bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Morphogenetic Protein-9–Stimulated Adipocyte-Derived Mesenchymal Progenitors Entrapped in a Thermoresponsive Nanocomposite Scaffold Facilitate Cranial Defect Repair
Authors: Lee Cody S. , Bishop Elliot S. , Dumanian Zari , Zhao Chen , Song Dongzhe , Zhang Fugui , Zhu Yunxiao , Ameer Guillermo A. , He Tong-Chuan , Reid Russell R. 
Published: March 2019

Abstract
Due to availability and ease of harvest, adipose tissue is a favorable source of progenitor cells in regenerative medicine, but has yet to be optimized for osteogenic differentiation. The purpose of this study was to test cranial bone healing in a surgical defect model utilizing bone morphogenetic protein-9 (BMP-9) transduced immortalized murine adipocyte (iMAD) progenitor cells in a citrate-based, phase-changing, poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN)-gelatin scaffold. Mesenchymal progenitor iMAD cells were transduced with adenovirus expressing either BMP-9 or green fluorescent protein control. Twelve mice underwent craniectomy to achieve a critical-sized cranial defect. The iMAD cells were mixed with the PPCN-gelatin scaffold and injected into the defects. MicroCT imaging was performed in 2-week intervals for 12 weeks to track defect healing. Histologic analysis was performed on skull sections harvested after the final imaging at 12 weeks to assess quality and maturity of newly formed bone. Both the BMP-9 group and control group had similar initial defect sizes (P = 0.21). At each time point, the BMP-9 group demonstrated smaller defect size, higher percentage defect healed, and larger percentage defect change over time. At the end of the 12-week period, the BMP-9 group demonstrated mean defect closure of 27.39%, while the control group showed only a 9.89% defect closure (P < 0.05). The BMP-9-transduced iMADs combined with a PPCN-gelatin scaffold promote in vivo osteogenesis and exhibited significantly greater osteogenesis compared to control. Adipose-derived iMADs are a promising source of mesenchymal stem cells for further studies in regenerative medicine, specifically bone engineering with the aim of potential craniofacial applications.
Trends and Outcomes of Management of Mandibular Fractures
Authors: Hassanein Ahmed Gaber 
Published: March 2019

Introduction:
the diversity of the causes of trauma produces different patterns of fractures depending on sociodemographics, lifestyle, industry, and outdoor activities. Mandibular fractures (MFs) are the commonest facial fractures. Reconstruction aims to restore the preinjury anatomy and function as much as possible.

Aim of the study:
to evaluate the demographics, etiologies, patterns, treatment modalities and outcomes of management of MFs in southern Egypt.

Patients and Methods:
records of 1371 patients with MFs were reviewed to study the incidence, causes, patterns, treatment modalities and outcomes of surgical management.

Results:
the study included 1152 (84.03%) males and 219 (15.97%) females. The second and third decades were the most vulnerable groups. Isolated MFs appeared in 75.49% of patients while in the others either zygoma and/or maxilla were affected. The commonest causes were road traffic accidents (66.89%) and fall from height (15.1%). The body was the commonest involved region (30.98%), followed by parasymphyseal region (24.33%). In 66.16% of patients, the treatment was open reduction and internal fixation while in 22.17%, closed reduction and intermaxillary fixation were used. 20.24% of the cases had 1 or more postoperative complications, mainly temporomandibular joint dysfunction in 64 cases, malocclusion in 58 cases, and paresthesia in 42 cases.

Conclusion:
the MFs are common in the youth. The road traffic accidents are the most common etiology. This can be reduced by simple measures like compulsory seat belts and wearing the helmet. Open reduction and internal fixation is the commonest treatment modality.
Medication-Related Osteonecrosis of the Jaw: The Use of Leukocyte-Platelet-Rich Fibrin as an Adjunct in the Treatment
Authors: Valente Nicola Alberto , Chatelain Sibylle , Alfonsi Fortunato , Mortellaro Carmen , Barone Antonio 
Published: March 2019

Abstract
Medication-related osteonecrosis of the jaw are bone exposures in the maxillofacial region that does not heal after 8 weeks from the observation of a health care provider in patients with history of the intake of antiresorptive agents and no previous irradiation of the craniofacial region. Initially attributed only to the intake of bisphosphonates they have later been associated also with the intake of other classes of antiresorptive medications.
This retrospective study analyzed records from patients with documented medication-related osteonecrosis of the jaws treated in our unit. Clinical data, comorbidities and concurrent medications, treatment outcome information such us number of repeated treatments needed, antibiotic used, type of treatment adopted were recorded. Baseline demographics for the included records of 15 patients (mean age: 64 years) revealed a treatment success rate of 73.3% (mean observation period: 42.2 months), failure rate of 26.6%, dental extraction trigger rate of 33.3%, and a spontaneous trigger rate of 40%.
Zolendronate and denosumav were the medications most frequently associated with the upset of medication-related osteonecrosis of the jaw (60% of the sample). In 8 cases out of the 11 that were successful, the surgical treatment had to be repeated more than once. Leukocyte-platelet-rich fibrin led to the resolution of 11 of the 14 cases in which it was used.
Endoscopic Medial Maxillectomy With Preservation of Inferior Turbinate: Assessing Results by Acoustic Rhinometry
Authors: Gras-Cabrerizo Juan R. , Martel-Martin Maria , Montserrat-Gili Joan R. , Pardo-Muñoz Laura , Prats-Morera Laura , Ademá-Alcover Joan M. , Massegur-Solench Humbert 
Published: March 2019

