bluuebunny/crossref_metadata_2025_split huggingface dataset:
KREAP: an automated Galaxy platform to quantify in vitro re-epithelialization kinetics
Authors: Fernandez-Gutierrez Marcela M , van Zessen David B H , van Baarlen Peter , Kleerebezem Michiel , Stubbs Andrew P 
Published: June 2018

Abstract

Background
In vitro scratch assays have been widely used to study the influence of bioactive substances on the processes of cell migration and proliferation that are involved in re-epithelialization. The development of high-throughput microscopy and image analysis has enabled scratch assays to become compatible with high-throughput research. However, effective processing and in-depth analysis of such high-throughput image datasets are far from trivial and require integration of multiple image processing and data extraction software tools.

Findings
We developed and implemented a kinetic re-epithelialization analysis pipeline (KREAP) in Galaxy. The KREAP toolbox incorporates freely available image analysis tools and automatically performs image segmentation and feature extraction of each image series, followed by automatic quantification of cells inside and outside the scratched area over time. The enumeration of infiltrating cells over time is modeled to extract three biologically relevant parameters that describe re-epithelialization kinetics. The output of the tools is organized, displayed, and saved in the Galaxy environment for future reference.

Conclusions
The KREAP toolbox in Galaxy provides an open-source, easy-to-use, web-based platform for reproducible image processing and data analysis of high-throughput scratch assays. The KREAP toolbox could assist a broad scientific community in the discovery of compounds that are able to modulate re-epithelialization kinetics.
Web-based versus in-person methods for training lay community health advisors to implement health promotion workshops: participant outcomes from a cluster-randomized trial
Authors: Holt Cheryl L , Tagai Erin K , Santos Sherie Lou Zara , Scheirer Mary Ann , Bowie Janice , Haider Muhiuddin , Slade Jimmie 
Published: June 2018

Abstract
Project HEAL (Health through Early Awareness and Learning) is an implementation trial that compared two methods of training lay peer community health advisors (CHAs)—in-person (“Traditional”) versus web-based (“Technology”)—to conduct a series of three evidence-based cancer educational workshops in African American churches. This analysis reports on participant outcomes from Project HEAL. Fifteen churches were randomized to the two CHA training methods and the intervention impact was examined over 24 months. This study was conducted in Prince George’s County, MD, and enrolled 375 church members age 40–75. Participants reported on knowledge and screening behaviors for breast, prostate, and colorectal cancer. Overall, cancer knowledge in all areas increased during the study period (p &lt; .001). There were significant increases in digital rectal exam (p &lt; .05), fecal occult blood test (p &lt; .001), and colonoscopy (p &lt; .01) at 24 months; however, this did not differ by study group. Mammography maintenance (56% overall) was evidenced by women reporting multiple mammograms within the study period. Participants attending all three workshops were more likely to report a fecal occult blood test or colonoscopy at 24 months (p &lt; .05) than those who attended only one. These findings suggest that lay individuals can receive web-based training to successfully implement an evidence-based health promotion intervention that results in participant-level outcomes comparable with (a) people trained using the traditional classroom method and (b) previous efficacy trials. Findings have implications for resources and use of technology to increase widespread dissemination of evidence-based health promotion interventions through training lay persons in community settings.
The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients
Authors: Inoue Akihiko , Hifumi Toru , Yonemoto Naohiro , Kuroda Yasuhiro , Kawakita Kenya , Sawano Hirotaka , Tahara Yoshio , Hase Mamoru , Nishioka Kenji , Shirai Shinichi , Hazui Hiroshi , Arimoto Hideki , Kashiwase Kazunori , Kasaoka Shunji , Motomura Tomokazu , Yasuga Yuji , Yokoyama Hiroyuki , Nagao Ken , Nonogi Hiroshi 
Published: June 2018

Objectives:
Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest.

Design:
A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study.

Setting:
Fourteen hospitals throughout Japan.

Patients:
Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011.

