bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of left ventricular assist device on heart failure patients: A bioinformatics analysis
Authors: Li Guanhua , Chen Zhibo , Zhang Yu , Wu Zhichao , Zheng Junmeng 
Published: December 2019

AbstractWith the acceleration of demographic aging, heart failure has become a global public health issue. Left ventricular assist device (LVAD) provides a therapeutic option serving as a bridge to transplantation or destination treatment for end‐stage heart failure. However, neither the molecular mechanism nor the gene expression profile of LVAD pathophysiology is well understood. Microarray dataset (GSE21610) was retrieved from the online database of the gene expression omnibus (GEO). Differentially expressed genes (DEGs) between microarrays obtained before and after LVAD therapy were analyzed using GEO2R. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out, followed by protein–protein interaction (PPI) network construction, which was further visualized by the Cytoscape software. Finally, a target gene‐microRNA (miRNA) network was built using the NetworkAnalyst to predict potential miRNA interactions. A total of 36 upregulated DEGs and 14 downregulated DEGs were screened out. Five hub genes with the highest degree of connectivity were identified, including CCL2, CX3CR1, CD163, TLR7, and SERPINE1. CCL2 was identified as the most outstanding hub gene which is specially regulated by miR‐124, miR‐141, and miR‐495. Our study indicates that CCL2 is crucial to the LVAD pathophysiology. The identified hub genes may be involved in cardiac inflammatory responses, remodeling, and the chemokine signaling pathway. These DEGs, pathways, hub genes, miRNAs are valuable for further investigations. This study provides a better understanding of the gene expression profile in LVAD pathophysiology.
Procalcitonin‐guided protocol decreased the antibiotic use in paediatric patients with severe bronchiolitis
Authors: Alejandre Carme , Balaguer Mònica , Guitart Carmina , Torrús Isabel , Felipe Aida , Launes Cristian , Cambra Francisco José , Jordan Iolanda 
Published: December 2019

AbstractAimOur aim was to determine the effectiveness and safety of a procalcitonin‐guided protocol to decrease antibiotic use in infants with severe bronchiolitis.MethodsThis prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin‐guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010‐2014 and 366 in 2015‐2017.ResultsWe recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0‐100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol.ConclusionThe implementation of a procalcitonin‐guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.
Probing renal blood volume with magnetic resonance imaging
Authors: Niendorf Thoralf , Seeliger Erdmann , Cantow Kathleen , Flemming Bert , Waiczies Sonia , Pohlmann Andreas 
Published: December 2019

AbstractDamage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level–dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T2*) in vivo, and is non‐invasive and indicative of renal tissue oxygenation. However, the renal T2* to tissue pO2relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI‐based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T2* are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol‐enhanced MRI in the equilibrium concentration regimen. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI‐based assessment of renal BVf.
Efficacy and safety of induction therapy with calcineurin inhibitors followed by vedolizumab maintenance in 71 patients with severe steroid‐refractory ulcerative colitis
Authors: Ollech Jacob E. , Dwadasi Sujaata , Rai Victoria , Peleg Noam , Normatov Inessa , Israel Amanda , Sossenheimer Philip H. , Christensen Britt , Pekow Joel , Dalal Sushila R. , Sakuraba Atsushi , Cohen Russell D. , Rubin David T. 
Published: December 2019

SummaryBackgroundFollowing induction therapy with a calcineurin inhibitor (CNI) in severe ulcerative colitis, transitioning to vedolizumab as maintenance therapy could be an option.AimTo report on the largest cohort of patients successfully induced with CNIs who were transitioned to vedolizumab maintenance therapy.MethodsThis is a retrospective observational study of adult patients with severe steroid‐refractory ulcerative colitis. Patients were included if they were induced with a CNI followed by maintenance therapy with vedolizumab between January 2014 and December 2018. The primary endpoint was colectomy‐free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid‐free and biochemical remission at week 14.ResultsA total of 71 patients (59% male) were treated with vedolizumab after induction therapy with CNIs for severe steroid‐refractory colitis. Patients were followed for a median time of 25 months (IQR 16‐36). Colectomy‐free survival rates from vedolizumab initiation were 93% at 3 months, 67% at 1 year and 55% at 2 years. At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At 1 and 2 years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab respectively. Vedolizumab was dose escalated to infusions every 4 weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1‐8.2). No serious adverse events were recorded in our patient cohort.ConclusionsTransitioning to vedolizumab following induction of remission with CNIs is effective and safe.
The role of academic buoyancy and emotions in students’ learning‐related expectations and behaviours in primary school
Authors: Hirvonen Riikka , Putwain David W. , Määttä Sami , Ahonen Timo , Kiuru Noona 
Published: December 2019

