bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue and in vitro characterization of a divergent TBEV-Eu strain from the Netherlands
Authors: Hoornweg Tabitha E. , Godeke Gert-Jan , Hoogerwerf Marieke N. , van Kasteren Puck B. , de Vries Ankje , Sprong Hein , Verjans Georges M. G. M. , van Riel Debby , Reimerink Johan H. J. , Rockx Barry , Reusken Chantal B. E. M. 
Published: February 2023

AbstractTick-borne encephalitis virus (TBEV) may cause tick-borne encephalitis (TBE), a potential life-threatening infection of the central nervous system in humans. Phylogenetically, TBEVs can be subdivided into three main subtypes, which differ in endemic region and pathogenic potential. In 2016, TBEV was first detected in the Netherlands. One of two detected strains, referred to as Salland, belonged to the TBEV-Eu subtype, yet diverged ≥ 2% on amino acid level from other members of this subtype. Here, we report the successful rescue of this strain using infectious subgenomic amplicons and its subsequent in vitro characterization by comparison to two well-characterized TBEV-Eu strains; Neudoerfl and Hypr. In the human alveolar epithelial cell line A549, growth kinetics of Salland were comparable to the high pathogenicity TBEV-Eu strain Hypr, and both strains grew considerably faster than the mildly pathogenic strain Neudoerfl. In the human neuroblastoma cell line SK-N-SH, Salland replicated faster and to higher infectious titers than both reference strains. All three TBEV strains infected primary human monocyte-derived dendritic cells to a similar extent and interacted with the type I interferon system in a similar manner. The current study serves as the first in vitro characterization of the novel, divergent TBEV-Eu strain Salland.
Predictors of shoulder dystocia at the time of operative vaginal delivery: a prospective cohort study
Authors: Bouchghoul Hanane , Hamel Jean-François , Mattuizzi Aurélien , Ducarme Guillaume , Froeliger Alizée , Madar Hugo , Sentilhes Loïc 
Published: February 2023

AbstractOur aim was to identify factors associated with shoulder dystocia following an attempted operative vaginal delivery (aOVD) in a prospective cohort study and to evaluate whether these factors can be used to accurately predict shoulder dystocia by building a score of shoulder dystocia risk. This was a planned secondary analysis of a prospective cohort study of deliveries with aOVD at term from 2008–2013. Cases were defined as women with shoulder dystocia following an aOVD defined as a delivery that requires additional obstetric maneuvers following failure of gentle downward traction on the fetal head to effect delivery of the shoulders. Multivariate logistic regression analyses were performed to determine risk factors for shoulder dystocia. Shoulder dystocia occurred in 57 (2.7%) of the 2118 women included. In the whole cohort, women with shoulder dystocia more often had a history of shoulder dystocia (3.5% vs. 0.2%, p = 0.01), and there was a significant interaction between aOVD and gestational age and the duration of the second stage of labor: women with shoulder dystocia more often had a gestational age > 40 weeks and a second stage of labor longer than 3 h specifically for midpelvic aOVD. In multivariable analysis, a history of shoulder dystocia was the only factor independently associated with shoulder dystocia following aOVD (aOR 27.00, 95% CI 4.10–178.00). The AUC for the receiver operating characteristic curve generated using a multivariate model with term interaction with head station was 0.70 (95% CI 0.62–0.77). The model failed to accurately predict shoulder dystocia.
Mutant structure of metabolic switch protein in complex with monomeric c-di-GMP reveals a potential mechanism of protein-mediated ligand dimerization
Authors: Dubey Badri Nath , Shyp Viktoriya , Fucile Geoffrey , Sondermann Holger , Jenal Urs , Schirmer Tilman 
Published: February 2023

