bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ginsenoside Rh2 mitigates doxorubicin‐induced cardiotoxicity by inhibiting apoptotic and inflammatory damage and weakening pathological remodelling in breast cancer‐bearing mice
Authors: Hou Jingang , Yun Yeejin , Cui Changhao , Kim Sunchang 
Published: May 2022

AbstractObjectivesThere are presently a few viable ways to reduce cardiotoxicity of doxorubicin (Dox). The combination of chemotherapy agents with natural compounds delivers greater efficacy and reduces adverse effects in recent researches for cancer treatment. Here, we examined the potential effect of ginsenoside Rh2 on a Dox‐based regimen in chemotherapy treatment.Materials and MethodsHuman breast tumour (MDA‐MB‐231) xenograft nude mice, human cardiac ventricle fibroblasts, and human umbilical vein endothelial cells (HUVEC) were employed in the present study. Histology, immunohistochemistry, immunofluorescence, western blot, antibody array, and RNA‐sequencing analyses were utilized to assess the protective effect of Rh2 on cardiotoxicity induced by Dox and the underlying mechanisms.ResultsRh2‐reduced cardiotoxicity by inhibiting the cardiac histopathological changes, apoptosis and necrosis, and consequent inflammation. Pathological remodelling was attenuated by reducing fibroblast to myofibroblast transition (FMT) and endothelial–mesenchymal transition (EndMT) in hearts. RNA‐sequencing analysis showed that Dox treatment predominantly targets cell cycle and attachment of microtubules and boosted tumour necrosis, chemokine and interferon‐gamma production, response to cytokine and chemokine, and T cell activation, whereas Rh2 regulated these effects. Intriguingly, Rh2 also attenuated fibrosis via promoting senescence in myofibroblasts and reversing established myofibroblast differentiation in EndMT.ConclusionsRh2 regulates multiple pathways in the Dox‐provoked heart, proposing a potential candidate for cancer supplement and therapy‐associated cardiotoxicity.
Consistent signals of a warming climate in occupancy changes of three insect taxa over 40 years in central Europe
Authors: Engelhardt Eva Katharina , Biber Matthias F. , Dolek Matthias , Fartmann Thomas , Hochkirch Axel , Leidinger Jan , Löffler Franz , Pinkert Stefan , Poniatowski Dominik , Voith Johannes , Winterholler Michael , Zeuss Dirk , Bowler Diana E. , Hof Christian 
Published: May 2022

AbstractRecent climate and land‐use changes are having substantial impacts on biodiversity, including population declines, range shifts, and changes in community composition. However, few studies have compared these impacts among multiple taxa, particularly because of a lack of standardized time series data over long periods. Existing data sets are typically of low resolution or poor coverage, both spatially and temporally, thereby limiting the inferences that can be drawn from such studies. Here, we compare climate and land‐use driven occupancy changes in butterflies, grasshoppers, and dragonflies using an extensive data set of highly heterogeneous observation data collected in the central European region of Bavaria (Germany) over a 40‐year period. Using occupancy models, we find occupancies (the proportion of sites occupied by a species in each year) of 37% of species have decreased, 30% have increased and 33% showed no significant trend. Butterflies and grasshoppers show strongest declines with 41% of species each. By contrast, 52% of dragonfly species increased. Temperature preference and habitat specificity appear as significant drivers of species trends. We show that cold‐adapted species across all taxa have declined, whereas warm‐adapted species have increased. In butterflies, habitat specialists have decreased, while generalists increased or remained stable. The trends of habitat generalists and specialists both in grasshoppers and semi‐aquatic dragonflies, however did not differ. Our findings indicate strong and consistent effects of climate warming across insect taxa. The decrease of butterfly specialists could hint towards a threat from land‐use change, as especially butterfly specialists' occurrence depends mostly on habitat quality and area. Our study not only illustrates how these taxa showed differing trends in the past but also provides hints on how we might mitigate the detrimental effects of human development on their diversity in the future.
ADAMTS‐4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy
Authors: Kalebota Natasa , Salai Grgur , Peric Porin , Hrkac Stela , Novak Rudjer , Durmis Kristina Kovac , Grgurevic Lovorka 
Published: May 2022

