bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective toxic effects of mefentrifluconazole in the early life stage of zebrafish (Danio rerio)
Authors: Li Yanhong , Ren Bo , Zhao Tingting , Chen Haiyue , Zhao Yuexing , Liang Hanlin , Liang Hongwu 
Published: March 2022

AbstractThe research on the enantioselective toxic effects of chiral pesticides on non‐target aquatic organisms has attracted more and more attention. This study investigated the enantioselective toxic effects of mefentrifluconazole (MFZ) on acute toxicity, developmental toxicity, locomotor behaviors, and the mRNA relative expression levels of genes related to neurodevelopment and cardiac development in zebrafish embryos or larvae. The 96‐h lethal concentration 50 (LC50) values (exposed to racemate and enantiomers of MFZ, that is, rac‐MFZ/(−)‐MFZ/(+)‐MFZ) were 1.010, 1.552, and 0.753 mg/L for embryo, and 0.753, 1.187, and 0.553 mg/L for larvae. The rac‐MFZ/(−)‐MFZ/(+)‐MFZ can affect the heart development of zebrafish embryos, accompanied by heart rate inhibition, yolk sac deformities, pericardial deformities, and down‐regulation of genes related to cardiotoxicity in larvae in an enantioselective manner. Moreover, the rac‐MFZ/(−)‐MFZ/(+)‐MFZ also can affect the neural development of zebrafish embryos, accompanied by autonomic movement inhibition, swimming speed and swimming distance abnormalities, and down‐regulation of genes related to neurotoxicity in larvae in an enantioselective manner. For all toxicity endpoints, the effect of the (+)‐MFZ to early‐staged zebrafish were significantly greater than that of (−)‐MFZ. These results will help distinguishing the difference of MFZ enantiomers to zebrafish, and provide scientific reference for improving the risk assessment of chiral pesticides MFZ.
Increased risk of genital warts in inflammatory bowel disease: A Danish registry‐based cohort study (1996–2018)
Authors: Elmahdi Rahma , Thomsen Louise T. , Iversen Aske T. , Allin Kristine H. , Kjær Susanne K. , Jess Tine 
Published: March 2022

AbstractBackgroundPatients with inflammatory bowel disease (IBD) are at increased risk of human papillomavirus (HPV) related cancers such as anal squamous cell carcinoma. However, risk of non‐malignant HPV infection has never been systematically studied in IBD. This study aims to assess the risk of genital warts (GW) in IBD patients.MethodsUsing the Danish nationwide registries, we identified 49,163 patients with IBD between 1996 and 2018 and matched them to 491,665 individuals from the general population by age, sex, and HPV immunisation. Cumulative incidence rates for GW in IBD and non‐IBD patients were calculated by age. Cox proportional regression analysis was used to calculate hazard ratios (HR) for GW in IBD compared to matched population and in Crohn's disease (CD) compared to ulcerative colitis (UC). We undertook subgroup analysis for risk of GW by sex, year of IBD diagnosis, contraceptive exposure and IBD treatment exposure.ResultsThe fully adjusted HR for GW in IBD patients compared to the matched non‐IBD population was 1.33 (95% CI: 1.19–1.49) and 1.13 (95% CI: 1.01, 1.27) in CD as compared to UC. This increased risk was particularly observed in female (HR: 1.54, 95% CI: 1.33–1.79) over male (HR: 1.14, 95% CI: 0.97–1.34) IBD patients, but was also found across all periods of diagnosis with IBD, regardless of contraceptive treatment exposure, and also seen in IBD patients who had never been exposed to immunosuppressive treatment (HR: 1.33, 95% CI: 1.19–1.49).ConclusionIn this nationwide, population‐representative cohort study, we observed a 33% increased risk of GW in patients with IBD compared to the matched population and a 13% increased risk of GW in CD compared with UC. This risk was particularly increased in female over male IBD patients and seen independent of IBD treatment exposure.
The diffusion of climate change adaptation policy
Authors: Schoenefeld Jonas J. , Schulze Kai , Bruch Nils 
Published: March 2022