AbstractBacterial second messengers c-di-GMP and (p)ppGpp have broad functional repertoires ranging from growth and cell cycle control to the regulation of biofilm formation and virulence. The recent identification of SmbA, an effector protein from Caulobacter crescentus that is jointly targeted by both signaling molecules, has opened up studies on how these global bacterial networks interact. C-di-GMP and (p)ppGpp compete for the same SmbA binding site, with a dimer of c-di-GMP inducing a conformational change that involves loop 7 of the protein that leads to downstream signaling. Here, we report a crystal structure of a partial loop 7 deletion mutant, SmbA∆loop in complex with c-di-GMP determined at 1.4 Å resolution. SmbA∆loop binds monomeric c-di-GMP indicating that loop 7 is required for c-di-GMP dimerization. Thus the complex probably represents the first step of consecutive c-di-GMP binding to form an intercalated dimer as has been observed in wild-type SmbA. Considering the prevalence of intercalated c-di-GMP molecules observed bound to proteins, the proposed mechanism may be generally applicable to protein-mediated c-di-GMP dimerization. Notably, in the crystal, SmbA∆loop forms a 2-fold symmetric dimer via isologous interactions with the two symmetric halves of c-di-GMP. Structural comparisons of SmbA∆loop with wild-type SmbA in complex with dimeric c-di-GMP or ppGpp support the idea that loop 7 is critical for SmbA function by interacting with downstream partners. Our results also underscore the flexibility of c-di-GMP, to allow binding to the symmetric SmbA∆loop dimer interface. It is envisaged that such isologous interactions of c-di-GMP could be observed in hitherto unrecognized targets.
Developmental programming: adverse sexually dimorphic transcriptional programming of gestational testosterone excess in cardiac left ventricle of fetal sheep
Authors: Ramamoorthi Elangovan Venkateswaran , Saadat Nadia , Ghnenis Adel , Padmanabhan Vasantha , Vyas Arpita K. 
Published: February 2023

AbstractAdverse in-utero insults during fetal life alters offspring’s developmental trajectory, including that of the cardiovascular system. Gestational hyperandrogenism is once such adverse in-utero insult. Gestational testosterone (T)-treatment, an environment of gestational hyperandrogenism, manifests as hypertension and pathological left ventricular (LV) remodeling in adult ovine offspring. Furthermore, sexual dimorphism is noted in cardiomyocyte number and morphology in fetal life and at birth. This study investigated transcriptional changes and potential biomarkers of prenatal T excess-induced adverse cardiac programming. Genome-wide coding and non-coding (nc) RNA expression were compared between prenatal T-treated (T propionate 100 mg intramuscular twice weekly from days 30 to 90 of gestation; Term: 147 days) and control ovine LV at day 90 fetus in both sexes. Prenatal T induced differential expression of mRNAs in the LV of female (2 down, 5 up) and male (3 down, 1 up) (FDR < 0.05, absolute log2 fold change > 0.5); pathways analysis demonstrated 205 pathways unique to the female, 382 unique to the male and 23 common pathways. In the male, analysis of ncRNA showed differential regulation of 15 lncRNAs (14 down, 1 up) and 27 snoRNAs (26 down and 1 up). These findings suggest sexual dimorphic modulation of cardiac coding and ncRNA with gestational T excess.
NMR-based metabolomics of plasma from dairy calves infected with two primary causal agents of bovine respiratory disease (BRD)
Authors: Santos-Rivera Mariana , Fitzkee Nicholas C. , Hill Rebecca A. , Baird Richard E. , Blair Ellianna , Thoresen Merrilee , Woolums Amelia R. , Meyer Florencia , Vance Carrie K. 
Published: February 2023

AbstractEach year, bovine respiratory disease (BRD) results in significant economic loss in the cattle sector, and novel metabolic profiling for early diagnosis represents a promising tool for developing effective measures for disease management. Here, 1H-nuclear magnetic resonance (1H-NMR) spectra were used to characterize metabolites from blood plasma collected from male dairy calves (n = 10) intentionally infected with two of the main BRD causal agents, bovine respiratory syncytial virus (BRSV) and Mannheimia haemolytica (MH), to generate a well-defined metabolomic profile under controlled conditions. In response to infection, 46 metabolites (BRSV = 32, MH = 33) changed in concentration compared to the uninfected state. Fuel substrates and products exhibited a particularly strong effect, reflecting imbalances that occur during the immune response. Furthermore, 1H-NMR spectra from samples from the uninfected and infected stages were discriminated with an accuracy, sensitivity, and specificity ≥ 95% using chemometrics to model the changes associated with disease, suggesting that metabolic profiles can be used for further development, understanding, and validation of novel diagnostic tools.
Bayesian estimation reveals that reproducible models in Systems Biology get more citations
Authors: Höpfl Sebastian , Pleiss Jürgen , Radde Nicole E. 
Published: February 2023

