bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings From a Randomized Trial
Authors: Bernstein David I. , Wald Anna , Warren Terri , Fife Kenneth , Tyring Stephen , Lee Patricia , Van Wagoner Nick , Magaret Amalia , Flechtner Jessica B. , Tasker Sybil , Chan Jason , Morris Amy , Hetherington Seth 
Published: January 2017

Abstract

Background.
Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant.

Methods.
Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose.

Results.
One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P &lt; .001] and from 15.0% to 10.3% for 100 µg [P &lt; .001]). Lesion rates were also significantly (P &lt; .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses.

Conclusions.
GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates.

Clinical Trials Registration.
NCT01667341 (funded by Genocea).
The spleen is the site where mast cells are induced in the development of food allergy
Authors: Toyoshima Shota , Wakamatsu Ei , Ishida Yasuo , Obata Yuuki , Kurashima Yosuke , Kiyono Hiroshi , Abe Ryo 
Published: January 2017

Abstract
It has been reported that splenic immune responses play pivotal roles in the development of allergic diseases; however, the precise role of the spleen remains unclear. Herein, we demonstrated a novel role of the spleen in the pathogenesis of food allergy (FA). We found that mast cells (MCs) developed from progenitor cells present in spleen during an antigen-specific T-cell response in vitro. In a Th2 response-mediated FA model, significant expansion of MCs was also observed in spleen. The incidence of allergic diarrhea was profoundly reduced in splenectomized mice, whereas adoptive transfer of in vitro-induced splenic MCs into these mice restored allergic symptoms, suggesting that the splenic MCs functioned as the pathogenic cells in the development of FA. The in vitro-generated MCs required not only IL-3 but also IFN-γ, and treatment of FA-induced mice with anti-IFN-γ antibody suppressed expansion of MCs in spleen as well as diarrhea development, highlighting that IFN-γ in the spleen orchestrated the development of FA, which was followed by a Th2 response in the local lesion. Overall, we propose that the role of the spleen in the development of FA is to provide a unique site where antigen-specific T cells induce development of pathogenic MCs.
Design and evaluation of a pharmacogenomics information resource for pharmacists
Authors: Romagnoli Katrina M , Boyce Richard D , Empey Philip E , Ning Yifan , Adams Solomon , Hochheiser Harry 
Published: January 2017

Abstract
Objective: To develop and evaluate a pharmacogenomics information resource for pharmacists.
Materials and Methods: We built a pharmacogenomics information resource presenting Food and Drug Administration (FDA) drug product labelling information, refined it based on feedback from pharmacists, and conducted a comparative usability evaluation, measuring task completion time, task correctness and perceived usability. Tasks involved hypothetical clinical situations requiring interpretation of pharmacogenomics information to determine optimal prescribing for specific patients.
Results: Pharmacists were better able to perform certain tasks using the redesigned resource relative to the Pharmacogenomic Knowledgebase (PharmGKB) and the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. On average, participants completed tasks in 107.5 s using our resource, compared to 188.9 s using PharmGKB and 240.2 s using the FDA table. Using the System Usability Scale, participants rated our resource 79.62 on average, compared to 53.27 for PharmGKB and 50.77 for the FDA table. Participants found the correct answers for 100% of tasks using our resource, compared to 76.9% using PharmGKB and 69.2% using the FDA table.
Discussion: We present structured, clinically relevant pharmacogenomic FDA drug product label information with visualizations to help explain the relationships between gene variants, drugs, and phenotypes. The results from our evaluation suggest that user-centered interfaces for pharmacogenomics information can increase ease of access and comprehension.
Conclusion: A clinician-focused pharmacogenomics information resource can answer pharmacogenomics-related medication questions faster, more correctly, and more easily than widely used alternatives, as perceived by pharmacists.
Comparison of three commercial knowledge bases for detection of drug-drug interactions in clinical decision support
Authors: Fung Kin Wah , Kapusnik-Uner Joan , Cunningham Jean , Higby-Baker Stefanie , Bodenreider Olivier 
Published: January 2017

