bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neurophysiology of paediatric movement disorders
Authors: McClelland Verity M. 
Published: September 2017

Purpose of review
To demonstrate how neurophysiological tools have advanced our understanding of the pathophysiology of paediatric movement disorders, and of neuroplasticity in the developing brain.

Recent findings
Delineation of corticospinal tract connectivity using transcranial magnetic stimulation (TMS) is being investigated as a potential biomarker for response to therapy. TMS measures of cortical excitability and neuroplasticity are also being used to investigate the effects of therapy, demonstrating neuroplastic changes that relate to functional improvements. Analyses of evoked potentials and event-related changes in the electroencephalogaphy spectral activity provide growing evidence for the important role of aberrant sensory processing in the pathophysiology of many different movement disorders. Neurophysiological findings demonstrate that children with clinically similar phenotypes may have differing underlying pathophysiology, which in turn may explain differential response to therapy. Neurophysiological parameters can act as biomarkers, providing a means to stratify individuals, and are well suited to provide biofeedback. They therefore have enormous potential to facilitate improvements to therapy.

Summary
Although currently a small field, the role of neurophysiology in paediatric movement disorders is poised to expand, both fuelled by and contributing to the rapidly growing fields of neuro-rehabilitation and neuromodulation and the move towards a more individualized therapeutic approach.
Deep brain stimulation for monogenic dystonia
Authors: Aravamuthan Bhooma R. , Waugh Jeff L. , Stone Scellig S. 
Published: September 2017

Purpose of review
Deep brain stimulation (DBS) has recently emerged as an important management option in children with medically refractory dystonia. DBS is most commonly used, best studied, and thought to be most efficacious for a select group of childhood or adolescent onset monogenic dystonias (designated with a standard ’DYT’ prefix). We review how to clinically recognize these types of dystonia and the relative efficacy of DBS for key monogenic dystonias.

Recent findings
Though used for dystonia in adults for several years, DBS has only lately been used in children. Recent evidence shows that patients with shorter duration of dystonia often experience greater benefit following DBS. This suggests that early recognition of the appropriate dystonic phenotypes and consideration of DBS in these patients may improve the management of dystonia.

Summary
DBS should be considered early in patients who have medically refractory dystonia, especially for the monogenic dystonias that have a high response rate to DBS. It is important to differentiate between these monogenic dystonias and dystonias of other causes to properly prognosticate for these patients and to determine whether DBS is an appropriate management option.
Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer
Authors: Feretis Michael , Wang Tengyao , Iype Satheesh , Duckworth Adam , Brais Rebecca , Basu Bristi , Jamieson Neville V. , Huguet Emmanuel , Balakrishnan Anita , Jah Asif , Praseedom Raaj K. , Harper Simon J. , Liau Siong-Seng 
Published: September 2017

Objectives
The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival.

Methods
Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1–2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses.

Results
The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables.

Conclusions
Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.
Development of the Aim to Decrease Anxiety and Pain Treatment for Pediatric Functional Abdominal Pain Disorders
Authors: Cunningham Natoshia R. , Nelson Sarah , Jagpal Anjana , Moorman Erin , Farrell Michael , Pentiuk Scott , Kashikar‐Zuck Susmita 
Published: September 2017

ABSTRACTObjectives:To evaluate the feasibility and acceptability of the Aim to Decrease Anxiety and Pain Treatment (ADAPT), a brief, on‐line and in‐person behavioral intervention targeting pain and anxiety in youth with functional abdominal pain disorders (FAPDs).Methods:Patients were recruited from several outpatient pediatric gastroenterology clinics. Nine participants (ages 9–13) completed the full protocol. Thematic analysis of detailed qualitative feedback was obtained via semistructured patient and caregiver interviews after treatment was conducted. Feasibility and preliminary outcomes were examined using nonparametric tests.Results:Preliminary results indicate that the ADAPT treatment is feasible, acceptable, and potentially effective for youth with FAPD. Treatment completers reported that they enjoyed the program and used the skills to manage their pain and worry. Results also indicated that the majority of participants experienced a reduction in anxiety and several reported reductions in pain and functional disability levels.Conclusions:Findings from this study suggest that targeting both pain and anxiety may positively impact outcomes in youth with FAPD. The ADAPT intervention has the potential to provide a cost effective and practical application of cognitive behavioral therapy using an innovative combination of in‐person and technology‐based platforms. Overall, the ADAPT intervention is a promising and innovative intervention to improve the outcomes of youth with FAPD.
Nutritional State and Feeding Behaviors of Children With Eosinophilic Esophagitis and Gastroesophageal Reflux Disease
Authors: Mehta Pooja , Furuta Glenn T. , Brennan Taryn , Henry Michelle L. , Maune Nancy Creskoff , Sundaram Shikha S. , Menard‐Katcher Calies , Atkins Dan , Takurukura Faith , Giffen Sandra , Pan Zhaoxing , Haas Angela M. 
Published: September 2017

