bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation
Authors: Knopp Tanja , Jung Rebecca , Wild Johannes , Bochenek Magdalena L , Efentakis Panagiotis , Lehmann Annika , Bieler Tabea , Garlapati Venkata , Richter Cindy , Molitor Michael , Perius Katharina , Finger Stefanie , Lagrange Jérémy , Ghasemi Iman , Zifkos Konstantinos , Kommoss Katharina S , Masri Joumana , Reißig Sonja , Randriamboavonjy Voahanginirina , Wunderlich Thomas , Hövelmeyer Nadine , Weber Alexander N R , Mufazalov Ilgiz A , Bosmann Markus , Bechmann Ingo , Fleming Ingrid , Oelze Matthias , Daiber Andreas , Münzel Thomas , Schäfer Katrin , Wenzel Philip , Waisman Ari , Karbach Susanne 
Published: June 2024

Abstract

Aims
The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study the role of myeloid cell-derived IL-6 in vascular disease.

Methods and results
Interleukin-6-overexpressing (IL-6OE) mice were generated and crossed with LysM-Cre mice, to generate mice (LysM-IL-6OE mice) overexpressing the cytokine in myeloid cells. Eight- to 12-week-old LysM-IL-6OE mice spontaneously developed inflammatory colitis and significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS) formation, and vascular dysfunction in resistance vessels. The latter phenotype was associated with decreased survival. Vascular dysfunction was accompanied by a significant accumulation of neutrophils, monocytes, and macrophages in the aorta, increased myeloid cell reactivity (elevated ROS production), and vascular fibrosis associated with phenotypic changes in vascular smooth muscle cells. In addition to elevated Mcp1 and Cxcl1 mRNA levels, aortae from LysM-IL-6OE mice expressed higher levels of inducible NO synthase and endothelin-1, thus partially accounting for vascular dysfunction, whereas systemic blood pressure alterations were not observed. Bone marrow (BM) transplantation experiments revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner.

Conclusion
Mice with conditional overexpression of IL-6 in myeloid cells show systemic and vascular inflammation as well as endothelial dysfunction. A decrease in circulating IL-6 levels by replacing IL-6-producing myeloid cells in the BM improved vascular dysfunction in this model, underpinning the relevant role of IL-6 in vascular disease.
Periprocedural acute haemodynamic decompensation during substrate-based ablation of scar-related ventricular tachycardia: a rare and unpredictable event
Authors: Stojadinović Predrag , Wichterle Dan , Peichl Petr , Čihák Robert , Aldhoon Bashar , Borišincová Eva , Štiavnický Petr , Hašková Jana , Ševčík Adam , Kautzner Josef 
Published: June 2024

Abstract

Aims
Patients with structural heart disease (SHD) undergoing catheter ablation (CA) for ventricular tachycardia (VT) are at considerable risk of periprocedural complications, including acute haemodynamic decompensation (AHD). The PAINESD score was proposed to predict the risk of AHD. The goal of this study was to validate the PAINESD score using the retrospective analysis of data from a large-volume heart centre.

Methods and results
Patients who had their first radiofrequency CA for SHD-related VT between August 2006 and December 2020 were included in the study. Procedures were mainly performed under conscious sedation. Substrate mapping/ablation was performed primarily during spontaneous rhythm or right ventricular pacing. A purposely established institutional registry for complications of invasive procedures was used to collect all periprocedural complications that were subsequently adjudicated using the source medical records. Acute haemodynamic decompensation triggered by CA procedure was defined as intraprocedural or early post-procedural (&lt;12 h) development of acute pulmonary oedema or refractory hypotension requiring urgent intervention. The study cohort consisted of 1124 patients (age, 63 ± 13 years; males, 87%; ischaemic cardiomyopathy, 67%; electrical storm, 25%; New York Heart Association Class, 2.0 ± 1.0; left ventricular ejection fraction, 34 ± 12%; diabetes mellitus, 31%; chronic obstructive pulmonary disease, 12%). Their PAINESD score was 11.4 ± 6.6 (median, 12; interquartile range, 6–17). Acute haemodynamic decompensation complicated the CA procedure in 13/1124 = 1.2% patients and was not predicted by PAINESD score with AHD rates of 0.3, 1.8, and 1.1% in subgroups by previously published PAINESD terciles (&lt;9, 9–14, and &gt;14). However, the PAINESD score strongly predicted mortality during the follow-up.

