bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical coherence tomography angiography enhances the detection of optic nerve damage in multiple sclerosis
Authors: Spain Rebecca I , Liu Liang , Zhang Xinbo , Jia Yali , Tan Ou , Bourdette Dennis , Huang David 
Published: August 2017

BackgroundQuantitative assessment of optic nerve damage is important in the evaluation of optic neuritis (ON) and multiple sclerosis (MS).ObjectiveTo detect optic nerve damage using optical coherence tomography (OCT) and OCT angiography in MS.MethodsPeripapillary retinal nerve fibre layer (NFL) thickness, macular ganglion cell complex (GCC) thickness and Optic Nerve Head Flow Index (ONH-FI) were measured. The ONH-FI was defined as flow signal averaged over the optic disc. Diagnostic accuracy was evaluated by the area under the receiver-operating characteristics curve (AROC).ResultsSixty-eight eyes of 45 MS participants and 55 eyes of 32 healthy controls (HCs) were analysed. Of MS eyes, 25 had a history of ON (MS+ON) and 43 didn’t (MS−ON). MS−ON and MS+ON eyes had reductions in ONH-FI (p=0.031 and p=0.001, respectively), GCC thickness (p=0.245 and p<0.001, respectively), and NFL thickness (p=0.003 and p=0.024, respectively), compared with HCs. The highest AROC (0.940) was achieved by the logistic regression combination of all three variables, which was significantly higher than other variables (p=0.018).ConclusionMS produces both retinal structural loss and decreased ONH perfusion in MS eyes with and without history of ON. The combination of perfusion and structural measurements enhances detection of optic nerve damage in MS. OCT angiography may be a useful additional retinal marker in evaluation of ON in MS.
Intermittent apnea elicits inactivity-induced phrenic motor facilitation via a retinoic acid- and protein synthesis-dependent pathway
Authors: Baertsch Nathan A. , Baker Tracy L. 
Published: August 2017

Respiratory motoneuron pools must provide rhythmic inspiratory drive that is robust and reliable, yet dynamic enough to respond to respiratory challenges. One form of plasticity that is hypothesized to contribute to motor output stability by sensing and responding to inadequate respiratory neural activity is inactivity-induced phrenic motor facilitation (iPMF), an increase in inspiratory output triggered by a reduction in phrenic synaptic inputs. Evidence suggests that mechanisms giving rise to iPMF differ depending on the pattern of reduced respiratory neural activity (i.e., neural apnea). A prolonged neural apnea elicits iPMF via a spinal TNF-α-induced increase in atypical PKC activity, but little is known regarding mechanisms that elicit iPMF following intermittent neural apnea. We tested the hypothesis that iPMF triggered by intermittent neural apnea requires retinoic acid and protein synthesis. Phrenic nerve activity was recorded in urethane-anesthetized and -ventilated rats treated intrathecally with an inhibitor of retinoic acid synthesis (4-diethlyaminobenzaldehyde, DEAB), a protein synthesis inhibitor (emetine), or vehicle (artificial cerebrospinal fluid) before intermittent (5 episodes, ~1.25 min each) or prolonged (30 min) neural apnea. Both DEAB and emetine abolished iPMF elicited by intermittent neural apnea but had no effect on iPMF elicited by a prolonged neural apnea. Thus different patterns of reduced respiratory neural activity elicit phenotypically similar iPMF via distinct spinal mechanisms. Understanding mechanisms that allow respiratory motoneurons to dynamically tune their output may have important implications in the context of respiratory control disorders that involve varied patterns of reduced respiratory neural activity, such as central sleep apnea and spinal cord injury.NEW & NOTEWORTHY We identify spinal retinoic acid and protein synthesis as critical components in the cellular cascade whereby repetitive reductions in respiratory neural activity elicit rebound increases in phrenic inspiratory activity.
Asymmetric vestibular stimulation reveals persistent disruption of motion perception in unilateral vestibular lesions
Authors: Panichi R. , Faralli M. , Bruni R. , Kiriakarely A. , Occhigrossi C. , Ferraresi A. , Bronstein A. M. , Pettorossi V. E. 
Published: August 2017

