bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional characterization of a mouse model for central post-stroke pain
Authors: Gritsch Simon , Bali Kiran Kumar , Kuner Rohini , Vardeh Daniel 
Published: March 2016

Background Stroke patients often suffer from a central neuropathic pain syndrome called central post-stroke pain. This syndrome is characterized by evoked pain hypersensitivity as well as spontaneous, on-going pain in the body area affected by the stroke. Clinical evidence strongly suggests a dysfunction in central pain pathways as an important pathophysiological factor in the development of central post-stroke pain, but the exact underlying mechanisms remain poorly understood. To elucidate the underlying pathophysiology of central post-stroke pain, we generated a mouse model that is based on a unilateral stereotactic lesion of the thalamic ventral posterolateral nucleus, which typically causes central post-stroke pain in humans. Results Behavioral analysis showed that the sensory changes in our model are comparable to the sensory abnormalities observed in patients suffering from central post-stroke pain. Surprisingly, pharmacological inhibition of spinal and peripheral key components of the pain system had no effect on the induction or maintenance of the evoked hypersensitivity observed in our model. In contrast, microinjection of lidocaine into the thalamic lesion completely reversed injury-induced hypersensitivity. Conclusions These results suggest that the evoked hypersensitivity observed in central post-stroke pain is causally linked to on-going neuronal activity in the lateral thalamus.
Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury
Authors: Kaji Kaori , Shinoda Masamichi , Honda Kuniya , Unno Syumpei , Shimizu Noriyoshi , Iwata Koichi 
Published: March 2016

Background Clinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27). Results Long-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons. Conclusions These findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are composed of connexin 43, plays a pivotal role in ectopic mechanical hypersensitivity in whisker pad skin following inferior alveolar nerve injury.
Crosstalk between astrocytic CXCL12 and microglial CXCR4 contributes to the development of neuropathic pain
Authors: Luo Xin , Tai Wai L , Sun Liting , Pan Zhiqiang , Xia Zhengyuan , Chung Sookja K , Cheung Chi Wai 
Published: March 2016

Background Chemokine axis chemokine C-X-C motif ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) is an emerging pain modulator, but mechanisms for its involvement in neuropathic pain remain unclear. Here, we aimed to study whether CXCL12/CXCR4 axis modulated the development of neuropathic pain via glial mechanisms. In this study, two mouse models of neuropathic pain, namely partial sciatic nerve ligation (pSNL) model and chronic post-ischemia pain (CPIP) model, were used. Results In the dorsal horn of L3–L5 segment of spinal cord, CXCL12 and CXCR4 were expressed in both astrocyte and microglia in normal mice. In the pSNL or CPIP model, the expression level of CXCL12 in the ipsilateral L3–L5 segment of mice spinal cord was increased in an astrocyte-dependent manner on post-operative day (POD) 3. Intrathecal administration of CXCL12 with AMD3100 (CXCR4 antagonist) or minocycline (microglia activation inhibitor), but not fluorocitrate (astrocyte activation inhibitor), reversed CXCL12-indued mechanical allodynia in naïve mice. In these models, AMD3100 and AMD3465 (CXCR4 antagonist), administered daily from 1 h before surgery and up to POD 3, attenuated the development of mechanical allodynia. Moreover, AMD3100 administered daily from 1 h before surgery and up to POD 3 downregulated mRNA levels of tumor necrosis factor alpha, interleukin 1β, and interleukin 6 in the ipsilateral L3–L5 segment of spinal cord in the pSNL and CPIP models on POD 3. Conclusion This study demonstrates the crosstalk between astrocytic CXCL12 and microglial CXCR4 in the pathogenesis of neuropathic pain using pSNL and CPIP models. Our results offer insights for the future research on CXCL12/CXCR4 axis and neuropathic pain therapy.
A whole health economy approach to reducing MRSA bacteraemia incidence in diabetic foot ulcer patients
Authors: Branton Fiona , Cathcart Elaine , Bellamy Elaine 
Published: March 2016

Introduction: Ulceration of the foot is a common problem among diabetic patients. Infection is a major risk in diabetic foot ulcers (DFU) and many of these are caused by Staphylococcus aureus, in particular meticillin-resistant strains (MRSA). The control and management of MRSA remains a significant challenge and all healthcare organisations in England are required to meet Zero Tolerance Objectives for cases of MRSA bacteraemia (MRSAB). This paper describes a collaborative approach across the health economy to investigate factors contributing to the acquisition of MRSA and MRSAB among DFU patients and make improvements to care to reduce the risk of healthcare-associated infections. Methods: A collaborative approach between acute and community healthcare providers and commissioners was used to conduct Root Cause Analysis and drive improvement to prevent MRSA transmission in DFU patients. Results: Screening of all DFU patients was initiated after 6 MRSAB were found to be associated with in DFU. In total 15 patients with the same MRSA antibiogram were identified. Following the implementation of actions focused on isolation, wound management, screening and cleaning no further cases were identified. Conclusion: This outbreak has demonstrated the value of cross-sector collaboration in investigating HCAI in patients with DFU, improving patient care and reducing the risk of MRSA transmission in these vulnerable patents.
Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients
Authors: Claushuis Theodora A. M. , van Vught Lonneke A. , Scicluna Brendon P. , Wiewel Maryse A. , Klein Klouwenberg Peter M. C. , Hoogendijk Arie J. , Ong David S. Y. , Cremer Olaf L. , Horn Janneke , Franitza Marek , Toliat Mohammad R. , Nürnberg Peter , Zwinderman Aeilko H. , Bonten Marc J. , Schultz Marcus J. , van der Poll Tom 
Published: March 2016

