bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel AKT1 Fusion–Driven Cancer
Authors: Slotkin Emily K. , Diolaiti Daniel , Shukla Neerav N. , Dela Cruz Filemon S. , Clark Jennifer J. , Gundem Gunes , Yellapantula Venkata D. , Levine Max F. , You Daoqi , Ma Peilin , Pachhal Sagarika , Ibanez Sanchez Glorymar , Benayed Ryma , Jungbluth Achim A. , Smyth Lillian M. , Mauguen Audrey , Gushterova Irena , Ding Hongxu , Spraggon Lee , Darnell Robert , Califano Andrea , Ladanyi Marc , Papaemmanuil Elli , Kung Andrew L. , Hyman David M. , Roberts Stephen S. 
Published: March 2019

Abstract

Despite the important role of the PI3K/AKT/mTOR axis in the pathogenesis of cancer, to date there have been few functional oncogenic fusions identified involving the AKT genes. A 12-year-old female with a histopathologically indeterminate epithelioid neoplasm was found to harbor a novel fusion between the LAMTOR1 and AKT1 genes. Through expanded use access, she became the first pediatric patient to be treated with the oral ATP-competitive pan-AKT inhibitor ipatasertib. Treatment resulted in dramatic tumor regression, demonstrating through patient-driven discovery that the fusion resulted in activation of AKT1, was an oncogenic driver, and could be therapeutically targeted with clinical benefit. Post-clinical validation using patient-derived model systems corroborated these findings, confirmed a membrane-bound and constitutively active fusion protein, and identified potential mechanisms of resistance to single-agent treatment with ipatasertib.

Significance:
This study describes the patient-driven discovery of the first AKT1 fusion–driven cancer and its treatment with the AKT inhibitor ipatasertib. Patient-derived in vitro and in vivo model systems are used to confirm the LAMTOR1–AKT1 fusion as a tumorigenic driver and identify potential mechanisms of resistance to AKT inhibition.
This article is highlighted in the In This Issue feature, p. 565
Concurrent Molecular Magnetic Resonance Imaging of Inflammatory Activity and Extracellular Matrix Degradation for the Prediction of Aneurysm Rupture
Authors: Brangsch Julia , Reimann Carolin , Kaufmann Jan O. , Adams Lisa C. , Onthank David C. , Thöne-Reineke Christa , Robinson Simon P. , Buchholz Rebecca , Karst Uwe , Botnar Rene M. , Hamm Bernd , Makowski Marcus R. 
Published: March 2019

Background:
Molecular magnetic resonance imaging is a promising modality for the characterization of abdominal aortic aneurysms (AAAs). The combination of different molecular imaging biomarkers may improve the assessment of the risk of rupture. This study investigates the feasibility of imaging inflammatory activity and extracellular matrix degradation by concurrent dual-probe molecular magnetic resonance imaging in an AAA mouse model.

Methods:
Osmotic minipumps with a continuous infusion of Ang II (angiotensin II; 1000 ng/[kg·min]) to induce AAAs were implanted in apolipoprotein-deficient mice (N=58). Animals were assigned to 2 groups. In group 1 (longitudinal group, n=13), imaging was performed once after 1 week with a clinical dose of a macrophage-specific iron oxide–based probe (ferumoxytol, 4 mgFe/kg, surrogate marker for inflammatory activity) and an elastin-specific gadolinium-based probe (0.2 mmol/kg, surrogate marker for extracellular matrix degradation). Animals were then monitored with death as end point. In group 2 (week-by-week-group), imaging with both probes was performed after 1, 2, 3, and 4 weeks (n=9 per group). Both probes were evaluated in 1 magnetic resonance session.

Results:

The combined assessment of inflammatory activity and extracellular matrix degradation was the strongest predictor of AAA rupture (sensitivity 100%; specificity 89%; area under the curve, 0.99). Information from each single probe alone resulted in lower predictive accuracy. In vivo measurements for the elastin- and iron oxide–probe were in good agreement with ex vivo histopathology (Prussian blue-stain:
R
2
=0.96,
P
<0.001; Elastica van Giesson stain:
R
2
=0.79,
P
<0.001). Contrast-to-noise ratio measurements for the iron oxide and elastin-probe were in good agreement with inductively coupled mass spectroscopy (
R
2
=0.88,
R
2
=0.75,
P
<0.001) and laser ablation coupled to inductively coupled plasma–mass spectrometry.