AbstractAdapting to some level of climate change has become unavoidable. However, there is surprisingly limited systematic knowledge about whether and how adaptation policies have diffused and could diffuse in the future. Most existing adaptation studies do not explicitly examine policy diffusion, which is a form of interdependent policy‐making among jurisdictions at the same or across different levels of governance. To address this gap, we offer a new interpretation and assessment of the extensive adaptation policy literature through a policy diffusion perspective; we pay specific attention to diffusion drivers and barriers, motivations, mechanisms, outputs, and outcomes. We assess the extent to which four motivations and related mechanisms of policy diffusion—interests (linked with learning and competition), rights and duties (tied to coercion), ideology, and recognition (both connected with emulation)—are conceptually and empirically associated with adaptation. We also engage with adaptation policy characteristics, contextual conditions (e.g., problem severity) and different channels of adaptation policy diffusion (e.g., transnational networks). We demonstrate that adaptation policy diffusion can be associated with different mechanisms, yet many of them remain remarkably understudied. So are the effects of adaptation policy diffusion in terms of changes in vulnerability and resilience. We thus identify manifold avenues for future research, and provide insights for practitioners who may hope to leverage diffusion mechanisms to enhance their adaptation efforts.This article is categorized under:
Policy and Governance > Multilevel and Transnational Climate Change Governance
Vulnerability and Adaptation to Climate Change > Institutions for Adaptation
Introduction
Authors: Bigotti Fabrizio , Barry Jonathan 
Published: March 2022

AbstractThe introduction focuses on the career and work of Santorio Santori. It notes the contrast between his great influence before 1800 and his neglect in subsequent scholarship and offers an explanation of this. It then provides a revised account of his life, drawing on many new archival discoveries (including a new portrait) as well as a close reading of his own publications. It shows the importance of his family’s technical background, and his education and ongoing collective work with the innovative and politically progressive circles of the Morisini family and Paolo Sarpi in Venice, whose influence assisted his career as a physician and then professor at Padua, as well as ensuring his loss of position when more conservative forces triumphed there. The key innovations in each of his publications are explored and explained, showing his consistent commitment to quantification of the body through experimentation based on new instruments, but his positioning of this work within a Galenic framework of medical research and practice. His relationship with Galileo is clarified, confirming Santorio’s independence as both a philosopher and an inventor of instruments such as the pulsilogium and thermometer, and a summary is given of the purposes for which Santorio designed his instruments. The corpuscularian philosophy which underpinned this work is explored in the next chapter.
‘Gears of an Inner Clock’: Santorio’s Theory of Matter and Its Applications
Authors: Bigotti Fabrizio 
Published: March 2022

AbstractThis chapter provides the first detailed analysis of Santorio’s theory of matter by looking at its sources, context, development and applications in medical diagnosis, natural philosophy and technology. In the first part, I discuss some problems posed by Santorio’s texts and style of writing, the intellectual background of the theory of matter Santorio proposed and some chronology for its development. In the second, I deal specifically with the architecture of the theory, gathering evidence and instances of it across Santorio’s published and unpublished output. Finally, in the third part, I analyse the various applications the theory was susceptible of, both in medicine and in natural philosophy, and show how Santorio’s programme of quantification was the outcome of a long-running endeavour that eventually culminated in a new vision of medicine and its possibilities.
Working-Class Women Living Religion in Finland at the Turn of the Twentieth Century
Authors: Markkola Pirjo 
Published: March 2022

AbstractMarkkola examines religion as lived and shared by working-class women in an industrial town in Finland. Her chapter explores women’s daily practices as well as various Lutheran and nonconformist revivalist arenas to practice religion at the turn of the twentieth century. These arenas constituted scenes of experience where individual experiences were acquired, interpreted, shared, confirmed, and turned into collective resources. The scenes of experience provided working-class women an institutional setting to give meaning to their religious experiences and taught them how to talk religion. The chapter shows that religious experiences and meanings given to faith by urban working-class women were full of nuances. Lived religion might have brought about obedience to authorities, as the labour movement assumed, but it could also encourage resistance.
Milli-magnetic monopole dark matter and the survival of galactic magnetic fields
Authors: Graesser Michael L. , Shoemaker Ian M. , Arellano Natalia Tapia 
Published: March 2022

