bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of acute ischemic stroke due to tandem occlusion: should endovascular recanalization of the extracranial or intracranial occlusive lesion be done first?
Authors: Rangel-Castilla Leonardo , Rajah Gary B. , Shakir Hakeem J. , Shallwani Hussain , Gandhi Sirin , Davies Jason M. , Snyder Kenneth V. , Levy Elad I. , Siddiqui Adnan H. 
Published: April 2017

OBJECTIVE
Acute tandem occlusions of the cervical internal carotid artery and an intracranial large vessel present treatment challenges. Controversy exists regarding which lesion should be addressed first. The authors sought to evaluate the endovascular approach for revascularization of these lesions at Gates Vascular Institute.

METHODS
The authors performed a retrospective review of a prospectively maintained, single-institution database. They analyzed demographic, procedural, radiological, and clinical outcome data for patients who underwent endovascular treatment for tandem occlusions. A modified Rankin Scale (mRS) score ≤ 2 was defined as a favorable clinical outcome.

RESULTS
Forty-five patients were identified for inclusion in the study. The average age of these patients was 64 years; the mean National Institutes of Health Stroke Scale score at presentation was 14.4. Fifteen patients received intravenous thrombolysis before undergoing endovascular treatment. Thirty-seven (82%) of the 45 proximal cervical internal carotid artery occlusions were atherothrombotic in nature. Thirty-eight patients underwent a proximal-to-distal approach with carotid artery stenting first, followed by intracranial thrombectomy, whereas 7 patients underwent a distal-to-proximal approach (that is, intracranial thrombectomy was performed first). Thirty-seven (82%) procedures were completed with local anesthesia. For intracranial thrombectomy procedures, aspiration alone was used in 15 cases, stent retrieval alone was used in 5, and a combination of aspiration and stent-retriever thrombectomy was used in the remaining 25. The average time to revascularization was 81 minutes. Successful recanalization (thrombolysis in cerebral infarction Grade 2b/3) was achieved in 39 (87%) patients. Mean National Institutes of Health Stroke Scale scores were 9.3 immediately postprocedure (p < 0.05) (n = 31), 5.1 at discharge (p < 0.05) (n = 31), and 3.6 at 3 months (p < 0.05) (n = 30). There were 5 in-hospital deaths (11%); and 2 patients (4.4%) had symptomatic intracranial hemorrhage within 24 hours postprocedure. Favorable outcomes (mRS score ≤ 2) were achieved at 3 months in 22 (73.3%) of 30 patients available for follow-up, with an mRS score of 3 for 7 of 30 (23%) patients.

CONCLUSIONS
Tandem occlusions present treatment challenges, but high recanalization rates were possible in the present series using acute carotid artery stenting and mechanical thrombectomy concurrently. Proximal-to-distal and aspiration approaches were most commonly used because they were safe, efficacious, and feasible. Further study in the setting of a randomized controlled trial is needed to determine the best sequence for the treatment approach and the best technology for tandem occlusion.
Transradial approach for mechanical thrombectomy in anterior circulation large-vessel occlusion
Authors: Sur Samir , Snelling Brian , Khandelwal Priyank , Caplan Justin M. , Peterson Eric C. , Starke Robert M. , Yavagal Dileep R. 
Published: April 2017

OBJECTIVE
The goals of this study were to describe the authors' recent institutional experience with the transradial approach to anterior circulation large-vessel occlusions (LVOs) in acute ischemic stroke patients and to report its technical feasibility.

METHODS
The authors reviewed their institutional database to identify patients who underwent mechanical thrombectomy via a transradial approach over the 2 previous years, encompassing their experience using modern techniques including stent retrievers.

RESULTS
Eleven patients were identified. In 8 (72%) of these patients the right radial artery was chosen as the primary access site. In the remaining patients, transfemoral access was initially attempted. Revascularization (modified Treatment in Cerebral Ischemia [mTICI] score ≥ 2b) was achieved in 10 (91%) of 11 cases. The average time to first pass with the stent retriever was 64 minutes. No access-related complications occurred.