Key Points
Thrombocytopenia on intensive care unit admission is independently associated with increased mortality in patients with sepsis. Thrombocytopenia is associated with a more disturbed host response in critically ill patients with sepsis independent of disease severity.
FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data
Authors: Li Yafang , Byun Jinyoung , Cai Guoshuai , Xiao Xiangjun , Han Younghun , Cornelis Olivier , Dinulos James E. , Dennis Joe , Easton Douglas , Gorlov Ivan , Seldin Michael F. , Amos Christopher I. 
Published: March 2016

Abstract
Background
Identifying subpopulations within a study and inferring intercontinental ancestry of the samples are important steps in genome wide association studies. Two software packages are widely used in analysis of substructure: Structure and Eigenstrat. Structure assigns each individual to a population by using a Bayesian method with multiple tuning parameters. It requires considerable computational time when dealing with thousands of samples and lacks the ability to create scores that could be used as covariates. Eigenstrat uses a principal component analysis method to model all sources of sampling variation. However, it does not readily provide information directly relevant to ancestral origin; the eigenvectors generated by Eigenstrat are sample specific and thus cannot be generalized to other individuals.

Results
We developed FastPop, an efficient R package that fills the gap between Structure and Eigenstrat. It can: 1, generate PCA scores that identify ancestral origins and can be used for multiple studies; 2, infer ancestry information for data arising from two or more intercontinental origins. We demonstrate the use of FastPop using 2318 SNP markers selected from the genome based on high variability among European, Asian and West African (African) populations. We conducted an analysis of 505 Hapmap samples with European, African or Asian ancestry along with 19661 additional samples of unknown ancestry. The results from FastPop are highly consistent with those obtained by Structure across the 19661 samples we studied. The correlations of the results between FastPop and Structure are 0.99, 0.97 and 0.99 for European, African and Asian ancestry scores, respectively. Compared with Structure, FastPop is more efficient as it finished ancestry inference for 19661 samples in 16 min compared with 21–24 h required by Structure. FastPop also provided scores based on SNP weights so the scores of reference population can be applied to other studies provided the same set of markers are used. We also present application of the method for studying four continental populations (European, Asian, African, and Native American).

Conclusions
We developed an algorithm that can infer ancestries on data involving two or more intercontinental origins. It is efficient for analyzing large datasets. Additionally the PCA derived scores can be applied to multiple data sets to ensure the same ancestry analysis is applied to all studies.
The modified S-iteration process for nonexpansive mappings in $\operatorname{CAT}(\kappa)$ spaces
Authors: Suparatulatorn Raweerote , Cholamjiak Prasit 
Published: March 2016

AbstractWe establish Δ-convergence results of a sequence generated by the modified S-iteration process for two nonexpansive mappings in complete $\operatorname {CAT}(\kappa)$
CAT
(
κ
)
spaces. Some numerical examples are also provided to compare with the Ishikawa-type iteration process. Our main result extends the corresponding results in the literature.
Characterization of neutrophil function in Papillon-Lefèvre syndrome
Authors: Roberts Helen , White Phillipa , Dias Irundika , McKaig Sarah , Veeramachaneni Ratna , Thakker Nalin , Grant Melissa , Chapple Iain 
Published: March 2016

