bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy
Authors: Saha Madhurima , Rizzo Skylar A , Ramanathan Manashwi , Hightower Rylie M , Santostefano Katherine E , Terada Naohiro , Finkel Richard S , Berg Jonathan S , Chahin Nizar , Pacak Christina A , Wagner Richard E , Alexander Matthew S , Draper Isabelle , Kang Peter B 
Published: March 2019

Abstract
MEGF10 myopathy is a rare inherited muscle disease that is named after the causative gene, MEGF10. The classic phenotype, early onset myopathy, areflexia, respiratory distress and dysphagia, is severe and immediately life-threatening. There are no disease-modifying therapies. We performed a small molecule screen and follow-up studies to seek a novel therapy. A primary in vitro drug screen assessed cellular proliferation patterns in Megf10-deficient myoblasts. Secondary evaluations were performed on primary screen hits using myoblasts derived from Megf10−/− mice, induced pluripotent stem cell-derived myoblasts from MEGF10 myopathy patients, mutant Drosophila that are deficient in the homologue of MEGF10 (Drpr) and megf10 mutant zebrafish. The screen yielded two promising candidates that are both selective serotonin reuptake inhibitors (SSRIs), sertraline and escitalopram. In depth follow-up analyses demonstrated that sertraline was highly effective in alleviating abnormalities across multiple models of the disease including mouse myoblast, human myoblast, Drosophila and zebrafish models. Sertraline also restored deficiencies of Notch1 in disease models. We conclude that SSRIs show promise as potential therapeutic compounds for MEGF10 myopathy, especially sertraline. The mechanism of action may involve the Notch pathway.
Norm contestation in the digital era: campaigning for refugee rights
Authors: Hall Nina 
Published: March 2019

Abstract
Activists in the internet era are taking action through online petitions, twitter storms and by forming new digital advocacy organizations such as Campact, 38 Degrees and GetUp!. However, no International Relations (IR) scholarship has systematically examined the role of digital advocacy organizations in norm contestation. Digital advocacy organizations warrant study given their international reach, their large memberships, their longevity, their frequent campaigning activity and their claimed impact. This article focuses on the responses of three digital advocacy organizations in Australia, the UK and Ireland to the same external crisis: an increasing number of refugees worldwide. It asks: when and why did these organizations engage in behavioural norm contestation during the refugee crisis? Their use of behavioural contestation is a puzzle, given that digital advocacy organizations have low implementation power. The article draws on interviews with activists and experts, and finds that advocacy groups firstly use discursive contestation (debating the meaning and importance of norms), and then may engage in behavioural contestation (influencing the implementation of norms). Discursive contestation is less costly, and perceived to be less effective, than behavioural contestation. The article suggests that digital advocacy organizations can mobilize people online and offline, and IR scholars should examine this important source of power. This article forms part of the special section of the May 2019 issue of International Affairs on ‘The dynamics of dissent’, guest-edited by Anette Stimmer and Lea Wisken.
Systematic Review With Meta-analysis: Epidemiology of Nonalcoholic Fatty Liver Disease in Patients With Inflammatory Bowel Disease
Authors: Zou Zi-Yuan , Shen Bo , Fan Jian-Gao 
Published: March 2019

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of NAFLD in IBD patients.

Methods
MEDLINE, Web of Science, Cochrane Library, and Scopus were searched (until August 2018) to identify observational studies that reported the prevalence and risk factors for NAFLD in IBD patients. Pooled prevalence, odds ratios (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated. Study quality was assessed using the modified Newcastle-Ottawa scale.

