bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral blood mononuclear cells are hypomethylated in active rheumatoid arthritis and methylation correlates with disease activity
Authors: Liebold Ilka , Grützkau Andreas , Göckeritz Anika , Gerl Velia , Lindquist Randall , Feist Eugen , Zänker Michael , Häupl Thomas , Poddubnyy Denis , Zernicke Jan , Smiljanovic Biljana , Alexander Tobias , Burmester Gerd R , Gay Steffen , Stuhlmüller Bruno 
Published: September 2020

Abstract

Objective
Epigenetic modifications are dynamic and influence cellular disease activity. The aim of this study was to investigate global DNA methylation in peripheral blood mononuclear cells (PBMCs) of RA patients to clarify whether global DNA methylation pattern testing might be useful in monitoring disease activity as well as the response to therapeutics.

Methods
Flow cytometric measurement of 5-methyl-cytosine (5′-mC) was established using the cell line U937. In the subsequent prospective study, 62 blood samples were investigated, including 17 healthy donors and 45 RA patients at baseline and after 3 months of treatment with methotrexate, the IL-6 receptor inhibitor sarilumab, and Janus kinase inhibitors. Methylation status was assessed with an anti-5′-mC antibody and analysed in PBMCs and CD4+, CD8+, CD14+ and CD19+ subsets. Signal intensities of 5′-mC were correlated with 28-joint DASs with ESR and CRP (DAS28-ESR and DAS28-CRP).

Results
Compared with healthy individuals, PBMCs of RA patients showed a significant global DNA hypomethylation. Signal intensities of 5′-mC correlated with transcription levels of DNMT1, DNMT3B and MTR genes involved in methylation processes. Using flow cytometry, significant good correlations and linear regression values were achieved in RA patients between global methylation levels and DAS28-ESR values for PBMCs (r = −0.55, P = 0.002), lymphocytes (r = −0.57, P = 0.001), CD4+ (r = −0.57, P = 0.001), CD8+ (r = −0.54, P = 0.001), CD14+ (r = −0.49, P = 0.008) and CD19+ (r = −0.52, P = 0.004) cells.

Conclusions
The degree of global DNA methylation was found to be associated with disease activity. Based on this novel approach, the degree of global methylation is a promising biomarker for therapy monitoring and the prediction of therapy outcome in inflammatory diseases.
ETF Arbitrage, Non-Fundamental Demand, and Return Predictability*
Authors: Brown David C , Davies Shaun William , Ringgenberg Matthew C 
Published: September 2020

Abstract
Non-fundamental demand shocks have significant effects on asset prices, but observing these shocks is challenging. We use the exchange-traded fund (ETF) primary market to study non-fundamental demand. Unique to the ETF market, specialized arbitrageurs called authorized participants correct violations of the law of one price between an ETF and its underlying assets by creating or redeeming ETF shares. We show theoretically and empirically that creation and redemption activities (ETF flows) provide signals of non-fundamental demand shocks. A portfolio that is short high-flow ETFs and long low-flow ETFs earns excess returns of 1.1–2.0% per month, consistent with non-fundamental demand distorting asset prices away from fundamental values. Moreover, we show non-fundamental demand imposes non-trivial costs on investors, leading to underperformance.
UNATTACHED 212PB FRACTION IN THE WORKER’S BREATHING ZONE AT HIGH THORON CONCENTRATIONS
Authors: Zhukovsky Michael , Vasyanovich Maksim , Onishchenko Aleksandra 
Published: September 2020

