bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic hyperinflation and intrinsic positive end-expiratory pressure in ARDS patients
Authors: Coppola Silvia , Caccioppola Alessio , Froio Sara , Ferrari Erica , Gotti Miriam , Formenti Paolo , Chiumello Davide 
Published: November 2019

Abstract
Background
In ARDS patients, changes in respiratory mechanical properties and ventilatory settings can cause incomplete lung deflation at end-expiration. Both can promote dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP). The aim of this study was to investigate, in a large population of ARDS patients, the presence of intrinsic PEEP, possible associated factors (patients’ characteristics and ventilator settings), and the effects of two different external PEEP levels on the intrinsic PEEP.

Methods
We made a secondary analysis of published data. Patients were ventilated with a tidal volume of 6–8 mL/kg of predicted body weight, sedated, and paralyzed. After a recruitment maneuver, a PEEP trial was run at 5 and 15 cmH2O, and partitioned mechanics measurements were collected after 20 min of stabilization. Lung computed tomography scans were taken at 5 and 45 cmH2O. Patients were classified into two groups according to whether or not they had intrinsic PEEP at the end of an expiratory pause.

Results
We enrolled 217 sedated, paralyzed patients: 87 (40%) had intrinsic PEEP with a median of 1.1 [1.0–2.3] cmH2O at 5 cmH2O of PEEP. The intrinsic PEEP significantly decreased with higher PEEP (1.1 [1.0–2.3] vs 0.6 [0.0–1.0] cmH2O; p < 0.001). The applied tidal volume was significantly lower (480 [430–540] vs 520 [445–600] mL at 5 cmH2O of PEEP; 480 [430–540] vs 510 [430–590] mL at 15 cmH2O) in patients with intrinsic PEEP, while the respiratory rate was significantly higher (18 [15–20] vs 15 [13–19] bpm at 5 cmH2O of PEEP; 18 [15–20] vs 15 [13–19] bpm at 15 cmH2O). At both PEEP levels, the total airway resistance and compliance of the respiratory system were not different in patients with and without intrinsic PEEP. The total lung gas volume and lung recruitability were also not different between patients with and without intrinsic PEEP (respectively 961 [701–1535] vs 973 [659–1433] mL and 15 [0–32] % vs 22 [0–36] %).

Conclusions
In sedated, paralyzed ARDS patients without a known obstructive disease, the amount of intrinsic PEEP during lung-protective ventilation is negligible and does not influence respiratory mechanical properties.
Mortality risk over time after early fluid resuscitation in African children
Authors: George Elizabeth C. , Kiguli Sarah , Olupot Peter Olupot , Opoka Robert O. , Engoru Charles , Akech Samuel O. , Nyeko Richard , Mtove George , Mpoya Ayub , Thomason Margaret J. , Crawley Jane , Evans Jennifer A. , Gibb Diana M. , Babiker Abdel G. , Maitland Kathryn , Walker A. Sarah 
Published: November 2019

Abstract
Background
African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear.

Methods
In a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20–40 ml/kg 5% albumin or 0.9% saline over 1–2 h or no bolus (control, 4 ml/kg/hour maintenance), overall and for different terminal clinical events (cardiogenic, neurological, respiratory, or unknown/other).

Results
Two thousand ninety-seven and 1041 children were randomised to bolus vs no bolus, of whom 254 (12%) and 91 (9%) respectively died within 28 days. Median (IQR) bolus fluid in the bolus groups received by 4 h was 20 (20, 40) ml/kg and was the same at 8 h; total fluids received in bolus groups at 4 h and 8 h were 38 (28, 43) ml/kg and 40 (30, 50) ml/kg, respectively. Total fluid volumes received in the control group by 4 h and 8 h were median (IQR) 10 (6, 15) ml/kg and 10 (10, 26) ml/kg, respectively. Mortality risk was greatest 30 min post-randomisation in both groups, declining sharply to 4 h and then more slowly to 28 days. Maximum mortality risk was similar in bolus and no bolus groups; however, the risk declined more slowly in the bolus group, with significantly higher mortality risk compared to the no bolus group from 1.6 to 101 h (4 days) post-randomisation. The delay in decline in mortality risk in the bolus groups was most pronounced for cardiogenic modes of death.