Intervention:
None.

Measurements and Main Results:
This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]–heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3–5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78–0.96; p = 0.004).

Conclusions:
Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.
Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients
Authors: van Keulen Kris , Knol Wilma , Belitser Svetlana V. , van der Linden Paul D. , Heerdink Eibert R. , Egberts Toine C. G. , Slooter Arjen J. C. 
Published: June 2018

Objectives:
To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium.

Design:
Prospective cohort study.

Setting:
Thirty-two–bed mixed intensive care in a tertiary care center.

Patients:
Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded.

Interventions:
None.

Measurements and Main Results:
The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73–1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15–1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12–2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73–3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16–1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07–2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium.

Conclusions:
Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.
Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update
Authors: Patsalos Philip N. , Spencer Edgar P. , Berry Dave J. 
Published: June 2018

Background:
Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, for example, pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug's prescribing indications, key pharmacokinetic characteristics, associated drug–drug pharmacokinetic interactions, and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total versus free concentrations in blood versus saliva) and sample collection and processing.

Methods:
The present review is based on published articles and searches in PubMed and Google Scholar, last searched in March 2018, in addition to references from relevant articles.

Results:
In total, 171 relevant references were identified and used to prepare this review.

Conclusions:
TDM provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), much data have accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide).
Modeling Tissue Heating From Exposure to Radiofrequency Energy and Relevance of Tissue Heating to Exposure Limits: Heating Factor
Authors: Foster Kenneth R. , Ziskin Marvin C. , Balzano Quirino , Bit-Babik Giorgi 
Published: June 2018

AbstractThis review/commentary addresses recent thermal and electromagnetic modeling studies that use image-based anthropomorphic human models to establish the local absorption of radiofrequency energy and the resulting increase in temperature in the body. The frequency range of present interest is from 100 MHz through the transition frequency (where the basic restrictions in exposure guidelines change from specific absorption rate to incident power density, which occurs at 3–10 GHz depending on the guideline). Several detailed thermal modeling studies are reviewed to compare a recently introduced dosimetric quantity, the heating factor, across different exposure conditions as related to the peak temperature rise in tissue that would be permitted by limits for local body exposure. The present review suggests that the heating factor is a robust quantity that is useful for normalizing exposures across different simulation models. Limitations include lack of information about the location in the body where peak absorption and peak temperature increases occur in each exposure scenario, which are needed for careful assessment of potential hazards. To the limited extent that comparisons are possible, the thermal model (which is based on Pennes’ bioheat equation) agrees reasonably well with experimental data, notwithstanding the lack of theoretical rigor of the model and uncertainties in the model parameters. In particular, the blood flow parameter is both variable with physiological condition and largely determines the steady state temperature rise. We suggest an approach to define exposure limits above and below the transition frequency (the frequency at which the basic restriction changes from specific absorption rate to incident power density) to provide consistent levels of protection against thermal hazards. More research is needed to better validate the model and to improve thermal dosimetry in general. While modeling studies have considered the effects of variation in thickness of tissue layers, the effects of normal physiological variation in tissue blood flow have been relatively unexplored.
The Feasibility of Retrofacial Approach for Cochlear Implantation
Authors: Yilmazer Rasim , Gerring Robert C. , Sidani Charif , Wolfovitz Amit , Angeli Simon I. , Telischi Fred F. 
Published: June 2018

Hypothesis:
The retrofacial approach is a feasible approach to the round window niche and that the Round window-Sigmoid sinus line will help determine the feasibility of retrofacial approach for cochlear implantation unless there is a very high jugular bulb.

Background:
When the round window cannot be visualized by facial recess approach during cochlear implantation, other conservative techniques can be used to improve visualization such as the retrofacial approach.