AbstractObjective: To compare 3 commercial knowledge bases (KBs) used for detection and avoidance of potential drug-drug interactions (DDIs) in clinical practice.Methods: Drugs in the DDI tables from First DataBank (FDB), Micromedex, and Multum were mapped to RxNorm. The KBs were compared at the clinical drug, ingredient, and DDI rule levels. The KBs were evaluated against a reference list of highly significant DDIs from the Office of the National Coordinator for Health Information Technology (ONC). The KBs and the ONC list were applied to a prescription data set to simulate their use in clinical decision support.Results: The KBs contained 1.6 million (FDB), 4.5 million (Micromedex), and 4.8 million (Multum) clinical drug pairs. Altogether, there were 8.6 million unique pairs, of which 79% were found only in 1 KB and 5% in all 3 KBs. However, there was generally more agreement than disagreement in the severity rankings, especially in the contraindicated category. The KBs covered 99.8–99.9% of the alerts of the ONC list and would have generated 25 (FDB), 145 (Micromedex), and 84 (Multum) alerts per 1000 prescriptions.Conclusion: The commercial KBs differ considerably in size and quantity of alerts generated. There is less variability in severity ranking of DDIs than suggested by previous studies. All KBs provide very good coverage of the ONC list. More work is needed to standardize the editorial policies and evidence for inclusion of DDIs to reduce variation among knowledge sources and improve relevance. Some DDIs considered contraindicated in all 3 KBs might be possible candidates to add to the ONC list.
Does MIS Surgery Allow for Shorter Constructs in the Surgical Treatment of Adult Spinal Deformity?
Authors: Uribe Juan S. , Beckman Joshua , Mummaneni Praveen V. , Okonkwo David , Nunley Pierce , Wang Michael Y. , Jr Gregory M. Mundis , Park Paul , Eastlack Robert , Anand Neel , Kanter Adam , Lamarca Frank , Fessler Richard , Shaffrey Chris I. , Lafage Virginie , Chou Dean , Deviren Vedat ,   The MIS-ISSG Group
Published: January 2017

Abstract

BACKGROUND: The length of construct can potentially influence perioperative risks in adult spinal deformity (ASD) surgery. A head-to-head comparison between open and minimally invasive surgery (MIS) techniques for treatment of ASD has yet to be performed.

OBJECTIVE: To examine the impact of MIS approaches on construct length and clinical outcomes in comparison to traditional open approaches when treating similar ASD profiles.

METHODS: Two multicenter databases for ASD, 1 involving MIS procedures and the other open procedures, were propensity matched for clinical and radiographic parameters in this observational study. Inclusion criteria were ASD and minimum 2-year follow-up. Independent t-test and chi-square test were used to evaluate and compare outcomes.

RESULTS: A total of 1215 patients were identified, with 84 patients matched in each group. Statistical significance was found for mean levels fused (4.8 for circumferential MIS [cMIS] and 10.1 for open), mean interbody fusion levels (3.6 cMIS and 2.4 open), blood loss (estimated blood loss 488 mL cMIS and 1762 mL open), and hospital length of stay (6.7 days cMIS and 9.7 days open). There was no significant difference in preoperative radiographic parameters or postoperative clinical outcomes (Owestry Disability Index and visual analog scale) between groups. There was a significant difference in postoperative lumbar lordosis (43.3° cMIS and 49.8° open) and pelvic incidence-lumbar lordosis correction (10.6° cMIS and 5.2° open) in the open group. There was no significant difference in reoperation rate between the 2 groups.

CONCLUSION: MIS techniques for ASD may reduce construct length, reoperation rates, blood loss, and length of stay without affecting clinical and radiographic outcomes when compared to a similar group of patients treated with open techniques.
Bending the Cost Curve—Establishing Value in Spine Surgery
Authors: Parker Scott L. , Chotai Silky , Devin Clinton J. , Tetreault Lindsay , Mroz Thomas E. , Brodke Darrel S. , Fehlings Michael G. , McGirt Matthew J. 
Published: January 2017

Abstract

BACKGROUND: As publically promoted by all stakeholders in health care reform, prospective outcomes registry platforms lie at the center of all current evidence-driven value-based models.