Conclusions
The increased risk from bolus therapy was not due to a mechanism occurring immediately after bolus administration. Excess mortality risk in the bolus group resulted from slower decrease in mortality risk over the ensuing 4 days. Thus, administration of modest bolus volumes appeared to prevent mortality risk declining at the same rate that it would have done without a bolus, rather than harm associated with bolus resulting from a concurrent increased risk of death peri-bolus administration.

Trial registration
ISRCTN69856593. Date of registration 15 December 2008.
Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study
Authors: Carrié Cédric , Chadefaux Grégoire , Sauvage Noémie , de Courson Hugues , Petit Laurent , Nouette-Gaulain Karine , Pereira Bruno , Biais Matthieu 
Published: November 2019

Abstract
Background
Augmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).

Methods
In this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.

Results
During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.

Conclusions
Higher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.
A comparison of clinical paediatric guidelines for hypotension with population-based lower centiles: a systematic review
Authors: Hagedoorn Nienke N. , Zachariasse Joany M. , Moll Henriette A. 
Published: November 2019

AbstractBackgroundDifferent definitions exist for hypotension in children. In this study, we aim to identify evidence-based reference values for low blood pressure and to compare these with existing definitions for systolic hypotension.MethodsWe searched online databases until February 2019 (including MEDLINE, EMBASE, Web of Science) using a comprehensive search strategy to identify studies that defined age-related centiles (first to fifth centile) for non-invasive systolic blood pressure in healthy children < 18 years. Existing cut-offs for hypotension were identified in international guidelines and textbooks. The age-related centiles and clinical cut-offs were compared and visualized using step charts.ResultsFourteen studies with population-based centiles were selected, of which 2 addressed children < 1 year. Values for the fifth centile differed 8 to 17 mmHg for age. We identified 13 clinical cut-offs of which only 5 reported accurate references. Age-related cut-offs for hypotension showed large variability (ranging from 15 to 30 mmHg). The clinical cut-offs varied in agreement with the low centiles. The definition from Paediatric Advanced Life Support agreed well for children < 12 years but was below the fifth centiles for children > 12 years. For children > 12 years, the definition of Parshuram’s early warning score agreed well, but the Advanced Paediatric Life Support definition was above the fifth centiles.ConclusionsThe different clinical guidelines for low blood pressure show large variability and low to moderate agreement with population-based lower centiles. For children < 12 years, the Paediatric Advanced Life Support definition fits best but it underestimates hypotension in older children. For children > 12 years, the Advanced Paediatric Life Support overestimates hypotension but Parshuram’s cut-off for hypotension in the early warning score agrees well. Future studies should focus on developing reference values for hypotension for acutely ill children.
The SOFA score—development, utility and challenges of accurate assessment in clinical trials
Authors: Lambden Simon , Laterre Pierre Francois , Levy Mitchell M. , Francois Bruno 
Published: November 2019

AbstractThe Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been widely validated as a tool for this purpose across a range of healthcare settings and environments.In recent years, the SOFA score has become extensively used in a range of other applications. A change in the SOFA score of 2 or more is now a defining characteristic of the sepsis syndrome, and the European Medicines Agency has accepted that a change in the SOFA score is an acceptable surrogate marker of efficacy in exploratory trials of novel therapeutic agents in sepsis. The requirement to detect modest serial changes in a patients’ SOFA score therefore means that increased clarity on how the score should be assessed in different circumstances is required.This review explores the development of the SOFA score, its applications and the challenges associated with measurement. In addition, it proposes guidance designed to facilitate the consistent and valid assessment of the score in multicentre sepsis trials involving novel therapeutic agents or interventions.ConclusionThe SOFA score is an increasingly important tool in defining both the clinical condition of the individual patient and the response to therapies in the context of clinical trials. Standardisation between different assessors in widespread centres is key to detecting response to treatment if the SOFA score is to be used as an outcome in sepsis clinical trials.
Differentially expressed tRFs in CD5 positive relapsed & refractory diffuse large B cell lymphoma and the bioinformatic analysis for their potential clinical use
Authors: Qu Qingyuan , Li Ying , Fang Xiaosheng , Zhang Lingyan , Xue Chao , Ge Xueling , Wang Xin , Jiang Yujie 
Published: November 2019

