bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diurnal variation of inflammatory plasma proteins involved in pain
Authors: Jasim Hajer , Carlsson Anders , Gerdle Björn , Ernberg Malin , Ghafouri Bijar 
Published: August 2019

Abstract

Introduction:
Proteomics is a powerful approach for biochemical research because it directly studies the main functional components of biochemical systems. The understanding of the normal fluctuations of the proteome in health is essential to identify pain-specific biomarkers.

Objective:
To investigate fluctuations of the plasma proteome in healthy pain-free individuals.

Methods:
Blood samples were structurally collected in the early morning and evening from 10 clinically healthy individuals (26.3 ± 3.3 years). High abundant proteins were removed from plasma, and proteins were then analysed by nanoliquid chromatography combined with mass spectrometry. In addition, an assay of 71 cytokines/chemokines/growth factors was analysed.

Results:
Multivariate statistical analysis displayed that there were up to 64 proteins whose expression levels were significantly altered between the plasma samples collected during the morning and evening; no changes existed for the assay. The levels of 34 proteins were increased and 30 proteins were decreased during the evening compared with the morning sample. The increased proteins were involved in the biological processes such as protein activation cascade, complement activation, and stress response. The decreased proteins were involved in regulation of endopeptidase activity, inflammatory response, and protein metabolic processes.

Conclusion:
The circadian variations in the plasma proteome stress the need to collect blood samples of both patients and controls at a fixed time of the day. The results in this study might be useful for better understanding of the complexity of individual variation in the human plasma proteome over time and provide a baseline for improved pain biomarker discovery.
Characterization of Interstitial Lung Disease Associated With Anti-Ribonucleoprotein Antibodies
Authors: Lhote Raphael , Grenier Philippe , Haroche Julien , Miyara Makoto , Boussouar Samia , Mathian Alexis , Pha Micheline , Amoura Zahir , Cohen Aubart Fleur 
Published: August 2019

Objectives
Interstitial lung disease (ILD) is a common feature of mixed connective tissue disease. However, many patients do not meet the criteria for mixed connective tissue disease and thus may be diagnosed as interstitial pneumonia with autoimmune features. The aim of this study was to characterize ILD associated with anti-ribonucleoprotein (RNP) antibodies.

Methods
Chest computed tomography scans of patients with anti-RNP antibody who were seen between January 2011 and October 2015 were reviewed. The underlying disease was classified with international criteria using clinical and serological features.

Results
Among 544 patients with anti-RNP antibodies, 188 had a chest computed tomography scan, and 48 (26%) of them had radiological features of ILD. The presence of ILD was significantly associated with dyspnea, crackles, arthritis, Raynaud phenomenon, myositis, and sicca syndrome. The most frequent pattern was nonspecific interstitial pneumonia in 39 patients (81%). Among patients with ILD, 17 (35%) had a radiological pattern consisting of cysts and ground-glass attenuation not fulfilling the lymphoid interstitial pneumonia criteria. In 3 patients, cysts were related to fibrosis; in 14 patients, cysts corresponded to an original ILD pattern.

Conclusions
Interstitial lung disease was found in 26% of patients with anti-RNP antibodies independently of the underlying disease. Anti-RNP–associated ILD mainly corresponds to nonspecific interstitial pneumonia or an original pattern consisting of cysts and ground-glass attenuation.
Patient-Reported Outcome Measures in Plastic Surgery
Authors: Sharma Kavita , Steele Kathryn , Birks Meg , Jones Georgina , Miller Gavin 
Published: August 2019