Self-motion perception was studied in patients with unilateral vestibular lesions (UVL) due to acute vestibular neuritis at 1 wk and 4, 8, and 12 mo after the acute episode. We assessed vestibularly mediated self-motion perception by measuring the error in reproducing the position of a remembered visual target at the end of four cycles of asymmetric whole-body rotation. The oscillatory stimulus consists of a slow (0.09 Hz) and a fast (0.38 Hz) half cycle. A large error was present in UVL patients when the slow half cycle was delivered toward the lesion side, but minimal toward the healthy side. This asymmetry diminished over time, but it remained abnormally large at 12 mo. In contrast, vestibulo-ocular reflex responses showed a large direction-dependent error only initially, then they normalized. Normalization also occurred for conventional reflex vestibular measures (caloric tests, subjective visual vertical, and head shaking nystagmus) and for perceptual function during symmetric rotation. Vestibular-related handicap, measured with the Dizziness Handicap Inventory (DHI) at 12 mo correlated with self-motion perception asymmetry but not with abnormalities in vestibulo-ocular function. We conclude that 1) a persistent self-motion perceptual bias is revealed by asymmetric rotation in UVLs despite vestibulo-ocular function becoming symmetric over time, 2) this dissociation is caused by differential perceptual-reflex adaptation to high- and low-frequency rotations when these are combined as with our asymmetric stimulus, 3) the findings imply differential central compensation for vestibuloperceptual and vestibulo-ocular reflex functions, and 4) self-motion perception disruption may mediate long-term vestibular-related handicap in UVL patients.NEW & NOTEWORTHY A novel vestibular stimulus, combining asymmetric slow and fast sinusoidal half cycles, revealed persistent vestibuloperceptual dysfunction in unilateral vestibular lesion (UVL) patients. The compensation of motion perception after UVL was slower than that of vestibulo-ocular reflex. Perceptual but not vestibulo-ocular reflex deficits correlated with dizziness-related handicap.
Personalized Medicine–Based Approach to Model Patterns of Chemoresistance and Tumor Recurrence Using Ovarian Cancer Stem Cell Spheroids
Authors: Raghavan Shreya , Mehta Pooja , Ward Maria R. , Bregenzer Michael E. , Fleck Elyse M. A. , Tan Lijun , McLean Karen , Buckanovich Ronald J. , Mehta Geeta 
Published: August 2017

Abstract
Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. To screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform.
Experimental Design: We initiated spheroids with primary aldehyde dehydrogenase–positive (ALDH+) CD133+ ovarian cancer stem cells (OvCSC) from different patient samples and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immunodeficient mice. Drug responses to cisplatin and ALDH-targeting compound or JAK2 inhibitor determined whether the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor reemergence in a personalized manner.
Results: OvCSC spheroids from different patients exhibited varying and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with a single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression, whereas those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH+ cells.
Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology and model tumor reemergence to identify new targeted therapeutics from an effective personalized medicine standpoint. Clin Cancer Res; 23(22); 6934–45. ©2017 AACR.
Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE
Authors: Alexander Brian M. , Ba Sujuan , Berger Mitchel S. , Berry Donald A. , Cavenee Webster K. , Chang Susan M. , Cloughesy Timothy F. , Jiang Tao , Khasraw Mustafa , Li Wenbin , Mittman Robert , Poste George H. , Wen Patrick Y. , Yung W.K. Alfred , Barker Anna D. 
Published: August 2017

Abstract
Glioblastoma (GBM) is a deadly disease with few effective therapies. Although much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is composed of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage to support registration. Therapeutic arms with biomarkers may be added to the trial over time, while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice. Clin Cancer Res; 24(4); 737–43. ©2017 AACR.
Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists
Authors: Eerenberg Elise , Cohen Alexander , Middeldorp Saskia , Raskob Gary , Büller Harry , Bleker Suzanne , Brekelmans Marjolein 
Published: August 2017

SummaryFactor Xa (fXa)-inhibitors are as effective and safer than vitamin-K–antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35% and 48% of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95% CI 0.36–0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22% of the fXa inhibitor and 25% of the VKA associated bleeds (OR 0.83, 95% CI 0.47–1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.
To Naturalize is to Differentiate
Authors: Ruper Stefani 
Published: August 2017

AbstractMany scholars have expressed fears that naturalism will homogenize religion, thereby reifying the concept and distorting the academy’s perception of local cultures. Yet this fear is misplaced. In fact, recent advances in cognitive science, most notably regarding the development of interactional theories of cognition, lend significant support to conceptualizing religion heterogeneously. In this paper I first explore Russell McCutcheon’s rationale for fearing naturalism. I then obviate McCutcheon’s fears by demonstrating how the interactionalist perspective in cognitive science both promotes a heterogeneous understanding of human behavior as well as refutes sui generis religion. I conclude by recommending fusing insights from interactionalism with a ground-up, sociological approach to “religion” such as Timothy Fitzgerald’s, which results in research methodology that is appropriately sensitive to the natural differences of behavior that have been historically identified as religious.
A New Approach to Streaming Data from the Cloud
Authors: Robinson Niall H. , Prudden Rachel , Arribas Alberto 
Published: August 2017