ABSTRACTObjective:As both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) are associated with malnutrition and feeding dysfunction, this study compares growth, nutrition, and feeding behaviors in children with GERD and EoE.Methods:Subjects ages 1 to 7 years with GERD or EoE were enrolled in a prospective study. Assessments included length/height, weight, 3‐day food diary, serum biomarkers of nutrition, and the Behavioral Pediatric Feeding Assessment Scale.Results:Mean weight‐for‐length z scores in GERD and EoE children were −0.93 and −1.14 (p = NS) and mean body mass index z scores were 0.29 and −0.13 (P = NS). Vitamin D intake was below the daily recommended intake in GERD subjects. EoE subjects’ intake was below daily recommended intake of Vitamin D and calcium. GERD and EoE groups both had normal intake of calories, carbohydrates, proteins, fats, and iron, and normal serum ferritin (25 vs 34 ng/mL), prealbumin (21 vs 20 mg/dL), parathyroid hormone (42 vs 37 pg/mL), and Vitamin D (both 30 ng/mL). Behavioral Pediatric Feeding Assessment Scale problem and frequency scores were similar in GERD and EoE subjects but were higher than those of a historical cohort of healthy controls (Hedges’ g of 0.95 and 1.1, respectively). EoE subjects on food allergen restriction diets had significantly less feeding dysfunction than those on regular diets.Conclusions:As a selected group of children with uncomplicated GERD or EoE were without nutritional deficiencies but had maladaptive feeding, providing anticipatory guidance to minimize mealtime challenges, monitoring for improvement, or referring to a feeding therapist, may be beneficial. A trial of food allergen restriction may provide additional benefit for those with EoE.
HIV Preexposure Prophylaxis Implementation at Local Health Departments: A Statewide Assessment of Activities and Barriers
Authors: Zhang Helen L. , Rhea Sarah K. , Hurt Christopher B. , Mobley Victoria L. , Swygard Heidi , Seña Arlene C. , McKellar Mehri S. 
Published: September 2017

Background:
Expanding access to HIV preexposure prophylaxis (PrEP) could help reduce rates of HIV infection in the United States. This study characterizes activities and barriers to PrEP implementation at local health departments (LHDs) in North Carolina (NC), which contains a large rural population.

Methods:
In May 2016, a web-based survey was distributed to health directors of all county and district health departments in NC to assess PrEP-related activities, perceived barriers to PrEP implementation, and desired PrEP-related resources.

Results:
Of 85 LHDs in NC, 56 (66%) responded to the survey. Of these, 2 (4%) reported PrEP prescribing and 7 (13%) externally referred for PrEP services. Among the 54 departments not prescribing PrEP, the most frequently cited reasons were cost concerns (n = 25, 46%), lack of formal prescribing protocols (n = 21, 39%), and belief that PrEP would be better managed at primary care or specialty clinics (n = 19, 35%). Among the 47 departments not prescribing or referring clients for PrEP, the most frequently cited reasons for the lack of PrEP referral were the absence of local PrEP providers (n = 29, 62%), lack of PrEP knowledge among staff (n = 13, 28%), and perceived lack of PrEP candidates (n = 12, 26%). The most frequently requested PrEP-related resources included training to help identify PrEP candidates (n = 39, 70%) and training on PrEP prescribing and management (n = 38, 68%).

Conclusions:
PrEP prescribing and referral among LHDs in NC remains extremely limited. Increased PrEP-related training and support for LHD-based providers could enhance PrEP access, especially in rural and underserved areas.
Multiparametric Magnetic Resonance Imaging of Prostate Cancer Bone Disease
Authors: Perez-Lopez Raquel , Nava Rodrigues Daniel , Figueiredo Ines , Mateo Joaquin , Collins David J. , Koh Dow-Mu , de Bono Johann S. , Tunariu Nina 
Published: September 2017

Objectives
The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases.

Materials and Methods
Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations. Univariate and multivariate logistic regression models were analyzed.

Results
Median ADC and nDWI signal was significantly higher, and median swFF was significantly lower, in bone metastases than nonmetastatic bone (P < 0.001). In the metastatic cohort, 31 (72.1%) of 43 biopsies had detectable cancer cells. Median ADC and swFF were significantly lower and median nDWI signal was significantly higher in biopsies with tumor cells versus nondetectable tumor cells (898 × 10−6 mm2/s vs 1617 × 10−6 mm2/s; 11.5% vs 62%; 5.3 vs 2.3, respectively; P < 0.001). Tumor cellularity inversely correlated with ADC and swFF, and positively correlated with nDWI signal (P < 0.001). In serial biopsies, taken before and after treatment, changes in multiparametric MRI parameters paralleled histological changes.

