bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Is Just the Beginning of Gene Expression Regulation: The Functional Significance of RNA-Binding Proteins to Post-transcriptional Processes in Plants
Authors: Prall Wil , Sharma Bishwas , Gregory Brian D 
Published: April 2019

AbstractPlants have developed sophisticated mechanisms to compensate and respond to ever-changing environmental conditions. Research focus in this area has recently shifted towards understanding the post-transcriptional mechanisms that contribute to RNA transcript maturation, abundance and function as key regulatory steps in allowing plants to properly react and adapt to these never-ending shifts in their environments. At the center of these regulatory mechanisms are RNA-binding proteins (RBPs), the functional mediators of all post-transcriptional processes. In plants, RBPs are becoming increasingly appreciated as the critical modulators of core cellular processes during development and in response to environmental stimuli. With the majority of research on RBPs and their functions historically in prokaryotic and mammalian systems, it has more recently been unveiled that plants have expanded families of conserved and novel RBPs compared with their eukaryotic counterparts. To better understand the scope of RBPs in plants, we present past and current literature detailing specific roles of RBPs during stress response, development and other fundamental transition periods. In this review, we highlight examples of complex regulation coordinated by RBPs with a focus on the diverse mechanisms of plant RBPs and the unique processes they regulate. Additionally, we discuss the importance for additional research into understanding global interactions of RBPs on a systems and network-scale, with genome mining and annotation providing valuable insight for potential uses in improving crop plants in order to maintain high-level production in this era of global climate change.
Searching for a Match: Structure, Function and Application of Sequence-Specific RNA-Binding Proteins
Authors: Dedow Lauren K , Bailey-Serres Julia 
Published: April 2019

Abstract
Plants encode over 1800 RNA-binding proteins (RBPs) that modulate a myriad of steps in gene regulation from chromatin organization to translation, yet only a small number of these proteins and their target transcripts have been functionally characterized. Two classes of eukaryotic RBPs, pentatricopeptide repeat (PPR) and pumilio/fem-3 binding factors (PUF), recognize and bind to specific sequential RNA sequences through protein–RNA interactions. These modular proteins possess helical structural units containing key residues with high affinity for specific nucleotides, whose sequential order determines binding to a specific target RNA sequence. PPR proteins are nucleus-encoded, but largely regulate post-transcriptional gene regulation within plastids and mitochondria, including splicing, translation and RNA editing. Plant PUFs are involved in gene regulatory processes within the cell nucleus and cytoplasm. The modular structures of PPRs and PUFs that determine sequence specificity has facilitated identification of their RNA targets and biological functions. The protein-based RNA-targeting of PPRs and PUFs contrasts to the prokaryotic cluster regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) that target RNAs in prokaryotes. Together the PPR, PUF and CRISPR-Cas systems provide varied opportunities for RNA-targeted engineering applications.
CAN SCATTER CORRECTION SOFTWARE REPLACE A GRID IN DR PELVIC EXAMINATIONS?
Authors: Precht Helle , Mørup Svea Deppe , Tingberg Anders , Outzen Claus Bjørn , Kusk Kirsten Weber , Nielsen Rita Møller , Midtgård Marie , Winther Martin Brændegaard , Waaler Dag , Kusk Martin Weber 
Published: April 2019

Abstract
The purpose was to examine if scatter correction software could replace a grid while maintaining image quality and reducing radiation dose for pelvic DR examinations. Grid images was produced with 70 kV and 16mAs. Anthropomorphic- and Contrast Detail RADiography (CDRAD) non-grid images were produced with 60 kV, 80 kV and 90 kV combined with five different mAs and scatter correction software. The anthropomorphic images were analyzed by absolute Visual Grading Analysis (VGA). The CDRAD images were analyzed using the CDRAD analysis software. The results showed a total of 54.6% non-grid images were evaluated as unsuitable for diagnostic use by the VGA. The CDRAD grid images showed that the IQF_inv values were significantly different (p = 0.0001) when compared to every group of non-grid images. Hereby, the conclusion stated that the scatter correction software did not compensate for the loss in image quality due to scattered radiation at the exposure levels included in a pelvic examination.
Towards regional responsible research and innovation? Integrating RRI and RIS3 in European innovation policy
Authors: Fitjar Rune Dahl , Benneworth Paul , Asheim Bjørn Terje 
Published: April 2019