Abstract
Classical aerosol physics predicts that it is impossible to observe noticeable values of the unattached fraction of decay products of thoron at typical concentrations of aerosol particles. The experimental data have shown that the unattached fraction of the thoron decay products in a monazite storage facility is in the range 0.3–0.6. This effect is caused by local increase in air exchange near the inlet of the sampling device at high 220Rn concentrations. It was found that a dynamic shift between the unattached and attached thoron decay products is also observed in the worker’s breathing zone at a high concentration of thoron. The 212Pb unattached fraction in worker’s breathing zone was ~0.4. It demonstrates that when evaluating inhalation exposure to the products of the decay of thoron, it is necessary to take into account the increase of the 212Pb unattached fraction in the worker’s breathing zone.
THE INFLUENCE OF THE EQUILIBRIUM FACTOR ON THE ESTIMATED ANNUAL EFFECTIVE DOSE FROM INHALED RADON DECAY PRODUCTS IN SELECTED WORKPLACES
Authors: Otahal Petr P S , Burian Ivo , Fialova Eliska , Vosahlik Josef 
Published: September 2020

Abstract
Measurements of activity concentration of radon gas and radon decay products were carried out in several workplaces including schools, radium spas, swimming pools, water treatment plants, caves and former mines. Based on these measurements, annual effective doses to workers were estimated and values of the equilibrium factor, F, were calculated. This paper describes the different approaches used to estimate the annual effective dose based on the dose coefficients recommended by the International Commission on Radiological Protection. Using the measured F values as opposed to the default F value of 0.4 changed the doses by about 5–95% depending mainly upon the ventilation conditions of the workplace.
Metabolites from Wild Potato Inhibit Virulence Factors of the Soft Rot and Blackleg Pathogen Pectobacterium brasiliense
Authors: Joshi Janak R. , Yao Linxing , Charkowski Amy O. , Heuberger Adam L. 
Published: September 2020

Potato (Solanum tuberosum L.) is the primary vegetable crop consumed worldwide and is largely affected by bacterial pathogens that can cause soft rot and blackleg disease. Recently, resistance to these diseases has been identified in the wild potato S. chacoense, and the mechanism of resistance is unknown. Here, it was hypothesized that S. chacoense stems or tubers have unique chemistry that confers resistance to the pathogen Pectobacterium brasiliense through bactericidal, bacteriostatic, or antivirulence activity. Stem and tuber metabolite extracts were collected from S. chacoense and tested for effects on Pectobacterium bacterial multiplication rates, and activity and expression of known exoenzymes and virulence genes using S. tuberosum extracts as a comparative control. Comparatively, the S. chacoense extracts did not affect bacterial multiplication rate; however, they did reduce pectinase, cellulase, and protease activities. The chemical extracts were profiled using a bioassay-guided fractionation, and a nontargeted metabolomics comparison of S. chacoense and S. tuberosum stems and tubers was performed. The data showed that selected alkaloids, phenolic amines, phenols, amines, and peptides are integrative chemical sources of resistance against the bacteria. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Chromosomal Abnormalities Detected by Karyotyping and Microarray Analysis in Twins With Structural Anomalies
Authors: Li L. , He Z. , Huang X. , Lin S. , Wu J. , Huang L. , Wan Y. , Fang Q. 
Published: September 2020

(Abstracted from Ultrasound Obstet Gynecol 2020;55:502–509)
Structural anomalies are frequently detected by prenatal ultrasound, and understanding the cause of such anomalies is important for genetic counseling and prenatal management. Chromosomal microarray analysis (CMA) has been shown to increase the rate of genetic diagnosis compared with karyotyping.
The Concept of Pain Inventory (COPI)
Authors: Pate Joshua W. , Simons Laura E. , Hancock Mark J. , Hush Julia M. , Noblet Tim , Pounder Meg , Pacey Verity 
Published: September 2020

Objectives:
Clinical guidelines recommend that health care providers assist children to understand their experience of persistent pain, with pain science education a key component of clinical management in pediatric pain clinics. Currently, no tool exists to assess a child’s concept of pain. The aim of this study was to develop such a tool and to evaluate its psychometric properties.

Methods:
After a rigorous process to generate items, assess content validity, evaluate readability and understandability, and pretest items, a cohort of 124 children (aged 8 to 12 y) independently completed the measure on 2 occasions, along with additional measures of pain, function, and pain-related distress.

