bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and genetic associations between reading and attention-deficit/hyperactivity disorder dimensions in adolescence
Authors: Plourde Vickie , Boivin Michel , Brendgen Mara , Vitaro Frank , Dionne Ginette 
Published: December 2016

AbstractMultiple studies have shown that reading abilities and attention-deficit/hyperactivity disorder symptoms, mainly inattention symptoms, are phenotypically and genetically associated during childhood. However, few studies have looked at these associations during adolescence to investigate possible developmental changes. The aim of the study is to examine the genetic and environmental etiology of the associations between inattention and hyperactivity reported by parents, and reading accuracy, reading speed, and word reading in a population-based twin sample (Quebec Newborn Twin Study). Participants were between 14 and 15 years of age at the time of testing (N= 668–837). Phenotypic results showed that when nonverbal and verbal abilities were controlled, inattention, but not hyperactivity/impulsivity, was a modest and significant predictor of reading accuracy, reading speed, and word reading. The associations between inattention and all reading abilities were partly explained by genetic and unique environmental factors. However, the genetic correlations were no longer significant after controlling for verbal abilities. In midadolescence, inattention is the attention-deficit/hyperactivity disorder dimension associated with reading abilities, but they could also share genetic factors with general verbal skills.
Regulation of ER stress-induced autophagy by GSK3β-TIP60-ULK1 pathway
Authors: Nie Tiejian , Yang Shaosong , Ma Hongwei , Zhang Lei , Lu Fangfang , Tao Kai , Wang Ronglin , Yang Ruixin , Huang Lu , Mao Zixu , Yang Qian 
Published: December 2016

AbstractEndoplasmic reticulum (ER) stress is involved in many cellular processes. Emerging evidence suggests that ER stress can trigger autophagy; however, the mechanisms by which ER stress regulates autophagy and its role in this condition are not fully understood. HIV Tat-interactive protein, 60 kDa (TIP60) is a newly discovered acetyltransferase that can modulate autophagy flux by activating ULK1 upon growth factor deprivation. In this study, we investigated the mechanisms by which ER stress induces autophagy. We showed that ER stress activates glycogen synthase kinase-3β (GSK3β). This led to a GSK3β-dependent phosphorylation of TIP60, triggering a TIP60-mediated acetylation of ULK1 and activation of autophagy. Inhibition of either GSK3β or TIP60 acetylation activities significantly attenuated ER stress-induced autophagy. Moreover, enhancing the level of TIP60 attenuated the level of CHOP after ER stress, and reduced the ER stress-induced cell death. In contrast, expression of TIP60 mutant that could not be phosphorylated by GSK3β exacerbated the generation of CHOP and increased the ER stress-induced cell death. These findings reveal that ER stress engages the GSK3β-TIP60-ULK1 pathway to increase autophagy. Attenuation of this pathway renders cells more sensitive to and increases the toxicity of ER stress.
Structural basis for regiospecific midazolam oxidation by human cytochrome P450 3A4
Authors: Sevrioukova Irina F. , Poulos Thomas L. 
Published: December 2016

Significance
Human cytochromes P450 (CYPs) play a leading role in detoxication by metabolizing drugs and other foreign compounds. CYP3A4 is the most important CYP because it oxidizes the majority of administered therapeutics and is implicated in drug–drug interactions, drug toxicity, and other adverse effects. To date, little is known about how CYP3A4 adjusts and reshapes the active site to accommodate and regioselectively oxidize a wide variety of compounds. The CYP3A4–midazolam cocrystal structure reveals a profound structural reorganization triggered by the substrate, which was anticipated but never before observed, which helps us better understand and explain experimental results and, by representing a conformational snapshot, could be used for computer modeling and molecular dynamics simulations to improve the outcomes for drug metabolism predictions.
Does women's employment enhance women's citizenship?
Authors: Jensen Per H. , Møberg Rasmus Juul 
Published: December 2016