Results
Of the 662 citations evaluated, 19 studies (including 5620 subjects) reported the prevalence of NAFLD in IBD population and were included for the analysis. The overall pooled prevalence was 27.5% (95% CI, 20.7%–34.2%). The prevalence was higher in older patients (MD = 8.22; 95% CI, 6.22–10.22), type 2 diabetes (OR = 3.85; 95% CI, 2.49–5.95), hypertension (OR = 3.18; 95% CI, 2.36–4.28), obesity (OR = 2.79; 95% CI, 1.73–4.50), insulin resistance (OR = 6.66; 95% CI, 1.28–34.77), metabolic syndrome (OR = 4.96; 95% CI, 3.05–8.05), chronic kidney disease (OR = 4.83; 95% CI, 1.79–13.04), methotrexate use (OR = 1.76; 95% CI, 1.02–3.06), surgery for IBD (OR = 1.28; 95% CI, 1.02–1.62), and longer duration of IBD (MD = 5.60; 95% CI, 2.24–8.97).

Conclusions
We found that NAFLD was not uncommon in the IBD population. Older age, metabolic risk factors, methotrexate use, prior surgery, and longer duration of IBD are predictors for the presence of NAFLD in IBD. Screening of NAFLD might be recommended among IBD patients with the aforementioned factors.
Does Cellular Metabolism from Primary Fibroblasts and Oxidative Stress in Blood Differ between Mammals and Birds? The (Lack-thereof) Scaling of Oxidative Stress
Authors: Jimenez A G , O’Connor E S , Tobin K J , Anderson K N , Winward J D , Fleming A , Winner C , Chinchilli E , Maya A , Carlson K , Downs C J 
Published: March 2019

AbstractAs part of mitonuclear communication, retrograde and anterograde signaling helps maintain homeostasis under basal conditions. Basal conditions, however, vary across phylogeny. At the cell-level, some mitonuclear retrograde responses can be quantified by measuring the constitutive components of oxidative stress, the balance between reactive oxygen species (ROS) and antioxidants. ROS are metabolic by-products produced by the mitochondria that can damage macromolecules by structurally altering proteins and inducing mutations in DNA, among other processes. To combat accumulating damage, organisms have evolved endogenous antioxidants and can consume exogenous antioxidants to sequester ROS before they cause cellular damage. ROS are also considered to be regulated through a retrograde signaling cascade from the mitochondria to the nucleus. These cellular pathways may have implications at the whole-animal level as well. For example, birds have higher basal metabolic rates, higher blood glucose concentration, and longer lifespans than similar sized mammals, however, the literature is divergent on whether oxidative stress is higher in birds compared with mammals. Herein, we collected literature values for whole-animal metabolism of birds and mammals. Then, we collected cellular metabolic rate data from primary fibroblast cells isolated from birds and mammals and we collected blood from a phylogenetically diverse group of birds and mammals housed at zoos and measured several parameters of oxidative stress. Additionally, we reviewed the literature on basal-level oxidative stress parameters between mammals and birds. We found that mass-specific metabolic rates were higher in birds compared with mammals. Our laboratory results suggest that cellular basal metabolism, total antioxidant capacity, circulating lipid damage, and catalase activity were significantly lower in birds compared with mammals. We found no body-size correlation on cellular metabolism or oxidative stress. We also found that most oxidative stress parameters significantly correlate with increasing age in mammals, but not in birds; and that correlations with reported maximum lifespans show different results compared with correlations with known aged birds. Our literature review revealed that basal levels of oxidative stress measurements for birds were rare, which made it difficult to draw conclusions.
Dispersion and volatility of TFPQ and TFPR: findings from three service industries
Authors: Morikawa Masayuki 
Published: March 2019

Abstract
This study presents the empirical findings on cross-sectional dispersion and time-series volatility of TFPQ and TFPR using high-frequency establishment-level panel data from three narrowly defined service industries. The within-industry dispersion of TFPQ is not larger than that of TFPR, and this finding differs from past studies on the manufacturing sector. Productivity dispersion is smaller when aggregated industry-level productivity is higher, and vice versa. Service producers with highly volatile productivity are less productive in both TFPQ and TFPR.
R&D offshoring and home industry productivity
Authors: de Rassenfosse Gaétan , Thomson Russell 
Published: March 2019