BackgroundAcademic buoyancy refers to students’ ability to come through ordinary challenges they face in the academic context, and it can positively contribute to students’ beliefs and behaviours in learning situations. Although buoyancy has been found to be related to positive academic outcomes, previous studies have not examined how buoyancy influences academic emotions in learning situations and how these emotions further affect students’ learning‐related expectations and behaviours.AimsThis study investigated to what extent academic buoyancy predicts students’ failure expectations, avoidance behaviour, and task‐oriented planning in learning situations, and to what extent academic emotions mediate the effect of academic buoyancy on these expectations and behaviours.SampleA total of 845 Finnish students in the sixth grade of primary school.MethodsSelf‐report data for academic buoyancy and academic emotions in the autumn semester and learning‐related expectations and behaviours in the spring semester were analysed using structural equation modelling, controlling for gender, grade point average, and previous levels of learning‐related expectations and behaviours.ResultsThe findings showed that high academic buoyancy indirectly predicted lower avoidance behaviour, fewer failure expectations, and higher task‐oriented planning via academic emotions. High academic buoyancy was related to high enjoyment and hope as well as low boredom and hopelessness, which further predicted low failure expectations. High hope and low boredom also predicted low avoidance behaviour, and high hope was associated with high task‐oriented planning.ConclusionsThe findings suggest that academic buoyancy supports positive expectations and adaptive behaviours in learning situations through the regulation of emotions.
Fulditoxin, representing a new class of dimeric snake toxins, defines novel pharmacology at nicotinic ACh receptors
Authors: Foo Chun Shin , Jobichen Chacko , Hassan‐Puttaswamy Varuna , Dekan Zoltan , Tae Han‐Shen , Bertrand Daniel , Adams David J. , Alewood Paul F. , Sivaraman J. , Nirthanan Selvanayagam , Kini R. Manjunatha 
Published: December 2019

Background and PurposeAnimal toxins have contributed significantly to our understanding of the neurobiology of receptors and ion channels. We studied the venom of the coral snake Micrurus fulvius fulvius and identified and characterized the structure and pharmacology of a new homodimeric neurotoxin, fulditoxin, that exhibited novel pharmacology at nicotinic ACh receptors (nAChRs).Experimental ApproachFulditoxin was isolated by chromatography, chemically synthesized, its structure determined by X‐ray crystallography, and its pharmacological actions on nAChRs characterized by organ bath assays and two‐electrode voltage clamp electrophysiology.Key ResultsFulditoxin's distinct 1.95‐Å quaternary structure revealed two short‐chain three‐finger α‐neurotoxins (α‐3FNTxs) non‐covalently bound by hydrophobic interactions and an ability to bind metal and form tetrameric complexes, not reported previously for three‐finger proteins. Although fulditoxin lacked all conserved amino acids canonically important for inhibiting nAChRs, it produced postsynaptic neuromuscular blockade of chick muscle at nanomolar concentrations, comparable to the prototypical α‐bungarotoxin. This neuromuscular blockade was completely reversible, which is unusual for snake α‐3FNTxs. Fulditoxin, therefore, interacts with nAChRs by utilizing a different pharmacophore. Unlike short‐chain α‐3FNTxs that bind only to muscle nAChRs, fulditoxin utilizes dimerization to expand its pharmacological targets to include human neuronal α4β2, α7, and α3β2 nAChRs which it blocked with IC50 values of 1.8, 7, and 12 μM respectively.Conclusions and ImplicationsBased on its distinct quaternary structure and unusual pharmacology, we named this new class of dimeric Micrurus neurotoxins represented by fulditoxin as Σ‐neurotoxins, which offers greater insight into understanding the interactions between nAChRs and peptide antagonists.
Haemodynamic effects of the flavonoid quercetin in rats revisited
Authors: Vrolijk Misha F. , van Essen Helma , Opperhuizen Antoon , Bast Aalt , Janssen Ben J. 
Published: December 2019