Abstract
Clinical care is often directed at improving patient's quality of life, the effectiveness of which can be measured by objective or subjective outcomes. Surgical intervention, especially in plastic and reconstructive surgery, can often provide hard objective measures, for example, breast size reduction after bilateral reduction mammaplasty, or improved joint position/movement after Dupuytren's surgery. These measurements do not describe how a particular intervention affects the patient's life, from their point of view.
Patient-reported outcome measures (PROMs) are validated questionnaires completed by patients about their health, functioning, health behaviors and quality of care. Patient-reported outcome measures reflect the patient's perspective and their use increases the meaningfulness of outcomes measured, for whatever purpose. There is therefore a growing interest in PROMs as part of routine clinical practice in the United Kingdom and worldwide.
This article aims to provide an introduction of PROMs to plastic surgeons, a description of how PROMs are developed and scored, along with the most commonly used tools currently most applicable to plastic surgery. The benefits of PROMs on a local, regional, and national level are discussed, and we aim to set out how these tools can be used in auditing individual and departmental performance against national standards. We will also provide suggestions for sustainable use of PROMs in the clinical environment, advice on choosing the right outcome measure, and our views on electronic data collection, analysis, and interpretation of the results.
Patient-reported outcome measures are highly relevant clinical practice and will undoubtedly with time become routine. We encourage plastic surgeons to explore the possibilities these tools can provide in helping improve the quality of care we deliver to our patients.
Autologous Fat Grafting in Young Patients
Authors: Maia Munique , Lukash Frederick N. 
Published: August 2019

Goals/Purpose
Rhinoplasty is the most common procedure seen in the teenage population. Many of these patients have facial imbalance both recognized and unrecognized by the individual and family. Most often it involves chin or midface deficiency. When the discussion involves the possibility of additional surgery, such as an alloplastic chin implant or a surgical osteotomy, the conversation halts because the patient and family seek a simpler solution.
Autologous fat transfer is a useful adjunct to achieve facial balance in chin and cheek in the teen population. More recently, we have been using this technique to correct facial disharmony in rhinoplasty patients.

Methods/Technique
Fat grafting was performed at the time of rhinoplasty in 22 patients (age, 15–19 years). Presurgical planning involved cephalometric and computer-enhanced photographic analysis of the face. Midface retrusion and underprojected mentum were treated. Deficient sites were treated with small aliquots of fat, which were injected into the supraperiosteal plane. The average amounts of fat grafting injected per region were 2 to 3 mL for the malar region and 8 to 10 mL for the chin and geniomandibular borders.

Results/Complications
Twenty-two patients underwent augmentation of soft tissue and skeletal deficiencies. Analysis of postoperative results showed excellent outcomes with enhancement of facial profile and proportions. The mean follow-up was 3 years. The majority of patients reported high degree of satisfaction. No complications were observed.

Conclusions
The combination of rhinoplasty and autologous fat grafting offers very satisfactory esthetic outcomes and improvement of facial balance with minimal added time, cost, and risk.
Gallstone Pancreatitis
Authors: Mueck Krislynn M. , Wei Shuyan , Pedroza Claudia , Bernardi Karla , Jackson Margaret L. , Liang Mike K. , Ko Tien C. , Tyson Jon E. , Kao Lillian S. 
Published: August 2019

Introduction:
Early cholecystectomy shortly after admission for mild gallstone pancreatitis has been proposed based on observational data. We hypothesized that cholecystectomy within 24 hours of admission versus after clinical resolution of gallstone pancreatitis that is predicted to be mild results in decreased length-of-stay (LOS) without an increase in complications.

Methods:
Adults with predicted mild gallstone pancreatitis were randomized to cholecystectomy with cholangiogram within 24 hours of presentation (early group) versus after clinical resolution (control) based on abdominal exam and normalized laboratory values. Primary outcome was 30-day LOS including readmissions. Secondary outcomes were time to surgery, endoscopic retrograde cholangiopancreatography (ERCP) rates, and postoperative complications. Frequentist and Bayesian intention-to-treat analyses were performed.

Results:
Baseline characteristics were similar in the early (n = 49) and control (n = 48) groups. Early group had fewer ERCPs (15% vs 29%, P = 0.038), faster time to surgery (16 h vs 43 h, P < 0.005), and shorter 30-day LOS (50 h vs 77 h, RR 0.68 95% CI 0.65 – 0.71, P < 0.005). Complication rates were 6% in early group versus 2% in controls (P = 0.613), which included recurrence/progression of pancreatitis (2 early, 1 control) and a cystic duct stump leak (early). On Bayesian analysis, early cholecystectomy has a 99% probability of reducing 30-day LOS, 93% probability of decreasing ERCP use, and 72% probability of increasing complications.