Abstract
Background
Patients diagnosed as diffuse large B cell lymphoma (DLBCL) with CD5 positive normally have a worse outcome and poorly respond to the regulatory treatment strategy.

Results
We recently reported differently expressed tRFs and their potential target-genes of tRFs in patients with CD5+ R/R DLBCL. Differently expressed tRFs were detected by Illumina NextSeq instrument and the results were verified by quantitative real-time reverse transcription-PCR. tRF2Cancer database was searched to compared with the results. Further research was performed through bio-informatic analysis including gene ontology (GO) and pathway enrichment analyses, etc. A total of 308 tRFs were identified. Two sequences (AS-tDR-008946, AS-tDR-013492) were chosen for further investigated.

Conclusions
The results of Bioinformatics analysis revealed that the target genes including NEDD4L and UBA52 and several associated pathways including PI3K/AKT and MAPK/ERK might be involved in the development of CD5+ R/R DLBCL. Our preliminary study on the associated tRFs might provide a valuable measure to explore the pathogenesis and progression of CD5+ R/R DLBCL.

Reviewers
This article was reviewed by Zhen Qing Ye, Nagarajan Raju and Jin Zhuang Dou.
Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis
Authors: Armstrong-Buisseret Lindsay , Brittain Clare , David Miruna , Dean Gillian , Griffiths Frances , Hepburn Trish , Jackson Louise , Kai Joe , Montgomery Alan , Roberts Tracy , Thandi Sukhwinder , Ross Jonathan D. C. 
Published: November 2019

Abstract
Background
Bacterial vaginosis (BV) affects 30–50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronidazole are effective but can result in side effects, and recurrence is common. This trial aims to investigate whether lactic acid gel is clinically effective and cost effective in the treatment of recurrent BV compared with metronidazole.

Methods
VITA is an open-label, multicentre, parallel group randomised controlled trial for women with a clinical diagnosis of BV and at least one previous BV episode in the past 2 years. Participants will be randomised 1:1 to intravaginal lactic acid gel 5 ml once daily for 7 days or oral metronidazole tablets 400 mg twice daily for 7 days. All participants will be followed up for 6 months to assess health status and healthcare costs. A subgroup will be interviewed to further explore adherence, tolerability and acceptability of treatment. The estimated sample size is 1900 participants to detect a 6% absolute increase in response rate to 86% in those receiving lactic acid gel. The primary outcome is participant-reported resolution of BV at Week 2.

Discussion
Results from this trial will help inform UK treatment guidelines for BV and may provide an alternative effective treatment for recurrent episodes of this condition which avoids repeated exposure to antibiotics.

Trial registration
ISRCTN, ISRCTN14161293. Registered on 8 September 2017.
Genome-wide survey of cytochrome P450 genes in the salmon louse Lepeophtheirus salmonis (Krøyer, 1837)
Authors: Humble Joseph L. , Carmona-Antoñanzas Greta , McNair Carol M. , Nelson David R. , Bassett David I. , Egholm Ingibjørg , Bron James E. , Bekaert Michaël , Sturm Armin 
Published: November 2019

Abstract
Background
The salmon louse (Lepeophtheirus salmonis) infests farmed and wild salmonid fishes, causing considerable economic damage to the salmon farming industry. Infestations of farmed salmon are controlled using a combination of non-medicinal approaches and veterinary drug treatments. While L. salmonis has developed resistance to most available salmon delousing agents, relatively little is known about the molecular mechanisms involved. Members of the cytochrome P450 (CYP) superfamily are typically monooxygenases, some of which are involved in the biosynthesis and metabolism of endogenous compounds, while others have central roles in the detoxification of xenobiotics. In terrestrial arthropods, insecticide resistance can be based on the enhanced expression of CYPs. The reported research aimed to characterise the CYP superfamily in L. salmonis and assess its potential roles in drug resistance.