ABSTRACT
The EU discourse on increasing female employment holds promise. The integration of women into the labour market supposedly supports economic growth, social cohesion, and citizenship. The question is, however, whether the expected consequences of female employment are consistent with reality. Using the EU discourse as a point of departure, this paper scrutinises the effects of female employment from a citizenship perspective in three European cities: Aalborg (Denmark), Leeds (England), and Bologna (Italy). Using survey data collected in the three cities, it quantitatively analyses whether employment counteracts poverty, supports social and political participation, and increases social trust. It also analyses whether there are spill-over effects from the different dimensions of citizenship; that is, whether poverty leads to social isolation, political apathy, and low levels of social trust. We find that unemployment is important for citizenship but that the differences between employed women and women outside the labour force are rather limited. We also find that the effect of a woman's position in the vertical and horizontal division of labour is rather limited, and no spill-over effects from economic hardship on other dimensions of citizenship exist. What matters for citizenship are personal and family characteristics as well as the city of residence.
Drug-drug interaction discovery and demystification using Semantic Web technologies
Authors: Noor Adeeb , Assiri Abdullah , Ayvaz Serkan , Clark Connor , Dumontier Michel 
Published: December 2016

Abstract
Objective: To develop a novel pharmacovigilance inferential framework to infer mechanistic explanations for asserted drug-drug interactions (DDIs) and deduce potential DDIs.
Materials and Methods: A mechanism-based DDI knowledge base was constructed by integrating knowledge from several existing sources at the pharmacokinetic, pharmacodynamic, pharmacogenetic, and multipathway interaction levels. A query-based framework was then created to utilize this integrated knowledge base in conjunction with 9 inference rules to infer mechanistic explanations for asserted DDIs and deduce potential DDIs.
Results: The drug-drug interactions discovery and demystification (D3) system achieved an overall 85% recall rate in terms of inferring mechanistic explanations for the DDIs integrated into its knowledge base, while demonstrating a 61% precision rate in terms of the inference or lack of inference of mechanistic explanations for a balanced, randomly selected collection of interacting and noninteracting drug pairs.
Discussion: The successful demonstration of the D3 system’s ability to confirm interactions involving well-studied drugs enhances confidence in its ability to deduce interactions involving less-studied drugs. In its demonstration, the D3 system infers putative explanations for most of its integrated DDIs. Further enhancements to this work in the future might include ranking interaction mechanisms based on likelihood of applicability, determining the likelihood of deduced DDIs, and making the framework publicly available.
Conclusion: The D3 system provides an early-warning framework for augmenting knowledge of known DDIs and deducing unknown DDIs. It shows promise in suggesting interaction pathways of research and evaluation interest and aiding clinicians in evaluating and adjusting courses of drug therapy.
Microbes, allergic sensitization, and the natural history of asthma
Authors: Anderson Halie M. , Jackson Daniel J. 
Published: December 2016

Purpose of review
Understanding factors that lead to asthma development in early life is essential to developing strategies aimed at primary or secondary prevention.

Recent findings
This article will review current evidence addressing the development of early life allergic sensitization in relation to microbes and the gut and airway microbiome. Wheezing illnesses, particularly viral, remain a significant risk factor for asthma inception; however, bacterial pathogens have recently emerged as an additional important contributor to asthma risk, either alone or as cofactors with viral infections. The combined influence and interaction of early life viral wheezing and aeroallergen sensitization is important, with allergic sensitization preceding the onset of viral wheeze. Lastly, we review recent data from longitudinal studies regarding the development of irreversible airway obstruction and its impact on the natural history of asthma.

Summary
The development of asthma remains complex and incompletely understood. There is interplay between genetic predisposition and environmental exposures, including allergens and microbes. Interventions aimed at these risk factors during the preschool years may prevent the longitudinal course of asthma progression to irreversible airway obstruction.
Measuring Glutamate Levels in the Brains of Fibromyalgia Patients and a Potential Role for Glutamate in the Pathophysiology of Fibromyalgia Symptoms
Authors: Pyke Tahni L. , Osmotherly Peter G. , Baines Surinder 
Published: December 2016

Objectives:
The aim of this study was to systematically review the literature concerning proton magnetic resonance spectroscopy (H-MRS) measured glutamate levels in specific brain regions of fibromyalgia (FM) patients to determine if there is a correlation between raised glutamate levels and the presentation of FM.