Conclusion:
In patients with predicted mild gallstone pancreatitis, cholecystectomy within 24 hours of admission reduced rate of ERCPs, time to surgery, and 30-day length-of-stay. Minor complications may be increased with early cholecystectomy. Identification of patients with predicted mild gallstone pancreatitis in whom early cholecystectomy is safe warrants further investigation.
Are results from randomized trials in anesthesiology robust or fragile? An analysis using the fragility index
Authors: Goerke Kale , Parke Matthew , Horn Jarryd , Meyer Chase , Dormire Kody , White Brad , Bright Trevor , Walters Corbin , Vassar Matt 
Published: August 2019

ABSTRACT

Aim:
In anesthesiology, the findings from randomized controlled trials often underpin guidelines influencing clinical decision-making and therefore directly affect patient care. The aim of this study is to evaluate the fragility index and fragility quotient of randomized controlled trials published in the eight highest ranked anesthesiology journals. In addition, we assess the extent to which risk of bias scores, loss to follow-up, Web of Science Citation Index, and journal impact factor influence fragility index and fragility quotient.

Methods:
We included randomized trials published between 2014 and 2016 from the eight highest ranking anesthesiology journals based on Clarivate Analytics’ Science Citation Index and Google Scholar Metrics: Anesthesiology subcategory. We included journals that published general anesthesia topics and omitted specialty anesthesia journals. The fragility index and fragility quotient for all included trials were calculated. Risk of bias for each trial was evaluated using the Cochrane ‘risk of bias’ Tool 2.0.

Results:
One hundred and thirty one randomized control trials were included in this analysis. The median fragility index was 3 (interquartile range 1.0–5.5) with a fragility quotient of 0.03 (interquartile range 0.01–0.08). In 11% (14/131) of trials, the number of patients lost to follow-up was greater than the corresponding fragility index. Weak correlations were found between fragility index and total sample size (r = 0.13) and between fragility index and event frequency (r = 0.19). A near-negligible correlation was found between 5-year impact factor and fragility index (r = −0.03) and, similarly, between fragility index and Science Citation Index (r = −0.05). Ten trials were at high risk of bias with the randomization process found to be the domain at the highest risk of bias.

Conclusion:
In assessing the fragility of randomized controlled trials published in the top eight anesthesiology journals, our study suggests that statistically significant results in these journals are disconcertingly fragile. The median fragility index calculated from our 131 primary studies reveals that only three nonevents must be replaced with events to negate statistical significance. Although a current scale does not exist for fragility index ranges, many trials published by the top journals in anesthesiology are based on concerning methodology and highly fragile outcomes. With small median sample sizes and few patient events characterizing a large number of these trials, many of today's current guidelines and clinical practices may be founded on research containing statistical significance but lacking clinical significance.
Elucidating user behaviours in a digital health surveillance system to correct prevalence estimates
Authors: Liu Dennis , Mitchell Lewis , Cope Robert C. , Carlson Sandra J. , Ross Joshua V. 
Published: August 2019

AbstractEstimating seasonal influenza prevalence is of undeniable public health importance, but remains challenging with traditional datasets due to cost and timeliness. Digital epidemiology has the potential to address this challenge, but can introduce sampling biases that are distinct to traditional systems. In online participatory health surveillance systems, the voluntary nature of the data generating process must be considered to address potential biases in estimates. Here we examine user behaviours in one such platform, FluTracking, from 2011 to 2017. We build a Bayesian model to estimate probabilities of an individual reporting in each week, given their past reporting behaviour, and to infer the weekly prevalence of influenza-like-illness (ILI) in Australia. We show that a model that corrects for user behaviour can substantially effect ILI estimates. The model examined here elucidates several factors, such as the status of having ILI and consistency of prior reporting, that are strongly associated with the likelihood of participating in online health surveillance systems. This framework could be applied to other digital participatory health systems where participation is inconsistent and sampling bias may be of concern.
A non-canonical role for p27Kip1in restricting proliferation of corneal endothelial cells during development
Authors: Defoe Dennis M. , Rao Huiying , Harris David J. , Moore Preston D. , Brocher Jan , Harrison Theresa A. 
Published: August 2019