Conclusion
Primarily substrate-based CA of SHD-related VT performed under conscious sedation is associated with a substantially lower rate of AHD than previously reported. The PAINESD score did not predict these events. The application of the PAINESD score to the selection of patients for pre-emptive mechanical circulatory support should be reconsidered.
Platform Law as EU Law
Authors: Mast Tobias 
Published: June 2024

Abstract
Digital platforms have become the subject of several legal acts within a relatively short period of time. The emerging European platform law faces particular challenges due to three specificities of platforms. First, the area to be regulated consists of the same platforms operating throughout the Union with a more or less uniform service in all Member States and beyond the Union. Second, the fact that the platforms can be used for almost unlimited purposes, whereas the Union does not have unlimited regulatory powers. Third, there is the dynamic development of the platform economy, which constantly presents us with new phenomena and potential risks, giving operators a knowledge advantage over regulators and generating a need for private ordering by platforms themselves.
In this combination, the legal challenges differ from the issues addressed by most other acts of the EU Digital Strategy: for example, the Data Governance Act focuses not on private but on public data owners, while the Data Act focuses on Internet of Things applications, which are not used as ubiquitously as digital platforms. Because of these particularities, an overarching view of the phenomena of platform regulation helps to provide a background against which the appropriateness of individual norms can be assessed. In order to structure the observations, the platform phenomenon will first be contrasted with that of the EU (I.), before the characteristics of platform law as supranational law (II.) and European administrative law (III.), as well as questions of the platform-related protection of fundamental rights are addressed (IV.).
Taxonomic and genomic attributes of oligotrophic soil bacteria
Authors: Dragone Nicholas B , Hoffert Michael , Strickland Michael S , Fierer Noah 
Published: June 2024

Abstract
Not all bacteria are fast growers. In soil as in other environments, bacteria exist along a continuum—from copiotrophs that can grow rapidly under resource-rich conditions to oligotrophs that are adapted to life in the “slow lane.” However, the field of microbiology is built almost exclusively on the study of copiotrophs due, in part, to the ease of studying them in vitro. To begin understanding the attributes of soil oligotrophs, we analyzed three independent datasets that represent contrasts in organic carbon availability. These datasets included 185 samples collected from soil profiles across the USA, 950 paired bulk soil and rhizosphere samples collected across Europe, and soils from a microcosm experiment where carbon availability was manipulated directly. Using a combination of marker gene sequencing and targeted genomic analyses, we identified specific oligotrophic taxa that were consistently more abundant in carbon-limited environments (subsurface, bulk, unamended soils) compared to the corresponding carbon-rich environment (surface, rhizosphere, glucose-amended soils), including members of the Dormibacterota and Chloroflexi phyla. In general, putative soil oligotrophs had smaller genomes, slower maximum potential growth rates, and were under-represented in culture collections. The genomes of oligotrophs were more likely to be enriched in pathways that allow oligotrophs to metabolize a range of energy sources and store carbon, while genes associated with energy-intensive functions like chemotaxis and motility were under-represented. However, few genomic attributes were shared, highlighting that oligotrophs likely use a range of different metabolic strategies and regulatory pathways to thrive in resource-limited soils.
Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales
Authors: Weston Gregory , Giri Abhigya , Komarow Lauren , Ge Lizhao , Baum Keri R , Abbenante Erin , Gallagher Jason C , Jacob Jesse T , Kaye Keith S , Kim Angela C , Huskins W Charles , Zervos Marcus , Herc Erica , Patel Robin , Van Duin David , Doi Yohei 
Published: June 2024

Abstract

Background
Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE).

Objectives
To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents.

Methods
Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures.

Results
The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients’ race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%–56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group.

Conclusions
Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.
A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii
Authors: Zhang Meng-Yue , Li Shuang , Wang Cai-Yun , Zhang Zi-Xuan , Han Yu-Ling , Liu Xin-Qi , Cheng Juan , Zhou Xun-Yong , Zhang Yi-Xuan 
Published: June 2024

Abstract

Objectives
Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections.

Methods
In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance.

Results
We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model.