AbstractEnvironmental datasets are becoming so large that they are increasingly being hosted in the compute cloud, where they can be efficiently analyzed and disseminated. However, this necessitates new ways of efficiently delivering environmental information across the Internet to users. We visualised a big atmospheric dataset in a web page by repurposing techniques normally used to stream HD video. You can try the prototype at http://demo.3dvis.informaticslab.co.uk/ng-3d-vis/apps/desktop/ or watch a video demonstration at www.youtube.com/watch?v=pzvk1ZNMvFY.
Vascular complications following intra-aortic balloon pump implantation: an updated review
Authors: de Jong Monique M , Lorusso Roberto , Al Awami Fatima , Matteuci Francesco , Parise Orlando , Lozekoot Pieter , Bonacchi Massimo , Maessen Jos G , Johnson Daniel M , Gelsomino Sandro 
Published: August 2017

Background: The use of the intra-aortic balloon pump (IABP) as a support device remains controversial due to the fact that a number of studies have shown no benefit in end mortality whilst using this device. One of the reasons for this could be the increase in vascular complications when using the pump. Therefore, the aim of the present review was to assess the current literature available with regards to IABP vascular complications during the clinical situation. Methods: A literature search was performed, searching for IABP complications in adult human studies between 1990 and 2016. Results: A total of 20 reports were identified as fitting the criteria of this study. The majority of vascular complications were limb ischemia, bleeding or mesenteric ischemia. The overall incidence of vascular complications ranged from 0.94% to 31.1%. Diabetes, peripheral vascular disease and hypertension, as well as smoking were all identified as risk factors for complications following IABP. Furthermore, studies supported the use of sheathless balloon insertion to reduce the risk of complications. Conclusion: Major vascular complications, including limb and mesenteric ischemia as well as bleeding and hemorrhage, have been associated with IABP. However, the incidence of these complications was generally low. Further studies are still required to truly understand the risk/benefit associated with the use of IABP.
Quantitative and qualitative MRI evaluation of cerebral small vessel disease in an elderly population: a longitudinal study
Authors: Nylander Ruta , Fahlström Markus , Rostrup Egill , Kullberg Joel , Damangir Soheil , Ahlström Håkan , Lind Lars , Larsson Elna-Marie 
Published: August 2017

Background Cerebral white matter hyperintensities (WMHs), lacunes, and microbleeds are seen on magnetic resonance imaging (MRI) in small vessel disease (SVD). Purpose To assess SVD on MRI and its evolution over five years in an elderly population and to investigate whether relative cerebral blood flow (rCBF) at baseline was related to the progression of white matter (WM) lesions. Material and Methods In a population-based study, 406 participants aged 75 years underwent morphological MRI of the brain and 252 of them again at age 80 years. At age 75 years, a perfusion scan was also done. WMHs were evaluated qualitatively (visual scoring) and quantitatively (CASCADE software). Lacunes and microbleeds were counted. Results A significant progression of the WMH score and WMH volume occurred over five years ( P < 0.0001). New lacunes were seen in 10%. Participants with new lacunes at age 80 years showed a more pronounced increase in WMHs (P < 0.0001). Microbleeds were present in 14% at age 75 years. The visual WMH score was significantly associated with the presence of microbleeds ( P < 0.0001). There was no relationship between total WM rCBF and WMH volume at age 75 years, and no significant associations between regional or total rCBF at age 75 years and changes in WMH volume over five years. The total WM and GM volume decreased significantly between the ages of 75 and 80 years ( P < 0.0001). Conclusion MRI manifestations of SVD progressed over five years in an elderly population (age range = 75–80 years). rCBF was not associated with WMH volume or progression of WMH volume.
Net stock issuance anomaly and cash flow explanation: A research note
Authors: Li Alan Meng , Naidu Dharmendra , Navissi Farshid , Ranjeeni Kumari 
Published: August 2017

Prior studies show that net stock issuance is negatively associated with the cross section of future stock returns, reflecting a market anomaly. Our study provides empirical evidence on whether cash flow can mitigate such anomaly. Consistent with prior research, we initially provide evidence of the anomaly in our sample and that the anomaly persists in the presence of cash flow. We then decompose net stock issuance into stock issues and stock repurchases and find that the anomaly is only driven by stock issues but not stock repurchases and that the stock issues’ anomaly persists even in the presence of cash flow. JEL Classification: G12, G14
Inhibition of monoacylglycerol lipase: Another signalling pathway for potential therapeutic targets in migraine?
Authors: Greco Rosaria , Demartini Chiara , Zanaboni Anna Maria , Berliocchi Laura , Piomelli Daniele , Tassorelli Cristina 
Published: August 2017