AbstractThis article develops a model for a regional responsible research and innovation (RRI) policy, integrating existing European Union policies on RRI, and on research and innovation strategies for smart specialisation (RIS3). RRI and RIS3 are central concepts in the EU’s innovation policy agenda, but there are tensions between the two approaches. The place-based approach inherent in RIS3 is missing from RRI, which has a fuzzy concept of geographical scale and is vulnerable to mismatches between the scale of innovations and of the associated governance networks involved in the innovation process. Meanwhile, the multitude of visions, values and stakeholder perceptions embodied in the RRI concept is countered by the more optimistic and unitary imagining of a regional future in RIS3. We highlight that Europe’s innovation challenges can only be resolved by leveraging the strengths of both types of innovation policy.
Quantitative electroencephalography measures in rapid eye movement and nonrapid eye movement sleep are associated with apnea–hypopnea index and nocturnal hypoxemia in men
Authors: Appleton Sarah L , Vakulin Andrew , D’Rozario Angela , Vincent Andrew D , Teare Alison , Martin Sean A , Wittert Gary A , McEvoy R Doug , Catcheside Peter G , Adams Robert J 
Published: April 2019

AbstractStudy ObjectivesQuantitative electroencephalography (EEG) measures of sleep may identify vulnerability to obstructive sleep apnea (OSA) sequelae, however, small clinical studies of sleep microarchitecture in OSA show inconsistent alterations. We examined relationships between quantitative EEG measures during rapid eye movement (REM) and non-REM (NREM) sleep and OSA severity among a large population-based sample of men while accounting for insomnia.MethodsAll-night EEG (F4-M1) recordings from full in-home polysomnography (Embletta X100) in 664 men with no prior OSA diagnosis (age ≥ 40) were processed following exclusion of artifacts. Power spectral analysis included non-REM and REM sleep computed absolute EEG power for delta, theta, alpha, sigma, and beta frequency ranges, total power (0.5–32 Hz) and EEG slowing ratio.ResultsApnea–hypopnea index (AHI) ≥10/h was present in 51.2% (severe OSA [AHI ≥ 30/h] 11.6%). In mixed effects regressions, AHI was positively associated with EEG slowing ratio and EEG power across all frequency bands in REM sleep (all p < 0.05); and with beta power during NREM sleep (p = 0.06). Similar associations were observed with oxygen desaturation index (3%). Percentage total sleep time with oxygen saturation <90% was only significantly associated with increased delta, theta, and alpha EEG power in REM sleep. No associations with subjective sleepiness were observed.ConclusionsIn a large sample of community-dwelling men, OSA was significantly associated with increased EEG power and EEG slowing predominantly in REM sleep, independent of insomnia. Further study is required to assess if REM EEG slowing related to nocturnal hypoxemia is more sensitive than standard PSG indices or sleepiness in predicting cognitive decline.
Autologous Platelet-Rich Plasma and Fibrin Glue Decrease Pain Following Excision and Primary Closure of Pilonidal Sinus
Authors: Alamdari Daryoush Hamidi , Motie Mohamad Reza , Kamalahmadi Nasim , Aliakbarian Mohsen 
Published: April 2019

ABSTRACT

BACKGROUND:
Pilonidal sinus is one of the most complicated chronic wounds common in younger adults. This disabling condition affects the natal clefts of the buttocks and often requires surgery.

OBJECTIVE:
To investigate the effect of autologous platelet-rich plasma and fibrin glue (PRP-FG) on pain reduction and the healing process of pilonidal sinus after excisional surgery with primary closure.

METHODS:
This randomized clinical trial study included 40 patients with pilonidal sinus admitted to a surgical ward. Patients were randomly divided into two groups: the control group, who underwent wide excision of the sinus with primary closure, and the case group, who had wide excision of the sinus with primary closure along with injection of autologous PRP-FG into the wound. For 6 months, patients were followed up for their severity of pain, wound healing process, the time it took them to get back to normal activities, infection, and other complications.