AbstractIntroductionOsteoarthritis (OA) and haemophilic arthropathy (HA) are clinically similar, but pathologically distinct conditions which result in joint pain and loss of function. Distinguishing their disease mechanisms is therefore a key step in the development of curative therapy, as opposed to current symptomatic treatments. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 is a metzincin‐family member proteoglycan with known local involvement in OA pathogenesis.AimTo investigate the potential differences and discriminatory potential of ADAMTS‐4 between OA and HA patients.MethodsWe determined ADAMTS‐4 plasma concentrations by ELISA in patients with HA and OA. This pilot cross‐sectional study included N = 40 male participants equally divided across four subgroups: haemophilia patients with severe or mild HA and control subjects with severe or mild/no OA.ResultsOur study showed a striking elevation in plasma ADAMTS‐4 expression levels in HA patients as compared to OA, as well as an increase in patients with severe as compared to mild HA. By performing the binomial logistical analysis and fitting the receiver–operator curve (ROC) (cut‐off probability .5), ADAMTS‐4 had a sensitivity of 95% and specificity of 50% in discriminating between HA and OA among our study participants.ConclusionUncovering the marked differences in plasma levels of ADAMTS‐4 in patients with HA versus OA potentially sheds new light on the mechanisms of HA pathogenesis and could foster more research into the roles ADAMTS‐4 and other matrix metalloproteinases (MMPs) play in HA versus OA.
Increased multimorbidity is associated with impaired cerebral and peripheral hemodynamic stabilization during active standing
Authors: Pérez‐Denia Laura , Claffey Paul , Byrne Lisa , Rice Ciara , Kenny Rose Anne , Finucane Ciarán 
Published: May 2022

AbstractBackgroundAge‐related morbidities and frailty are associated with impaired blood pressure (BP) and heart rate (HR) recovery after standing. Here we investigate how multimorbidity affects cerebral and peripheral hemodynamics during standing in a large sample of older patients.MethodsPatients were recruited from a national Falls and Syncope Unit. They underwent an active stand test (5–10 min lying +3 min standing) with monitoring of continuous BP, HR, total peripheral resistance (TPR), stroke volume (SV), and a near‐infrared spectroscopy (NIRS) derived cerebral tissue saturation index (TSI). A multimorbidity count was derived from a 26‐item list of conditions. Features derived from the signals included: nadir, overshoot, value at 30 s, steady‐state and recovery rate. Robust linear regression was used to assess the association between multimorbidity, TSI and peripheral hemodynamics while correcting for covariates. A p‐value <0.05 was considered statistically significant.ResultsMultimorbidity was associated with poorer recovery of TSI at 30 s after standing (β: −0.15, CI:[−0.25–0.06], p = 0.009) independent of all peripheral hemodynamics. Impaired diastolic BP (DBP) recovery at 30s (β:−1.34, CI:[−2.29–0.40], p = 0.032), DBP steady‐state (β:−1.18, CI:[−2.04–0.32], p = 0.032), TPR overshoot‐to‐nadir difference (β:−0.041, CI:[−0.070–0.013], p = 0.045), and SV at 30s (β:1.30, CI:[0.45 2.15], p = 0.027) were also associated with increasing multimorbidity. After sex stratification, only females demonstrated impaired TSI with multimorbidity at overshoot (β: −0.19, CI: [−0.32 ‐0.07], p = 0.009), 30 s (β: −0.22 [−0.35–0.10], p = 0.005) and steady‐state (β: −0.20, CI:[−0.35–0.04], p = 0.023), independent of peripheral hemodynamics.ConclusionsTransient cerebral oxygenation and peripheral hemodynamic responses are impaired with multimorbidity (frailty) in older patients, particularly in females. This study demonstrates the feasibility of using NIRS in this clinical context and may inform the development of clinical management strategies targeting both cerebral oxygenation and blood pressure impairments in patients with faints and falls.
Effect of educational interventions on level of epilepsy knowledge in children with epilepsy and parents: Systematic review and meta‐analysis
Authors: Turan Fatma D. , Yangöz Şefika T. 
Published: May 2022