OBJECTIVE: To demonstrate the variability in outcomes and cost at population level and individual patient level for patients undergoing spine surgery for degenerative diseases.

METHODS: Retrospective analysis of prospective longitudinal spine registry data was conducted. Baseline and postoperative 1-year patient-reported outcomes were recorded. Previously published minimal clinically important difference for Oswestry Disability Index (14.9) was used. Back-related resource utilization and quality-adjusted life years (QALYs) were assessed. Variations in outcomes and cost were analyzed at population level and at the individual patient level.

RESULTS: A total of 1454 patients were analyzed. There was significant improvement in patient-reported outcomes at postoperative 1 year (P < .0001). For patients demonstrating health benefit at population level, 12.5%, n = 182 of patients experienced no gain from surgery and 38%, n = 554 failed to achieve minimal clinically important difference. Mean 1-year QALY-gained was 0.29; 18% of patients failed to report gain in QALY. For patients with 2-year follow-up, surgery resulted in 0.62 QALY-gained at average direct cost of $28 953. A wide variation in both QALY-gained and cost was observed.

CONCLUSION: Spine treatments that on average are cost-effective may have wide variability in value at the individual patient level. The variability demonstrated here represents an opportunity, through registries, to identify specific care that may be less effective, and refine patient-specific care delivery and indications to drive overall group-level treatment value. Understanding value of spine care at an individualized as well as population level will allow clinicians, and eventually payers, to better target resources for improving care for nonresponders, ultimately driving up the average health for the whole population.
Novel Osteobiologics and Biomaterials in the Treatment of Spinal Disorders
Authors: Hsu Wellington K. , Goldstein Christina L , Shamji Mohammed F. , Cho Sam K. , Arnold Paul M. , Fehlings Michael G. , Mroz Tom E. 
Published: January 2017

Abstract
Spinal osteobiologics have evolved substantially in this century after the development of many product categories such as growth factors, allograft, and stem cells. The indications for the use of novel biologics within spine surgery are rapidly expanding as the mechanism of each is elucidated. While the knowledge base of bone morphogenetic protein increases with each subsequent year, the application of new nanotechnology and cell-based strategies are being reported. This review will discuss the most recent data in novel osteobiologics, and where we could use future study.
Neurosurgical Practice in Transition: A Review
Authors: Kim Dong H. , Dagi T. Forcht , Bean James R. 
Published: January 2017

Abstract
Neurosurgery is experiencing a period of acute change driven by 2 forces: (1) the perception that the healthcare system in the United States is wasteful and that patients are receiving low “value” care, (2) the belief that quality and long-term outcomes can be measured accurately. We believe 3 important shifts will emerge as a result of these forces. First, payment models will change. They will become anchored to a concept of population health, with capitation payments on a per-patient basis going to provider entities that undertake financial risk. Second, fee-for-service payments will be tied increasingly to administrative and clinical quality measures. Finally, out-of-pocket costs for patients will increase and affect both treatment decisions and willingness to participate in restrictive health care networks. In this review, we describe these changes and discuss possible consequences. We note the changing demographics of neurosurgical practices. Overall, independent private practices, managed by the neurosurgeons, will decline. The proportion of fee-for-service cases will decrease while cases reimbursed through capitation will increase. Physician integration with provider organizations, whether via full employment, a “lease,” or some other arrangement, will also increase. We note the increasing importance of quality measures, and how they are likely to affect neurosurgical practices and reimbursement. We describe the advantages and disadvantages of fee-for-service and population health; describe opportunities and risks arising from these transitions; and outline strategies to thrive in a changing environment.
Prediction of Cerebral Hyperperfusion After Carotid Artery Stenting by Cerebral Angiography and Single-Photon Emission Computed Tomography Without Acetazolamide Challenge
Authors: Ohta Tsuyoshi , Nakahara Ichiro , Matsumoto Shoji , Ishibashi Ryota , Miyata Haruka , Nishi Hidehisa , Watanabe Sadayoshi , Nagata Izumi 
Published: January 2017

Abstract

BACKGROUND: Definitive preoperative predictors of cerebral hyperperfusion following carotid artery stenting are yet to be established.

