bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth Arrest and DNA-damage–inducible Protein 45β-mediated DNA Demethylation of Voltage-dependent T-type Calcium Channel 3.2 Subunit Enhances Neuropathic Allodynia after Nerve Injury in Rats
Authors: Lai Cheng-Yuan , Hsieh Ming-Chun , Ho Yu-Cheng , Lee An-Sheng , Wang Hsueh-Hsiao , Cheng Jen-Kun , Chau Yat-Pang , Peng Hsien-Yu 
Published: March 2017

Abstract

Background
Growth arrest and DNA-damage–inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage–inducible protein 45β–dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear.

Methods
Adult male Sprague–Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage–inducible protein 45β messenger RNA–targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage–inducible protein 45β, Ro 25–6981 (an NR2B-bearing N-methyl-d-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings.

Results
Nerve ligation-enhanced growth arrest and DNA-damage–inducible protein 45β expression (n = 6) in ipsilateral dorsal horn neurons accompanied with behavioral allodynia (n = 7). Focal knockdown of growth arrest and DNA-damage–inducible protein 45β expression attenuated ligation-induced allodynia (n = 7) by reducing the binding of growth arrest and DNA-damage–inducible protein 45β to the voltage-dependent T-type calcium channel 3.2 subunit promoter (n = 6) that decreased expression of and current mediated by the voltage-dependent T-type calcium channel 3.2 subunit (both n = 6). In addition, NR2B-bearing N-methyl-d-aspartate receptors and calmodulin-dependent protein kinase II act in an upstream cascade to increase growth arrest and DNA-damage–inducible protein 45β expression, hence enhancing demethylation at the voltage-dependent T-type calcium channel 3.2 subunit promoter and up-regulating voltage-dependent T-type calcium channel 3.2 subunit expression. Intrathecal administration of Ro 25–6981, KN-93, or a growth arrest and DNA-damage–inducible protein 45β–targeting small interfering RNA (n = 6) reversed the ligation-induced enrichment of unmodified cytosine at the voltage-dependent T-type calcium channel 3.2 subunit promoter by increasing the associated 5-formylcytosine and 5-carboxylcytosine levels.

Conclusions
By converting 5-formylcytosine or 5-carboxylcytosine to unmodified cytosine, the NR2B-bearing N-methyl-d-aspartate receptor, calmodulin-dependent protein kinase II, or growth arrest and DNA-damage–inducible protein 45β pathway facilitates voltage-dependent T-type calcium channel 3.2 subunit gene demethylation to mediate neuropathic allodynia.
Clinical Judgment Is Not Reliable for Reducing Whole-body Computed Tomography Scanning after Isolated High-energy Blunt Trauma
Authors: Mistral Thomas , Brenckmann Vivien , Sanders Laurence , Bosson Jean-Luc , Ferretti Gilbert , Thony Frederic , Galvagno Samuel M. , Payen Jean-François , Bouzat Pierre 
Published: March 2017

Abstract

Background
The purpose of this study was to test the diagnostic performance of clinical judgment for the prediction of a significant injury with whole-body computed tomography scanning after high-energy trauma.

Methods
The authors conducted an observational prospective study in a single level-I trauma center. Adult patients were included if they had an isolated high-energy injury. Senior trauma leaders were asked to make a clinical judgment regarding the likelihood of a significant injury before performance of a whole-body computed tomography scan. Clinical judgments were recorded using a probability diagnosis scale. The primary endpoint was the diagnosis of a serious-to-critical lesion on the whole-body computed tomography scan. Diagnostic performance was assessed using receiver operating characteristic analysis.

Results
Of the 354 included patients, 127 patients (36%) had at least one injury classified as abbreviated injury score greater than or equal to 3. The area under the receiver operating characteristic curve of the clinical judgment to predict a serious-to-critical lesion was 0.70 (95% CI, 0.64 to 0.75%). The sensitivity of the clinical judgment was 82% (95% CI, 74 to 88%), and the specificity was 49% (95% CI, 42 to 55%). No patient with a strict negative clinical examination had a severe lesion (n = 19 patients). The sensitivity of the clinical examination was 100% (95% CI, 97 to 100%) and its specificity was 8% (95% CI, 5 to 13%).

Conclusions
Clinical judgment alone is not sufficient to reduce whole-body computed tomography scan use. In patients with a strictly normal physical examination, whole-body computed tomography scanning might be avoided, but this result deserves additional study in larger and more diverse populations of trauma patients.
Guided Growth: A Novel Treatment for Anterolateral Bowing of the Tibia
Authors: Kennedy Jim , O’Toole Patrick , Baker Joseph F. , Moore David 
Published: March 2017

Background:
Tibial pseudoarthrosis is a source of considerable morbidity in children with neurofibromatosis. Preventing the progression of anterolateral bowing of the tibia (ALBT) to tibial pseudoarthrosis is difficult. The aim of this paper is to report the successful use of guided growth to prevent tibial pseudoarthrosis in a child with neurofibromatosis.