AbstractAim and ObjectivesThe aim of the study was to synthesise the effect of educational interventions on the level of epilepsy knowledge in children with epilepsy and parents.BackgroundEducational interventions are commonly used to provide knowledge about epilepsy management. One of the most important responsibilities of nurses is to inform children with epilepsy and parents in a skilful way.DesignSystematic review and meta‐analysis based on PRISMA 2020.MethodsWe searched CINAHL, Cochrane Library, Science Direct, Web of Science, Ovid, PubMed, Scopus, Springer Link, ProQuest, TR Index ending March 2021. The review followed the PRISMA guidelines. This meta‐analysis was analysed in Comprehensive Meta‐Analysis version 3 software. The risk of bias of included studies was assessed with the Cochrane handbook. The results were the level of epilepsy knowledge of children and parents.ResultsTen studies meeting the inclusion criteria were included in this meta‐analysis, including four randomised studies and six non‐randomised studies. Educational interventions had large effect on improving the level of epilepsy knowledge in children with epilepsy (p < .001, Hedge's g = 1.19) and parents (p < .001, Hedge's g = 1.41). As a result of the subgroup analyses, significant differences were found only in the type of educational intervention. It was found that traditional education is more effective than technology‐based education in improving the level of epilepsy knowledge in parents (p = .005, Hedge's g = 1.77).ConclusionEducational interventions have high and beneficial effect on the level of epilepsy knowledge in the children with epilepsy and parents; can be used as effective interventions in the epilepsy management. However, due to low number of randomised controlled studies, further high‐quality randomised controlled studies are needed about this topic.Relevance to clinical practiceThe findings will contribute to the use of educational interventions in the epilepsy management for health professionals, especially nurses. Thus these interventions will contribute to improving epilepsy management of children with epilepsy and parents.
Ruminal responses, digestibility, and blood parameters of beef cattle fed diets without forage with different hybrids and processing of the corn
Authors: da Mata Débora G. , Ítavo Luís C. V. , Ferreira Ítavo Camila C. B. , Ferreira João D. de Jesus , Paulino Pedro V. R. , de Moraes Gabriella J. , Niwa Marcus V. G. , Kozerski Noemila D. , Leal Eduardo S. , Mioto da Costa Marlova C. 
Published: May 2022

AbstractThe objective of this study was to evaluate the effects of corn hybrid and processing methods on intake and digestibility of nutrients, rumen fermentation and blood metabolites of steers fed no‐forage finishing diets. Four ruminally fistulated Nellore castrated steers (502 ± 15 kg initial body weight) were distributed in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement consisting of two corn hybrids (semi‐dent and flint) and two processing methods (dry milled and high moisture grain). Interactions of hybrid and processing methods were observed on intake of dry matter (DM), organic matter (OM) and crude protein (CP), as well as on digestibility of DM and CP, rumen pH and ammonia nitrogen (N‐NH3). There was no interaction between hybrid and processing for the volatile fatty acids (VFA) total, acetate (C2), propionate (C3), isobutyric (iC4) and valeric (nC5) concentrations. VFA total concentration shown an average of 103.4 mmol/L. The C2 and C3 concentrations had no effect of the hybrid or processing with averages of 58.7 mmol/L for C2, and 31.3 mmol/l for C3. There was an effect of the processing method on starch consumption and fecal pH, the highest values were observed in grains with high moisture content. Starch digestibility was 0.89 g/g in dry milled and 0.96 g/g in high moisture corn. The greatest digestibility of starch in high moisture corn, irrespective of the corn hybrid, provided evidence of an increase in the energy supply, which may improve the feed efficiency and growth performance of cattle fed no‐roughage finishing diets.
Safety of oral afoxolaner formulated with or without milbemycin oxime in homozygousMDR1‐deficient collie dogs
Authors: Drag Marlene , Tielemans Eric , Mitchell Elizabeth 
Published: May 2022