OBJECTIVE: To determine the preprocedural risk factors for cerebral hyperperfusion phenomenon (CHP) following carotid artery stenting.

METHODS: Patients undergoing preprocedural single-photon emission computed tomography (SPECT) and cerebral angiography prior to their first carotid artery stenting were monitored for occurrence of CHP. In addition to patient characteristics, we investigated imaging parameters, such as cerebral blood flow, cerebral vasoreactivity, and asymmetry index on SPECT, and presence of near occlusion and leptomeningeal anastomosis on cerebral angiography.

RESULTS: Out of 100 patients (mean age: 73.0 ± 7.6 years; 85 men), 9 developed CHP. On multivariate logistic regression analysis, asymmetry index (%) on SPECT (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.70-0.93, P = .003) and presence of leptomeningeal anastomosis on cerebral angiography (OR 72.1, 95% CI 3.52-1480, P = .006) were independent predictors of CHP.

CONCLUSION: Combined use of cerebral angiography and SPECT may obviate the need for acetazolamide challenge to predict the risk of CHP following carotid artery stenting.
Multimodality Treatment of Skull Base Chondrosarcomas: The Role of Histology Specific Treatment Protocols
Authors: Raza Shaan M. , Gidley Paul W. , Meis Jeanne M. , Grosshans David R. , Bell Diana , DeMonte Franco 
Published: January 2017

Abstract

BACKGROUND: Limited data exist to guide the multimodality management of chondrosarcomas (CSAs) arising in the skull base.

OBJECTIVE: To determine the impact of histological subtype/grade on progression-free survival (PFS) and the indications for surgery, radiation, and chemotherapy based on histology.

METHODS: A retrospective review was performed of 37 patients (conventional type: 81%, mesenchymal: 16.2%, dedifferentiated: 2.7%) treated at The University of Texas M.D. Anderson Cancer Center. Of the conventional subtype, 23% were grade 1, 63% were grade 2, and 14% were grade 3. In addition to surgery, mesenchymal/dedifferentiated CSAs (18% of the cohort) underwent neoadjuvant chemotherapy and 48.6% of the overall cohort received adjuvant radiotherapy. Histological grade/subtype and treatment factors were assessed for impact on median PFS (primary outcome).

RESULTS: Conventional subtype vs mesenchymal/dedifferentiated was positively associated with median PFS (166 vs 24 months, P < .05). Increasing conventional grade inversely correlated with median PFS (P < .05). Gross total resection positively impacted PFS in conventional CSAs (111.8 vs 42.9 months, P = .201) and mesenchymal/dedifferentiated CSAs (58.2 vs 1.0 month, P < .05). Adjuvant radiotherapy significantly impacted PFS in conventional grades 2 and 3 (182 vs 79 months, P < .05) and a positive trend with mesenchymal/dedifferentiated CSAs (43.5 vs 22.0 months). Chemotherapy improved PFS for mesenchymal/dedifferentiated CSAs (50 vs 9 months, P = .089).

CONCLUSION: There is a potential need for histological subtype/grade specific treatment protocols. For conventional CSAs, surgery alone provides optimal results grade 1 CSAs, while resection with adjuvant radiotherapy yields the best outcome for grade 2 and 3 CSAs. Improvements in PFS seen with neoadjuvant therapy in mesenchymal/dedifferentiated CSAs indicate a potential role for systemic therapies. Larger studies are necessary to confirm the proposed treatment protocols.
Health-Related Quality of Life Dynamics 2 Years Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study Using EQ-5D
Authors: von Vogelsang Ann-Christin , Thelin Eric Peter , Hakim Ramil , Svensson Mikael 
Published: January 2017

Abstract

BACKGROUND
Previous studies have shown that aneurysmal subarachnoid hemorrhage (aSAH) affects health-related quality of life (HRQoL) to a large extent. However, longitudinal studies on HRQoL after aSAH are scarce, and there is limited knowledge whether different HRQoL dimension scores change over time, and if so, if the scoring differs from results from the general population.

OBJECTIVE
To evaluate HRQoL dynamics over time, 2 years following aSAH, and compare the results with general population.