CONCLUSIONS
Transradial access for mechanical thrombectomy in anterior circulation LVOs is safe and feasible. Further comparative studies are needed to determine criteria for selecting the transradial approach in this setting.
Introduction to Deep Brain Stimulation
Authors: Lozano Andres M. , Gross Robert E. 
Published: April 2017

It is estimated that over 160,000 patients worldwide have received deep brain stimulation (DBS) to date predominantly for Parkinson's disease and other movement disorders. With the success of this therapy, a greater appreciation of the clinical benefits and adverse effects is being realized. Neurosurgeons are increasingly paying attention to the technical details of these procedures and optimizing targeting, surgical techniques, and programming to improve outcomes.In this issue, the nuances of surgical techniques for DBS are covered by Dr. House. Dr. Toda et al. and Mr. Chartrain et al. tackle the approach to treating tremors, either essential tremor or Holmes tremor, using either a single target or, in cases of difficult-to-treat tremors, using more than one target and interleaving the stimulation. These abstracts and videos will be appreciated by both those who are being initiated to DBS and the more seasoned practitioners who are looking for helpful hints to tackle challenging cases.
Coaxial interleaved stimulation of the thalamus and subthalamus for treatment of Holmes tremor
Authors: Toda Hiroki , Nishida Namiko , Iwasaki Koichi 
Published: April 2017

Holmes tremor is often treated with multiple deep brain stimulation (DBS) electrodes. The authors describe a novel technique to suppress the tremors by effectively utilizing a single electrode.A 16-year-old boy presented with severe right arm tremor following a midbrain injury. A DBS electrode was implanted into the ventral oralis nucleus of the thalamus (VO) and the subthalamic region. While individual stimulation of each target was ineffective, an interleaved dual stimulation of both targets has been effective for 6 years.Coaxial interleaved stimulation of the VO and the subthalamic region is useful for treating Holmes tremor.The video can be found here: https://youtu.be/tSwGh3vy68c.
Deep brain stimulation of the ventralis intermedius nucleus for the treatment of essential tremor
Authors: Chartrain Alexander G. , Awad Ahmed J. , Rasouli Jonathan J. , Rothrock Robert J. , Kopell Brian H. 
Published: April 2017

A 59-year-old woman with a 30-year history of essential tremor refractory to medical therapy underwent staged deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM). Left-sided lead placement was performed first. Once in the operating room, microelectrode recording (MER) was performed to confirm the appropriate trajectory and identify the VIM border with the ventralis caudalis nucleus. MER was repeated after repositioning 2 mm anteriorly to reduce the likelihood of stimulation-induced paresthesias. Physical examination prior to permanent lead placement demonstrated micro-lesion effect, suggesting optimal trajectory. After implantation of the permanent lead, physical examination showed excellent results.The video can be found here: https://youtu.be/nn3KRdmRCZ4.
Technical nuances to minimize common complications of deep brain stimulation
Authors: House Paul 
Published: April 2017

The implantation of deep brain stimulator electrodes is associated with infrequent complications. These complications are consistent across prospective trials and include infection, skin erosion, hemorrhage, and lead misplacement. Nuances of surgical technique can be used to minimize the risk of these commonly noted complications. Several of these technical nuances are highlighted in this video submission.The video can be found here: https://youtu.be/GL09W9p013g.
Cost-effectiveness Analysis for Genotyping before Allopurinol Treatment to Prevent Severe Cutaneous Adverse Drug Reactions
Authors: Ke Ching-Hua , Chung Wen-Hung , Wen Yen-Hsia , Huang Yaw-Bin , Chuang Hung-Yi , Tain You-Lin , Wang Yu-Ching Lily , Wu Cheng-Chih , Hsu Chien-Ning 
Published: April 2017