Background:
The aim of this study is to demonstrate the effectiveness of the Endoscopic Medial Maxillectomy technique with the preservation of the nasal anatomy and function of the inferior turbinate.

Methods:
From January 2005 to December 2016, the authors performed 27 Endoscopic Medial Maxillectomy with preservation of inferior turbinate on 26 patients. The most frequent pathologies diagnosed were inverted papillomas (13/27) and antrochoanal polyps (7/27). There were 21 primary lesions and 6 patients had been previously treated. There were 19 males and 7 females. On 11 patients the authors could perform an acoustic rhinometry at 4 months postoperatively.

Results:
The authors did not find any recurrences. In all cases the authors note the presence of the C-notch being the narrowest area of the nasal cavity, on both the surgical and nonsurgical nasal fossa. The mean area for the C-notch in the nonsurgical nasal cavities was 0.50 cm2 (0.18–0.82) and it was 0.57 cm2 (0.08–1.06) in the surgical nasal cavities. The increase of the C-notch after nasal decongestion was 0.10 cm2 in nonsurgical cavities and it was 0.03 cm2 in the surgical cavities. The mean distance for the C-notch was 2.18 cm and 2.36 cm before and after nasal decongestion in the nonsurgical fossae. In the surgical cavities were 2.31 and 2.37  cm respectively.

Conclusions:
The authors’ rhinometrics data suggest that Endoscopic Medial Maxillectomy with preservation of inferior turbinate is an effective technique that preserves the anatomic structure and the functions of the inferior turbinate after its resection and reposition.
A Simulation-Based Pilot Study of a Mobile Application (NRP Prompt) as a Cognitive Aid for Neonatal Resuscitation Training
Authors: Chan Natalie H. , Mistry Niraj , Campbell Douglas M. 
Published: March 2019

Introduction
Despite standardized neonatal resuscitation program (NRP) training, retention and adherence to the NRP algorithm remain a challenge. Cognitive aids can potentially improve acquisition and application of NRP knowledge and skills. The objective of this study was to determine whether an interactive mobile application providing audiovisual prompts, NRP Prompt, can help novice NRP providers learn the NRP algorithm more effectively and therefore improve their NRP performance.

Methods
First- and second-year residents from family medicine and obstetrics and gynecology attending NRP training were randomized into intervention and control groups. Resident pairs used standard visual aids with NRP Prompt (intervention) or visual aids only (control) in two simulated neonatal resuscitation training sessions with each resident taking turns as a team leader. Pairs were then evaluated in a third simulation that was video recorded, where neither group used cognitive aids. The primary outcome was comparing resuscitation performance. Secondary outcomes included the following: times to positive-pressure ventilation, intubation, and chest compressions.

Results
Thirty-nine residents participated, of which 18 received the intervention. Neonatal resuscitation program performance scores did not significantly differ (P = 0.69). Wilcoxon rank-sum tests showed no significant differences in secondary outcomes of times to positive-pressure ventilation (P = 0.43), intubation (P = 0.44), or chest compressions (P = 0.35).

Conclusions
Training using NRP Prompt did not improve performance scores in simulated neonatal resuscitations immediately after training. Potential reasons include voice prompts in their current format being distracting and lack of customizability to user preferences. Future development of prompting applications should apply a user-centered design approach to optimize the ability to meet end-user needs.
Long-term prescription opioid utilization, substance use disorders, and opioid overdoses after adolescent trauma
Authors: Bell Teresa M. , Raymond Jodi , Vetor Ashley , Mongalo Alejandro , Adams Zachary , Rouse Thomas , Carroll Aaron 
Published: March 2019

BACKGROUND
Injured adolescents have a 56% increased risk of developing a substance use disorder (SUD) within 3 years of their injury. The transition from medical prescription opioid use to nonmedical use in adolescent trauma patients has not been longitudinally studied long-term. The aim of this study is to describe 5-year patterns of opioid use in a cohort of injured adolescents as well as the proportion of patients experiencing overdose and SUD diagnoses.