Abstract
Dark sectors with Abelian gauge symmetries can interact with ordinary matter via kinetic mixing. In such scenarios, magnetic monopoles of a broken dark U(1) will appear in our sector as confined milli-magnetically charged objects under ordinary electromagnetism. Halo ellipticity constraints are shown to significantly bound the strength of dark magnetic Coulomb monopole interactions. The bound magnetic monopole ground state, which in vacuum is stable and has no magnetic charge or moment, is shown to become quantum mechanically unstable in the presence of an external, ordinary magnetic field. If these states contribute sizably to the local dark matter density, they extract significant energy from the galactic magnetic field. We revise and extend this “Parker Bound” on galactic magnetic energy loss to milli-magnetic monopoles which leads to the strongest existing constraints on these states, satisfying our halo ellipticity bounds, over a wide range of magnetic monopole masses.
Patterns of microbial abundance and heterotrophic activity along nitrogen and salinity gradients in coastal wetlands
Authors: Batanero Gema L. , Green Andy J. , Amat Juan A. , Vittecoq Marion , Suttle Curtis A. , Reche Isabel 
Published: March 2022

AbstractCoastal wetlands are valuable aquatic ecosystems with high biological productivity, which provide services such as a reduction in nitrogen loading into coastal waters and storage of organic carbon acting as carbon dioxide sinks. The predicted rise of sea level or freshwater extractions, particularly in the arid Mediterranean biome, will salinize many coastal wetlands. However, there is considerable uncertainty about how salinization will affect microbial communities and biogeochemical processes. We determined the abundance of total prokaryotes, cyanobacteria, and viruses and quantified the heterotrophic production of prokaryotes sensitive- (predominantly Bacteria) and resistant- (predominantly Archaea) to erythromycin in 112 ponds from nine coastal wetlands. We explored the main drivers of prokaryotic abundance and heterotrophic production using generalized linear models (GLMs). The best GLM, including all the wetlands, indicated that the concentration of total dissolved nitrogen (TDN) positively affected the total abundance of prokaryotes and the heterotrophic erythromycin-resistant (ery-R) production. In contrast, heterotrophic erythromycin-sensitive (ery-S) production was negatively related to TDN. This negative relationship appeared to be mediated by salinity and virus abundance. Heterotrophic ery-S production declined as salinity and virus abundance increased. Consequently, we observed a switch from heterotrophic ery-S production towards ery-R production as salinity and virus abundance increased. Our results imply that microbial activity will change from heterotrophic bacterial-dominated processes to archaeal-dominated processes with anthropogenic nitrogen and salinization increases. However, more studies are required to link the mineralization rates of dissolved nitrogen and organic carbon with specific archaeal taxa to enable more accurate predictions on future scenarios in coastal wetlands.
Psychische Langzeitfolgen von Krebserkrankungen
Authors: Weis Joachim 
Published: March 2022

ZusammenfassungDie Inzidenz von Krebserkrankungen hat in den westlichen Industrienationen in den letzten Jahrzehnten stetig zugenommen. Die Anzahl der Neuerkrankungen liegt in Deutschland aktuellen Schätzungen zufolge bei ca. 500.000 pro Jahr. Aufgrund der verbesserten Früherkennung sowie der Fortschritte in den Behandlungsmöglichkeiten haben sich jedoch die Überlebenszeiten bei den meisten Tumorarten erhöht. In der Folge hat auch die Zahl der Langzeitüberlebenden (≥ 5 Jahre nach Diagnose oder Ende der Behandlung) zugenommen. Trotz der Erfolge der Tumortherapie können Langzeitüberlebende von verschiedenen körperlichen oder seelischen Problemen in der Folge der Erkrankung und/oder Therapie betroffen sein. Dieser Artikel gibt einen Überblick über die psychischen Folgeprobleme, insbesondere Angst, Depression, psychosoziale Aspekte der Lebensqualität, neuropsychologische Defizite sowie Erschöpfungszustände (Fatigue). In einem abschließenden Fazit werden Empfehlungen für psychosoziale Interventionen sowie für die Verbesserung der psychosozialen Versorgung von Langzeitüberlebenden gegeben.
Plastics in stomachs of northern fulmars Fulmarus glacialis collected at sea off east Greenland: latitude, age, sex and season
Authors: van Franeker Jan A. , Jensen Jens-Kjeld , Simonsen Poul Johannes , Bravo Rebolledo Elisa L. , Kühn Susanne 
Published: March 2022