Objective.Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 screening compared with using other available urate-lowering agents (ULA).Methods.A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLA-B*58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening. A 1-year time frame and third-party payer perspective were modeled for both the entire cohort (base-case) and for the subgroup of patients with chronic kidney disease (CKD).Results.The incremental cost-effectiveness ratio of genetic screening prior to ULA therapy was estimated as New Taiwan (NT) $234,610 (US$7508) per QALY gained in the base-case cohort. For patients with CKD, it was estimated as NT$230,925 (US$7390) per QALY. The study results were sensitive to the probability of benzbromarone/febuxostat-related hypersensitivity, and a negative predicted value of genotyping.Conclusion.HLA-B*58:01 screening gave good value for money in preventing allopurinol-induced SCAR in patients indicated for ULA therapy. In addition to the costs of genotyping, it is important to monitor ULA safety closely in adopting HLA-B*58:01 screening in practice.
Validation of a Knowledge Transfer Tool for the Knee Inflammation MRI Scoring System for Bone Marrow Lesions According to the OMERACT Filter: Data from the Osteoarthritis Initiative
Authors: Jaremko Jacob L. , Azmat Omar , Lambert Robert G. , Bird Paul , Haugen Ida K. , Jans Lennart , Weber Ulrich , Winn Naomi , Zubler Veronika , Maksymowych Walter P. 
Published: April 2017

Objective.To assess feasibility and reliability of scoring bone marrow lesions (BML) on knee magnetic resonance imaging (MRI) in osteoarthritis using the Outcome Measures in Rheumatology Knee Inflammation MRI Scoring System (KIMRISS), with a Web-based interface and online training with real-time iterative calibration.Methods.Six readers new to the KIMRISS (3 radiologists, 3 rheumatologists) scored sagittal T2-weighted fat-saturated MRI in 20 subjects randomly selected from the Osteoarthritis Initiative data, at baseline and 1-year followup. In the KIMRISS, the reader moves a transparent overlay grid within a Web-based interface to fit bones, then clicks or touches each region containing BML per slice, to score 1 if BML is present. Regional and total scores are automatically calculated. Outcomes include the interreader intraclass correlation coefficients (ICC) and the smallest detectable change (SDC).Results.Scoring took 3–12 min per scan and all readers rated the process as moderately to very user friendly. Despite a low BML burden (average score 2.8% of maximum possible) and small changes, interobserver reliability was moderate to high for BML status and change in the femur and tibia (ICC 0.78–0.88). Four readers also scored the patella reliably, whereas 2 readers were outliers, likely because of image artifacts. SDC of 1.5–5.6 represented 0.7% of the maximum possible score.Conclusion.We confirmed feasibility of knee BML scoring by new readers using interactive training and a Web-based touch-sensitive overlay system, finding high reliability and sensitivity to change. Further work will include adjustments to training materials regarding patellar scoring, and study in therapeutic trial datasets with higher burden of BML and larger changes.
Decreased Cardiovascular Mortality in Patients with Incident Rheumatoid Arthritis (RA) in Recent Years: Dawn of a New Era in Cardiovascular Disease in RA?
Authors: Myasoedova Elena , Gabriel Sherine E. , Matteson Eric L. , Davis John M. , Therneau Terry M. , Crowson Cynthia S. 
Published: April 2017

Objective.To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000–07 versus the previous decades, compared with non-RA subjects.Methods.The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980–2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade.Results.The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000–07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6–4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0–2.7%) than patients diagnosed in 1990–99 (7.1%, 95% CI 3.9–10.1% and 4.5%, 95% CI 1.9–7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19–0.94; CHD death: HR 0.21, 95% CI 0.05–0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000–07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively).Conclusion.Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.
Developing a Core Set of Outcome Measures for Behçet Disease: Report from OMERACT 2016
Authors: Hatemi Gulen , Meara Alexa , Ozguler Yesim , Direskeneli Haner , Mahr Alfred , Easley Ebony , Gurcan Mert , Davis Trocon , Gul Ahmet , Yazici Yusuf , Zottenberg Katelyn , Esatoglu Sinem Nihal , Erer Burak , Kamali Sevil , Yazici Hasan , Cronholm Peter F. , Merkel Peter A. 
Published: April 2017