Conclusions
Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.
Reducing Wait Times at Customs to Boost Trade: How Implementing the Trade Facilitation Agreement Can Expand Trade among AfCFTA Countries?
Authors: de Melo Jaime , Sorgho Zakaria , Wagner Laurent 
Published: June 2024

Abstract
All WTO members participate in the Trade Facilitation Agreement (TFA), a rules-based bottom-up approach built on monitorable provisions (e.g., the publication of information, advance rulings, appeal or review of decisions, transparency and border agency cooperation) aimed at reducing time in customs. The paper draws on the OECD indicators of the state of implementation of provisions in the TFA summarised in a TFI (Trade Facilitation Index) to estimate the reduction in waiting time at customs for a large sample of 160 countries.
Implementing the TFA could be a significant complement to the African Continental Free Trade Area (AfCFTA)'s objectives. The paper's estimates suggest that a realistic implementation of TFA measures could reduce time in customs for imports by 3.7 days and by 1.9 days for exports. Using extraneous estimates from customs-level transactions, this translates to a reduction tariff Ad-Valorem Equivalent (AVE) in the range 3.5%–7% for imports and 8% extra growth for exports.
The large differences in interests across AfCFTA participants—landlocked-coastal, resource-rich and resource-poor, large-small—suggest large gains from reducing tariffs on intra-African trade. However, tariff reductions face the zero-sum hurdle of negotiations involving rent transfers across and within countries. By avoiding rent-transfer issues, this paper suggests that taking seriously the TFA provisions would be a powerful complement to the AfCFTA's tariff-reduction agenda.
Transcriptomic analysis of sheep hypothalamus discloses regulatory genes potentially involved in sex-dependent differences in body weight of progeny born to dams supplemented with omega-3 fatty acids or methionine during late-gestation
Authors: Rosa-Velazquez Milca , Ahn Jinsoo , Lee Kichoon , Relling Alejandro E 
Published: June 2024

Abstract
Fetal programming research conducted in sheep has reported sexually dimorphic responses on growth of the progeny born to in-utero methionine or omega-3 fatty acids supplementation. However, the biological mechanism behind the nutrient by sex interaction as a source of variation in offspring body weight is still unknown. A high-throughput RNA sequencing data of hypothalamus samples from 17 lambs were used in the current study to identify differentially expressed genes (DEGs) between males and females born to dams supplemented with different nutrients during late-gestation. Ewes received a basal diet without omega-3 fatty acids or methionine supplementation as the control (CONT); omega-3 fatty acids supplementation (FAS), or methionine supplementation (METS). A list of regulated genes was generated. Data were compared as CONT vs. FAS and CONT vs. METS. For CONT vs. METS, a treatment by sex interaction was found (adjusted P-value &lt; 0.05) on 121 DEGs (112 upregulated and 9 downregulated) on female lambs born to METS compared with METS males. Importantly, with the sex interaction term, more than 100 genes were upregulated in female lamb’s hypothalamuses born to METS. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) were performed using the DEGs from female lambs. Terms under biological process (related to morphogenesis, organism, and tissue development), cellular component (related to chromatin, extracellular components), and molecular function (involved in chromatin structure and transcription and factors linked to binding DNA) were presented (adjusted P-value &lt; 0.05) for GO. For the IPA, the top-scoring network was developmental disorder, endocrine system development and function, and organ morphology. Only a few differences were observed in the comparison between the interaction of sex and treatment for the CONT vs. FAS comparison. The markedly increased number of DEGs substantially involved in developmental and growth processes indicates the extent to which maternal methionine supplementation causes the sexually dimorphic effects observed in the offspring.
Plastomes of Nothofagus reflect a shared biogeographic history in Patagonia
Authors: Juri Gabriela , Ripa Ramiro R , Premoli Andrea C 
Published: June 2024

Abstract
Plastomes are used in phylogenetic reconstructions because of their relatively conserved nature. Nonetheless, some limitations arise, particularly at lower taxonomic levels due to reduced interspecific polymorphisms and frequent hybridization events that result in unsolved phylogenies including polytomies and reticulate evolutionary patterns. Next-generation sequencing technologies allow access to genomic data and strongly supported phylogenies, yet biased topologies may be obtained due to insufficient taxon sampling. We analyze the hypothesis that intraspecific plastome diversity reflects biogeographic history and hybridization cycles among taxa. We generated 12 new plastome sequences covering distinct latitudinal locations of all species of subgenus Nothofagus from North Patagonia. Chloroplast genomes were assembled, annotated, and searched for simple sequence repeats (SSRs). Phylogenetic reconstructions included species and sampled locations. The six Nothofagus species analyzed were of similar size and structure; only Nothofagus obliqua of subgenus Lophozonia, used as an outgroup, presented slight differences in size. We detected a variable number of SSRs in distinct species and locations. Phylogenetic analyses of plastomes confirmed that subgenus Nothofagus organizes into two monophyletic clades each consisting of individuals of different species. We detected a geographic structure within subgenus Nothofagus and found evidence of local chloroplast sharing due to past hybridization, followed by adaptive introgression and ecological divergence. These contributions enrich the comprehension of transversal evolutionary mechanisms such as chloroplast capture and its implications for phylogenetic and phylogenomic analyses.
The rural mosque uncovered in the Andalusi village of La Graja (eleventh century ce)
Authors: Jiménez-Castillo Pedro , Simón García José L , Moreno Narganes José Mª 
Published: June 2024