AbstractThe Systems Biology community has taken numerous actions to develop data and modeling standards towards FAIR data and model handling. Nevertheless, the debate about incentives and rewards for individual researchers to make their results reproducible is ongoing. Here, we pose the specific question of whether reproducible models have a higher impact in terms of citations. Therefore, we statistically analyze 328 published models recently classified by Tiwari et al. based on their reproducibility. For hypothesis testing, we use a flexible Bayesian approach that provides complete distributional information for all quantities of interest and can handle outliers. The results show that in the period from 2013, i.e., 10 years after the introduction of SBML, to 2020, the group of reproducible models is significantly more cited than the non-reproducible group. We show that differences in journal impact factors do not explain this effect and that this effect increases with additional standardization of data and error model integration via PEtab. Overall, our statistical analysis demonstrates the long-term merits of reproducible modeling for the individual researcher in terms of citations. Moreover, it provides evidence for the increased use of reproducible models in the scientific community.
Systematic analysis of CNGA3 splice variants identifies different mechanisms of aberrant splicing
Authors: Reuter Peggy , Walter Magdalena , Kohl Susanne , Weisschuh Nicole 
Published: February 2023

AbstractAchromatopsia is an autosomal recessive cone photoreceptor disease that is frequently caused by pathogenic variants in the CNGA3 gene. Here, we present a systematic functional analysis of 20 CNGA3 splice site variants detected in our large cohort of achromatopsia patients and/or listed in common variant databases. All variants were analyzed by functional splice assays based on the pSPL3 exon trapping vector. We demonstrated that ten variants, both at canonical and non-canonical splice sites, induced aberrant splicing, including intronic nucleotide retention, exonic nucleotide deletion and exon skipping, resulting in 21 different aberrant transcripts. Of these, eleven were predicted to introduce a premature termination codon. The pathogenicity of all variants was assessed based on established guidelines for variant classification. Incorporation of the results of our functional analyses enabled re-classification of 75% of variants previously classified as variants of uncertain significance into either likely benign or likely pathogenic. Our study is the first in which a systematic characterization of putative CNGA3 splice variants has been performed. We demonstrated the utility of pSPL3 based minigene assays in the effective assessment of putative splice variants. Our findings improve the diagnosis of achromatopsia patients, who may thus benefit from future gene-based therapeutic strategies.
MosChito rafts as effective and eco-friendly tool for the delivery of a Bacillus thuringiensis-based insecticide to Aedes albopictus larvae
Authors: Pitton Simone , Negri Agata , Pezzali Giulia , Piazzoni Marco , Locarno Silvia , Gabrieli Paolo , Quadri Roberto , Mastrantonio Valentina , Urbanelli Sandra , Porretta Daniele , Bandi Claudio , Epis Sara , Caccia Silvia 
Published: February 2023

AbstractAdult mosquito females, through their bites, are responsible for the transmission of different zoonotic pathogens. Although adult control represents a pillar for the prevention of disease spread, larval control is also crucial. Herein we characterized the effectiveness of a suitable tool, named “MosChito raft”, for the aquatic delivery of a Bacillus thuringiensis var. israelensis (Bti) formulate, a bioinsecticide active by ingestion against mosquito larvae. MosChito raft is a floating tool composed by chitosan cross-linked with genipin in which a Bti-based formulate and an attractant have been included. MosChito rafts (i) resulted attractive for the larvae of the Asian tiger mosquito Aedes albopictus, (ii) induced larval mortality within a few hours of exposure and, more importantly, (iii) protected the Bti-based formulate, whose insecticidal activity was maintained for more than one month in comparison to the few days residual activity of the commercial product. The delivery method was effective in both laboratory and semi-field conditions, demonstrating that MosChito rafts may represent an original, eco-based and user-friendly solution for larval control in domestic and peri-domestic aquatic habitats such as saucers and artificial containers in residential or urban environments.
Effect of bulky anions on the liquid-liquid phase transition in phosphonium ionic liquids: Ambient and high-pressure dielectric studies
Authors: Yao B. , Paluch M. , Wojnarowska Z. 
Published: February 2023