AbstractA sample of 145 stomachs from fulmars hunted 100 km offshore east Greenland 64° 30′ N in early June 2015 was analysed for abundance of plastic litter. Overall, 86% of the stomachs contained plastics with an average of 13.5 particles, and 0.14 g per stomach. A proportion of 42% of the stomachs exceeded the level of 0.1 g plastic, whereas the international policy target aims at a reduction to less than 10%. The observed quantity of ingested plastic fits a pattern of reduced plastic abundance at higher latitudes, at greater distance from densely populated and industrialised areas. A subsample of 20 fulmars of known age and sex indicated that young birds contained more plastic than adults, and females more than males. Indirect evidence from age and sex composition in the full sample supported these findings. Further confirmation was found in literature and by re-analysis of earlier datasets. Differences in colony attendance could explain the combined effects of age, sex, and possibly season on plastic abundance in the stomachs. With a consistent monitoring sampling regime, such variations do not impair the results, but for evaluation of regional patterns from incidental observations or the planning of new monitoring schemes they are important.
Parvimonas micra is associated with tumour immune profiles in molecular subtypes of colorectal cancer
Authors: Löwenmark Thyra , Li Xingru , Löfgren-Burström Anna , Zingmark Carl , Ling Agnes , Kellgren Therese G. , Larsson Pär , Ljuslinder Ingrid , Wai Sun Nyunt , Edin Sofia , Palmqvist Richard 
Published: March 2022

AbstractThe importance of the tumour microbiome in different aspects of colorectal cancer (CRC) has been increasingly recognised, but many questions remain. The aim of this study was to explore the effect of specific CRC associated microbes on the tumour immune response, which has a considerable prognostic value in CRC. We applied specific qPCR to detect Parvimonas micra and Fusobacterium nucleatum in tumour tissues from an immunologically well-characterised cohort of 69 CRC patients. This cohort included detailed analyses of immune profiles based on flow cytometry and transcriptomics in tumour tissue and blood, along with comprehensive analyses of molecular subtypes. P. micra and F. nucleatum were detected in 24% and 64% of tumour tissues, respectively. We found a significant association of P. micra with high-grade tumours and tumours of CMS1 subtype. F. nucleatum was significantly associated with right-sided tumours, microsatellite instability, and CMS1 tumours. The immunological analyses revealed significant associations of P. micra with activated CD69+ T lymphocytes and increased antigen-presenting HLA-DR+ B lymphocytes. P. micra was also positively associated with M1 and M2 macrophage traits. The impact of P. micra tumour colonisation on the immune response was further assessed using transcriptomics in validation of our findings. No associations were found between F. nucleatum and immune profiles in this study. Our findings support novel associations between P. micra and the immune response in CRC. A better understanding of these interactions might help to identify important predictive and prognostic tools as well as new targets for therapy.
First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers
Authors: Felip Enriqueta , Moreno Victor , Morgensztern Daniel , Curigliano Giuseppe , Rutkowski Piotr , Trigo José Manuel , Calvo Aitana , Kowalski Dariusz , Cortinovis Diego , Plummer Ruth , Maio Michele , Ascierto Paolo A. , Vladimirov Vladimir I. , Cervantes Andres , Zudaire Enrique , Hazra Anasuya , T’jollyn Huybrecht , Bandyopadhyay Nibedita , Greger James G. , Attiyeh Edward , Xie Hong , Calvo Emiliano 
Published: March 2022

Abstract
Purpose
To assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cetrelimab (JNJ-63723283), a monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced/refractory solid tumors in the phase 1/2 LUC1001 study.

Methods
In phase 1, patients with advanced solid tumors received intravenous cetrelimab 80, 240, 460, or 800 mg every 2 weeks (Q2W) or 480 mg Q4W. In phase 2, patients with melanoma, non-small-cell lung cancer (NSCLC), and microsatellite instability–high (MSI-H)/DNA mismatch repair-deficient colorectal cancer (CRC) received cetrelimab 240 mg Q2W. Response was assessed Q8W until Week 24 and Q12W thereafter.