Objective.The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group has been working toward developing a data-driven core set of outcome measures for use in clinical trials of Behçet’s syndrome [Behçet disease (BD)]. This paper summarizes the group’s work through OMERACT 2016, discussions during the meeting, and the future research agenda.Methods.Qualitative patient interviews were conducted among 20 patients with BD who have different types of organ involvement. A 3-round Delphi among BD experts and patients was initiated to identify domains, subdomains, and outcomes to be assessed in clinical trials of BD. The results of these studies were discussed during OMERACT 2016 and next steps were planned.Results.Patients’ perspectives and priorities were identified through qualitative interviews that identified candidate domains and subdomains for inclusion in the Delphi and characterized some shortcomings of the currently used patient-reported outcomes in BD. The first round of the Delphi was completed and several domains or subdomains were endorsed by the experts and/or the patients. Because many more items were endorsed than would be feasible to assess during a clinical trial, rating and ranking of items by physicians and patients was planned as a next critical step. The challenges of assessing specific organ system involvement was also discussed.Conclusion.The OMERACT Behçet Syndrome Working Group research program will identify core domains for assessment in BD with the goal of developing a core set of outcome measures for use in all trials of BD with the option to incorporate additional outcomes for specific organ involvement.
Le lien conjugal à l’épreuve de la maladie d’Alzheimer
Authors: Pria Veillon Hélène 
Published: April 2017

Cet article présente les résultats d’une étude exploratoire qualitative portant sur les modalités de réaménagement du lien conjugal lorsque l’un des membres du couple est atteint d’une maladie d’Alzheimer ou d’une démence apparentée et est placé en institution. L’analyse s’appuie sur le concept de « perte ambiguë » (Boss, 2002), l’approche systémique du fonctionnement du couple (Caillé, 2004) et le concept de « loyauté » (Boszormenyi-Nagy, 1973). Cette étude suggère des premières pistes de réflexion pour mettre en place un accompagnement des conjoints valides pour les aider à revisiter leur modèle de couple et à s’engager dans un processus de reconstruction identitaire leur permettant d’accepter la perte ambiguë de leur partenaire dément et placé en institution.
Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration
Authors: Ball Jennifer A. , Vlisidou Isabella , Blunt Matthew D. , Wood Will , Ward Stephen G. 
Published: April 2017

Abstract
H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src kinase to activate a negative regulator of PI3K signaling, SHIP-1 via phosphorylation, providing a molecular mechanism for H2O2-induced chemotaxis deficiency. We hypothesize that although H2O2 serves as an early recruitment trigger for innate immune cells, it appears to operate as an inhibitor of T lymphocyte immune adaptive responses that are not required until later in the repair process.
IFN Regulatory Factor 3 Potentiates Emphysematous Aggravation by Lipopolysaccharide
Authors: Ishii Takashi , Hosoki Keisuke , Nikura Yuichi , Yamashita Naohide , Nagase Takahide , Yamashita Naomi 
Published: April 2017