Materials and Methods:
The electronic databases—MEDLINE, EMBASE Classic+Embase, PsychINFO, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effect, Cochrane Central Register of Controlled Trials—were searched to find original studies that used H-MRS to measure glutamate concentrations in the brains of FM patients.

Results:
Nine studies with a total of 482 participants were selected for inclusion in the review. Seven of the 8 studies that investigated an association between cerebral glutamate levels and FM, showed a positive association. Brain regions identified as having increased glutamate levels include the posterior cingulate gyrus, posterior insula, ventrolateral prefrontal cortex, and amygdala. One study reported a decrease in glutamate levels in the hippocampus of FM patients compared with healthy controls. Seven of the 8 studies that analyzed the correlations between cerebral glutamate levels and FM symptoms, found a significant positive correlation.

Discussion:
Although the cause of FM remains inconclusive, there is converging data in favor of a dysregulation of pain processing in the central nervous system of FM patients, particularly associated with an increase in cerebral glutamate levels. Furthermore, there is evidence to support an association between increased glutamate levels and an increase in FM symptoms.
Safe zones of pin insertion in the pelvis and acetabulum: a cadaver study
Authors: Meselhy Mohammed Anter , Essmat Emad Eldin , Ali Ali Mohamed , Singer Mohamed Salah 
Published: December 2016

Background:
The external fixator is used in emergency stabilization of unstable pelvic fractures; however, its role as a definitive fixation device remains unestablished. The main problem is the risk of injury to surrounding neurovascular structures with no definite safe corridors for pin insertion. The purpose of the current cadaver study is to outline safe corridors in the pelvis and acetabulum and directions for pin insertion.

Methods:
A cadaver study using two bony and three cadaver pelves was undertaken. Half pins were inserted in specific demarcated sites and tested for resistance to pullout and safety of nearby neurovascular structures.

Results:
The iliac crest, anterior inferior iliac spine, anterior superior iliac spine, posterior inferior iliac spine, and posterior superior iliac spine, supraacetabular region, ischial tuberosity both triangular and quadrangular areas, anterior column of the acetabulum lateral to the anterior superior iliac spine, and the lateral 1 cm of ala of the sacrum are safe pin insertion sites, while the area 1 cm medial to both the anterior inferior iliac spine and the anterior superior iliac spine, and the rest of the ala of the sacrum are unsafe.

Conclusions:
There are many safe areas for half pin insertion in pelvic and acetabular fractures, while there are other unsafe areas. Adequate knowledge of the safe sites and direction of pin insertion decreases the risks of neurovascular injury and allows a wider use of external fixators in pelvic and acetabular fractures.
Factors Associated With Patient-Initiated Telephone Calls After Orthopaedic Trauma Surgery
Authors: Hadeed Michael M. , Kandil Abdurrahman , Patel Vandan , Morrison Avery , Novicoff Wendy M. , Yarboro Seth R. 
Published: December 2016

Objectives:
The primary aim of this study is to investigate the incidence of early patient-initiated postoperative telephone calls and reasons for those calls. Secondary goals are to determine perioperative predictive factors for calls including the procedures most frequently associated with them.

Design:
Retrospective chart review.

Setting:
Academic Level-1 Trauma Center.

Patients/Participants:
Six hundred eighty-four patients who underwent surgical treatment by our orthopaedic trauma division between 01/01/2014 and 31/12/2014.

Main Outcome Measurements:
Patient-initiated telephone call documented within 14 days after discharge.

Results:
Twenty-nine percent (n = 199) of patients initiated a telephone call within 14 days after discharge. The most common reasons for telephone calls were pain control (22%), bathing/dressing/wound questions (16%), and questions regarding discharge medications (8%). The procedures associated with the highest percentage of telephone calls were tibial shaft intramedullary nailing (36.0%), calcaneus open reduction internal fixation (31.3%), and cephalomedullary nailing for proximal femur fractures (29.3%). Perioperative factors predictive of an increase in phone calls included discharge directly to home, higher baseline level of health of the patient (based on comorbidities and the American Society for Anesthesiologists score), and a more robust support network (based on marital and employment status).