Background and PurposeThe flavonoid quercetin increased the in vitro potency of the α1‐antagonist tamsulosin to reduce phenylephrine‐dependent arterial contractions by 10‐fold. To examine if this supplement–drug interaction luxates hypotensive and orthostatic events in vivo, several set of studies were conducted in spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto [WKY]) rats.Experimental ApproachFirst, in rats pretreated with quercetin or its vehicle, responses to phenylephrine and tamsulosin were examined. Second, tamsulosin‐induced changes in renal, mesenteric, hindquarter and carotid conductance were compared in quercetin‐ and vehicle‐treated rats instrumented with Doppler flow probes. Animals were also placed on a tilt table to record regional haemodynamic changes to orthostatic challenges. Third, adult SHR were instrumented with telemeters to measure 24‐hr patterns of BP. Recordings were made before and during a 5‐week oral treatment of quercetin. Finally, pre‐hypertensive SHR were treated with quercetin from 4 to 8 weeks of age and arterial pressure was measured at 8 and 12 weeks.Key ResultsPretreatment with quercetin did not influence the responses to phenylephrine and tamsulosin, in neither WKY nor SHR. While tamsulosin treatment and tilting lowered BP and increased conductance in all vascular beds, effect size was not influenced by pretreatment with quercetin. Prolonged treatment with quercetin, in either prehypertensive SHR or adult SHR with established hypertension did not lower BP.Conclusions and ImplicationsCumulatively, these data demonstrate that quercetin does not amplify haemodynamic effects of tamsulosin or tilting in vivo in rats and has no effect on BP development in SHR.
Identification, preclinical profile, and clinical proof of concept of an orally bioavailable pro‐drug of miridesap
Authors: Richards Duncan , Bamford Mark , Liefaard Lia , Haque Nazneen , Lewis Gareth , Storey Jim , Fernando Disala , Kumar Subramanya , Thompson Douglas , Holmes Duncan S. 
Published: December 2019

Background and PurposeMiridesap, a depleter of serum amyloid P component (SAP), forms an essential component of a novel approach to remove systemic amyloid deposits; low oral bioavailability necessitates that it is given parenterally. We sought to identify and clinically characterise a pro‐drug that preserves the pharmacological properties of miridesap while having adequate oral bioavailability and physical stability.Experimental ApproachWe utilised a preclinical screening cascade focused on appropriate physicochemical properties, physical and gut stability, and conversion to miridesap in liver microsomes and blood. GSK3039294 (GSK294) had the desired in vitro profile and progressed to preclinical in vivo pharmacokinetic and safety assessments. Based on a favourable profile, it was tested in healthy participants after single and repeat dosing.Key ResultsGSK294 was highly soluble and stable in simulated gastric and intestinal fluids, stable in intestinal microsomes, and permeable in Madine Darby Canine Kidney type II cells. GSK294 was rapidly hydrolysed to miridesap and its mono pro‐drug ester in blood and liver microsomes. GSK294 showed good oral bioavailability of miridesap in rats and dogs. Following administration of GSK294 600 mg QD for 7 days in humans, pharmacodynamically active concentrations of miridesap were achieved with substantial and sustained depletion of plasma SAP. The study was terminated due to observations of arrhythmia, the relation of which to GSK294 remains unclear.Conclusion and ImplicationsUsing a preclinical screening cascade, we identified a pro‐drug for a palindromic molecule with unique pharmacology (miridesap). The pro‐drug depleted circulating SAP with a time course and extent similar to that of parenterally administered miridesap.
Ant‐termite interactions: an important but under‐explored ecological linkage
Authors: Tuma Jiri , Eggleton Paul , Fayle Tom M. 
Published: December 2019

ABSTRACTAnimal interactions play an important role in understanding ecological processes. The nature and intensity of these interactions can shape the impacts of organisms on their environment. Because ants and termites, with their high biomass and range of ecological functions, have considerable effects on their environment, the interaction between them is important for ecosystem processes. Although the manner in which ants and termites interact is becoming increasingly well studied, there has been no synthesis to date of the available literature. Here we review and synthesise all existing literature on ant–termite interactions. We infer that ant predation on termites is the most important, most widespread, and most studied type of interaction. Predatory ant species can regulate termite populations and subsequently slow down the decomposition of wood, litter and soil organic matter. As a consequence they also affect plant growth and distribution, nutrient cycling and nutrient availability. Although some ant species are specialised termite predators, there is probably a high level of opportunistic predation by generalist ant species, and hence their impact on ecosystem processes that termites are known to provide varies at the species level. The most fruitful future research direction will be to evaluate the impact of ant–termite predation on broader ecosystem processes. To do this it will be necessary to quantify the efficacy both of particular ant species and of ant communities as a whole in regulating termite populations in different biomes. We envisage that this work will require a combination of methods, including DNA barcoding of ant gut contents along with field observations and exclusion experiments. Such a combined approach is necessary for assessing how this interaction influences entire ecosystems.
Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early‐life risk factors and late asthma outcomes
Authors: Deliu Matea , Fontanella Sara , Haider Sadia , Sperrin Matthew , Geifman Nophar , Murray Clare , Simpson Angela , Custovic Adnan 
Published: December 2019

