bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the cost-effectiveness of dexrazoxane for the prevention of anthracycline-related cardiotoxicity in children with sarcoma and haematologic malignancies: a European perspective
Authors: Dewilde Sarah , Carroll Kevin , Nivelle Emilia , Sawyer James 
Published: February 2020

Abstract
Background
Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m2. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established.

Methods
A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain.

Results
Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany.

Conclusions
Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m2 are included in the model.
HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study
Authors: Orta-Resendiz Aurelio , Rodriguez-Diaz Roberto A. , Angulo-Medina Luis A. , Hernandez-Flores Mario , Soto-Ramirez Luis E. 
Published: February 2020

AbstractBackgroundIn resource-limited settings, multi-experienced HIV infected patients are often prescribed raltegravir for salvage therapy. Patients failing raltegravir-containing regimens require other drugs including other integrase inhibitors. In this context, real-life data about the resistance and cross-resistance pathways between integrase inhibitors is limited. The aim of this study was to investigate integrase resistance pathways in a cohort of Mexican multi-experienced patients failing of a raltegravir-containing salvage regimen.MethodsTwenty-five plasma samples from subjects failing antiretroviral regimens which included raltegravir were obtained from various healthcare centres from 2009 to 2017 in Mexico. Antiretroviral history and demographics were collected. Samples were processed for integrase resistance genotyping testing by sequencing. The viral sequences were analysed with the Stanford HIV drug resistance database algorithm. Data was analysed with SPSS Statistics software.ResultsWe found a mean viral load of 4.17 log10 c/mL (SD 1.11) at the time of virologic failure. Forty-eight percent of the samples were raltegravir resistant. The Y143R/H/C substitutions were the most prevalent, followed by the N155H, and both Q148H/K and G140S/A in the same proportion. The Q148 + G140 combination was found in (12%) of the samples. Cross-resistance to elvitegravir was found in 83.3% and in 18.2% for both dolutegravir and bictegravir. Thirteen samples (52%) were susceptible to the four integrase strand-transfer inhibitors.ConclusionsOur findings suggest a high occurrence of resistance and cross-resistance to other integrase inhibitors among multi-experienced subjects failing raltegravir. We found a modestly lower proportion of cross-resistance to dolutegravir than data from clinical trials. Likely this drug could be used for salvage therapy. Explanations for the absence of mutations in half of the samples, other than reduced adherence, should be further investigated. Close surveillance is needed.
GEARing smart environments for pediatric motor rehabilitation
Authors: Kokkoni Elena , Mavroudi Effrosyni , Zehfroosh Ashkan , Galloway James C. , Vidal Renè , Heinz Jeffrey , Tanner Herbert G. 
Published: February 2020

Abstract
Background
There is a lack of early (infant) mobility rehabilitation approaches that incorporate natural and complex environments and have the potential to concurrently advance motor, cognitive, and social development. The Grounded Early Adaptive Rehabilitation (GEAR) system is a pediatric learning environment designed to provide motor interventions that are grounded in social theory and can be applied in early life. Within a perceptively complex and behaviorally natural setting, GEAR utilizes novel body-weight support technology and socially-assistive robots to both ease and encourage mobility in young children through play-based, child-robot interaction. This methodology article reports on the development and integration of the different system components and presents preliminary evidence on the feasibility of the system.

Methods
GEAR consists of the physical and cyber components. The physical component includes the playground equipment to enrich the environment, an open-area body weight support (BWS) device to assist children by partially counter-acting gravity, two mobile robots to engage children into motor activity through social interaction, and a synchronized camera network to monitor the sessions. The cyber component consists of the interface to collect human movement and video data, the algorithms to identify the children’s actions from the video stream, and the behavioral models for the child-robot interaction that suggest the most appropriate robot action in support of given motor training goals for the child. The feasibility of both components was assessed via preliminary testing. Three very young children (with and without Down syndrome) used the system in eight sessions within a 4-week period.