Conclusions:
This study identifies the incidence and common reasons for patient-initiated calls after orthopaedic trauma surgery and an analysis of perioperative factors predictive of increased phone calls. These data give direction for communication at the time of discharge to improve efficiency, patient care, and patient satisfaction.

Level of Evidence:
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Gradual Deformity Correction in Blount Disease
Authors: Mayer Stephanie W. , Hubbard Elizabeth W. , Sun Dan , Lark Robert K. , Fitch Robert D. 
Published: December 2016

Background:
Blount disease is a disorder of the posteromedial proximal tibial physis which causes a progressive varus, procurvatum, and internal rotation deformity of the tibia. Untreated, it can cause significant limb malalignment. The goal of this study is to evaluate the results of correction of Blount disease using types of external fixation.

Methods:
We conducted a retrospective review of 41 patients (51 limbs) who underwent correction of Blount disease with an Ilizarov external fixator or a Taylor spatial frame (TSF) by a single surgeon. The medial proximal tibial angle (MPTA), mean axis deviation (MAD), posterior proximal tibial angle, and joint line congruence angle (JLCA) were measured on radiographs preoperatively, at frame removal and at final follow-up.

Results:
The average age at treatment was 9.6 years old, with a mean follow-up time of 34 months. Mean preoperative MPTA, MAD, and JLCA were significantly improved at the time of frame removal as well as at final follow-up with no significant changes in correction between the time of frame removal and final follow-up. There was no difference in MPTA and MAD in patients treated with an Ilizarov frame versus a TSF. MPTA, MAD, and JLCA all significantly improved regardless of the underlying diagnosis (infantile vs. adolescent Blount disease) or history of prior surgical intervention. The most common complication was superficial pin-site infection.

Conclusions:
Both Iliazarov and TSF are viable treatment options for infantile and adolescent Blount disease, with the ability to significantly improve both the limb mechanical axis and the mechanical axis of the affected tibia. Correction can be attained regardless of whether patients have previously failed surgical intervention.

Level of Evidence:
Level III—retrospective comparative study.
What’s New in Congenital Scoliosis?
Authors: Pahys Joshua M. , Guille James T. 
Published: December 2016

Background:
Congenital scoliosis is a failure of vertebral formation, segmentation, or a combination of the 2 arising from abnormal vertebral development during weeks 4 to 6 of gestation. The associated spinal deformity can be of varying severity and result in a stable or progressive deformity based on the type and location of the anomalous vertebra(e). Bracing for congenital scoliosis is rarely indicated, while recent reports have demonstrated the utility of serial derotational casting for longer curves with multiple anomalous vertebrae as an effective “time buying strategy” to delay the need for surgery. Earlier hemivertebra excision and short-segment posterior spinal fusion have been advocated to prevent future curve progression of the deformity and/or the development of large compensatory curves. It has been shown in recent long-term follow-up studies that growth rates of the vertebral body and spinal canal are not as dramatically affected by pedicle screw instrumentation at a young age as once thought. Growth friendly surgery with either spine-based or rib-based anchors has demonstrated good results with curve correction while maintaining spinal growth. Rib-based anchors are typically more commonly indicated in the setting of chest wall abnormalities and/or when spinal anatomy precludes placement of spinal instrumentation. Recently, magnetically controlled growing rods have shown promising results in several studies that include a small subset of congenital scoliosis cases.

Methods:
A literature search was performed to identify existing studies related to the treatment of congenital scoliosis published from January 1, 2005 to June 1, 2016. Databases included PubMed, Medline, and the Cochrane Library. The search was limited to English articles and yielded 36 papers. This project was initiated by the Pediatric Orthopaedic Society of North America Publications Committee and was reviewed and approved by the Pediatric Orthopaedic Society of North America Presidential Line.

Results:
A total of 36 papers were selected for review based upon new findings. Classic manuscripts on congenital scoliosis are also included to provide sufficient background information.