AbstractAfoxolaner, an insecticide and acaricide compound of the isoxazoline class, is available for dogs as an oral ectoparasiticide medicine (NexGard®) and as an oral endectoparasiticide medicine in combination with milbemycin oxime (MO), a macrocyclic lactone (NexGard® Spectra). The safety of these two compounds, alone or in combination, was investigated in homozygous MDR1‐deficient collie dogs, in two studies. Overall, 30 adult collie dogs were treated once orally, 9 with a placebo, 9 with afoxolaner, 6 with MO, and 6 with a combination of afoxolaner and MO. For afoxolaner, the mean investigated dosage corresponded to 3.8 and 4.7 multiples of the maximum recommended therapeutic doses (RTD) in NexGard® and NexGard® Spectra, respectively. For MO, the mean investigated dosage corresponded to 4.7 multiples of the maximum RTD in NexGard® Spectra. Dogs were closely monitored for adverse reactions on the day of treatment and for the following two days. No significant adverse reaction was observed in any dog from the afoxolaner or the afoxolaner + MO groups; in the MO‐only treated group, mild and transient neurological signs were observed during the 4–8 h post‐treatment window. These studies demonstrated a high level of safety of oral afoxolaner, alone or in combination with milbemycin oxime, in homozygous MDR1‐deficient dogs.
The UvrA‐like protein Ecm16 requires ATPase activity to render resistance against echinomycin
Authors: Erlandson Amanda , Gade Priyanka , Menikpurage Inoka P. , Kim Chu‐Young , Mera Paola E. 
Published: May 2022

AbstractBacteria use various strategies to become antibiotic resistant. The molecular details of these strategies are not fully understood. We can increase our understanding by investigating the same strategies found in antibiotic‐producing bacteria. In this work, we characterize the self‐resistance protein Ecm16 encoded by echinomycin‐producing bacteria. Ecm16 is a structural homolog of the nucleotide excision repair protein UvrA. Expression of ecm16 in the heterologous system Escherichia coli was sufficient to render resistance against echinomycin. Ecm16 binds DNA (double‐stranded and single‐stranded) using a nucleotide‐independent binding mode. Ecm16’s binding affinity for DNA increased by 1.7‐fold when the DNA is intercalated with echinomycin. Ecm16 can render resistance against echinomycin toxicity independently of the nucleotide excision repair system. Similar to UvrA, Ecm16 has ATPase activity, and this activity is essential for Ecm16’s ability to render echinomycin resistance. Notably, UvrA and Ecm16 were unable to complement each other's function. Together, our findings identify new mechanistic details of how a refurbished DNA repair protein Ecm16 can specifically render resistance to the DNA intercalator echinomycin.
Biodiversity for resilience—What is needed for allergic children
Authors: Haahtela Tari 
Published: May 2022

AbstractWhat is needed for our children facing unprecedented challenges of modern time? Biodiversity, both for immunological and psychological well‐being and resilience. That is also the keyword for the children with allergies and asthma. The cultural evolution with advanced technology and medicine along with major move to urban environment has profoundly changed our lifestyle and surroundings. We are increasingly disconnected from our evolutionary home, soil, natural waters, and air we used to breathe. The ecosystem of human body and mind has been tested, survived, and evolved closely in relation with other ecosystems. For balance and tolerance, immune regulatory circuits need training by microbes, biogenic chemicals, and close relation to natural environment throughout life. This is addressed by the biodiversity hypothesis of tolerance/resilience for health, supported by the pioneering real‐world interventions and a few controlled studies. No need to go “back to nature,” but we must take natural elements back to our everyday life to breathe, eat, drink, and touch. The change for better is plausible and cost‐effective, as shown by the Finnish and other European initiatives, but needs contribution of the whole society.
Genetic variation in CaTIFY4b contributes to drought adaptation in chickpea
Authors: Barmukh Rutwik , Roorkiwal Manish , Garg Vanika , Khan Aamir W. , German Liam , Jaganathan Deepa , Chitikineni Annapurna , Kholova Jana , Kudapa Himabindu , Sivasakthi Kaliamoorthy , Samineni Srinivasan , Kale Sandip M. , Gaur Pooran M. , Sagurthi Someswar Rao , Benitez‐Alfonso Yoselin , Varshney Rajeev K. 
Published: May 2022

SummaryChickpea production is vulnerable to drought stress. Identifying the genetic components underlying drought adaptation is crucial for enhancing chickpea productivity. Here, we present the fine mapping and characterization of ‘QTL‐hotspot’, a genomic region controlling chickpea growth with positive consequences on crop production under drought. We report that a non‐synonymous substitution in the transcription factor CaTIFY4b regulates seed weight and organ size in chickpea. Ectopic expression of CaTIFY4b in Medicago truncatula enhances root growth under water deficit. Our results suggest that allelic variation in ‘QTL‐hotspot’ improves pre‐anthesis water use, transpiration efficiency, root architecture and canopy development, enabling high‐yield performance under terminal drought conditions. Gene expression analysis indicated that CaTIFY4b may regulate organ size under water deficit by modulating the expression of GRF‐INTERACTING FACTOR1 (GIF1), a transcriptional co‐activator of Growth‐Regulating Factors. Taken together, our study offers new insights into the role of CaTIFY4b and on diverse physiological and molecular mechanisms underpinning chickpea growth and production under specific drought scenarios.
The irony of Confucius
Authors: Amarantidou Dimitra 
Published: May 2022