Results:
The resulting unidimensional 14-item Concept of Pain Inventory (COPI) had acceptable internal consistency (α= 0.78) and moderate test-retest reliability (intraclass correlation coefficient (3,1) = 0.55; 95% CI, 0.37-0.68). Higher COPI scores reflect greater alignment with contemporary pain science. COPI scores were inversely correlated with pain intensity and functional disability, but unrelated to pain catastrophizing and pain-related fear. At 1 to 2 months’ follow-up, baseline COPI scores were inversely correlated with clinical variables of functional disability and pain intensity.

Discussion:
These results support the COPI as a brief, psychometrically sound tool to assess a child’s concept of pain. Clinically, this tool may facilitate individualized pain science education to target identified conceptual “gaps” or misconceptions and to evaluate the effectiveness of pain science education in children. Further research examining its efficacy and impact is warranted.
Progress of antibiotic-loaded bone cement in joint arthroplasty
Authors: Xu Yi-Ming , Peng Hui-Ming , Feng Bin , Weng Xi-Sheng 
Published: September 2020

AbstractBone cement, consisting of polymethyl methacrylate, is a bioinert material used for prothesis fixation in joint arthroplasty. To treat orthopedic infections, such as periprosthetic joint infection, antibiotic-loaded bone cement (ALBC) was introduced into clinical practice. Recent studies have revealed the limitations of the antibacterial effect of ALBC. Moreover, with the increase in high infection risk patients and highly resistant microbes, more researches and modification of ALBC are required. This paper reviewed latest findings about ALBC for most popular and destructive pathogens, summarized the influence of antibiotic kind, drug dosage, application method, and environment towards characteristic of ALBC. Subsequently, new cement additives and clinical applications of ALBC in joint arthroplasty were also discussed.
Effect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach
Authors: Downes Kevin J. , Zane Nicole R. , Zuppa Athena F. 
Published: September 2020

Background:
Vancomycin is eliminated by glomerular filtration, but current approaches to estimate kidney function in children are unreliable. The authors sought to compare the suitability of cystatin C (CysC)-based glomerular filtration rate equations with the most commonly used creatinine-based equation, bedside Schwartz, to estimate vancomycin clearance (CL).

Methods:
This prospective observational study enrolled critically ill patients (2–18 years) receiving intravenous vancomycin at the Children's Hospital of Philadelphia during December 2015–November 2017. Vancomycin levels were collected during clinical care and at 3 times during a single dosing interval. Plasma CysC was measured within 24 hours before intravenous vancomycin (baseline) initiation or immediately after enrollment and along with the third pharmacokinetic sample. Nonlinear mixed effects modeling was performed using NONMEM software. Covariate selection was used to test model fit with inclusion of the estimated glomerular filtration rate (eGFR) on CL using bedside Schwartz versus various published CysC-based equations.

Results:
In total, 83 vancomycin levels were obtained from 20 children. The median age was 12.7 years; 6 patients were women. A 1-compartment model best described the data; CL was allometrically scaled to 0.75. During covariate selection, inclusion of the eGFR calculated using a CysC-based equation significantly improved model fit [reduction in objective function value (OFV) range: −17.191 to −18.704] than bedside Schwartz (∆OFV −12.820). Including the full age spectrum equation, an eGFR equation based on both creatinine and CysC, led to the largest OFV reduction (−22.913); female sex was also a significant covariate of CL in the model. Final model pharmacokinetic indices were CL = 0.29 L/h/kg0.75 and volume of distribution = 0.48 L/kg.

Conclusions:
CysC-based equations help better estimate vancomycin CL than bedside Schwartz in critically ill children.
Population Pharmacokinetic Models of Antituberculosis Drugs in Patients: A Systematic Critical Review
Authors: Otalvaro Julian D. , Hernandez Alher M. , Rodriguez Carlos A. , Zuluaga Andres F. 
Published: September 2020

Background:
Tuberculosis (TB) remains one of the most important infectious diseases. Population pharmacokinetic (pop-PK) models are widely used to individualize dosing regimens of several antibiotics, but their application in anti-TB drug studies is scant. The aim of this study was to provide an insight regarding the status of pop-PK for these drugs and to compare results obtained through both parametric and nonparametric approaches to design precise dosage regimens.