ABSTRACT
This article examines the rural mosque recently excavated in the archaeological site of La Graja (Higueruela, Albacete). This is a very important find from a historical point of view, since there is little archaeological evidence for this type of building despite the fact that many examples must have existed in al-Andalus. This congregational mosque served the inhabitants of an Andalusi village (Ar. qarya) and other small hamlets in its vicinity. It was built in the early eleventh century ce and abandoned, along with the rest of the settlement, towards the end of the century. Owing to its good state of preservation, its constructive characteristics and architectural plan could be analysed in detail. The most interesting aspect of this find was, however, that it was possible to study the mosque in the spatial context of the village as a whole. This reveals aspects of urban planning at the time of the mosque’s construction and, therefore, the social structure of the group of founding settlers. The excavation also provided relevant data about the uses of the space around the prayer hall and how its presence affected the evolution of the urban layout of the village.
Evaluation of PET/CT imaging with [89Zr]Zr-DFO-girentuximab: a phase 1 clinical study in Japanese patients with renal cell carcinoma (Zirdac-JP)
Authors: Nakaigawa Noboru , Hasumi Hisashi , Utsunomiya Daisuke , Yoshida Keisuke , Ishiwata Yoshinobu , Oka Takashi , Hayward Colin , Makiyama Kazuhide 
Published: June 2024

Abstract

Background
PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC.

Methods
Eligible adult patients received 37 MBq (± 10%; 10 mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72 h and Day 5 ± 2 d after administration.

Results
[89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean ± standard deviation) (1.365 ± 0.245 mGy/MBq), kidney (1.126 ± 0.190 mGy/MBq), heart wall (1.096 ± 0.232 mGy/MBq), and spleen (1.072 ± 0.466 mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470 mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported.

Conclusions
This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.
CCD UBV(RI)KC photometry and dynamics of the open cluster NGC 1513
Authors: Akkaya Oralhan İnci , Çakmak Hikmet , Karataş Yüksel , Michel Raúl , Bonatto Charles 
Published: June 2024

ABSTRACT
We derive astrophysical parameters of the open cluster NGC 1513 by means of colour indices built with new CCD UBV(RI)KC photometry. Based on early-type members, the mean foreground reddening and total to selective extinction ratio are E(B − V) = 0.79 ± 0.09 mag and RV = 2.85 ± 0.05. Through the differential grid method, we derive the metal abundance [Fe/H] = −0.06 dex (Z = +0.013), which is consistent with the value [Fe/H] = −0.088 of the bright giant member – LAMOST 695710060. Z = +0.013 isochrone fit to the V × (B − V) colour–magnitude diagram leads to a turn-off age of 224 ± 27 Myr (thus an intermediate-age cluster), and a distance modulus of (V0 − MV) = 10.90 ± 0.15 mag, thus implying a distance from the Sun d = 1514 ± 105 pc. Within the uncertainties, our photometric distance is consistent with the value d = 1435 ± 14 pc from the Gaia DR3 parallax. We find signs of small mass segregation through a minimum spanning tree analysis for the 190 most massive stars, together with the rather steep mass function (χ = +2.39) slope. The high core to half-light radius ratio Rcore/Rh = 0.82, together with the compact half-light to tidal radius ratio Rh/Rt = 0.22, suggest that it is probably related to cluster-formation effects, due to little dynamical evolution, instead of driving its dynamical evolution by internal relaxation. Indeed, NGC 1513 is located in the second quadrant (ℓ = 152${_{.}^{\circ}}$59 and Galactocentric distance RGC = 9.57 kpc), which tends to minimize tidal effects by external processes and tidal disruption. Therefore, internal mass segregation effects in NGC 1513 seem to be more efficient than cluster evaporation processes. We find that NGC 1513 migrated about 0.50 kpc from its birth place.