Background Drugs that modulate endocannabinoid signalling are effective in reducing nociception in animal models of pain and may be of value in the treatment of migraine. Methods We investigated the anti-nociceptive effects of inhibition of monoacylglycerol lipase (MGL), a key enzyme in the hydrolysis of the 2-arachidonoylglycerol, in a rat model of migraine based on nitroglycerin (NTG) administration. We evaluated c-fos expression in specific brain areas and nociceptive behavior in trigeminal and extra-trigeminal body areas. Results URB602, a reversible MGL inhibitor, did not show any analgesic effect in the tail flick test, but it inhibited NTG-induced hyperalgesia in both the tail flick test and the formalin test applied to the hind paw or to the orofacial area. Quite unexpectedly, URB602 potentiated formalin-induced hyperalgesia in the trigeminal area when used alone. The latter result was also confirmed using a structurally distinct, irreversible MGL inhibitor, JZL184. URB602 did not induce neuronal activation in the area of interest, but significantly reduced the NTG-induced neuronal activation in the ventrolateral column of the periaqueductal grey and the nucleus trigeminalis caudalis. Conclusions These findings support the hypothesis that modulation of the endocannabinoid system may be a valuable approach for the treatment of migraine. The topographically segregated effect of MGL inhibition in trigeminal/extra-trigeminal areas calls for further mechanistic research.
Hematologic, Biochemical, and Endocrine Parameters in Horses With Tooth Resorption and Hypercementosis
Authors: Earley Edward T. , Rawlinson Jennifer R. , Baratt Robert M. , Galloway Stephen S. , Smedley Rebecca C. , Scarlett Janet M. , Refsal Kent R. , Dotzel Allison. R. , Cox Victor. S. , Perkins Gillian A. 
Published: August 2017

Background: Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a frequently diagnosed condition in adult horses. The underlying etiology is still unknown. Hematologic, biochemical, and endocrine values have not been reported in EOTRH-affected horses. Objectives: The main objective of the study was to describe the hematologic, biochemical, and endocrine parameters in horses with EOTRH. Study Design: Descriptive cross-sectional study of client-owned animals with EOTRH. Methods: A complete blood count, biochemistry panel, and endocrine profile were performed in horses diagnosed with EOTRH. Diagnosis was based on oral and radiographic examination findings and confirmed with histopathology. Results: Eighteen horses with EOTRH aged 10 to 32 years from various regions of the United States were sampled. The only consistent abnormality on the complete blood cell count and chemistry panel was hypoalbuminemia (88%). Endocrine parameters demonstrated no major abnormalities in the functioning of the thyroid and pituitary pars intermedia. The parathyroid hormone concentration was increased in 7 (47%) of 15 horses with an elevated 25-hydroxy vitamin D in 3 (17%) of 17 horses. Main Limitations: The main limitations of this study are the small sample size and lack of age-matched and management-matched control horses. Conclusions: The relevance of elevated parathyroid hormone in this study cannot be determined due to the lack of age-based controls and large population studies. With the small population evaluated in this study, there are no obvious hematological, biochemical, and endocrine changes evident. Further evaluation with signalment-matched controls will be necessary to evaluate some trends noted in the laboratory values.
The intertwined relationship between patient education, hospital waiting times and hospital utilization
Authors: Schulz Maike 
Published: August 2017

Background Hospital waiting times are established instruments to ration healthcare when resources are scarce. However, higher educated patients may be better able to influence access to, and exit from, hospital care when waiting times are long. Methods Based on a representative sample of 11 European countries from the Survey of Health, Ageing and Retirement in Europe (SHARE) collected in 2004/2005, this paper investigates whether the relationship between individual educational background and hospital utilization depends on the prevalent hospital waiting times in a country. Logistic regression with interaction effects between individual education and average waiting times per country are conducted. Results Primary education is significantly associated with a lower probability of visiting a hospital overnight (OR = 0.88) compared to secondary and tertiary education. Patients in countries with long waiting times had shorter stays (OR = 0.92), and the significant interaction effect indicates that lower educated patients have longer hospital stays than higher educated patients in countries where waiting times tend to be long (OR = 1.06). Conclusions While the findings imply that educational differences exist with regard to hospital care, future research should investigate potential underlying mechanisms, i.e. patients' perceived access barriers and the perceived quality of hospital treatment.