Conclusions
Multiparametric MRI provides valuable information about mCRPC bone metastases. These data further clinically qualify DWI as a response biomarker in mCRPC.
Multimodality Radionuclide Imaging in a Patient With Hereditary Paraganglioma-Pheochromocytoma Syndrome
Authors: Yim So Y. , Moncayo Valeria M. , Pasquel Francisco J. , Halkar Raghuveer K. 
Published: September 2017

Abstract
Hereditary paraganglioma (PGL)-pheochromocytoma (PCC) syndrome is a genetic disorder caused by a mutation of the tumor suppressor gene SDHD that results in a predisposition for head and neck PGLs and PCCs. We present a case of a 33-year-old woman where 18F-FDG PET/CT showed areas of increased uptake in both the adrenal and cervical regions, consistent with PCCs and PGLs, respectively. Further imaging revealed that PCCs were 123I-MIBG avid, whereas the PGLs were 111In-octreotide avid. This demonstrates the varying sensitivities of different imaging modalities in regard to neuroendocrine tumors and the potential for treatment using multiple targeted therapies.
Comparative Effectiveness of Ultrasonography, 99mTc-Sestamibi, and 18F-Fluorocholine PET/CT in Detecting Parathyroid Adenomas in Patients With Primary Hyperparathyroidism
Authors: Thanseer NTK , Bhadada Sanjay Kumar , Sood Ashwani , Mittal Bhagwant Rai , Behera Arunanshu , Gorla Arun Kumar Reddy , Kalathoorakathu Renjith R. , Singh Priyanka , Dahiya Divya , Saikia Uma Nahar , Rao Sudhaker D. 
Published: September 2017

Purpose
Accurate preoperative localization of parathyroid lesion(s) is crucial for successful surgical management of primary hyperparathyroidism (PHPT). This study was conducted to compare the effectiveness of ultrasonography (USG) of the neck, 99mTc-sestamibi (MIBI) imaging with or without SPECT/CT, and 18F-fluorocholine (FCH) PET/CT imaging in the preoperative localization of parathyroid lesions in patients with PHPT.

Methods
Fifty-four consecutive patients with PHPT were included in this prospective study who underwent preoperative localization of the parathyroid lesion(s) using 3 diagnostic modalities followed by surgery. The sensitivity, positive predictive value, and accuracy of the 3 imaging procedures to accurately detect abnormal parathyroid glands were determined using histopathology as criterion standard with postoperative biochemical response confirmation.

Results

18F-fluorocholine PET/CT detected 52 of 54 patients and 52 of 56 lesions with histopathologically proven parathyroid adenomas on patient-based and lesion-based analysis, respectively. Preoperative USG, MIBI, and FCH PET/CT localized abnormal parathyroid gland(s) in 39 (72.2%), 43 (79.6%), and 54 (100%) patients, respectively. The sensitivity and positive predictive value were 69.3% and 87.1% for USG, 80.7% and 97.6% for MIBI, and 100% and 96.3% for FCH PET/CT. The accuracy was 62.9%, 79.6%, and 96.3% for USG, MIBI, and FCH PET/CT, respectively, in patient-wise analysis. In 6 patients with ectopic lesions, FCH PET/CT demonstrated higher sensitivity and accuracy than MIBI and USG (100% vs 66.6% and 16.7%, respectively).

Conclusions
Among the 3 imaging techniques tested simultaneously, FCH PET/CT was superior for accurate preoperative localization of parathyroid adenomas, especially for ectopic or small parathyroid lesions.
Tumour virology in the era of high-throughput genomics
Authors: Tang Ka-Wei , Larsson Erik 
Published: September 2017

With the advent of massively parallel sequencing, oncogenic viruses in tumours can now be detected in an unbiased and comprehensive manner. Additionally, new viruses or strains can be discovered based on sequence similarity with known viruses. Using this approach, the causative agent for Merkel cell carcinoma was identified. Subsequent studies using data from large collections of tumours have confirmed models built during decades of hypothesis-driven and low-throughput research, and a more detailed and comprehensive description of virus–tumour associations have emerged. Notably, large cohorts and high sequencing depth, in combination with newly developed bioinformatical techniques, have made it possible to rule out several suggested virus–tumour associations with a high degree of confidence. In this review we discuss possibilities, limitations and insights gained from using massively parallel sequencing to characterize tumours with viral content, with emphasis on detection of viral sequences and genomic integration events.
This article is part of the themed issue ‘Human oncogenic viruses’.
Tumour viruses and innate immunity
Authors: Hopcraft Sharon E. , Damania Blossom 
Published: September 2017