Conclusions:
This study demonstrates the potential of the concurrent assessment of inflammatory activity and extracellular matrix degradation by dual-probe molecular magnetic resonance imaging in an AAA mouse model. Based on the combined information from both molecular probes, the rupture of AAAs could reliably be predicted.
Incremental Prognostic Value of Guideline-Directed Medical Therapy, Transradial Access, and Door-to-Balloon Time on Outcomes in ST-Segment–Elevation Myocardial Infarction
Authors: Huded Chetan P. , Kumar Anirudh , Johnson Michael , Abdallah Mouin , Ballout Jad A. , Kravitz Kathleen , Menon Venu , Gullett Travis C. , Hantz Scott , Ellis Stephen G. , Podolsky Seth R. , Meldon Stephen W. , Kralovic Damon M. , Brosovich Deborah , Smith Elizabeth , Kapadia Samir R. , Khot Umesh N. 
Published: March 2019

Background:
Systems to improve ST-segment–elevation myocardial infarction (STEMI) care have traditionally focused on improving door-to-balloon time. However, prompt guideline-directed medical therapy and transradial primary percutaneous coronary intervention (PCI) are also associated with reduced STEMI mortality. The incremental prognostic value of each facet of STEMI care on clinical outcomes within a STEMI system of care is unknown.

Methods and Results:

We implemented systems-based strategies at our hospital to improve 3 STEMI care metrics: (1) prompt guideline-directed medical therapy before sheath insertion for PCI, (2) use of transradial primary PCI, and (3) door-to-balloon time. We assessed the incremental association of metrics achieved with in-hospital adverse events and 30-day mortality. Of 1272 consecutive patients with STEMI treated with PCI at our hospital (January 1, 2011, to December 31, 2016), the percentage with achievement of zero, 1, 2, or 3 STEMI care metrics was 7.1%, 24.1%, 43.8%, and 25.1%; and 30-day mortality was 15.6%, 8.6%, 3.6%, and 3.2%, respectively (log-rank
P
<0.001). After adjusting for known clinical predictors of STEMI in-hospital mortality, achievement of at least 2 STEMI care metrics was associated with significantly reduced in-hospital mortality (odds ratio, 0.39; 95% CI, 0.16–0.96;
P
=0.041). Each metric provided incremental prognostic value when modeled in stepwise order of their occurrence in clinical practice (final model C statistic, 0.677;
P
<0.001).

Conclusions:
Prompt guideline-directed medical therapy before sheath insertion for PCI, transradial primary PCI, and door-to-balloon time add incremental prognostic value in STEMI care. Expanding STEMI systems of care from a singular focus on door-to-balloon time to a comprehensive focus on multifaceted STEMI care offers an opportunity to further improve STEMI outcomes.
THE CAUSAL EFFECTS OF ECONOMIC, POLITICAL AND SOCIAL GLOBALIZATION ON MIGRANTS: A PANEL DATA ANALYSIS FOR SELECTED OECD COUNTRIES
Authors: KURT Ünzüle 
Published: March 2019

Although it mostly includes economic factors in its origin, the statement of “the removal of inter-country borders”, included in the definition of globalization, also includes inter-country human movement, which makes it a social concept. Migration is a factor that causes significant changes in the socio-cultural and economic structures of the migration-receiving country. Accordingly, in order to be able to explain the economic effects of globalization concept, it becomes important to identify how this concept affects labor markets of countries. The effects of globalization on migration received by OECD countries were attempted to be explained from this perspective in the study by investigating the interaction of migration concept, effective on labor structures of countries, with globalization. In the present study, the relationship between globalization and migration in the period of 2000-2014 for selected 30 OECD countries was investigated with Dumitrescu and Hurlinpanel causality test. As a result of the test, the presence of a causality relationship was identified between globalization and migration in the relevant period for 30 OECD countries.
Historiography in the Service of the Muftī: Ibn Taymiyya on the Origins and Fallacies of Ziyārāt
Authors: Talmon-Heller Daniella 
Published: March 2019