AbstractAlthough the first-order liquid–liquid phase transition (LLT) has been reported to exist in various systems (i.e., phosphorus, silicon, water, triphenyl phosphite, etc.), it is still one of the most challenging problems in the field of physical science. Recently, we found that this phenomenon occurs in the family of trihexyl(tetradecyl)phosphonium [P666,14]+ based ionic liquids (ILs) with different anions (Wojnarowska et al in Nat Commun 13:1342, 2022). To understand the molecular structure–property relationships governing LLT, herein, we examine ion dynamics of two other quaternary phosphonium ILs containing long alkyl chains in cation and anion. We found that IL with the anion containing branched –O–(CH2)5–CH3 side chains does not reveal any signs of LLT, while IL with shorter alkyl chains in the anion brings a hidden LLT, i.e., it overlaps with the liquid-glass transition. Ambient pressure dielectric and viscosity measurements revealed a peculiar behavior of ion dynamics near Tg for IL with hidden LLT. Moreover, high-pressure studies have shown that IL with hidden LLT has relatively strong pressure sensitivity compared to the one without first-order phase transition. At the same time, the former exposes the inflection point indicating the concave-convex character of logτσ(P) dependences.
circRNA-ZCCHC14 affects the chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells by regulating GREM1 through miR-181a
Authors: Zhao Daohong , Chen Hong , Zhong Jia , Zhou Xizong , Zhang Jun , Zhang Yuhao 
Published: February 2023

AbstractcircRNAs play an important role in the progression of osteoarthritis (OA). Therefore, we aimed to reveal the mechanism of action of circRNA-ZCCHC14 in OA. OA animal and cell models were constructed, and clinical samples were collected. The expression of circRNA-ZCCHC14 and miR-181a was detected by RT‒qPCR. The chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells (PBMSCs) was detected by Alcian blue staining. The expression of chondrogenic differentiation-related proteins was detected by Western blotting. Double fluorescein experiments verified the targeting relationship of miR-181a with circRNA-ZCCHC14 and GREM1. Upregulation of circRNA-ZCCHC14 was observed in blood, in BMP-2- and TGF-β3-treated PBMSCs from OA patients and in animal models. Knockdown of circRNA-ZCCHC14 promoted the chondrogenic differentiation ability of PBMSCs. circRNA-ZCCHC14 was found to bind to miR-181a and negatively regulate miR-181a expression. Inhibition of miR-181a reversed the promoting effect of circRNA-ZCCHC14 knockdown on the chondrogenic differentiation ability of PBMSCs. GREM1 was identified as a target of miR-181a. Overexpression and knockdown of GREM1 regulated the expression of BMP2, which in turn affected the chondrogenic differentiation ability of PBMSCs, indicating that GREM1 and BMP2 have antagonistic effects and that they jointly regulate the chondrogenic differentiation of PBMSCs. circRNA-ZCCHC14 may promote the chondrogenic differentiation ability of PBMSCs by regulating miR-181a and inhibiting the expression of GREM1.
Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7ADR breast cancer cells
Authors: Abdel-Sattar Ola E. , Allam Rasha Mosa , Al-Abd Ahmed M. , Avula Bharathi , Katragunta Kumar , Khan Ikhlas A. , El-Desoky Ahmed M. , Mohamed Shanaz O. , El-Halawany Ali , Abdel-Sattar Essam , Meselhy Meselhy R. 
Published: February 2023