Methods:
With local ethical approval, we reviewed the case notes and radiographs of a child with pronounced ALBT who was treated with guided growth to correct the deformity and prevent fracture.

Results:
At 4-year follow-up guided growth has successfully corrected the deformity and prevented tibial pseudoarthrosis.

Conclusions:
This is the first report of the use of guided growth to prevent the progression of ALBT to pseudoarthrosis of the tibia in a child with neurofibromatosis.

Level of Evidence:
Level IV.
Telemonitoring in IVF/ICSI
Authors: Gerris Jan 
Published: March 2017

Purpose of review
Traditionally, ovarian stimulation for IVF/intracytoplasmic sperm injection is performed by healthcare professionals, requiring the patient to make frequent visits to these centres. We describe the rationale, research findings and early clinical experience with home-based sonography for IVF patients.

Recent findings
Published experience indicates that selected patients are able to procure video sequences themselves; they value the empowerment, discretion and decreased stress involved in these visits; partner involvement increases as well.

Summary
Experience is still limited but consistently indicate patients’ willingness and competence to procure sonograms; home sonography is positive from the patients’ perspective but may be disruptive form the healthcare provider's point of view.
Team Approach Helps Patient Survive High-voltage Electric Burn
Authors: Saied Noha , Harfoush Ahmed , Ayed Tamer , Moustafa Alaa , Hassan Rania , Eldolify Ezz , Abdelaziz Hany 
Published: March 2017

Summary:
A 20-year-old man was subjected to high-voltage electric burn, which was occupational. The patient was admitted to AlGalaa Military Medical Complex almost 2 weeks after the accident had happened. According to Lund and Browder’s chart, the patient had a 40% total body surface area burn involving the upper limbs, anterior and posterior trunks, and the left thigh (third- and fourth-degree burns). The aim of this study was to stabilize the patient by conducting lifesaving operations in multiple scheduled sessions, bilateral below-elbow amputations, escharotomies, and excision of affected ribs and cartilages. A left latissimus dorsi flap used to cover the left side of the anterior chest wall. Skin grafting (split thickness, meshed 1:3) was done to cover the raw areas. Multiple aggressive operations by a multidisciplinary team saved the patient’s life. The victim suffered a major injury and was handicapped, but he survived. It was not necessary to replace the excised ribs with prosthesis because of the preserved sternum. An electric burn poses a burden on many people in addition to the patients themselves.
Neuron-restrictive silencer factor–mediated downregulation of μ-opioid receptor contributes to the reduced morphine analgesia in bone cancer pain
Authors: Zhu Chao , Tang Jun , Ding Tan , Chen Lei , Wang Wei , Mei Xiao-Peng , He Xiao-Tao , Wang Wen , Zhang Li-Dong , Dong Yu-Lin , Luo Zhuo-Jing 
Published: March 2017

Abstract
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively. Additionally, chromatin immunoprecipitation assays were used to detect NRSF binding to the promoter of MOR. Furthermore, NRSF was genetically knocked out by antisense oligodeoxynucleotide, and the expression of MOR and the effect of morphine were subsequently analyzed. Our results indicated that in a sarcoma murine model, NRSF expression is upregulated in dorsal root ganglion neurons, and the expression of NRSF mRNA is significantly negatively correlated with MOR mRNA expression. Additionally, chromatin immunoprecipitation analysis revealed that NRSF binding to the neuron-restrictive silencer element within the promoter area of the MOR gene is promoted with a hypoacetylation state of histone H3 and H4. Furthermore, genetically knocking down NRSF with antisense oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic morphine analgesia. The present results suggest that in sarcoma-induced bone cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of morphine analgesia. Epigenetically, up-regulation of MOR could substantially improve the effect of system delivery of morphine.
Examining Emergency Department Treatment Processes in Severe Pediatric Traumatic Brain Injury
Authors: Ajdari Ali , Boyle Linda Ng , Kannan Nithya , Rowhani-Rahbar Ali , Wang Jin , Mink Richard , Ries Benjamin , Wainwright Mark , Groner Jonathan I. , Bell Michael J. , Giza Chris , Zatzick Douglas F. , Ellenbogen Richard G. , Mitchell Pamela H. , Rivara Frederick P. , Vavilala Monica S. 
Published: March 2017

Background:
In the treatment of pediatric traumatic brain injury (TBI), timely treatment of patients can affect the outcome. Our objectives were to examine the treatment process of acute pediatric TBI and the impact of non–value-added time (NVAT) on patient outcomes.