METHODS
Our retrospective cohort study consisted of 736 patients aged 12 years to 18 years who were admitted for trauma from 2011 to 2013. We examined up to 5 years of regional health information exchange data containing information on prescription fills as well as diagnoses from inpatient, outpatient, and emergency department encounters.

RESULTS
At 1 year, over 20% of adolescents filled more than two opioid prescriptions after being discharged for their injury; and at 4 years, over 13% had received more than eight opioid fills. Over the 5-year period, 11% received an opioid antagonist injection, 14% received an SUD diagnosis, and 8% had an overdose diagnosis. Relatively few patients had diagnoses for other mental health conditions including depression (5.5%), posttraumatic stress disorder (2.1%), and chronic pain (3.6%).

CONCLUSION
Opioid usage remains high for multiple years in a subset of the adolescent trauma population. Mental health diagnosis rates were substantially lower in injured adolescents than what has been reported in adults. However, overdose and SUD diagnoses occur in over 1 in 10 adolescents within 5 years of their injury.

LEVEL OF EVIDENCE
Prognostic and epidemiological study, level IV.
Earlier time to hemostasis is associated with decreased mortality and rate of complications: Results from the Pragmatic Randomized Optimal Platelet and Plasma Ratio trial
Authors: Chang Ronald , Kerby Jeffrey D. , Kalkwarf Kyle J. , Van Belle Gerald , Fox Erin E. , Cotton Bryan A. , Cohen Mitchell J. , Schreiber Martin A. , Brasel Karen , Bulger Eileen M. , Inaba Kenji , Rizoli Sandro , Podbielski Jeanette M. , Wade Charles E. , Holcomb John B. 
Published: March 2019

BACKDROP
Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported.

METHODS
Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism.

RESULTS
Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p < 0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94–0.99), AKI (RR, 0.97; 95% CI, 0.96–0.98), ARDS (RR, 0.98; 95% CI, 0.97–0.99), MOF (RR, 0.94; 95% CI, 0.91–0.97), and sepsis (RR, 0.98; 95% CI, 0.96–0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96–1.03).

CONCLUSION
Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator.

LEVEL OF EVIDENCE
Therapeutic/care management, level III.
An analysis of pediatric trauma center undertriage in a mature trauma system
Authors: Rogers Amelia T. , Horst Michael A. , Vernon Tawnya M. , Gaines Barbara A. , Bradburn Eric H. , Cook Alan D. , Jammula Shreya , Rogers Frederick B. 
Published: March 2019

BACKGROUNDImproved mortality as a result of appropriate triage has been well established in adult trauma and may be generalizable to the pediatric trauma population as well. We sought to determine the overall undertriage rate (UTR) in the pediatric trauma population within Pennsylvania (PA). We hypothesized that a significant portion of pediatric trauma population would be undertriaged.METHODSAll pediatric (age younger than 15) admissions meeting trauma criteria (International Classification of Diseases, Ninth Revision: 800–959) from 2003 to 2015 were extracted from the Pennsylvania Health Care Cost Containment Council (PHC4) database and the Pennsylvania Trauma Systems Foundation (PTSF) registry. Undertriage was defined as patients not admitted to PTSF-verified pediatric trauma centers (n = 6). The PHC4 contains inpatient admissions within PA, while PTSF only reports admissions to PA trauma centers. ArcGIS Desktop was used for geospatial mapping of undertriage.RESULTSA total of 37,607 cases in PTSF and 63,954 cases in PHC4 met criteria, suggesting UTR of 45.8% across PA. Geospatial mapping reveals significant clusters of undertriage regions with high UTR in the eastern half of the state compared to low UTR in the western half. High UTR seems to be centered around nonpediatric facilities. The UTR for patients with a probability of death 1% or less was 39.2%.CONCLUSIONUndertriage is clustered in eastern PA, with most areas of high undertriage located around existing trauma centers in high-density population areas. This pattern may suggest pediatric undertriage is related to a system issue as opposed to inadequate access.LEVEL OF EVIDENCERetrospective study, without negative criteria, Level III.
The changing concepts in the neuropathology of acquired demyelinating central nervous system disorders
Authors: Lassmann Hans 
Published: March 2019

Purpose of review
Research on multiple sclerosis (MS) pathogenesis and therapy is to a large extent driven by results obtained in experimental autoimmune encephalomyelitis (EAE). This approach provided deep insights into the mechanism of brain inflammation and immune mediated tissue injury and, thus, most of our currently established therapies for MS patients have been developed with profound contributions of experimental autoimmune research. Recent data, which are summarized in this review article, however, show important differences between EAE and MS.