AbstractThis essay demonstrates Ibn Taymiyya’s engagement of historiography in iftāʼ. It draws upon fatwās on pilgrimage to Ascalon, travel to shrines of al-Ḥusayn in Ascalon and Cairo, and visits to Jerusalem and Hebron. Ibn Taymiyya weaves sophisticated historical narratives into his legal reasoning against visiting tombs of prophets and Ahl al-Bayt. He exposes lacunas, contradictions and unreasonable assertions in truisms about bodies of prophets and saints and their cults. He argues against ziyāra to such sites, blaming Shīʿīs for spreading the innovation at a particularly vulnerable time for Islam. His attack on notions of the religious merits of Jerusalem and of murābaṭa hinges upon his reconstruction of the history the Dome of the Rock and of the Islamic frontier. History leads him to stress the temporality of territorial definitions and their dependence on context. His argumentation resonates in works of later writers, demonstrating the continuing relevance of his fatwās.
Resurrection of the Dead, Exaltation of the New Struggles
Authors: Webber Jeffery R. 
Published: March 2019

Abstract
This ‘editorial perspective’ offers reflection on Marxist theory in the narrow domain of social movements and social-movement studies. It offers a brief survey of international class struggles over the last few decades to situate the discussion. It then focuses on the problem of capitalism for social-movement studies, and the particular issue of capitalist totality. It argues that an expansive, processual, historical and temporal conception of class struggle needs to be at the centre of any adequate Marxist approach to social movements, and shows why and how this is so by delving into some contemporary debates over dominant forms of collective action – strike and riot. It also highlights the dialectical relations between production, reproduction and social reproduction, and how the latest revivals of Marxist feminism might guide us through the morass. Finally, it suggests that struggles across these interrelated domains can be linked through an ‘infrastructure of dissent’.
Disability Studies in Education – Building Platforms to Reclaim Disability and Recognise Disablement
Authors: Slee Roger , Corcoran Tim , Best Marnie 
Published: March 2019

Abstract
This paper provides the historical and theoretical foundations for the emergent field of Disability Studies in Education. Disability Studies in Education proceeds from the trans-disciplinary work we find in the continuing development of Disability Studies. It applies the principles and conceptual threads of Disability Studies to critique the ableist traditions, structures and cultures of education and to suggest how education might be otherwise. The paper makes clear the distinction between special education and disability studies in education. Special education has proven its resilience and willingness to appropriate the discourse of inclusive education in order to adapt and sustain its core assumptions about children with disabilities and their education. Accordingly, it is critical that this journal make explicit the distinctions between the conceptual foundations and practical applications of special education and Disability Studies in Education. This first paper is an attempt at draw these lines of distinctions and the aspirations for the Journal of Disability Studies in Education.
Openness, Inflation and Output Under Alternative Monetary Policies: A Structuralist Approach
Authors: Basu Rilina , Das Nandini , Nag Ranjanendra Narayan 
Published: March 2019

This article theoretically revisits the issue of how trade openness and inflation are interconnected in the light of conduct and optimal design of monetary policy. Central banks in open economies all over the world face a problematic dilemma when it comes to providing a nominal anchor to the economy in the sense that they have to choose between monetary targeting and inflation targeting. The experience has been varied worldwide with respect to these alternative policies in containing inflation. Different dimensions of openness like fully flexible exchange rate and capital mobility have also had significant impacts on the outcomes of policy changes. In this paper, we have constructed two theoretical open macro-economy models using the AD-AS framework under regressive expectations. The first model considers interest-rate targeting incorporating Taylor rule, whereas the second one deals with monetary targeting. The models show that alternate monetary policy rules do not change the basic results of different macroeconomic policies, although the underlying transmission mechanisms are quite different. JEL Codes: E12, E31, E43, E52, F41
The Effect of Symptom Clusters on Quality of Life Among Patients With Type 2 Diabetes
Authors: Li Hongjin , Ji Meihua , Scott Paul , Dunbar-Jacob Jacqueline M. 
Published: March 2019

Purpose The purpose of this study was to examine the collective effect of a symptom cluster (depression, anxiety, fatigue, and impaired sleep quality) at baseline on the quality of life (QOL) of patients with type 2 diabetes (T2DM) over time. Methods This was a secondary data analysis of 302 patients with T2DM who presented with both hypertension and hyperlipidemia. All of the participants were enrolled in a randomized controlled intervention study testing strategies to improve medication adherence. The psychological symptoms and QOL were assessed at baseline, 6 months, and 12 months. Cluster analysis was used to identify subgroups of patients based on the severity of symptoms at baseline. Results Hierarchical cluster analysis identified 4 patient subgroups: all low severity, mild, moderate, and all high severity. There were significant differences in patients’ QOL overall among the 4 subgroups. Compared with the all-low-severity subgroup, subgroups with higher severity of the 4 symptoms had poorer QOL across all 3 time points. QOL was most impacted by trait anxiety across the 3 time points. Conclusion QOL was significantly impacted by psychological symptom clusters among patients with T2DM. Healthcare providers should not neglect psychological symptoms that patients experience. It is important to assess and manage these symptoms to improve QOL among patients with diabetes.
Inter-observer agreement of color duplex ultrasound of central vein stenosis in hemodialysis patients
Authors: Razek Ahmed AKA , Khalek Ahmed MA , Elwakeel Hossam , Ebrahim Moataz A 
Published: March 2019