Methods:
Thirteen adult dry cadaveric temporal bones were studied. Computed tomography (CT) scan was obtained on all temporal bones. An imaginary Round window-Sigmoid sinus line was drawn on the axial images. We assessed whether this line is anterior (including intersection) or posterior to the facial nerve (FN). The following closest distances were measured on CT scans: 1) posterior semicircular canal (PSC)-FN, 2) PSC-Stapedius muscle, 3) PSC-Jugular bulb, 4) lateral semicircular canal (LSC)-Jugular bulb, 5) sigmoid sinus-FN. A canal wall-up mastoidectomy, facial recess, and retrofacial approach were performed in all specimens. We have noted whether we need a standard or an extended mastoidectomy.

Results:
The Round window-Sigmoid sinus line was posterior to the FN in all specimens. The retrofacial approach was feasible and the round window was visualized in all specimens. Extended mastoidectomy was required in seven specimens and the PSC-FN was ≤ 3 mm in five of them.

Conclusion:
Retrofacial approach is feasible in cochlear implantation when the Round window-Sigmoid sinus line is posterior to the FN and the jugular bulb is not obstructing the round window.
Effects of Cartilage Overlay on the Tympanic Membrane: Lessons From a Temporal Bone Study for Cartilage Tympanoplasty
Authors: Eldaebes Mostafa M.A.S. , Landry Thomas G. , Bance Manohar L. 
Published: June 2018

Hypothesis:
Placing cartilage grafts on different tympanic membrane (TM) locations will affect sound transfer function, and the effects will differ according to the part of the TM modified.

Background:
Cartilage tympanoplasty is increasingly popular because of lower reperforation rates, and better long-term stability. In this temporal bone study, we investigated the effect of placing cartilage grafts over different parts of the normal TM on sound transmission.

Methods:
In 10 human fresh frozen temporal bones, umbo and stapes vibrations to acoustic stimuli from 250 to 8000 Hz were measured at multiple points using a scanning laser vibrometer. Four different cartilage arrangements were measured in each temporal bone. 1) Overlay condition leaving an umbo rim of normal TM (Umbo Rim). 2) Overlay condition leaving annular rim of normal TM (Annular Rim). 3) Overlay condition leaving both rims of normal TM (Two Rims). 4) Overlay condition leaving no normal TM exposed (No Rims).

Results:
At low frequencies, there was a statistically significant decrease in velocity from baseline for the No Rims (umbo mean −4 dB; stapes −6 dB) and Umbo Rim (umbo −4 dB; stapes −3.7 dB) conditions. All conditions showed significant decreases for middle frequencies (umbo −4.0, −5.9, −7.4 and −6.3 dB; stapes −10.8, −6.6, −6.3 and −7.7 dB) and high frequencies (umbo −13.2, −3.0, −3.1 and −5.5 dB; stapes −4.6, −2.4, −2.6 and −3.5 dB). Results are in order for No Rims, Umbo Rim, Two Rims, and Annular Rim conditions.

Conclusion:
In the low frequencies, it seems to matter where the cartilage is placed, and in particular the annular rim of the TM seems to be important for the low-frequency acoustic transfer function. In the higher frequencies, all graft placements caused some drop at all frequencies. In all frequencies, effects were modest by clinical standards.
Testability Study of the Titmus V3 Test in Pre-school Children
Authors: Furr Bruce Alan , Musch David C. , Andrews Chris A. , Schumann Rachel 
Published: June 2018