Results
All subjects completed the 8-session protocol, participated in all tasks involving the selected objects of the enriched environment, used the BWS device and interacted with the robots in all eight sessions. Action classification algorithms to identify early child behaviors in a complex naturalistic setting were tested and validated using the video data. Decision making algorithms specific to the type of interactions seen in the GEAR system were developed to be used for robot automation.

Conclusions
Preliminary results from this study support the feasibility of both the physical and cyber components of the GEAR system and demonstrate its potential for use in future studies to assess the effects on the co-development of the motor, cognitive, and social systems of very young children with mobility challenges.
Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection
Authors: Sebrow Jeffrey , Goff Stephen P. , Griffin Daniel O. 
Published: February 2020

AbstractTransfection, the process of introducing purified nucleic acids into cells, and viral transduction, viral-mediated nucleic acid transfer, are two commonly utilized techniques for gene delivery in the research setting. Transfection allows purified nucleic acid to be introduced into target cells through chemical-based techniques, nonchemical methods or particle-based methods, while viral transduction employs genomes or vectors based on adenoviruses, retroviruses (e.g. lentiviruses), adeno-associated viruses, or hybrid viruses. Transfected DNAs are often tested for potential effects on subsequent transduction, but it is not clear whether transfection itself rather than the particular nucleic acid being introduced might impact subsequent viral transfection. We observed a significant association between successfully transfected mobilized peripheral blood CD34+ human stem and progenitor cells (HSPCs) and permissiveness to subsequent lentiviral transduction, which was not evident in other cells such as 293 T cells and Jurkat cells. This association, apparently specific to CD34+ human stem and progenitor cells (HSPCs), is critical to both research and clinical applications as these cells are a frequent target of transfection and viral transduction owing to the durable nature of these cells in living systems. This finding may also present a significant opportunity to enhance the success of viral transduction for clinical applications.
Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage
Authors: Barna Lilla , Walter Fruzsina R. , Harazin András , Bocsik Alexandra , Kincses András , Tubak Vilmos , Jósvay Katalin , Zvara Ágnes , Campos-Bedolla Patricia , Deli Mária A. 
Published: February 2020

Abstract
Background
Excitotoxicity is a central pathological pathway in many neurological diseases with blood–brain barrier (BBB) dysfunction. Kainate, an exogenous excitotoxin, induces epilepsy and BBB damage in animal models, but the direct effect of kainate on brain endothelial cells has not been studied in detail. Our aim was to examine the direct effects of kainate on cultured cells of the BBB and to test three anti-inflammatory and antioxidant drugs used in clinical practice, simvastatin, edaravone and dexamethasone, to protect against kainate-induced changes.

Methods
Primary rat brain endothelial cell, pericyte and astroglia cultures were used to study cell viability by impedance measurement. BBB permeability was measured on a model made from the co-culture of the three cell types. The production of nitrogen monoxide and reactive oxygen species was followed by fluorescent probes. The mRNA expression of kainate receptors and nitric oxide synthases were studied by PCR.

Results
Kainate damaged brain endothelial cells and made the immunostaining of junctional proteins claudin-5 and zonula occludens-1 discontinuous at the cell border indicating the opening of the barrier. The permeability of the BBB model for marker molecules fluorescein and albumin and the production of nitric oxide in brain endothelial cells were increased by kainate. Simvastatin, edaravone and dexamethasone protected against the reduced cell viability, increased permeability and the morphological changes in cellular junctions caused by kainate. Dexamethasone attenuated the elevated nitric oxide production and decreased the inducible nitric oxide synthase (NOS2/iNOS) mRNA expression increased by kainate treatment.

Conclusion
Kainate directly damaged cultured brain endothelial cells. Simvastatin, edaravone and dexamethasone protected the BBB model against kainate-induced changes. Our results confirmed the potential clinical usefulness of these drugs to attenuate BBB damage.
Cerebrospinal fluid dynamics modulation by diet and cytokines in rats
Authors: Alimajstorovic Zerin , Pascual-Baixauli Ester , Hawkes Cheryl A. , Sharrack Basil , Loughlin A. Jane , Romero Ignacio A. , Preston Jane E. 
Published: February 2020

Abstract
Background
Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined.