Results
In phase 1, 58 patients received cetrelimab. Two dose-limiting toxicities were reported and two recommended phase 2 doses (RP2D) were defined (240 mg Q2W or 480 mg Q4W). After a first dose, mean maximum serum concentrations (Cmax) ranged from 24.7 to 227.0 µg/mL; median time to Cmax ranged from 2.0 to 3.2 h. Pharmacodynamic effect was maintained throughout the dosing period across doses. In phase 2, 146 patients received cetrelimab 240 mg Q2W. Grade ≥ 3 adverse events (AEs) occurred in 53.9% of patients. Immune-related AEs (any grade) occurred in 35.3% of patients (grade ≥ 3 in 6.9%). Overall response rate was 18.6% across tumor types, 34.3% in NSCLC, 52.6% in programmed death ligand 1–high (≥ 50% by immunohistochemistry) NSCLC, 28.0% in melanoma, and 23.8% in centrally confirmed MSI-H CRC.

Conclusions
The RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors.

Trial registrations
NCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016–002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017.
Not all that looks fractured is broken—multipartite humeral epicondyles in children
Authors: Schmid Andrea , Lois Anna-Maria , Metz Corona , Grunz Jan-Peter , Veldhoen Simon 
Published: March 2022

Abstract
Objective
Multipartite epicondyles may mimic fractures in the setting of pediatric elbow trauma. This study examines the prevalence of multipartite epicondyles during skeletal development and their association with pediatric elbow fractures.

Materials and methods
In this retrospective analysis, 4282 elbow radiographs of 1265 elbows of 1210 patients aged 0–17 years were reviewed. The radiographs were analyzed by two radiologists in consensus reading, and the number of visible portions of the medial and lateral epicondyles was noted. For elbows in which epicondylar ossification was not yet visible, the epicondyles were already fused with the humerus or could not be sufficiently evaluated due to projection issues or because osteosynthesis material was excluded. In total, 187 elbows were included for the lateral and 715 for the medial epicondyle analyses.

Results
No multipartite medial epicondyles were found in patients without history of elbow fracture, whereas 9% of these patients had multipartite lateral epicondyles (p < 0.01). Current or previous elbow fractures increased the prevalence of multipartite epicondyles, with significant lateral predominance (medial epicondyle + 9% vs. lateral + 24%, p < 0.0001). Including all patients regardless of a history of elbow fracture, multipartite medial epicondyles were observed in 3% and multipartite lateral epicondyles in 18% (p < 0.0001). There was no gender difference in the prevalence of multipartition of either epicondyle, regardless of a trauma history.

Conclusion
Multipartite medial epicondyles occur in patients with current or previous elbow fractures only, whereas multipartite lateral epicondyles may be constitutional. Elbow fractures increase the prevalence of multipartite epicondyles on both sides, with significant lateral predominance.

Key Points
• Multipartite medial epicondyles should be considered of traumatic origin.
• Multipartite lateral epicondyles may be constitutional.
• Elbow fractures increase the prevalence of multipartite epicondyles on both sides with lateral predominance.
Impacts of dynamical downscaling on circulation type statistics in the Euro-CORDEX ensemble
Authors: Røste Julie , Landgren Oskar A. 
Published: March 2022

AbstractAtmospheric circulation type classification methods were applied to an ensemble of 57 regional climate model simulations from Euro-CORDEX, their 11 boundary models from CMIP5 and the ERA5 reanalysis. We applied a field anomaly technique to focus on the departure from the domain-wide daily mean. We then compared frequencies of the different circulation types in the simulations with ERA5 and found that the regional models add value especially in the summer season. We applied three different classification methods (the subjective Grosswettertypes and the two optimisation algorithms SANDRA and distributed k-means clustering) from the cost733class software and found that the results are not particularly sensitive to choice of circulation classification method. There are large differences between models. Simulations based on MIROC-MIROC5 and CNRM-CERFACS-CNRM-CM5 show an over-representation of easterly flow and an under-representation of westerly. The downscaled results retain the large-scale circulation from the global model most days, but especially the regional model IPSL-WRF381P changes the circulation more often, which increases the error relative to ERA5. Simulations based on ICHEC-EC-EARTH and MPI-M-MPI-ESM-LR show consistently smaller errors relative to ERA5 in all seasons. The ensemble spread is largest in summer and smallest in winter. Under the future RCP8.5 scenario, the circulation changes in the summer season, with more than half of the ensemble showing a decrease in frequency of the Central-Eastern European high, the Scandinavian low as well as south-southeasterly flow. There is in general a strong agreement in the sign of the change between the regional simulations and the data from the corresponding global model.