Abstract
Offshoring research and development (R&D) commonly invokes concerns regarding the loss of high value jobs and a hollowing out of technological capabilities, but it can also benefit domestic firms by enabling them to tap into the global technological frontier. We study the effect of R&D offshoring on industrial productivity in the home country using industry-level data for 18 OECD countries over a 26-year period. Simultaneity between productivity and R&D offshoring is addressed by using foreign tax policy as an instrument for offshored R&D. We show that R&D offshoring contributes positively to productivity in the home country, irrespective of the host country destination.
Finite-time terminal synergetic control of a class of nonlinear systems with unmatched uncertainties
Authors: Ahifar Azadeh , Noei Abolfazl Ranjbar , Rahmani Zahra 
Published: March 2019

Abstract
In this paper, the problem of finite-time tracking for nth-order uncertain nonlinear systems with unmatched uncertainties is addressed. Using a terminal synergetic manifold, a controller is provided to force the tracking error to the origin in finite time in the presence of unmatched uncertainties. With this method, chattering problem is completely removed without defining a new function. Lyapunov theory is used to prove the stability of the proposed method. The proposed controller provides the convergence of finite-time tracking error to zero by suitable performance that is theoretically analysed and proved through simulation.
Comparative Analysis of the Antiviral Effects Mediated by Type I and III Interferons in Hepatitis B Virus–Infected Hepatocytes
Authors: Bockmann Jan-Hendrik , Stadler Daniela , Xia Yuchen , Ko Chunkyu , Wettengel Jochen M , Schulze zur Wiesch Julian , Dandri Maura , Protzer Ulrike 
Published: March 2019

Abstract

Background
Type III interferons (IFNs) (λ1–3) activate similar signaling cascades as type I IFNs (α and β) via different receptors. Since IFN-α and lymphotoxin-β activate cytosine deamination and subsequent purging of nuclear hepatitis B virus (HBV) DNA, we investigated whether IFN-β and -λ may also induce these antiviral effects in differentiated HBV-infected hepatocytes.

Methods
After determining the biological activity of IFN-α2, -β1, -λ1, and -λ2 in differentiated hepatocytes, their antiviral effects were analyzed in HBV-infected primary human hepatocytes and HepaRG cells.

Results
Type I and III IFNs reduced nuclear open-circle DNA and covalently closed circular DNA (cccDNA) levels in HBV-infected cells. IFN-β and -λ were at least as efficient as IFN-α. Differential DNA-denaturing polymerase chain reaction and sequencing analysis revealed G-to-A sequence alterations of HBV cccDNA in IFN-α, -β, and -λ–treated liver cells indicating deamination. All IFNs induced apolipoprotein B messenger RNA–editing enzyme–catalytic polypeptide-like (APOBEC) deaminases 3A and 3G within 24 hours of treatment, but IFN-β and -λ induced longer-lasting expression of APOBEC deaminases in comparison to IFN-α.

Conclusions
IFN-β, IFN-λ1, and IFN-λ2 induce cccDNA deamination and degradation at least as efficiently as IFN-α, indicating that these antiviral cytokines are interesting candidates for the design of new therapeutic strategies aiming at cccDNA reduction and HBV cure.
Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR)
Authors: Dimitriou Vassiliki , Biehl Lena M , Hamprecht Axel , Vogel Wichard , Dörfel Daniela , Peter Silke , Schafhausen Philippe , Rohde Holger , von Lilienfeld-Toal Marie , Klassert Tilman E , Slickers Peter , Ehricht Ralf , Slevogt Hortense , Christ Hildegard , Hellmich Martin , Farowski Fedja , Tsakmaklis Anastasia , Higgins Paul G , Seifert Harald , Vehreschild Maria J G T 
Published: March 2019

Abstract

Objectives
We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients.

Methods
We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology–oncology departments. Patients colonized with ESBL-EC/KP received a 7 day antimicrobial regimen of oral colistin (2 × 106 IU 4×/day), gentamicin (80 mg 4×/day) and fosfomycin (three administrations of 3 g every 72 h), or placebo. Faecal, throat and urine specimens were collected on day 0, 6 ± 2, 11 ± 2, 28 ± 4 and 42 ± 4 after treatment initiation, and the quantitative burden of ESBL-EC/KP, resistance genes and changes in intestinal microbiota were analysed. Clinicaltrials.gov: NCT01931592.