Methods
In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C–C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC).

Results
Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/μl controls, and 7.09 ± 0.26 mmH2O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage.

Conclusions
Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.
Combination of post-fascia iliaca compartment block and dexmedetomidine in pain and inflammation control after total hip arthroplasty for elder patients: a randomized control study
Authors: Liu Xiaofen , Hu Xianwen , Li Rui , Zhang Ye 
Published: February 2020

Abstract
Objective
This study aims to investigate the efficiency of fascia iliaca compartment block (FICB) combined with dexmedetomidine (DEX) in postoperative and inflammation management for elder patients after total hip arthroplasty.

Methods
The present randomized controlled study included a total of 119 elder patients who received total hip arthroplasty in our hospital from March 2016 to December 2018. These patients were divided into three groups: control group, patients received routine general anesthesia; FICB group, patients received additional FICB after surgery; and combined group, patients received both pre-treatment of DEX and post-treatment of fascia iliaca compartment block. The serum levels of interleukin (IL)-1β, IL-6, and C-reactive protein (CRP) were measured by ELISA. The visual analog scale (VAS) score was measured at 12, 24, 48, and 72 h after surgery, and the patient-controlled intravenous analgesia (PCIA) pressing time within 48 h after surgery was also recorded. The Pittsburgh sleep quality index (PSQI) was used to measure the sleep quality before and at 1 month after surgery.

Results
The VAS scores were significantly lower in patients in the combined group, when compared with the other two groups, at 12, 24, 48, and 72 h after surgery. In addition, the VAS scores at all time points were significantly lower in the FICB group than the control group. The PCIA pressing times were also remarkably lower in the combined group. At 4, 24, 48, and 72 h after surgery, the serum levels of these inflammatory factors were the lowest in the combined group, and the PSQI scores were significantly lower in the combined group, when compared with the other two groups, while the control group had the highest PSQI scores among the three groups. There was no severe side effects and significant difference observed.

Conclusion
FICB combined with DEX reduced the postoperative pain, improved the sleep condition, and decreased the serum levels of inflammatory factors after total hip arthroplasty.
Do storage solutions protect endothelial function of arterialized vein graft in an experimental rat model?
Authors: Fouquet Olivier , Blossier Jean-David , Dang Van Simon , Robert Pauline , Barbelivien Agnès , Pinaud Frédéric , Binuani Patrice , Eid Maroua , Henrion Daniel , Baufreton Christophe , Loufrani Laurent 
Published: February 2020

Abstract
Background
This study aims to compare the effects of storage solutions commonly used in coronary artery bypass grafting on the vascular reactivity in vein graft interposed in arterial position in syngeneic rats.

Methods
Twenty-seven male Lewis rats were sacrified to sample a vein graft implanted 6 weeks ago into abdominal aorta position. The vein grafts were inferior venae cavae initially pretreated with heparinized saline solution (HS) or autologous heparinized blood (AHB) or our referent solution, GALA. The endothelial functionality, the in situ Reactive Oxygen Species (ROS) levels and the histological characteristics were conducted from segments of arterialized vein graft.

Results
At 6 weeks, graft thrombosis occurred respectively in 22% of AHB group, 62.5% in the HS group and 82.5% in the GALA group. In each group, significative intimal hyperplasia was observed. After 6 weeks, an endothelium-remodeling layer associated with an increase of wall thickness was observed in each group. Endothelium-dependent tone was reduced in the vein graft regardless of the group. No difference was observed concerning the ROS in vein graft between the different groups. In distal aortic sections, ROS levels were increased in HS and GALA groups.