AbstractThe cell cycle regulator p27Kip1is a critical factor controlling cell number in many lineages. While its anti-proliferative effects are well-established, the extent to which this is a result of its function as a cyclin-dependent kinase (CDK) inhibitor or through other known molecular interactions is not clear. To genetically dissect its role in the developing corneal endothelium, we examined mice harboring two loss-of-function alleles, a null allele (p27−) that abrogates all protein function and a knockin allele (p27CK−) that targets only its interaction with cyclins and CDKs. Whole-animal mutants, in which all cells are either homozygous knockout or knockin, exhibit identical proliferative increases (∼0.6-fold) compared with wild-type tissues. On the other hand, use of mosaic analysis with double markers (MADM) to produce infrequently-occurring clones of wild-type and mutant cells within the same tissue environment uncovers a roughly three- and six-fold expansion of individualp27CK−/CK−andp27−/−cells, respectively. Mosaicism also reveals distinct migration phenotypes, withp27−/−cells being highly restricted to their site of production andp27CK−/CK−cells more widely scattered within the endothelium. Using a density-based clustering algorithm to quantify dispersal of MADM-generated clones, a four-fold difference in aggregation is seen between the two types of mutant cells. Overall, our analysis reveals that, in developing mouse corneal endothelium, p27 regulates cell number by acting cell autonomously, both through its interactions with cyclins and CDKs and through a cyclin-CDK-independent mechanism(s). Combined with its parallel influence on cell motility, it constitutes a potent multi-functional effector mechanism with major impact on tissue organization.
Extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli isolates causing bacteremia in the Netherlands (2014 – 2016) differ in clonal distribution, antimicrobial resistance gene and virulence gene content
Authors: van Hout Denise , Verschuuren Tess D. , Bruijning-Verhagen Patricia C.J. , Bosch Thijs , Schürch Anita C. , Willems Rob J.L. , Bonten Marc J.M. , Kluytmans Jan A.J.W. 
Published: August 2019

ABSTRACTBackgroundKnowledge on the molecular epidemiology of Escherichia coli causing E. coli bacteremia (ECB) in the Netherlands is mostly based on extended-spectrum beta-lactamase-producing E. coli (ESBL-Ec). We determined differences in clonality and resistance and virulence gene (VG) content between non-ESBL-producing E. coli (non-ESBL-Ec) and ESBL-Ec blood isolates with different epidemiological characteristics.Materials/methodsA random selection of non-ESBL-Ec isolates as well as all available ESBL-Ec blood isolates was obtained from two Dutch hospitals between 2014 and 2016. Whole genome sequencing was performed to infer sequence types (STs), serotypes, acquired antibiotic resistance genes and VG scores, based on presence of 49 predefined putative pathogenic VG.ResultsST73 was most prevalent among the 212 non-ESBL-Ec (N=26, 12.3%) and ST131 among the 69 ESBL-Ec (N=30, 43.5%). Prevalence of ST131 among non-ESBL-Ec was 10.4% (N=22, P value < 0.001 compared to ESBL-Ec). O25:H4 was the most common serotype in both non-ESBL-Ec and ESBL-Ec. Median acquired resistance gene counts were 1 (IQR 1 – 6) and 7 (IQR 4 – 9) for non-ESBL-Ec and ESBL-Ec, respectively (P value < 0.001). Among non-ESBL-Ec, acquired resistance gene count was highest among blood isolates from a primary gastro-intestinal focus (median 4, IQR 1 – 8). Median VG scores were 13 (IQR 9 – 20) and 12 (IQR 8 – 14) for non-ESBL-Ec and ESBL-Ec, respectively (P value = 0.002). VG scores among non-ESBL-Ec from a primary urinary focus (median 15, IQR 11 – 21) were higher compared to non-ESBL-Ec from a primary gastro-intestinal (median 10, IQR 6 – 13) or hepatic-biliary focus (median 11, IQR 5 – 18) (P values = 0.007 and 0.036, respectively). VG content varied between different E. coli STs.ConclusionsNon-ESBL-Ec and ESBL-Ec blood isolates from two Dutch hospitals differed in clonal distribution, resistance gene and VG content. Also, resistance gene and VG content differed between non-ESBL-Ec from different primary foci of ECB.
Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity
Authors: Barberio Matthew D. , Nadler Evan P. , Sevilla Samantha , Lu Rosemary , Harmon Brennan , Hubal Monica J. 
Published: August 2019