RESULTS:
In the first and second week after surgery, the severity of pain in the case group was reduced significantly in comparison with the control group. Healing time decreased but not significantly. There was no significant difference in infection and recurrence between the two groups.

CONCLUSIONS:
The addition of PRP-FG has the potential to reduce pain significantly in primary closure of pilonidal sinus.
Use of Silver-Containing Hydrofiber and Chlorhexidine-Impregnated Tulle Gras Dressings for Second-Degree Burns
Authors: Pamuk Cebeci Sevil , Acaroğlu Rengin 
Published: April 2019

ABSTRACT

OBJECTIVE:
This study evaluated the use of silver-containing hydrofiber and chlorhexidine-impregnated tulle gras dressings for second-degree burns.

METHODS:
This randomized clinical study consisted of 60 patients with second-degree burns. Data were collected using a Patient Identification Form, Wound Assessment Form, and Pain Assessment Scale. Following dressing application, wounds were assessed on days 7, 15, and 22. Study procedures were continued until full epithelialization occurred.

RESULTS:
After the seventh day of follow-up, significant improvement was noted in the experimental group in terms of wound exudate, wound debridement, pain intensity, and analgesic agent administration. After the 15th day of follow-up, there was a significant decrease in epithelialization time in the experimental group. Exudate control was better in patients whose burns were treated with silver-containing hydrofiber dressings, and they needed less debridement and fewer analgesics because of infrequent dressing changes. Lower pain scores were reported, the burn area reduced more quickly, and faster epithelialization and wound healing were achieved.

CONCLUSIONS:
The authors conclude that silver-containing hydrofiber dressings are an effective wound care material that improve the wound healing process. More studies comparing it and other wound care materials could improve the quality of healthcare for patients with burns.
Student Experience of Self-Care in an Online Master of Science in Nursing Course
Authors: Brown Cynthia J. , Bar Bonnie 
Published: April 2019

Abstract
The purpose of this qualitative study was to discover students’ experience of self-care in an online master of science in nursing course. The course included caring groups, organized small groups to provide support. The analysis of the personal reflective summaries of 37 students revealed two main themes and five subthemes. Two overarching themes illuminated “Finding Our Inner Selves” and “A Lasting Journey and Not a Destination.” The students valued a focus on self-care, goal setting, and support from family, friends, and caring groups. Many mentioned that self-care is an ongoing work in progress.
Empirical Grouping of Pain Zones in Fibromyalgia
Authors: Vallejo Miguel A. , Rivera Javier , Vallejo-Slocker Laura 
Published: April 2019

Objectives:
Widespread pain is important for the diagnosis of fibromyalgia (FM). For this purpose, the sum of pain regions obtained from a topographical distribution has been used to compute a Widespread Pain Index (WPI), but there is no empirical basis for choosing the regions. The aim of this study was to find an empirical distribution of the pain regions.

Materials and Methods:
We evaluated 228 female patients with FM. They completed the Fibromyalgia Survey Questionnaire, Fibromyalgia Impact Questionnaire (FIQ), Combined Index of Severity in Fibromyalgia (ICAF), and Short Form-36 Health Survey. The pain regions of the WPI were grouped by the topographical distribution (WPIR) and compared with a new empirical distribution (WPIE) obtained through exploratory factor analysis. A decision- tree analysis was conducted to identify the optimal algorithm for selecting pain regions related to the severity of FM.

Results:
The WPIE has a normal distribution compared with the WPIR. It also shows higher correlations with FM severity. From the factor analysis, 4 factors explain 48.5% of the variance. Two factors (emotional and physical) can conform to the decision-tree analysis using the dependent variables FIQ and ICAF. These factors are very congruent with the cutoff points previously proposed for FIQ and ICAF. The emotional factor is the first in the decision-tree.