Conclusions
Storage solutions used in this experimental model of vein graft implanted in arterial position cause graft injury and a complete disappearance of vascular reactivity. GALA solution did not reduce intimal risk hyperplasia when the vein graft was exposed to arterial flow in a rat model.
Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines
Authors: Lu Peng-De , Zhao Yong-Hua 
Published: February 2020

AbstractNuclear factor-kappa B (NF-κB) is a kind of multi-functional nuclear transcription factor involved in regulating gene transcription to influence pathological evolution of inflammatory and immune diseases. Numerous literature evidence that NF-κB pathway plays an essential role in pathogenic development of ulcerative colitis (UC). UC is a chronic non-specific inflammatory bowel disease, and until now, therapeutic agents for UC including aminosalicylates, corticosteroids and immune inhibitors still cannot exert satisfied effects on patients. In recent years, Chinese medicines suggest the advantages of alleviating symptoms and signs, decreasing side-effects and recurrence, whose one of mechanisms is related to regulation of NF-κB pathway. In this review, we categorize Chinese medicines according to their traditional therapeutic functions, and summarize the characteristics of Chinese medicines targeting NF-κB pathway in UC treatment. It indicates that 85 kinds of Chinese medicines’ compounds and formulae can directly act on NF-κBp65; while 58 Chinese medicines’ ingredients and formulae indirectly suppress NF-κBp65 by regulation of its upstream or other related pathways. Moreover, by the analysis of Chinese medicines’ category based on their traditional functions, we conclude the category of dampness-drying and detoxificating medicine targeting NF-κB pathway accounts for primary status for amelioration of UC. Simultaneously, this review also contributes to the choices of Chinese medicine category and provides curative potential of Chinese medicines for clinical UC treatment.
Oral disorders in children with Prader-Willi syndrome: a case control study
Authors: Munné-Miralvés Carla , Brunet-Llobet Lluís , Cahuana-Cárdenas Abel , Torné-Durán Sergi , Miranda-Rius Jaume , Rivera-Baró Alejandro 
Published: February 2020

Abstract
Introduction
Prader-Willi Syndrome (PWS) is a genetic disorder caused by the lack of expression of certain paternal genes located on chromosome 15q11-q13. This anomaly causes cognitive, neurological and endocrine abnormalities, among which one of the most important is hyperphagia. The aim of this study was to assess the oral health of children with PWA and to establish preventive criteria.

Results
Thirty patients with PWS (mean age 10.2 years) and 30 age- and gender-matched controls were included in the study. Twenty-six patients with PWS(86.6%) followed dietary treatment prescribed by their endocrinologist. Individuals with PWS had a mean caries index of 53.3% and Decayed Missing Filled teeth (DMFT) index 2.5, and 53.3% had gingivitis, in the control group the respective figures were 43.3%, 0.93, and 60%. Only the DMFT index (p 0.017) presented significant differences. Regarding stimulated salivary secretion, patients with PWS presented a mean of 0.475 ml/min with a pH of 6.15, while controls presented a mean of 0.848 ml/min with a pH of 7.53; the differences between the groups were statistically significant in both cases (p 0.032 and p 0.0001 respectively). The population with PWS presented a higher plaque index (> 2) than their healthy peers, but the differences were not significant.

Conclusion
Pediatric patients with Prader-Willi syndrome have an increased risk of caries and gingivitis. The children with this syndrome have a decreased salivary flow and a more acidic salivary pH. In these patients, dental care is an essential part of their multidisciplinary medical treatment.
Lactate kinetics in ICU patients using a bolus of 13C-labeled lactate
Authors: Grip Jonathan , Falkenström Tobias , Promsin Panuwat , Wernerman Jan , Norberg Åke , Rooyackers Olav 
Published: February 2020

Abstract
Background
Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied.

Aim
To establish and validate a feasible method to study lactate kinetics in critically ill patients.

Methods
Healthy volunteers (n = 6) received a bolus dose of 13C-labeled lactate (20 μmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance (Ra) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10).

Results
Ra for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 μmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques.

Conclusion
This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients.

Trial registration
ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true