Methods:
Data for 136 pediatric trauma patients (age < 18 years) with severe TBI from 2 trauma centers in the United States were collected. A process flow and value stream map identified NVATs and their sources in the treatment process. Cluster and regression analysis were used to examine the relationship between NVAT, as a percentage of the patient's length of stay (LOS), and the patient outcome, measured by their corresponding Glasgow outcome scale.

Results:
There were 14 distinct sources of NVAT identified. A regression analysis showed that increased NVAT was associated with less favorable outcomes (relative ratio = 1.015, confidence interval = [1.002–1.029]). Specifically, 1% increase in the NVAT-to-LOS ratio was associated with a 1.5% increase in the chance of a less favorable outcome (i.e., death or vegetative state).

Conclusion:
The NVAT has a significant impact on the outcome of pediatric TBI, and every minute spent on performing non–value-added processes can lead to an increase in the likelihood of less favorable outcomes.
Hospitalist Versus Subspecialist Perspectives on Reasons, Timing, and Impact of Consultation
Authors: Pacitti Kelly , Mathew Anne , Royse Amanda , Elliott John O. , Jordan Kim 
Published: March 2017

Background:
Hospitalists frequently consult medical subspecialists in the management of inpatients. Given the potential impact on health resource utilization, it is important to understand the working relationship between these groups.

Methods:
A cross-sectional survey of hospitalists, n = 655, and subspecialists across Ohio (nephrologists and endocrinologists), n = 293, was conducted to investigate perceptions and communication about reasons, timing, and impact of hospital consultations.

Results:
Survey response rate was 13.3%. Hospitalists were more likely to report subspecialty request to serve as admitting physician with subsequent consultation 63.2% versus 26.7%, p < .001. Hospitalists with a daily workload ≥15 patients per day were more likely to report that this impeded their ability to manage details of patient care versus hospitalists with <15 patients per day, 53.2% versus 24.1%, p = .02, and resulted in subspecialty consultation for problems manageable by the hospitalist, 38.3% versus 6.9%, p = .003. Hospitalists were less likely than subspecialists to report major impact from consultation 50.0% versus 81.0%, p = .001 and they were more likely to report direct communication for urgent consults 97.3% versus 48.8%, p < .001.

Conclusions:
Future work should be aimed at addressing hospitalist workload, improving communication, and ensuring appropriate need and timing of consultation.
Bilateral Labyrinthine and Internal Auditory Canal Enhancement in an Infant With Severe Labyrinthine Dysplasia: A Previously Unreported Phenomenon
Authors: Anzalone Charles L. , Ho Mai Lan , Patel Neil S. , Schimmenti Lisa A. , DeJong Melissa D. , Carlson Matthew L. 
Published: March 2017

Objective:
To describe a novel case of congenital profound bilateral sensorineural hearing loss in a patient with bilateral nodular internal auditory canal and labyrinthine enhancement and temporal bone dysplasia.

Patients:
A 76-day-old female was referred to the authors’ center for evaluation of congenital deafness. Behavioral observations and objective audiometric evaluation demonstrated bilateral profound sensorineural hearing loss and a comprehensive multidisciplinary evaluation identified compound heterozygous pathogenic variants in MYO7A, a gene associated with Usher Syndrome Type 1B or DFNB2. Computed tomography and contrast-enhanced magnetic resonance imaging studies demonstrated bilateral temporal bone anomalies with unique middle and inner ear malformations, as well as unique contrast enhancement in the membranous labyrinth, internal auditory canals, and cranial nerves, which have not been previously described with MYO7A variants.

Interventions:
Given the potential risk for progressive bilateral labyrinthitis ossificans, bilateral simultaneous cochlear implantation was performed at 4 months of age.

Main Outcome Measures:
Subsequent audiologic follow up after implantation shows significantly improved access to auditory information and increased vocalizations. At last testing, speech and language skills for both receptive and expressive language abilities were found to be commensurate with her chronological age.

Conclusion:
We report a novel presentation and imaging findings of congenital bilateral profound sensorineural hearing loss in a patient with nodular internal auditory canal and labyrinthine enhancement and coexisting inner ear dysplasia. Despite the multiple radiologic abnormalities, the patient has demonstrated good benefit from cochlear implantation. Future study of rare variants of congenital deafness, such as this, is critical toward defining new disease processes and determining optimal treatment.
Increase of Intra-abdominal Adipose Tissue in Pediatric Crohn Disease
Authors: Frivolt Klara , Hetterich Holger , Schwerd Tobias , Hajji Mohammad-Samer , Bufler Philip , Coppenrath Eva , Koletzko Sibylle 
Published: March 2017

ABSTRACT

Background and Objective:
Recent evidence points toward an active immunological role of intra-abdominal adipose tissue in Crohn disease (CD). We quantified the abdominal adipose tissue compartments using magnetic resonance imaging (MRI) in 27 pediatric patients with CD compared with 14 controls undergoing MRI examination for other reasons.