AbstractIn this article, I present different readings of Confucius's irony in theAnalects(orLunyu論語) and expand on the implications of irony for how we perceive Confucius. Scholars who have appreciated the irony of Confucius tend to see it as distinctive of an unsagely, everyday man, often juxtaposed to the dominant image of the Master as a hyperserious sage. Moreover, irony is considered a pedagogical tool. These readings mainly recognizeverbal irony(Confucius means the opposite of what he says). I discuss a second type of irony:complex irony(Confucius both means and does not mean what he says). I argue that sageliness is not incompatible with irony, and further propose that complex irony can be found beyond the sentence level; it can be the feature of the relation between specific sayings. Adapting to his interlocutors' diverse personalities and needs, and to a constantly changing world, Confucius sometimes provides different and even conflicting answers to the same questions, based on contextual appropriateness. Each answer is meant to be taken literally and fits one concrete situation. The same answer, however, can be simultaneously ineffective or even dangerous in another albeit seemingly similar context. Thus Confucius sometimes both means what he says and does not mean it in an absolute sense.
Treating people where they are: Nurse‐led micro‐elimination of hepatitis C in supported housing sites for networks of people who inject drugs in Victoria, Canada
Authors: Selfridge Marion , Barnett Tamara , Lundgren Karen , Guarasci Kellie , Milne Rozalyn , Drost Anne , Fraser Chris 
Published: May 2022

AbstractTo achieve the World Health Organization's goal of eliminating hepatitis C (HCV) by 2030 requires enhanced HCV testing and treatment among people who use drugs (PWUD). Micro‐elimination of HCV is a strategy to target HCV testing and treatment efforts to specific segments of the population. From February to December 2018 nurses initiated a “seek & treat” micro‐elimination approach, increasing outreach and removing barriers to accessing HCV treatment in a clinic setting by testing and treating individuals, including PWUD, where they live. The aim of this study was to evaluate the proportion of clients with HCV antibodies and HCV RNA and the response to direct acting agent (DAA therapy) among people who live at or have social connections to local supportive housing sites through this nurse‐led micro‐elimination project in Victoria, Canada. A chart review of electronic medical records and case management documentation was used to collect relevant data of participants treated with DAA therapy, identified through specific housing site testing and outreach interventions. In total, 180 people were tested for HCV antibodies, 72 (40%) were antibody positive: 51 (28%) were RNA positive, 13 (7%) had spontaneously cleared and 8 (4%) had been previously treated. Of the 51 that were currently living with HCV, 43 people were started on treatment, 39 have achieved sustained virologic response (SVR). By providing treatment to clients in their homes and with their friends, clinicians have been able to treat clients, including those with limited contact with the health care system.
An One-Factor Copula Mixed Model for Joint Meta-Analysis of Multiple Diagnostic Tests
Authors: Nikoloulopoulos Aristidis K. 
Published: May 2022

AbstractAs meta-analysis of multiple diagnostic tests impacts clinical decision making and patient health, there is an increasing body of research in models and methods for meta-analysis of studies comparing multiple diagnostic tests. The application of the existing models to compare the accuracy of three or more tests suffers from the curse of multi-dimensionality, that is, either the number of model parameters increases rapidly or high dimensional integration is required. To overcome these issues in joint meta-analysis of studies comparing T &gt; 2 diagnostic tests in a multiple tests design with a gold standard, we propose a model that assumes the true positives and true negatives for each test are conditionally independent and binomially distributed given the 2T-variate latent vector of sensitivities and specificities. For the random effects distribution, we employ a one-factor copula that provides tail dependence or tail asymmetry. Maximum likelihood estimation of the model is straightforward as the derivation of the likelihood requires bi-dimensional instead of 2T-dimensional integration. Our methodology is demonstrated with an extensive simulation study and an application example that determines which is the best test for the diagnosis of rheumatoid arthritis.