Purpose To assess the inter-observer agreement of color duplex ultrasound of central vein stenosis in hemodialysis patients. Patients and methods This prospective study was conducted on 35 hemodialysis patients with suspected central vein stenosis. All patients underwent color flow duplex examination of the subclavian, internal jugular and brachiocephalic veins in hemodialysis patients. Image analysis was performed by two reviewers for diameter reduction, peak venous velocity ratio, post-stenotic turbulent flow, waveform changes, and thrombus formation. Results There was no significant difference between both observers for diameter reduction ( p = 0.105) and for the mean peak systolic velocity ratio ( p = 0.515). The overall inter-observer agreement of color duplex ultrasound of central vein stenosis was excellent ( k = 0.84, percent agreement = 89.7%, P = 0.001). There was excellent inter-observer agreement of both reviewers for diameter reduction ( k = 0.928, percent agreement = 97.14%), peak venous velocity ratio ( k = 0.7, percent agreement = 85.7%), waveform changes ( k = 0.62, percent agreement = 77.14%), post-stenotic turbulent flow ( k = 0.866, percent agreement = 88.6%), thrombus formation ( k = 1, percent agreement = 100%). Conclusion We concluded that color duplex ultrasound is a reliable and reproducible method for diagnosis of central vein stenosis in hemodialysis patients.
RNA-seq of circular RNAs identified circPTPN22 as a potential new activity indicator in systemic lupus erythematosus
Authors: Miao Q , Zhong Z , Jiang Z , Lin Y , Ni B , Yang W , Tang J 
Published: March 2019

Background Circular RNAs (circRNAs) are possible biomarkers for many diseases, but the knowledge of circRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) remains limited. This study aimed to assess the expression of circRNAs in PBMCs from patients with SLE and healthy individuals by RNA sequencing (RNA-seq). Methods In total, 128 circRNAs were significantly differentially expressed including 39 upregulated and 89 downregulated circRNAs in four new-onset SLE patients compared with three healthy controls. After verification of the four candidate circRNAs in 49 patients with SLE and 37 controls using quantitative real-time polymerase chain reaction (qRT-PCR) assays, a previously undescribed circRNA with potential translation activity, circPTPN22, was selected to confirm its clinical significance. Results Bioinformatics analysis demonstrated that the parent gene of circPTPN22 was protein tyrosine phosphatase non-receptor type 22 (PTPN22), a potent regulator of T cell activation. The downregulation of circPTPN22 in patients with SLE was strongly negatively correlated with their Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. circRNA-miRNA-mRNA co-expression network analysis indicated a correlation between circPTPN22 and the miRNAs and mRNAs related to immunological regulation including the development of SLE. Patients with higher SLEDAI scores had lower circPTPN22 expression levels, and long-term hormone treatment significantly increased circPTPN22 levels. Receiver operating characteristic curve analysis indicated that circPTPN22 has good diagnostic value for SLE. Conclusion Our data demonstrated the aberrant expression of circRNAs in patients with SLE compared with healthy controls; circPTPN22 might function as a diagnostic and disease severity indicator in SLE.
Studying the role of 10-2 visual field test in different stages of glaucoma
Authors: Tomairek Reham Hosny , Aboud Safaa Awadallah , Hassan Mansour , Mohamed Alyaa H 
Published: March 2019