Methods:
First, a systematic approach was implemented, searching in PubMed and Google Scholar. Articles that did not include human patients, that lacked an explicit structural model, that analyzed drugs inactive against M. tuberculosis, or were without full-text access, were excluded. Second, the PK parameters were summarized and categorized as parametric versus nonparametric results. Third, a Monte Carlo simulation was performed in Pmetrics using the results of both groups, and an error term was built to describe the imprecision of each PK modeling approach.

Results:
Thirty-three articles reporting at least 1 pop-PK model of 19 anti-TB drug were found; 46 different models including PK parameter estimates and their relevant covariates were also reported. Only 9 models were based on nonparametric approaches. Rifampin was the drug most studied, but only using parametric approaches. The simulations showed that nonparametric approaches improve the error term compared with parametric approaches.

Conclusions:
More and better models, ideally using nonparametric approaches linked with clear pharmacodynamic goals, are required to optimize anti-TB drug dosing, as recommended in the WHO End TB strategy.
Onset of the climacteric phase by the mid-forties associated with impaired insulin sensitivity: a birth cohort study
Authors: Savukoski Susanna M. , Suvanto Eila T. J. , Auvinen Juha P. , Pesonen Paula R. O. , Keinänen-Kiukaanniemi Sirkka M. , Puukka Katri S. , Ebeling Tapani , Niinimäki Maarit J. 
Published: September 2020

Abstract

Objective:
To investigate whether the early-onset menopausal transition is associated with deteriorated glucose tolerance in women in their mid-forties.

Methods:
A cross-sectional analysis of a cohort study including 2,632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle-stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users.

Results:
Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2,253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increased glycated hemoglobin (P < 0.001), 2-hour oral glucose tolerance test 30- and 60-minute insulin (P = 0.040 and 0.006, respectively), and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decreased the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly.

Conclusions:
Earlier onset of climacteric transition is associated with impaired insulin sensitivity in middle-aged women.

Video Summary:
http://links.lww.com/MENO/A648.
Impact of a Best Practice Prevention Bundle on Central Line-associated Bloodstream Infection (CLABSI) Rates and Outcomes in Pediatric Hematology, Oncology, and Hematopoietic Cell Transplantation Patients in Inpatient and Ambulatory Settings
Authors: Ardura Monica I. , Bibart Mindy J. , Mayer Lauren C. , Guinipero Terri , Stanek Joseph , Olshefski Randal S. , Auletta Jeffery J. 
Published: September 2020

Background:
Pediatric hematology, oncology, and hematopoietic cell transplantation (HCT) patients are at increased risk for bloodstream infections. The authors sought to evaluate the influence of a standardized best practice central venous catheter (CVC) maintenance bundle on the burden of and risk factors for mucosal barrier injury (MBI) and non-MBI central line-associated bloodstream infections (CLABSIs) across a common inpatient and ambulatory continuum in this high-risk population.

Methods:
A retrospective cohort study of patients with underlying malignancy, hematologic disorders, and HCT recipients with a CVC in place at the time of CLABSI diagnosis in both inpatient and ambulatory settings from January 1, 2012 to December 31, 2016. Descriptive, nonparametric statistics were used to describe patient characteristics and outcomes. Logistic regression analyses were applied to identify potential risk factors for inpatient versus ambulatory and MBI versus non-MBI CLABSI.

Results:
During the 5-year period, 118 of 808 (14.6%) patients had 159 laboratory-confirmed CLABSIs for ambulatory and inpatient CLABSI rates of 0.27 CLABSI/1000 and 2.2 CLABSI/1000 CVC days, respectively. CLABSI occurred more frequently in hospitalized patients after HCT and with underlying leukemia, most frequently caused by Gram-negative bacteria. MBI CLABSI accounted for 42% of all CLABSI with a 3-fold higher risk in hospitalized patients. Having multiple CVC or a CVC that was not a port independently associated with higher CLABSI risk.