Discussion:
WPIE has a normal distribution and shows better predictive qualities than WPIR. The emotional factor is conceptualized as emotional because of the relative importance of the right hemisphere in negative emotions and pain. The physical factor could be responsible for the decreased ability to coordinate left-right stepping.
Development and Validation of a Sensitive UHPLC-MS/MS–Based Method for the Analysis of Folylpolyglutamate Synthetase Enzymatic Activity in Peripheral Blood Mononuclear Cells: Application in Rheumatoid Arthritis and Leukemia Patients
Authors: Muller Ittai B. , Lin Marry , Struys Eduard A. , Heydari Paniz , Hebing Renske C. F. , Nurmohamed Mike T. , van der Laken Conny , Lems Willem F. , Cloos Jacqueline , Jansen Gerrit , de Jonge Robert 
Published: April 2019

Background:
Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs such as methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. To date, assessment of FPGS catalytic activity relies on assays using radioactive substrates that are labor-intensive and require relatively large numbers of cells. Here, we describe a nonradioactive, ultra–high-performance liquid chromatography–tandem mass spectrometer (UHPLC-MS/MS)–based method allowing for sensitive and accurate measurements of FPGS activity in low cell numbers (ie, 1–2 × 106) of biological specimens, including leukemic blast cells of acute lymphoblastic leukemia patients and peripheral blood mononuclear cells of patients with RA.

Methods:
The UHPLC-MS/MS assay was validated with 2 CCRF-CEM human leukemia cells, one proficient and one deficient in FPGS activity. Linearity of time and protein input were tested by measuring FPGS activity at 30–180 minutes of incubation time and 10–300 mcg protein extract. In addition, FPGS enzyme kinetic parameters were assessed.

Results:
The FPGS enzymatic assay showed a linear relation between FPGS activity and protein input (R2 ≥ 0.989) as well as incubation time (R2 ≥ 0.996). Moreover, the UHPLC-MS/MS method also allowed for evaluation of FPGS enzyme kinetic parameters revealing Km values for the substrates MTX and L-glutamic acid of 64 µmol/L and 2.2 mmol/L, respectively. The mean FPGS activity of acute lymphoblastic leukemia blast cells (n = 4) was 3-fold higher than that of CCRF-CEM cells and 44-fold and 88-fold higher than that of peripheral blood mononuclear cells from MTX-naive (n = 9) and MTX-treated RA patients (n = 6), respectively.

Conclusions:
Collectively, given its sensitivity with low cell numbers and avoidance of radioactive substrates, UHPLC-MS/MS–based analysis of FPGS activity may be eligible for routine therapeutic drug monitoring of MTX in RA and leukemia for therapy (non)response evaluations.
Evaluation of Medication Adherence and Pharmacokinetics of Dasatinib for Earlier Molecular Response in Japanese Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Pilot Study
Authors: Iwamoto Takuya , Monma Fumihiko , Ohishi Kohshi , Umino Akira , Suzuki Kei , Oka Koji , Kawakami Keiki , Sekine Takao , Okuda Masahiro , Katayama Naoyuki 
Published: April 2019

Background:
Tyrosine kinase inhibitors markedly improve the survival for patients with chronic myeloid leukemia (CML). However, a decrease in adherence leads to undesired therapeutic outcomes. In this study, the relationships among adherence, pharmacokinetics, response, and adverse effects for dasatinib treatment were prospectively investigated.

Methods:
This study was a prospective cohort study of patients with newly diagnosed CML at 4 general hospitals and 1 university hospital. Patients started to receive dasatinib 100 mg once daily. A Medication Event Monitoring System was used to assess medication adherence and the medication possession ratio during the 12 months. Plasma concentrations of dasatinib were measured using liquid chromatograph-tandem mass spectrometry (LC-MS/MS), and therapy responses were assessed at 3, 6, and 12 months after treatment.