AbstractThe members of the genus Phyllanthus have long been used in the treatment of a broad spectrum of diseases. They exhibited antiproliferative activity against various human cancer cell lines. Breast cancer is the most diagnosed cancer and a leading cause of cancer death among women. Doxorubicin (DOX) is an anticancer agent used to treat breast cancer despite its significant cardiotoxicity along with resistance development. Therefore, this study was designed to assess the potential cytotoxicity of P. niruri extracts (and fractions) alone and in combination with DOX against naïve (MCF-7) and doxorubicin-resistant breast cancer cell lines (MCF-7ADR). The methylene chloride fraction (CH2Cl2) showed the most cytotoxic activity among all tested fractions. Interestingly, the CH2Cl2-fraction was more cytotoxic against MCF-7ADR than MCF-7 at 100 µg/mL. At sub-cytotoxic concentrations, this fraction enhanced the cytotoxic effect of DOX against the both cell lines under investigation (IC50 values of 0.054 µg/mL and 0.14 µg/mL vs. 0.2 µg/mL for DOX alone against MCF-7) and (1.2 µg/mL and 0.23 µg/mL vs. 9.9 µg/mL for DOX alone against MCF-7ADR), respectively. Further, TLC fractionation showed that B2 subfraction in equitoxic combination with DOX exerted a powerful synergism (IC50 values of 0.03 µg/mL vs. 9.9 µg/mL for DOX alone) within MCF-7ADR. Untargeted metabolite profiling of the crude methanolic extract (MeOH) and CH2Cl2 fraction exhibiting potential cytotoxicity was conducted using liquid chromatography diode array detector-quadrupole time-of-flight mass spectrometry (LC-DAD-QTOF). Further studies are needed to separate the active compounds from the CH2Cl2 fraction and elucidate their mechanism(s) of action.
DeepAction: a MATLAB toolbox for automated classification of animal behavior in video
Authors: Harris Carl , Finn Kelly R. , Kieseler Marie-Luise , Maechler Marvin R. , Tse Peter U. 
Published: February 2023

AbstractThe identification of animal behavior in video is a critical but time-consuming task in many areas of research. Here, we introduce DeepAction, a deep learning-based toolbox for automatically annotating animal behavior in video. Our approach uses features extracted from raw video frames by a pretrained convolutional neural network to train a recurrent neural network classifier. We evaluate the classifier on two benchmark rodent datasets and one octopus dataset. We show that it achieves high accuracy, requires little training data, and surpasses both human agreement and most comparable existing methods. We also create a confidence score for classifier output, and show that our method provides an accurate estimate of classifier performance and reduces the time required by human annotators to review and correct automatically-produced annotations. We release our system and accompanying annotation interface as an open-source MATLAB toolbox.
Large network community detection by fast label propagation
Authors: Traag Vincent A. , Šubelj Lovro 
Published: February 2023

AbstractMany networks exhibit some community structure. There exists a wide variety of approaches to detect communities in networks, each offering different interpretations and associated algorithms. For large networks, there is the additional requirement of speed. In this context, the so-called label propagation algorithm (LPA) was proposed, which runs in near-linear time. In partitions uncovered by LPA, each node is ensured to have most links to its assigned community. We here propose a fast variant of LPA (FLPA) that is based on processing a queue of nodes whose neighbourhood recently changed. We test FLPA exhaustively on benchmark networks and empirical networks, finding that it can run up to 700 times faster than LPA. In partitions found by FLPA, we prove that each node is again guaranteed to have most links to its assigned community. Our results show that FLPA is generally preferable to LPA.
Association of glaucoma and lifestyle with incident cardiovascular disease: a longitudinal prospective study from UK Biobank
Authors: Choi Jin A , Lee Su-Nam , Jung Sang-Hyuk , Won Hong-Hee , Yun Jae-Seung 
Published: February 2023

AbstractThe shared pathophysiological features of the cerebrovascular disease (CVD) and glaucoma suggest an association between the two diseases. Using the prospective UK Biobank cohort, we examined the associations between glaucoma and incident CVD and assessed the extent to which a healthy lifestyle reduced the CVD risk in subjects with glaucoma, using a scoring system consisting of four factors: current smoking, obesity, regular physical activity, and a healthy diet. During a mean follow-up time of 8.9 years, 22,649 (4.9%) incident CVD cases were documented. Multivariable Cox regression analyses revealed that subjects with glaucoma were significantly more likely to exhibit incident CVD (hazard ratio [HR]:1.19, 95% confidence interval [CI] 1.03–1.37; p = 0.016) than controls. In the further subgroup analyses, glaucoma increased incident CVD risk both in the young (40–55 years) and the old (56–70 years) and in both sexes, with higher risk in the young (HR: 1.33, CI 1.02–1.74) and female subjects (HR: 1.32, CI 1.14–1.52). When we analyze the associations between glaucoma and incident CVD by lifestyle factors, the highest absolute risks were observed in individuals with both glaucoma and an unhealthy lifestyle (HR: 2.66, CI 2.22–3.19). In conclusion, glaucoma was an independent risk factor for incident CVD. A healthy lifestyle was associated with a substantially lower risk for CVD incidence among adults with glaucoma.