METHODS
In a prospective cohort design, 88 consecutive aSAH patients (85% of eligible) were followed up with the generic HRQoL instrument EQ-5D at 3 time points: 6 months, 1 year, and 2 years after the onset. Data were collected in 2006 to 2009, and the results were compared with a general population sample from the Stockholm Public Health Survey 2006, matched by age and sex.

RESULTS
Overall HRQoL in the aSAH sample was stationary over time. Improved function was only found in the usual activities dimension (P = .026). HRQoL was most affected in participants reporting comorbidity. Compared with the general population, women in the aSAH sample reported significantly more problems in 4 out of 5 dimensions (mobility, self-care, usual activities, and anxiety/depression). Men in the aSAH sample reported significantly more problems in the usual activities dimension in comparison to the general population.

CONCLUSION
HRQoL is stationary during the first 2 years following aSAH, and is significantly worse when compared to the general population. Rehabilitation efforts should be initiated shortly after hospitalization.
Endovascular Treatment of Middle Cerebral Artery M2 Occlusion Strokes: Clinical and Procedural Predictors of Outcomes
Authors: Mokin Maxim , Primiani Christopher T , Ren Zeguang , Kan Peter , Duckworth Edward , Turner Raymond D , Turk Aquilla S , Fargen Kyle M , Dabus Guilherme , Linfante Italo , Dumont Travis M , Brasiliense Leonardo B C , Shallwani Hussain , Snyder Kenneth V , Siddiqui Adnan H , Levy Elad I 
Published: January 2017

Abstract

BACKGROUND
Patients with strokes from M2 segment middle cerebral artery (MCA) occlusion have been underrepresented in recent randomized trials of endovascular therapy.

OBJECTIVE
To better understand the clinical, imaging, and procedural predictors of successful recanalization and clinical outcomes in this population of patients.

METHODS
We performed a multicenter retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics.

RESULTS
One hundred and seventeen patients were included in analysis (median admission National Institutes of Health stroke scale [NIHSS] score 15, mean age 67.0 ± 14.5, 42% females). Good clinical outcome at 3 months (modified Rankin scale [mRS] ≤ 2) was achieved in 56% of patients. Treatment beyond 6 h of symptoms onset (P = .69, OR 0.80, 95% CI 0.38-1.73) and age over 80 (P = .47, OR 0.65, 95% CI 0.25-1.70) were not predictive of poor outcome. NIHSS > 15 was a strong predictor of clinical outcome, based on mRS distribution at 3 months (P = .0085, OR 0.35, 95% CI 0.16-0.74). Direct aspiration and primary stent retriever thrombectomy approaches showed similar radiographic and clinical success rates.

CONCLUSION
Advanced age and time to treatment beyond 6 h from symptom onset were not predictive of clinical outcome with thrombectomy. NIHSS score above 15 was a strong predictor of outcome. Direct aspiration and primary stent retriever thrombectomy showed similar efficacy.
Exceptional preservation of soft tissue in a new specimen of Eoconfuciusornis and its biological implications
Authors: Zheng Xiaoting , O’Connor Jingmai K. , Wang Xiaoli , Pan Yanhong , Wang Yan , Wang Min , Zhou Zhonghe 
Published: January 2017

Abstract
We report on an exceptional specimen of Eoconfuciusornis preserving rare soft-tissue traces of the ovary and wing. Ovarian follicles preserve a greater hierarchy than observed in Jeholornis and enantiornithines, suggesting confuciusornithiforms evolved higher rates of yolk deposition in parallel with the neornithine lineage. The preserved soft tissues of the wing indicate the presence of a propatagium and postpatagium, whereas an alular patagium is absent. Preserved remnants of the internal support network of the propatagium bear remarkable similarity to that of living birds. Soft tissue suggests the confuciusornithiform propatagium could maintain a cambered profile and generate lift. The feathers of the wing preserve remnants of their original patterning; however, this is not strongly reflected by observable differences under scanning electron microscopy (SEM). The tail plumage lacks elongate rectrices, suggesting that the earliest known confuciusornithiforms were sexually dimorphic in their plumage.