SIGNIFICANCEVision screening can identify people who have vision problems requiring a comprehensive examination. When children are screened, the most prevalent serious problem is amblyopia secondary to uncorrected ametropia. Screening also identifies strabismus, which can lead to loss of binocularity. Early diagnosis permits treatment with restoration of balanced vision and binocularity.PURPOSEThe study evaluated the testability of the Titmus V3 Vision Screener as a method to screen vision and strabismus in pre-school children.METHODSPre-school children between 36 and 66 months of age underwent vision screening in six Michigan counties. The State of Michigan screening consists of the LEA Symbols test for visual acuity and the stereo butterfly for near-strabismus testing. The proposed Titmus V3 screening tests were the LEA Symbols slide for vision and near-strabismus test slide. Primary and secondary objectives of this study were to evaluate the percentage of pre-school children who completed the Titmus V3 screening tests for vision and near strabismus and factors associated with an inability to complete the tests, contrasting the pass/fail results between the state and Titmus V3 results.RESULTSTwo-hundred sixty-three children were tested. The percentages of children unable to score on the Titmus V3 instrument versus the state's LEA Symbols test were 16.0% and 5.3%, respectively. The percentage of children unable to score on the Titmus V3 near-strabismus test slide was 6.9 versus 3.4% on the State of Michigan stereo butterfly test. Younger age at testing was the most important factor associated with the inability to complete testing.CONCLUSIONSBecause of testability limitations and higher failure rates relative to the State of Michigan testing methods, the Titmus V3 screening device is not a feasible alternative to the standard methods used by the State of Michigan for vision and near-strabismus screening among the pre-school subjects we tested.
Interocular Asymmetry of the Ganglion Cell–inner Plexiform Layer in Diabetic Retinopathy
Authors: Lim Hyung Bin , Lee Woo Hyuk , Jo Young Joon , Kim Jung Yeul 
Published: June 2018

SIGNIFICANCE
The interocular difference in the ganglion cell–inner plexiform layer thickness showed a significant correlation with the diabetic retinopathy (DR) severity.

PURPOSE
The purpose of this study was to analyze the interocular differences in the foveal, retinal nerve fiber layer (RNFL), and ganglion cell–inner plexiform layer (GC-IPL) thickness of DR patients using spectral-domain optical coherence tomography.

METHODS
A total of 508 eyes from 254 patients with different severities of DR and 184 eyes from 92 control subjects were included. The GC-IPL, foveal, and RNFL thicknesses were measured, and the interocular differences in these thicknesses were correlated in control subjects and DR patients.

RESULTS
The interocular difference in the average GC-IPL thickness significantly increased with the severity of DR. The interocular differences in the average GC-IPL thicknesses of the severe nonproliferative DR (NPDR) and the proliferative DR patients were significantly higher than those of the control group. However, there was no significant difference in thickness between the control group and the group with mild to moderate NPDR. In the group with proliferative DR, the interocular difference in the average GC-IPL was greater than those in the central foveal and RNFL thicknesses. Multivariate regression analyses showed that the DR severity and the interocular difference in central foveal thickness were significantly correlated with the interocular difference in the average GC-IPL thickness.

CONCLUSIONS
The interocular differences in the central foveal, RNFL, and GC-IPL thicknesses significantly increased with increased DR severity. However, there was no significant difference between the control group and the group with mild to moderate NPDR. The GC-IPL differences showed a significant correlation with DR severity. These findings may be an indicator of DR progression.
Case Series: Corneal Epithelial Macrocysts in Scleral Contact Lenses Post–penetrating Keratoplasty
Authors: Nguyen Linda Trang , Yang David , Vien Lee 
Published: June 2018

SIGNIFICANCE
Transitory corneal epithelial macrocysts associated with scleral contact lens wear post–penetrating keratoplasty are observed in areas of corneal edema. The macrocysts do not appear to result in complications that would prevent successful wear of scleral contact lenses.

PURPOSE
The purpose of this study is to report three cases of transitory corneal epithelial macrocysts associated with scleral lenses in post–penetrating keratoplasty corneas.

CASE REPORTS
Three cases including anterior segment photographs and anterior segment optical coherence tomography highlight the clinical presentation of transient corneal epithelial macrocysts.

CONCLUSIONS
Corneal edema and anatomical alterations after penetrating keratoplasty along with the negative pressure underneath a scleral contact lens are hypothesized to have caused the transient epithelial macrocysts observed in these cases. Because of the transitory nature of these cysts without evidence of consequent corneal damage or cyst rupture over years of observance, we believe that it is safe for these patients to continue wearing scleral contact lenses with routine follow-up.