Abstract
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is often induced by infection and often has a poor prognosis. Bacterial LPS activates innate immune receptor TLR4 followed by activation of a transcriptional factor IFN regulatory factor-3 (IRF3) as well as NF-κB, resulting in upregulation of various inflammatory mediators. To clarify the role of IRF3 in the pathogenesis of LPS-triggered COPD exacerbation, porcine pancreatic elastase (PPE) followed by LPS was administered intranasally to wild-type (WT) or IRF3−/− male mice. Sequential quantitative changes in emphysema were evaluated by microcomputed tomography, and lung histology was evaluated at the sixth week. WT mice treated with PPE and LPS exhibited enlarged alveolar spaces, whereas this feature was attenuated in similarly treated IRF3−/− mice. Moreover, LPS-induced emphysema aggravation was detected only in WT mice. Analysis of acute inflammation induced by PPE plus LPS revealed that the lungs of treated IRF3−/− mice had decreased mRNA transcripts for MCP-1, MIP-1α, TNF-α, and IFN-γ–inducible protein-10 but had increased neutrophils. IRF3 was involved in the production of mediators from macrophages, alveolar epithelial cells, and neutrophils. Furthermore, compared with isolated WT neutrophils from inflamed lung, those of IRF3−/− neutrophils exhibited impaired autophagic activation, phagocytosis, and apoptosis. These results suggest that IRF3 accelerated emphysema formation based on distinct profiles of mediators involved in LPS-induced COPD exacerbation. Regulation of the IRF3 pathway can affect multiple cell types and contribute to ameliorate pathogenesis of infection-triggered exacerbation of COPD.
Invariant NKT Cell Activation Is Potentiated by Homotypic trans-Ly108 Interactions
Authors: Baglaenko Yuriy , Cruz Tleugabulova Mayra , Gracey Eric , Talaei Nafiseh , Manion Kieran Patricia , Chang Nan-Hua , Ferri Dario Michael , Mallevaey Thierry , Wither Joan E. 
Published: April 2017

Abstract
Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and are rapidly activated to produce large quantities of cytokines and chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes that provide key homotypic interactions between signaling lymphocyte activation molecule (SLAM) family members. However, the role of SLAM receptors in the differentiation of iNKT cell effector subsets and activation has not been explored. In this article, we show that C57BL/6 mice containing the New Zealand Black Slam locus have profound alterations in Ly108, CD150, and Ly9 expression that is associated with iNKT cell hyporesponsiveness. This loss of function was only apparent when dendritic cells and iNKT cells had a loss of SLAM receptor expression. Using small interfering RNA knockdowns and peptide-blocking strategies, we demonstrated that trans-Ly108 interactions between dendritic cells and iNKT cells are critical for robust activation. LY108 costimulation similarly increased human iNKT cell activation. Thus, in addition to its established role in iNKT cell ontogeny, Ly108 regulates iNKT cell function in mice and humans.
Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation
Authors: Tao Jianli , Zhang Xiao-Wei , Jin Jianshi , Du Xiao-Xia , Lian Tengfei , Yang Jing , Zhou Xiang , Jiang Zhengfan , Su Xiao-Dong 
Published: April 2017

Abstract
The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediates innate immune responses against invading pathogens, or against self-dsDNA, which causes autoimmune disorders. Upon nonspecific binding of cytosolic B–form DNA, cGAS synthesizes the second messenger 2′3′-cGAMP and triggers STING-dependent signaling to produce type I IFNs. The cGAS comprises less-conserved N-terminal residues and highly conserved nucleotidyltransferase/Mab21 domains. The function and structure of the well-conserved domains have been extensively studied, whereas the physiological function of the N-terminal domain of cGAS is largely uncharacterized. In this study we used a single-molecule technique combined with traditional biochemical and cellular assays to demonstrate that binding of nonspecific dsDNA by the N-terminal domain of cGAS promotes its activation. We have observed that the N terminus of human cGAS (hcGAS-N160) undergoes secondary structural change upon dsDNA binding in solution. Furthermore, we showed that the hcGAS-N160 helps full length hcGAS to expand the binding range on λDNA and facilitates its binding efficiency to dsDNA compared with hcGAS without the 160 N-terminal residues (hcGAS-d160). More importantly, hcGAS-N160 endows full length hcGAS relatively higher enzyme activity and stronger activation of STING/IRF3-mediated cytosolic DNA signaling. These findings strongly indicate that the N-terminal domain of cGAS plays an important role in enhancing its function.