Results:
Ten patients were included. An extremely high medication adherence for dasatinib was observed; the median medication possession ratio was 99.4%. All 9 CML patients with breakpoints in the major BCR-ABL achieved major molecular response (MMR; major BCR-ABL transcript level below 0.1% on the International Scale) within 12 months, and 5 achieved MMR within 6 months. The receiver operating characteristic curve analysis revealed that the cutoff value for the dasatinib area under the concentration–time curve was 336.1 ng × h/mL (accuracy 88.9%, sensitivity 80.0%, specificity 100%, and receiver operating characteristic curve–area under the concentration–time curve 0.800) for achieving MMR within 6 months. Two patients had interrupted dasatinib treatment because of pleural effusion and diarrhea with intestinal edema, respectively. These edematous adverse events developed after plasma dasatinib Cmin surpassed 3.0 ng/mL.

Conclusions:
A Medication Event Monitoring System was applied for the direct evaluation of oral dasatinib adherence for the first time, and the clinical effect of dasatinib was investigated under the strict monitoring of patient adherence. Although this study had a small sample size, the plasma concentration monitoring of dasatinib is considered to be useful to predict an earlier molecular response with fewer edematous adverse events.
Outcomes of Descemet-Stripping Automated Endothelial Keratoplasty in Congenital Hereditary Endothelial Dystrophy
Authors: Mohebbi Masoomeh , Nabavi Amin , Fadakar Kaveh , Hashemi Hassan 
Published: April 2019

Objectives:
To evaluate the outcomes and complications of Descemet-stripping automated endothelial keratoplasty (DSAEK) in children with congenital hereditary endothelial dystrophy (CHED).

Methods:
Eighteen eyes from 10 children with CHED who underwent standard phakic DSAEK were enrolled in this retrospective interventional case series. Medical records including slit-lamp biomicroscopy, cycloplegic refraction, visual acuity, and measurements of central corneal thickness, corneal topography, and endothelial cell density were evaluated. All complications were recorded.

Results:
The mean age of cases was 8.1±4.2 (range: 3–16) years at the time of surgery. Descemet-stripping automated endothelial keratoplasty was performed successfully in all eyes, which survived in 16/18 (88.9%) of cases during a median follow-up period of 38 (range 19–64) months. In patients with clear graft, best-corrected visual acuity was improved to a range of 20/100 to 20/40 and improved to fix and follow in one younger child. Endothelial cell density decreased by an average of 42.1%, comparing baseline and 6-month follow-up and was relatively stable thereafter. A marked flattening of the anterior corneal curvature (mean change of anterior K reading: +2.56±3.14 diopters) was observed after DSAEK. The only major complication in patients with clear graft was intraocular pressure elevation in 61.1% of the eyes, which was easily controlled with one antiglaucoma medication. None of the eyes developed cataract.

Conclusion:
Descemet-stripping automated endothelial keratoplasty is a safe and successful procedure in children with an acceptable graft survival in a mid-term follow-up period. A marked hyperopic shift could occur after DSAEK in children with CHED.
Axon degeneration: mechanistic insights lead to therapeutic opportunities for the prevention and treatment of peripheral neuropathy
Authors: DiAntonio Aaron 
Published: April 2019

Abstract
Peripheral neuropathy is the most common neurodegenerative disease affecting hundreds of millions of patients worldwide and is an important cause of chronic pain. Typical peripheral neuropathies are characterized by dysesthesias including numbness, crawling skin, a sensation of “pins and needles,” and burning and stabbing pain. In addition, peripheral neuropathy can affect the motor and autonomic systems leading to symptoms such as weakness, constipation, and dysregulation of blood pressure. Peripheral neuropathies can be either hereditary or acquired and are a common consequence of diabetes and treatment with chemotherapy agents. Many neuropathies are due to degeneration of long axons; however, the mechanisms driving axon loss were unknown, and so no therapies are available to preserve vulnerable axons and prevent the development of peripheral neuropathy. With the recent identification of SARM1 as an injury-activated NADase enzyme that triggers axon degeneration, there is now a coherent picture emerging for the mechanism of axonal self-destruction. Here, we will present evidence that inhibiting the SARM1 pathway can prevent the development of peripheral neuropathy, describe the emerging mechanistic understanding of the axon degeneration program, and discuss how these mechanistic insights may be translated to the clinic for the prevention and treatment of peripheral neuropathy and other neurodegenerative disorders.