Results
As the manufacture of colistin powder was suspended worldwide, the study was terminated prematurely. Overall, 29 (18 verum/11 placebo) out of 47 patients were enrolled. The short-term intestinal eradication was marginal at day 6 (verum group 15/18, 83.3% versus placebo 2/11, 18.2%; relative risk 4.58, 95% CI 1.29–16.33; Fisher’s exact test P = 0.001) and not evident at later timepoints. Quantitative analysis showed a significant decrease of intestinal ESBL-EC/KP burden on day 6. Sustained intestinal eradication (day 28 + 42) was not achieved (verum, 38.9% versus placebo, 27.3%; P = 0.299). In the verum group, mcr-1 genes were detected in two faecal samples collected after treatment. Microbiome analysis showed a significant decrease in alpha diversity and a shift in beta diversity.

Conclusions
In this prematurely terminated study of a 7 day oral antimicrobial eradication regimen, short-term ESBL-EC/KP suppression was marginal, while an altered intestinal microbiota composition was clearly apparent.
Digital biomarkers from geolocation data in bipolar disorder and schizophrenia: a systematic review
Authors: Fraccaro Paolo , Beukenhorst Anna , Sperrin Matthew , Harper Simon , Palmier-Claus Jasper , Lewis Shôn , Van der Veer Sabine N , Peek Niels 
Published: March 2019

AbstractObjectiveThe study sought to explore to what extent geolocation data has been used to study serious mental illness (SMI). SMIs such as bipolar disorder and schizophrenia are characterized by fluctuating symptoms and sudden relapse. Currently, monitoring of people with an SMI is largely done through face-to-face visits. Smartphone-based geolocation sensors create opportunities for continuous monitoring and early intervention.Materials and MethodsWe searched MEDLINE, PsycINFO, and Scopus by combining terms related to geolocation and smartphones with SMI concepts. Study selection and data extraction were done in duplicate.ResultsEighteen publications describing 16 studies were included in our review. Eleven studies focused on bipolar disorder. Common geolocation-derived digital biomarkers were number of locations visited (n = 8), distance traveled (n = 8), time spent at prespecified locations (n = 7), and number of changes in GSM (Global System for Mobile communications) cell (n = 4). Twelve of 14 publications evaluating clinical aspects found an association between geolocation-derived digital biomarker and SMI concepts, especially mood. Geolocation-derived digital biomarkers were more strongly associated with SMI concepts than other information (eg, accelerometer data, smartphone activity, self-reported symptoms). However, small sample sizes and short follow-up warrant cautious interpretation of these findings: of all included studies, 7 had a sample of fewer than 10 patients and 11 had a duration shorter than 12 weeks.ConclusionsThe growing body of evidence for the association between SMI concepts and geolocation-derived digital biomarkers shows potential for this instrument to be used for continuous monitoring of patients in their everyday lives, but there is a need for larger studies with longer follow-up times.
Inheritance and Realized Heritability of Resistance to Imidacloprid in the Brown Planthopper, Nilaparvata lugens (Hemiptera: Delphacidae), From Indonesia
Authors: Diptaningsari Danarsi , Trisyono Y Andi , Purwantoro Aziz , Wijonarko Arman 
Published: March 2019