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system.
This article is part of the themed issue ‘Human oncogenic viruses’.
Viral hepatitis and liver cancer
Authors: Ringehan Marc , McKeating Jane A. , Protzer Ulrike 
Published: September 2017

Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors.
This article is part of the themed issue ‘Human oncogenic viruses’.
Deletion of murine IQGAP1 results in increased mTOR activation and blunted ketogenic response
Authors: Erickson Hanna , Anakk Sayeepriyadarshini 
Published: September 2017

AbstractIQ motif-containing GTPase Activating Protein 1 (IQGAP1) is a ubiquitously expressed scaffolding protein that integrates signaling from multiple cellular processes including motility, adhesion, and proliferation. Here, we show that IQGAP1 is induced in the liver upon fasting and can also regulate β-oxidation and ketone body synthesis. Utilizing ketogenic diet and pharmacologic activation we identified that hepatic PPARα activity is compromised inIqgap1-/-mice. Our data show that IQGAP1 interacts with the mechanistic target of rapamycin (mTOR) and IQGAP1 deletion results in enhanced mTOR complex 1 (mTORC1) activation. Conversely, ectopic expression of IQGAP1 inIqgap1-/-mice was sufficient to suppress mTORC1 signaling. We also confirmed that modulation of mTORC1 signaling by IQGAP1 is cell autonomous. This increased mTORC1 activation impedes PPARα signaling since mTORC1 inhibition restored a subset of metabolic genes inIqgap1-/-mice. Overall, we demonstrate a previously unidentified role for IQGAP1 as an important regulator of mTORC1 activity and long-term ketosis.
Comparison of seven single cell Whole Genome Amplification commercial kits using targeted sequencing
Authors: Biezuner Tamir , Raz Ofir , Amir Shiran , Milo Lilach , Adar Rivka , Fried Yael , Ainbinder Elena , Shapiro Ehud 
Published: September 2017

AbstractAdvances in biochemical technologies have led to a boost in the field of single cell genomics. Observation of the genome at a single cell resolution is currently achieved by pre-amplification using whole genome amplification (WGA) techniques that differ by their biochemical aspects and as a result by biased amplification of the original molecule. Several comparisons between commercially available single cell dedicated WGA kits (scWGA) were performed, however, these comparisons are costly, were only performed on selected scWGA kit and more notably, are limited by the number of analyzed cells, making them limited for reproducibility analysis. We benchmarked an economical assay to compare all commercially available scWGA kits that is based on targeted sequencing of thousands of genomic regions, including highly mutable genomic regions (microsatellites), from a large cohort of human single cells (125 cells in total). Using this approach, we could analyze the genome coverage, the reproducibility of genome coverage and the error rate of each kit. Our experimental design provides an affordable and reliable comparative assay that simulates a real single cell experiment. Results demonstrate the needfor a dedicated kit selection depending on the desired single cell assay.
Compensatory evolution facilitates the acquisition of multiple plasmids in bacteria
Authors: Santos-Lopez Alfonso , Bernabe-Balas Cristina , San Millan Alvaro , Ortega-Huedo Rafael , Hoefer Andreas , Ares-Arroyo Manuel , Gonzalez-Zorn Bruno 
Published: September 2017

AbstractThe coexistence of multicopy plasmids is a common phenomenon. However, the evolutionary forces promoting these genotypes are poorly understood. In this study, we have analyzed multiple ColE1 plasmids (pB1000, pB1005 and pB1006) coexisting withinHaemophilus influenzaeRdKW20 in all possible combinations. When transformed into the naïve host, each plasmid type presented a particular copy number and produced a specific resistance profile and biological cost, whether alone or coexisting with the other plasmids. Therefore, there was no fitness advantage associated with plasmid coexistence that could explain these common plasmid associations in nature. Using experimental evolution, we showed howH. influenzaeRd was able to completely compensate the fitness cost produced by any of these plasmids. Crucially, once the bacterium has compensated for a first plasmid, the acquisition of new multicopy plasmid(s) did not produced any extra biological cost. We argue therefore that compensatory adaptation pave the way for the acquisition of multiple coexisting ColE1 plasmids.ImportanceAntibiotic resistance is a major concern for human and animal health. Plasmids play a major role in the acquisition and dissemination of antimicrobial resistance genes. In this report we investigate, for the first time, how plasmids are capable to cohabit stably in populations. This coexistence of plasmids is driven by compensatory evolution alleviating the cost of a first plasmid, which potentiates the acquisition of further plasmids at no extra cost. This phenomenon explains the high prevalence of plasmids coexistance in wild type bacteria, which generates multiresistant clones and contributes to the maintenance and spread of antibiotic resistance genes within bacterial populations.