Conclusions:
In our cohort, non-MBI CLABSI continued to account for the majority of CLABSI. CVC type is independently associated with higher overall CLABSI risk. Further studies are needed to reliably define additional prevention strategies when CLABSI maintenance bundles elements are optimized in this high-risk population.
Predictors of State-Level Stay-at-Home Orders in the United States and Their Association With Mobility of Residents
Authors: Gigliotti Philip , Martin Erika G. 
Published: September 2020

Objective:
To evaluate predictors of stay-at-home order adoption among US states, as well as associations between order enactment and residents' mobility.

Design:
We assess associations between state characteristics and adoption timing. We also assess associations between enactment and aggregate state-level measures of residents' mobility (Google COVID-19 Community Mobility Reports).

Setting:
The United States.

Participants:

Adoption population: 50 US states and District of Columbia. Mobility population: state residents using devices with GPS tracking accessible by Google.

Intervention and Exposures:

State characteristics: COVID-19 diagnoses per capita, 2016 Trump vote share, Republican governor, Medicaid expansion status, hospital beds per capita, public health funding per capita, state and local tax revenue per capita, median household income, population, percent residents 65 years or older, and percent urban residents. Mobility exposure: indicator of order enactment by March 29, 2020 (date of mobility data collection).

Main Outcome Measures:

Order adoption timing: days since adoption of first order. Mobility: changes in mobility to 6 locations from February 6 to March 29, 2020.

Results:
In bivariate models, order adoption was associated with COVID-19 diagnoses (hazard ratio [HR] = 1.01; 95% confidence interval [CI], 1.00 to 1.01), Republican governor (HR = 0.24; 95% CI, 0.13 to 0.44), Medicaid expansion (HR = 2.50; 95% CI, 1.40 to 4.48), and hospital capacity (HR = 0.43; 95% CI, 0.26 to 0.70), consistent with findings in the multivariate models. Order enactment was positively associated with time at home (beta (B) = 1.31; 95% CI, 0.35 to 2.28) and negatively associated with time at retail and recreation (B = −7.17; 95% CI, −10.89 to −3.46) and grocery and pharmacy (B = −8.28; 95% CI, −11.97 to −4.59) locations. Trump vote share was associated with increased mobility for 4 of 6 mobility measures.

Conclusions and Relevance:
While politics influenced order adoption, public health considerations were equally influential. While orders were associated with decreased mobility, political ideology was associated with increased mobility under social distancing policies.
Multilevel Dysvascular Injury of the Hand: Replantation versus Revision Amputation
Authors: Kwak Sang Ho , Lee Sang Hyun , Rhee Seung Joon , Jang Hyo Seok , Kim Dong Hee , Kim Yong Jin 
Published: September 2020

Background:
Multilevel dysvascular injury of the hand can be treated with replantation or revision amputation. The authors compared both modalities regarding functional outcomes, patient-reported outcomes, and required resources, as relevant studies are scarce.

Methods:
In this retrospective review of consecutive case series (replantation, n = 8; revision amputation, n = 11), clinical results and functional outcomes (including grip strength, range of motion, sensory recovery, and grip or pinch ability) were assessed. Patient-reported outcomes, required hospital resources, and treatment cost until 1 year after surgery were compared between both groups.

Results:
Six patients used passive prostheses, two used body-powered prostheses, and three did not use a prosthesis in the revision amputation group. All patients in the replantation group could grip objects and had restored hands, with protective sensory recovery and substantial wrist motion, whereas six patients in the revision amputation group were unable to grip or pinch objects. Replantation was associated with superior patient-reported outcomes, but required more hospital resources and treatment costs.

Conclusions:
This study suggests that in the treatment of multilevel dysvascular injury of the hand, the surgical method should be chosen on a case-by-case basis. For better functional and patient-reported outcomes, replantation is preferred. Revision amputation can be performed in the absence of sufficient hospital resources and to reduce treatment cost. These findings can aid in the preoperative counseling of patients with multilevel dysvascular injury of the hand.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.