Methods
Lepeophtheirus salmonis CYPs were identified by homology searches of the genome and transcriptome of the parasite. CYP transcript abundance in drug susceptible and multi-resistant L. salmonis was assessed by quantitative reverse transcription PCR, taking into account both constitutive expression and expression in parasites exposed to sublethal levels of salmon delousing agents, ecdysteroids and environmental chemicals.

Results
The above strategy led to the identification of 25 CYP genes/pseudogenes in L. salmonis, making its CYP superfamily the most compact characterised for any arthropod to date. Lepeophtheirus salmonis possesses homologues of a number of arthropod CYP genes with roles in ecdysteroid metabolism, such as the fruit fly genes disembodied, shadow, shade, spook and Cyp18a1. CYP transcript expression did not differ between one drug susceptible and one multi-resistant strain of L. salmonis. Exposure of L. salmonis to emamectin benzoate or deltamethrin caused the transcriptional upregulation of certain CYPs. In contrast, neither ecdysteroid nor benzo[a]pyrene exposure affected CYP transcription significantly.

Conclusions
The parasite L. salmonis is demonstrated to possess the most compact CYP superfamily characterised for any arthropod to date. The complement of CYP genes in L. salmonis includes conserved CYP genes involved in ecdysteroid biosynthesis and metabolism, as well as drug-inducible CYP genes. The present study does not provide evidence for a role of CYP genes in the decreased susceptibility of the multiresistant parasite strain studied.
Effects of metformin on metabolism of white and brown adipose tissue in obese C57BL/6J mice
Authors: Yuan Tao , Li Juan , Zhao Wei-Gang , Sun Wei , Liu Shuai-Nan , Liu Quan , Fu Yong , Shen Zhu-Fang 
Published: November 2019

Abstract
Background
To investigate effects of metformin on the regulation of proteins of white adipose tissue (WAT) and brown adipose tissue (BAT) in obesity and explore the underlying mechanisms on energy metabolism.

Methods
C57BL/6J mice were fed with normal diet (ND, n = 6) or high-fat diet (HFD, n = 12) for 22 weeks. HFD-induced obese mice were treated with metformin (MET, n = 6). After treatment for 8 weeks, oral glucose tolerance test (OGTT) and hyperinsulinemic–euglycemic clamp were performed to evaluate the improvement of glucose tolerance and insulin sensitivity. Protein expressions of WAT and BAT in mice among ND, HFD, and MET group were identified and quantified with isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC–MS/MS. The results were analyzed by MASCOT, Scaffold and IPA.

Results
The glucose infusion rate in MET group was increased significantly compared with HFD group. We identified 4388 and 3486 proteins in WAT and BAT, respectively. As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively. In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly.

Conclusions
Metformin improved the body weight and insulin sensitivity of obese mice. Meanwhile, metformin might ameliorate endoplasmic reticulum stress in WAT, and affect fatty acid metabolism in WAT and BAT. CPT1 might be a potential target of metformin in WAT and BAT.
Stowaway miniature inverted repeat transposable elements are important agents driving recent genomic diversity in wild and cultivated carrot
Authors: Macko-Podgórni Alicja , Stelmach Katarzyna , Kwolek Kornelia , Grzebelus Dariusz 
Published: November 2019