Objective: To assess the role of 10-2 visual field (VF) test in different stages of glaucoma. Methods: In our prospective comparative study, 24-2 and 10-2 VF tests were done for 115 eyes with different stages of glaucomatous damage or glaucoma suspects. Optical coherence tomography (OCT) was performed in 79 eyes. We compared field changes of the central 10° on 10-2 and 24-2 tests and studied the correlation between the mean deviation (MD) measured by the two tests. Results: In seven glaucoma suspects, glaucoma diagnosis was missed by 24-2 test but was detected by 10-2 test and confirmed by OCT. In the eyes with early damage, there was no correlation between 10-2 and 24-2 tests regarding the MD of the central 10º. In moderate and severe stages, there was a significant correlation between the results of 24-2 and 10-2 tests. Conclusion: We concluded that 10-2 test could help confirm glaucoma diagnosis in glaucoma suspects missed by 24-2 test before resorting to the more expensive OCT. In early glaucoma, we noted that 10-2, as confirmed by OCT, was a beneficial addition to 24-2 test for precise measurement of the MD and detection of defects of the central 10º missed by 24-2 test, where more intense treatment should be considered to preserve the threatened central visual function. In moderate and severe cases, the role of 10-2 test was not as pivotal as in early cases, but still it was useful for assessment of residual central visual function in severe cases with absolute central 10º defects on 24-2 test for proper management.
Home-based video visits for pediatric patients with poorly controlled type 1 diabetes
Authors: Crossen Stephanie , Glaser Nicole , Sauers-Ford Hadley , Chen Shelby , Tran Victoria , Marcin James 
Published: March 2019

Introduction Management of type 1 diabetes (T1D) is labor-intensive, requiring multiple daily blood glucose measurements and insulin injections. Patients are seen quarterly by providers, but evidence suggests more frequent contact is beneficial. Current technology allows secure, remote sharing of diabetes data and video-conferencing between providers and patients in their home settings. Methods Home-based video visits were provided for six months to pediatric T1D patients with poor glycemic control, indicated by a hemoglobin A1c (HbA1c) ≥8% at enrollment. Video visits were conducted every 4–8 weeks in addition to regularly scheduled clinic visits. Dates of clinic visits and HbA1c values were abstracted from the medical record at baseline and six months. Patients were surveyed at video visits regarding technical issues, and after six months a standardized survey was administered to assess satisfaction with video-based care. Results A total of 57 patients enrolled and 36 completed six months of video visits. Patients completing six months averaged 4.0 video visits (SD 1.1). Their frequency of in-person care also increased from 3.2 clinic visits/year at baseline to 3.7 clinic visits/year during the study ( P = 0.04). Mean HbA1c reduction among patients completing six months was 0.8% (95% CI 0.2–1.4%); 94% of these patients were “very satisfied” while 6% were “somewhat satisfied” with the experience. Discussion This study demonstrates that home-based video visits are feasible and satisfactory for pediatric patients with poorly controlled T1D. Furthermore, use of video visits can improve frequency of subspecialty care and resulting glycemic control in this population.
4G versus 3G-enabled telemedicine in prehospital acute stroke care
Authors: Winter B , Wendt M , Waldschmidt C , Rozanski M , Kunz A , Geisler F , Grittner U , Kaczmarek S , Ebinger M , Audebert HJ ,   for the Stroke Emergency Mobile (STEMO) Consortium
Published: March 2019

Background Time to reperfusion treatment is closely related to outcome in ischemic stroke. Prehospital stroke work-up in CT-equipped mobile stroke units is effective in reducing time to thrombolytic treatment. Current evidence predominantly comes from mobile stroke units staffed with neurologists but telemedicine-guided management may be acceptable for providing neurological expertise in ambulances. With unsatisfactory experiences in third-generation (3G)-based approaches, fourth-generation (4G) networks may provide adequate audio-visual quality but systematic comparisons of technological parameters and decision-making are lacking. Methods Trained actors presented stroke symptoms and paramedics assisted the remotely guided extended National Institutes of Health Stroke Scale (eNIHSS) assessment on the mobile stroke unit in Berlin, Germany. We compared technical parameters of 4G and 3G connections, assessed audio-visual quality of examination, and analyzed reliability of neurological assessment and treatment decisions made by the remote neurologist versus the mobile stroke unit neurologist. Results 4G and 3G connections were evaluated in 40 scenarios each. Connectivity was not available in 17% of 4G- and 15% of 3G-attempts with 6% simultaneous unavailability of both networks. The remote examiners graded audio and video quality in 4G better than in 3G with slightly shorter assessment duration in 4G (mean: 9 (SD:5) vs. mean 11 (SD:3) min, p = 0.10). Reliability of the eNIHSS sum scores was high with intraclass correlation coefficients of 0.99 (95% CI: 0.987–1.00) for 4G and 0.98 (95% CI: 0.96–0.99) for 3G. None of the remote treatment decisions differed from onsite decisions. Conclusions 4G mobile communications provided higher quality of video-examination and allowed reliable remote assessment of stroke symptoms but coverage was still incomplete in both networks.