Recent findings
EAE models perfectly reproduce a disease, now called myelin oligodendrocyte glycoprotein (MOG) antibody-associated inflammatory demyelinating disease, which, however, is different from classical MS. In MS, the inflammatory reaction in the brain is dominated by CD8+ T-lymphocyte and CD20+ B cells. Demyelination in MS appears to be triggered by soluble factors, produced by T cells and/or B cells, which are different from anti-MOG antibodies seen in EAE, and induce widespread MS like primary demyelination and tissue damage associated with oxidative injury, mitochondrial damage and subsequent ‘virtual’ hypoxia.

Summary
To define the antigenic target of the inflammatory reaction, the nature of the inflammatory response and the mechanisms of tissue injury are key topics of ongoing MS research.
Emerging treatments for cluster headache: hopes and disappointments
Authors: Magis Delphine 
Published: March 2019

Purpose of review
Cluster headache stands among the worst debilitating pain conditions. Available treatments for cluster headache have often disabling side effects, are not tolerated, or are ineffective. The management of drug-refractory chronic forms is challenging. New treatments are warranted and reported here.

Recent findings
In cluster headache acute treatment, delivery systems like Demand Valve Oxygen or nonrebreather-type masks could enhance the effectiveness of inhaled oxygen therapy. Noninvasive vagus nerve stimulation relieves cluster headache pain at short-term in episodic patients. Sphenopalatine ganglion stimulation combines acute and preventive properties in subsets of patients and is of interest in selected refractory chronic forms. In cluster headache prevention, ‘hypothalamic’ deep brain stimulation is being refined using slightly different stereotactic coordinates or lower risk methods like endoventricular stimulation. Anti-CGRP monoclonal antibodies provide interesting results in episodic cluster headache, have a good safety profile, but do not appear effective in chronic cluster headache.

Summary
These novel approaches provide additional alternatives to conventional cluster headache management, but results obtained in chronic forms are often disappointing. Research on cluster headache is often hampered by the lack of awareness in the medical world and by the relatively low prevalence of cluster headache compared with migraine. However, common features shared by these two primary headaches could help developing disease-specific therapies.
An Option to Consider for Alternating Hemiplegia of Childhood: Aripiprazole
Authors: Dundar Nihal Olgac , Cavusoglu Dilek , Kaplan Yusuf Cem , Hasturk Mehmet Oytun 
Published: March 2019

Abstract
Alternating hemiplegia of childhood (AHC) is an infrequent neurological disorder characterized by recurrent transient attacks of hemiplegia that last minutes to days and impress either side of the body, dystonic or tonic attacks, and nystagmus. Cognitive or neurological deficits with progressive course are another findings. Epileptic seizures may occur in some patients. We report the medical treatment in a case of AHC in a-12-year-old male patient with convulsions. The patient did not respond to available therapies for AHC, except for aripiprazole. After the initiation of aripiprazole therapy, duration and frequency of hemiplegia episodes were decreased. Also, he is currently seizure-free with topiramate treatment for 3 months. On follow-up, a compound heterozygous ATP1A3 mutation c.868C > T (p.R290C)/c.684 + 1G > A was determined. Aripiprazole may reduce the attacks of AHC, which are resistant to other available therapies.
Origins and evolution of CRISPR-Cas systems
Authors: Koonin Eugene V. , Makarova Kira S. 
Published: March 2019

CRISPR-Cas, the bacterial and archaeal adaptive immunity systems, encompass a complex machinery that integrates fragments of foreign nucleic acids, mostly from mobile genetic elements (MGE), into CRISPR arrays embedded in microbial genomes. Transcripts of the inserted segments (spacers) are employed by CRISPR-Cas systems as guide (g)RNAs for recognition and inactivation of the cognate targets. The CRISPR-Cas systems consist of distinct adaptation and effector modules whose evolutionary trajectories appear to be at least partially independent. Comparative genome analysis reveals the origin of the adaptation module from casposons, a distinct type of transposons, which employ a homologue of Cas1 protein, the integrase responsible for the spacer incorporation into CRISPR arrays, as the transposase. The origin of the effector module(s) is far less clear. The CRISPR-Cas systems are partitioned into two classes, class 1 with multisubunit effectors, and class 2 in which the effector consists of a single, large protein. The class 2 effectors originate from nucleases encoded by different MGE, whereas the origin of the class 1 effector complexes remains murky. However, the recent discovery of a signalling pathway built into the type III systems of class 1 might offer a clue, suggesting that type III effector modules could have evolved from a signal transduction system involved in stress-induced programmed cell death. The subsequent evolution of the class 1 effector complexes through serial gene duplication and displacement, primarily of genes for proteins containing RNA recognition motif domains, can be hypothetically reconstructed. In addition to the multiple contributions of MGE to the evolution of CRISPR-Cas, the reverse flow of information is notable, namely, recruitment of minimalist variants of CRISPR-Cas systems by MGE for functions that remain to be elucidated. Here, we attempt a synthesis of the diverse threads that shed light on CRISPR-Cas origins and evolution.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.