wenpei 
Published: December 2021

AbstractCDC42 is a member of the Rho‐GTPase family and is involved in a variety of cellular functions including regulation of cell cycle progression, constitution of the actin backbone and membrane transport. In particular, CDC42 plays a key role in the establishment of polarity in female vertebrate oocytes, and essential to this major regulatory role is its local occupation of specific regions of the cell to ensure that the contractile ring is assembled at the right time and place to ensure proper gametogenesis. The multifactor controlled ‘inactivation‐activation’ process of CDC42 also allows it to play an important role in the multilevel signalling network, and the synergistic regulation of multiple genes ensures maximum precision during gametogenesis. The purpose of this paper is to review the role of CDC42 in the control of gametogenesis and to explore its related mechanisms, with the aim of further understanding the great research potential of CDC42 in female vertebrate germ cells and its future clinical translation.
The Implementation of Economic Rules: From the Stability and Growth Pact to the European Semester
Authors: Mariotto Camilla 
Published: December 2021

AbstractCountry‐specific recommendations (CSRs) were introduced by the Stability and Growth Pact and offered guidance to countries in fiscal policies. Coordination was very limited and unsystematic in terms of policies and obligations. In the aftermath of the euro area financial crisis, the European Union reinforces the pre‐existing policy cycle with the European Semester. Why do countries implement CSRs? Are there explanatory differences in their implementation before and after the introduction of the European Semester? We argue that the study of the entire history of the CSRs provides a unique chance to unravel opposite causal mechanisms. Employing an original dataset, we show that, in the first period, electoral proximity reduces implementation. We find also that, if a country is in (out of) the euro area, it is more (less) inclined to adhere to the CSRs as inflation increases. In the European Semester, instead, inflationary pressure and higher costs of enforcement increase implementation.
Adverse clinical outcomes among youths with nonsuicidal self‐injury and suicide attempts: a longitudinal cohort study
Authors: Bjureberg Johan , Kuja‐Halkola Ralf , Ohlis Anna , Lichtenstein Paul , D’Onofrio Brian M. , Hellner Clara , Cederlöf Martin 
Published: December 2021

BackgroundMore knowledge about risks of clinical outcomes associated with nonsuicidal self‐injury (NSSI) and suicide attempts (SAs) is needed to inform risk assessment and intervention.MethodsLongitudinal cohort study based on 1,855 youths was clinically assessed for NSSI and SA, and followed up (from December, 2011 to December 2013) for the outcomes; diagnosed self‐injury, alcohol/substance use disorder, and psychiatric inpatient care data derived from Swedish registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the outcomes were estimated with Cox regressions, and additionally adjusted for the potential effect of sex and the number of clinical assessments. NSSI and SA were treated as time‐varying covariates.ResultsYouths with NSSI had elevated risks of all outcomes, compared with youths without NSSI or SA; the HR was 2.3, 95% confidence interval [1.6, 3.4] for self‐injury, 1.4 [0.9, 2.1] for alcohol/substance use disorder, and 1.3 [1.0, 1.7] for psychiatric inpatient care. Youths with SA displayed higher risks for the outcomes than the NSSI group; the HR was 5.5 [2.4, 12.6] for self‐injury, 2.0 [0.9, 4.4] for alcohol/substance use disorder, and 2.6 [1.5, 4.5] for psychiatric inpatient care. Youths with both NSSI and SA showed similar risks as youths with SA; HR 4.1 [2.0, 8.3] for self‐injury, 2.0 [1.1, 4.1] for alcohol/substance use disorder, but a higher risk of psychiatric inpatient care; HR 5.0 [3.1, 7.9]. All results remained virtually unchanged in the adjusted analyses.ConclusionsYouths with NSSI and/or SA had higher risks for subsequent adverse clinical outcomes. These excess risks were more pronounced among youths with SA and youths with both NSSI and SA, and the risk for psychiatric inpatient care was particularly high in youths with both NSSI and SA. Our findings suggest that early interventions for youths with NSSI or SA should not exclusively focus on suicide prevention, but also consider the risk of subsequent alcohol/substance use disorder.