AbstractIntroductionExacerbation‐prone asthma subtype has been reported in studies using data‐driven methodologies. However, patterns of severe exacerbations have not been studied.ObjectiveTo investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age.MethodsWe applied longitudinal k‐means clustering to derive exacerbation trajectories among 887 participants from a population‐based birth cohort with severe wheeze exacerbations confirmed in healthcare records. We examined early‐life risk factors of the derived trajectories, and their asthma‐related outcomes and lung function in adolescence.Results498/887 children (56%) had physician‐confirmed wheeze by age 8 years, of whom 160 had at least one severe exacerbation. A two‐cluster model provided the optimal solution for severe exacerbation trajectories among these 160 children: “Infrequent exacerbations (IE)” (n = 150, 93.7%) and “Early‐onset frequent exacerbations (FE)” (n = 10, 6.3%). Shorter duration of breastfeeding was the strongest early‐life risk factor for FE (weeks, median [IQR]: FE, 0 [0‐1.75] vs. IE, 6 [0‐20], P < .001). Specific airway resistance (sRaw) was significantly higher in FE compared with IE trajectory throughout childhood. We then compared children in the two exacerbation trajectories with those who have never wheezed (NW, n = 389) or have wheezed but had no severe exacerbations (WNE, n = 338). At age 8 years, FEV1/FVC was significantly lower and FeNO significantly higher among FE children compared with all other groups. By adolescence (age 16), subjects in FE trajectory were significantly more likely to have current asthma (67% FE vs. 30% IE vs. 13% WNE, P < .001) and use inhaled corticosteroids (77% FE vs. 15% IE vs. 18% WNE, P < .001). Lung function was significantly diminished in the FE trajectory (FEV1/FVC, mean [95%CI]: 89.9% [89.3‐90.5] vs. 88.1% [87.3‐88.8] vs. 85.1% [83.4‐86.7] vs. 74.7% [61.5‐87.8], NW, WNE, IE, FE respectively, P < .001).ConclusionWe have identified two distinct trajectories of severe exacerbations during childhood with different early‐life risk factors and asthma‐related outcomes in adolescence.
In vitro retention force changes during cyclic dislodging of three novel attachment systems for implant overdentures with different implant angulations
Authors: Maniewicz Sabrina , Badoud Isabelle , Herrmann François R. , Chebib Najla , Ammann Patrick , Schimmel Martin , Müller Frauke , Srinivasan Murali 
Published: December 2019

AbstractObjectivesThis in vitro study aimed to compare changes in retentive force due to cyclic dislodging of three novel un‐splinted attachments.Materials and MethodsExperimental models simulating a mandibular two‐implant overdenture situation, with implants positioned with various interimplant discrepancies (0°, 20°, 40°, and 60°) were fabricated. Three attachment systems were tested, “N”: a straight or 15°‐angulated stud; “L”: a sole straight stud; and “C”: a straight or individually angulated stud. All models underwent wet testing and were subjected to 10,000 insertion–removal cycles in a universal testing machine. The mean retentive forces were calculated for cycles 10, 100, 1,000, 5,000, and 10,000. Multiple mixed‐effects linear regression models were applied for statistical analyses (⍺ < 0.05).Results“N” demonstrated an increasing retention until 1,000 cycles, which subsequently diminished back to its initial retention at 10,000 cycles, showing no significant loss during the entire experiment. Statistical models demonstrated no effect of implant angulation on retention, except for 60° after 10,000 cycles (p < .05). “L” showed an early peak at 100 cycles and did not significantly lose retentive force before 5,000 cycles. Angulations of 40° or higher were shown to lead to lower retentive forces (0° vs. 40° cycle 5,000: p < .05; 0° vs. 60° cycle 100: p < .05, ≥cycle 1,000: p < .001). “C” showed stable retentive forces with no significant loss only at 10,000 cycles (all angles: p < .001) or 5,000 cycles (0° vs. 60°: p < .05).ConclusionsAll systems showed retentive forces promising successful clinical use in implant overdentures, even in situations with extremely angulated implants. Specific abutments compensating interimplant angulation maintain retention longer in situations with high axe divergencies.