Abstract
The brown planthopper, Nilaparvata lugens Stål., is a major insect pest causing serious damage to the rice crop in many rice-producing countries. The aim of the study was to determine the inheritance characteristics and realized heritability of resistance to imidacloprid in N. lugens from Banyumas, Central Java Province, Indonesia. The five generations of selection increased the resistance ratio (RR) from 46.20-fold at generation 45 (G45) to 150.39-fold (G49) compared with the laboratory-susceptible population. The LC50 values of imidacloprid for the progeny of reciprocal crosses, F1 and F1’, showed no significant differences, indicating that imidacloprid resistance was inherited autosomally in N. lugens. The degree of dominance (D) values for F1 and F1’ were 0.65 and 0.64, respectively, suggesting that imidacloprid resistance in N. lugens was expressed as an incompletely dominant trait. Chi-square analysis based on the monogenic hypothesis indicated that imidacloprid resistance in N. lugens was polygenic. Furthermore, the estimation realized heritability value (h2) was 0.0893. These results would be useful to determine an effective resistance management strategies in N. lugens.
HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade
Authors: Prat Aleix , Pascual Tomás , De Angelis Carmine , Gutierrez Carolina , Llombart-Cussac Antonio , Wang Tao , Cortés Javier , Rexer Brent , Paré Laia , Forero Andres , Wolff Antonio C , Morales Serafín , Adamo Barbara , Brasó-Maristany Fara , Vidal Maria , Veeraraghavan Jamunarani , Krop Ian , Galván Patricia , Pavlick Anne C , Bermejo Begoña , Izquierdo Miguel , Rodrik-Outmezguine Vanessa , Reis-Filho Jorge S , Hilsenbeck Susan G , Oliveira Mafalda , Dieci Maria Vittoria , Griguolo Gaia , Fasani Roberta , Nuciforo Paolo , Parker Joel S , Conte PierFranco , Schiff Rachel , Guarneri Valentina , Osborne C Kent , Rimawi Mothaffar F 
Published: March 2019

Abstract

Background
Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy.

Methods
A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II–III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12–24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated.

Results
A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P &lt; .001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P = .01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P &lt; .001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P = .02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P = .01).

Conclusions
Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer.
A Re-Examination of D-H-M in the Meṣad ḤAshavyahu Ostracon (KAI 200)
Authors: Noll Sonja 
Published: March 2019

Abstract
Although the contents of the seventh-century bce letter found on ostraca fragments at Meṣad ḤAshavyahu are relatively well understood, the proposed interpretation of one word has been too quickly accepted and should be challenged. This is the interpretation of , in line 14, as a form of , which is said to mean ‘be silent’. The association with is not a foregone conclusion, however, and a survey of the biblical corpus demonstrates that a connection between II- and II- roots is exceptional rather than the norm. Furthermore, the existence of the root is itself uncertain, and the claim that it means ‘be silent’ is questionable rather than established. Finally, the only biblical use of the root , in Jer. 14:9, seems to have similar connotations and should be used to help interpret in the letter.
Pipeline Endovascular Device vs Stent-Assisted Coiling in Small Unruptured Aneurysms: A Cost-Effectiveness Analysis
Authors: Malhotra Ajay , Wu Xiao , Brinjikji Waleed , Miller Timothy , Matouk Charles C , Sanelli Pina , Gandhi Dheeraj 
Published: March 2019

Abstract

BACKGROUND
Both stent-assisted coiling (SAC) and flow diversion with the Pipeline Embolization device (PED; Medtronic Inc) have been shown to be safe and clinically effective for treatment of small (<10 mm) unruptured aneurysms. However, the economic impact of these different techniques has not been established.

OBJECTIVE
To analyze the cost-effectiveness between stent-assisted coiling and flow diversion using PED, including procedural costs, long-term outcomes, and aneurysm recurrence.

METHODS
A decision-analytical study was performed with Markov modeling methods to simulate patients undergoing SAC or PED for treatment for unruptured aneurysms of sizes 5 and 7 mm. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed.

RESULTS
In base case calculation and PSA, PED was the dominant strategy for both the size groups, with and without consideration of indirect costs. One-way sensitivity analyses show that the conclusion remained robust when varying the retreatment rate of SAC from 0% to 50%, and only changes when the retreatment rate of PED > 49%. PED remained the more cost-effective strategy when the morbidity and mortality of PED increased by <55% and when those of SAC decreased by <37%. SAC only became cost-effective when the total cost of PED is >$73000 more expensive than the total cost of SAC.

CONCLUSION
With increasing use of PED for treatment of small unruptured anterior circulation aneurysms, our study indicates that PED is cost-effective relative to stent coiling irrespective of aneurysm size. This is due to lower aneurysm recurrence rate, as well as better health outcomes.