AbstractBackgroundMiniature inverted repeat transposable elements (MITEs) are small non-autonomous DNA transposons that are ubiquitous in plant genomes, and are mobilised by their autonomous relatives.StowawayMITEs are derived from and mobilised by elements from themarinersuperfamily. Those elements constitute a significant portion of the carrot genome; however the variation caused byDaucus carota StowawayMITEs (DcStos), their association with genes and their putative impact on genome evolution has not been comprehensively analysed.ResultsFourteen families ofStowawayelementsDcStos occupy about 0.5% of the carrot genome. We systematically analysed 31 genomes of wild and cultivatedDaucus carota, yielding 18.5 thousand copies of these elements, showing remarkable insertion site polymorphism.DcStoelement demography differed based on the origin of the host populations, and corresponded with the four major groups ofD. carota,wild European, wild Asian, eastern cultivated and western cultivated. TheDcStos elements were associated with genes, and most frequently occurred in 5′ and 3′ untranslated regions (UTRs). Individual families differed in their propensity to reside in particular segments of genes. Most importantly,DcStocopies in the 2 kb regions up- and downstream of genes were more frequently associated with open reading frames encoding transcription factors, suggesting their possible functional impact. More than 1.5% of allDcStoinsertion sites in different host genomes contained different copies in exactly the same position, indicating the existence of insertional hotspots. TheDcSto7b family was much more polymorphic than the other families in cultivated carrot. A line of evidence pointed at its activity in the course of carrot domestication, and identifiedDcmar1 as an active carrotmarinerelement and a possible source of the transposition machinery forDcSto7b.ConclusionStowawayMITEs have made a substantial contribution to the structural and functional variability of the carrot genome.
Mediation effects of depression and anxiety on social support and quality of life among caregivers of persons with severe burns injury
Authors: Bonsu Kevin , Kugbey Nuworza , Ayanore Martin Amogre , Atefoe Ethel Akpene 
Published: November 2019

Abstract
Objective
Caregiving is associated with several psychosocial challenges including stress, depression and anxiety. These challenges have been found to have significant negative impacts on the health and wellbeing of caregivers, but the mechanisms of these effects are poorly understood. This study examined whether depression and anxiety serve as mediators between social support and quality of life caregivers of persons with severe burns injury.

Results
A sample of 100 caregivers of persons with severe burns injury were administered questionnaires to assess their depression, anxiety, social support and quality of life. Findings show that depression and anxiety were negatively correlated with quality of life whereas social support was positively correlated with quality of life. Results further showed that only depression significantly mediated the link between social support and quality of life among the caregivers. These findings emphasize the need to screen caregivers for common mental health problems and provide them support in the caregiving process to promote their health and wellbeing.
Protocol optimization for a fast, simple and economical chemical reduction synthesis of antimicrobial silver nanoparticles in non-specialized facilities
Authors: Vazquez-Muñoz Roberto , Arellano-Jimenez M. Josefina , Lopez Fernando D. , Lopez-Ribot Jose L. 
Published: November 2019

Abstract
Objective
Silver nanoparticles (AgNPs) can be difficult or expensive to obtain or synthesize for laboratories in resource-limited facilities. The purpose of this work was to optimize a synthesis method for a fast, facile, and cost-effective synthesis of AgNPs with antimicrobial activity, which can be readily implemented in non-specialized facilities and laboratories.

Results
The optimized method uses a rather simple and rapid chemical reduction process that involves the addition of a polyvinylpyrrolidone solution to a warmed silver nitrate solution under constant vigorous stirring, immediately followed by the addition of sodium borohydride. The total synthesis time is less than 15 min. The obtained AgNPs exhibit an aspect ratio close to 1, with an average size of 6.18 ± 5 nm. AgNPs displayed potent antimicrobial activity, with Minimal Inhibitory Concentration values of ≤ 4 µg mL−1 for Staphylococcus aureus and ≤ 2 µg mL−1 for Candida albicans. The resulting method is robust and highly reproducible, as demonstrated by the characterization of AgNPs from different rounds of syntheses and their antimicrobial activity.