Methods:
Total (TAAT), subcutaneous (SCAT) and intra-abdominal (IAAT) adipose tissue areas were measured by semiautomatic segmentation on a transverse slice centered on the umbilicus (mean ± standard deviation in square centimeter) using standard T1-weighted sequences. IAAT/TAAT and IAAT/height ratios were calculated and analyzed for associations with disease duration, phenotype, or therapy.

Results:
Patients with CD (median age 15.0 years, range 7.7–17.9, 18/27 boys, median disease duration 29 months, range 0–136) compared to controls (median age 13.9 years, range 3.3–17.8, 4/14 boys) had higher IAAT area (42.3 ± 21.0 vs 28.7 ± 11.6, P = 0.0494) but similar SCAT and TAAT areas (104.6 ± 72.8 vs 96.5 ± 50.8, P = 0.8170 and 146.9 ± 87.3 vs 125.3 ± 61.5, P = 0.7417, respectively). IAAT/TAAT ratio was higher in patients with CD compared to controls (0.32 ± 0.10 vs 0.24 ± 0.04, P = 0.0081). Patients with disease duration >2 years (n = 14) had higher IAAT/TAAT ratio than those with shorter disease and controls (0.35 ± 0.10 vs 0.28 ± 0.08, P = 0.0288 and 0.24 ± 0.04, P = 0.0009, respectively). In these patients, increased IAAT/height ratio was associated with complicated disease (P = 0.043, r = 0.573). No association was found between IAAT/TAAT ratio and actual disease activity or therapy.

Conclusions:
IAAT is increased in pediatric CD and correlates with disease duration. Assessment of IAAT accumulation may be considered in future MRI scores for inflammation and bowel damage in CD and during follow-up of different therapeutic interventions.
Precursor processes of human self-initiated action
Authors: Khalighinejad Nima , Schurger Aaron , Desantis Andrea , Zmigrod Leor , Haggard Patrick 
Published: March 2017

AbstractA gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such “readiness potentials” (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalised self-initiated actions as endogenous ‘skip’ responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial variability of EEG could carry as much information about the source of skip decisions as the mean RP. EEG variability decreased more markedly prior to self-initiated compared to externally-triggered skip actions. This convergence suggests a consistent preparatory process prior to self-initiated action. A leaky stochastic accumulator model could reproduce this convergence given the additional assumption of a systematic decrease in input noise prior to self-initiated actions. Our results may provide a novel neurophysiological perspective on the topical debate regarding whether self-initiated actions arise from a deterministic neurocognitive process, or from neural stochasticity. We suggest that the key precursor of self-initiated action may manifest as a reduction in neural noise.
Visualizing Structure and Transitions for Biological Data Exploration
Authors: Moon Kevin R. , van Dijk David , Wang Zheng , Gigante Scott , Burkhardt Daniel B. , Chen William S. , Yim Kristina , van den Elzen Antonia , Hirn Matthew J. , Coifman Ronald R. , Ivanova Natalia B. , Wolf Guy , Krishnaswamy Smita 
Published: March 2017

AbstractWith the advent of high-throughput technologies measuring high-dimensional biological data, there is a pressing need for visualization tools that reveal the structure and emergent patterns of data in an intuitive form. We present PHATE, a visualization method that captures both local and global nonlinear structure in data by an information-geometric distance between datapoints. We perform extensive comparison between PHATE and other tools on a variety of artificial and biological datasets, and find that it consistently preserves a range of patterns in data including continual progressions, branches, and clusters. We define a manifold preservation metric DEMaP to show that PHATE produces quantitatively better denoised embeddings than existing visualization methods. We show that PHATE is able to gain unique insight from a newly generated scRNA-seq dataset of human germ layer differentiation. Here, PHATE reveals a dynamic picture of the main developmental branches in unparalleled detail, including the identification of three novel subpopulations. Finally, we show that PHATE is applicable to a wide variety of datatypes including mass cytometry, single-cell RNA-sequencing, Hi-C, and gut microbiome data, where it can generate interpretable insights into the underlying systems.
Towards the human cellular microRNAome
Authors: McCall Matthew N. , Kim Min-Sik , Adil Mohammed , Patil Arun H. , Lu Yin , Mitchell Christopher J. , Leal-Rojas Pamela , Xu Jinchong , Kumar Manoj , Dawson Valina L. , Dawson Ted M. , Baras Alexander S. , Rosenberg Avi Z. , Arking Dan E. , Burns Kathleen H. , Pandey Akhilesh , Halushka Marc K. 
Published: March 2017

AbstractmicroRNAs are short RNAs that serve as master regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell autonomously and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data has caused considerable confusion and comprehensive cell-level data does not yet exist. Here we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent super-enhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 2,632 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder suggesting Drosha and Dicer-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to deconvolute variable cellular composition of adipose tissue samples highlighting one use of this cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.