AbstractBackgroundEpigenetic changes in visceral adipose tissue (VAT) with obesity and their effects on gene expression are poorly understood, especially during emergent obesity in youth. The current study tested the hypothesis that methylation and gene expression profiles of key growth factor and inflammatory pathways such as PI3K/AKT signaling are altered in VAT from obese compared to non-obese youth.MethodsVAT samples from adolescent females grouped as Lean (L; n=15; age=15±3 yrs, BMI=21.9±3.0 kg/m2) or Obese (Ob; n=15, age=16±2 yrs, BMI=45.8±9.8 kg/m2) were collected. Global methylation (n=20) and gene expression (N=30) patterns were profiled via microarray and interrogated for differences between groups by ANCOVA (p<0.05), followed by biological pathway analysis.ResultsOverlapping differences in methylation and gene expression in 317 genes were found in VAT from obese compared to lean groups. PI3K/AKT Signaling (p=1.83×10−6; 10/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. mRNA upregulations in the PI3K/AKT Signaling Pathway genes TFAM (p=0.03; Fold change=1.8) and PPP2R5C (p=0.03, FC=2.6) were confirmed via qRT-PCR.ConclusionOur analyses show obesity-related differences in DNA methylation and gene expression in visceral adipose tissue of adolescent females. Specifically, we identified methylation site/gene expression pairs differentially regulated and mapped these differences to PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by obesity-related changes in DNA methylation.
Leptin Resistance in the Ovary of Obese Mice Is Associated with Profound Changes in the Transcriptome of Cumulus Cells
Authors: Wołodko Karolina , Walewska Edyta , Adamowski Marek , Castillo-Fernandez Juan , Kelsey Gavin , Galvão António 
Published: August 2019

ABSTRACTBackground/AimsObesity is associated with infertility, decreased ovarian performance and lipotoxicity. However, little is known about the aetiology of these reproductive impairments. Here, we hypothesise that the majority of changes in ovarian physiology in diet-induced obesity (DIO) are a consequence of transcriptional changes downstream of altered leptin signalling. Therefore, we investigated the extent to which leptin signalling is altered in the ovary upon obesity with particular emphasis on effects on cumulus cells (CCs), the intimate functional companions of the oocyte. Furthermore, we used the pharmacological hyperleptinemic (LEPT) mouse model to compare transcriptional profiles to DIO.MethodsMice were subjected to DIO for 4 and 16 weeks (wk) and leptin treatment for 16 days, to study effects in the ovary in components of leptin signalling at the transcript and protein levels, using Western blot, Real-time PCR and immunostaining. Furthermore, we used low-cell RNA sequencing to characterise changes in the transcriptome of CCs in these models.ResultsIn the DIO model, obesity led to establishment of ovarian leptin resistance after 16 wk high fat diet (HFD), as evidenced by increases in the feedback regulator suppressor of cytokine signalling 3 (SOCS3) and decreases in the positive effectors phosphorylation of tyrosine 985 of leptin receptor (ObRb-pTyr985) and Janus kinase 2 (pJAK2). Transcriptome analysis of the CCs revealed a complex response to DIO, with large numbers and distinct sets of genes deregulated at early and late stages of obesity; in addition, there was a striking correlation between body weight and global transcriptome profile of CCs. Further analysis indicated that the transcriptome profile in 4 wk HFD CCs resembled that of LEPT CCs, in the upregulation of cellular trafficking and impairment in cytoskeleton organisation. Conversely, after 16 wk HFD CCs showed expression changes indicative of augmented inflammatory responses, cell morphogenesis, and decreased metabolism and transport, mainly as a consequence of the physiological changes of obesity.ConclusionObesity leads to ovarian leptin resistance and major time-dependent changes in gene expression in CCs, which in early obesity may be caused by increased leptin signalling in the ovary, whereas in late obesity are likely to be a consequence of metabolic changes taking place in the obese mother.