Conclusions:
Congenital scoliosis represents a wide range of pathology from the simple, stable hemivertebra to the complex, progressive spinal deformity with chest wall abnormalities and associated cardiac, renal, and neural axis anomalies. This paper reviews the natural history and associated anomalies with congenital scoliosis as well as the most up-to-date classification schemes and various treatment options for the care of this challenging patient population.

Level of Evidence:
Level 5.
Concurrent driver mutations/rearrangements in non-small-cell lung cancer
Authors: Tabchi Samer , Kourie Hampig R. , Klastersky Jean 
Published: December 2016

Purpose of review
The concept of mutually exclusive oncogenic driver alterations has prevailed over the past decade, but recent reports have stressed the possible occurrence of dual-positive non-small-cell lung cancer (NSCLC) and even triple-positive disease for these oncogenes. This entity presents novel prognostic and therapeutic challenges. The present review highlights the available data in an effort to clarify the clinical and pathological significance of coexisting mutations as well as the subsequent therapeutic consequences.

Recent findings
Patients with a known driver oncogene can be successfully treated with the appropriate tyrosine kinase inhibitor, which will provide them with significant responses and lesser toxicities compared with cytotoxic therapy. Unfortunately, most patients will eventually progress. Although some resistance mechanisms have been identified, others remain to be determined but the emergence of secondary oncogenes could be part of the answer.

Summary
Approximately 20–25% of NSCLC harbor treatable driver mutations/rearrangements; epidermal growth factor receptor mutation, anaplastic lymphoma kinase and ROS-1 gene rearrangements are the main alterations for which a Food and Drug Administration-approved tyrosine kinase inhibitor can be used.
Because of recent technological advances, high sensitivity assays with a broad range of genomic targets have become more easily accessible in clinical practice, which has led to an increased detection of coexisting driver alterations in patients with advanced NSCLC. The prognostic/predictive and therapeutic implications of this novel entity are still unsettled for the time being. Randomized trials specifically designed to address this subset of patients will soon be necessary to help determine the optimal therapeutic agent to administer.
Critical aspects to achieve a high-quality melanoma clinic
Authors: Dummer Reinhard , Ramelyte Egle , Levesque Mitch , Goldinger Simone M. , Braun Ralph P. 
Published: December 2016

Purpose of review
With incidence of melanoma growing worldwide and new therapies prolonging the survival of patients with advanced disease, complex medical care is needed.

Recent findings
Best care of complicated melanoma cases is achieved in specialized referral centers. Aims to provide optimized melanoma therapy, best patient-reported treatment outcome, and successful clinical and translational research, necessitate a dedicated interdisciplinary team.

Summary
We report on critical aspects of the interaction between patients, medical care givers, clinical trial and biobanking teams, and emphasize the importance of interdisciplinary tumor boards. Specialized skin cancer nurses and local patient advocacy groups should be involved in patient care and could be the binding link between the patients and the treatment team.
Treatment of Acne Scars on Darker Skin Types Using a Noninsulated Smooth Motion, Electronically Controlled Radiofrequency Microneedles Treatment System
Authors: Pudukadan David 
Published: December 2016

BACKGROUND
Noninvasive technologies for treating acne scars use radiofrequency (RF)-emitting microneedles for both mechanical disruption of fibrotic strands and heat-mediated collagen remodeling.

OBJECTIVE
Efficacy and safety evaluation of electronically controlled noninsulated RF microneedling system on acne scars in patients with dark skin.

METHODS
Nineteen patients, 24 to 51 years old, skin types III to V, with acne scars were enrolled in the study. Each patient had 3 treatment sessions at monthly intervals using a multisource RF treatment platform with a microneedle RF applicator. Efficacy was evaluated by the Goodman and Barron's Global Qualitative Acne Scarring System.

RESULTS
No bleeding points occurred during treatments. Post-treatment erythema was observed immediately after the treatment and lasted up to 10 hours after the treatment. Improvement of at least 1 acne scar grade was noted in 11 of 19 patients (57.9%) after 1 month and in 9 of 9 patients (100%) after 3 months.

CONCLUSION
The tested noninsulated electronically controlled RF microneedles were found to be safe and efficient in the treatment of atrophic acne scars in skin types III to V with minimal pain or downtime.