Abstract
Papillon-Lefévre syndrome is a rare, inherited, autosomal-recessive disease, characterized by palmoplantar keratosis and severe prepubertal periodontitis, leading to premature loss of all teeth. Papillon-Lefévre syndrome is caused by a mutation in the cathepsin C gene, resulting in complete loss of activity and subsequent failure to activate immune response proteins. Periodontitis in Papillon-Lefévre syndrome is thought to arise from failure to eliminate periodontal pathogens as a result of cathepsin C deficiency, although mechanistic pathways remain to be elucidated. The aim of this study was to characterize comprehensively neutrophil function in Papillon-Lefévre syndrome. Peripheral blood neutrophils were isolated from 5 patients with Papillon-Lefévre syndrome, alongside matched healthy control subjects. For directional chemotactic accuracy, neutrophils were exposed to the chemoattractants MIP-1α and fMLP and tracked by real-time videomicroscopy. Reactive oxygen species generation was measured by chemiluminescence. Neutrophil extracellular trap formation was assayed fluorometrically, and proinflammatory cytokine release was measured following overnight culture of neutrophils with relevant stimuli. Neutrophil serine protease deficiencies resulted in a reduced ability of neutrophils to chemotax efficiently and an inability to generate neutrophil extracellular traps. Neutrophil extracellular trap-bound proteins were also absent in Papillon-Lefévre syndrome, and Papillon-Lefévre syndrome neutrophils released higher levels of proinflammatory cytokines in unstimulated and stimulated conditions, and plasma cytokines were elevated. Notably, neutrophil chemoattractants MIP-1α and CXCL8 were elevated in Papillon-Lefévre syndrome neutrophils, as was reactive oxygen species formation. We propose that relentless recruitment and accumulation of hyperactive/reactive neutrophils (cytokines, reactive oxygen species) with increased tissue transit times into periodontal tissues, alongside a reduced antimicrobial capacity, create a locally destructive chronic inflammatory cycle in Papillon-Lefévre syndrome.
Implementation of a Lung Cancer Nurse Navigator Enhances Patient Care and Delivery of Systemic Therapy at the British Columbia Cancer Agency, Vancouver
Authors: Zibrik Kelly , Laskin Janessa , Ho Cheryl 
Published: March 2016

Purpose: A nurse navigator (NN) pilot project for patients with lung cancer was implemented in British Columbia, a publicly funded health-care system. The purpose was to improve referral practices, timelines, and availability of molecular testing for patients with advanced non–small-cell lung cancer (NSCLC). Methods: Patients with stage IIIB/IV NSCLC referred to the BC Cancer Agency, Vancouver, in 2011 and 2014, pre- and post-implementation of an NN, were included. Referral patterns, systemic therapy, radiotherapy (XRT) timelines, and molecular testing practices were compared. Results: The study included 408 patients: 212 in 2011 and 196 in 2014. Medical oncology (MO) end points comparing 2011 data with 2014 findings revealed that referral rates remained stable, and the proportion of patients who received systemic therapy increased from 57% to 69% (P = .05). Time from referral to MO consult was 18 days in 2011 versus 15.5 days in 2014 (P = .11); referral to systemic treatment was reduced from 48 to 38 days (P = .016). Comparison of molecular testing showed time between referral and the epidermal growth factor (EGFR) result was reduced from 34 days in 2011 to 20 days in 2014 (P < .001); rates of testing increased from 62% to 91%, respectively (P < .001); and EGFR mutation-positive rates were 19% versus 26%, respectively (P = .26). The radiation oncology (RO) end point results were as follows: 87% of patients were referred for RO consults in 2011 versus 80% in 2014 (P = .05), and the same proportion of patients received XRT (91% v 87%, respectively). Time from referral to RO consult decreased from 10 days in 2011 to 8 days in 2014 (P = .005); and referral to XRT in 2011 and 2014 was 18 days versus 11.5 days, respectively (P < .001). Conclusion: Implementation of an NN was associated with reduced wait times and increased molecular testing, improving appropriate delivery of first-line targeted therapy. NN involvement facilitates correct allocation of physician and clinical resources.
Work Habits Are Valid Components of Evaluations of Anesthesia Residents Based on Faculty Anesthesiologists’ Daily Written Comments About Residents
Authors: Dexter Franklin , Masursky Danielle , Szeluga Debra , Hindman Bradley J. 
Published: March 2016

BACKGROUND:
In our department, faculty anesthesiologists routinely evaluate the resident physicians with whom they worked in an operative setting the day before, providing numerical scores to questions. The faculty can also enter a written comment if so desired. Because residents’ work habits are important to anesthesiology program directors, and work habits can improve with feedback, we hypothesized that faculty comments would include the theme of the anesthesia resident’s work habits.

METHODS:
We analyzed all 6692 faculty comments from January 1, 2011, to June 30, 2015. We quantified use of the theme of Dannefer et al.’s work habit scale, specifically the words and phrases in the scale, and synonyms to the words.

RESULTS:
Approximately half (50.7% [lower 99.99% confidence limit, 48.4%]) of faculty comments contained the theme of work habits. Multiple sensitivity analyses were performed excluding individual faculty, residents, and words. The lower confidence limits for comments containing the theme were each >42.7%.

CONCLUSIONS:
Although faculty anesthesiologists completed (numerical) questions based on the American College of Graduate Medical Education competencies to evaluate residents, an important percentage of written comments included the theme of work habits. The implication is that the theme has validity as one component of the routine evaluation of anesthesia residents.
On the Origin of Chinese Tonal Prosody: Argumentation from a Case Study of Shen Yue's Poems
Authors: Zhang Hongming 
Published: March 2016

Abstract
Shen Yue 沈約 (441–513) is widely believed to have created the poetic metrical theory of si sheng ba bing 四聲八病 (four tones and eight defects) and divided the four tones into ping 平 (level tone) and ze 仄 (oblique tone) categories, thus forming the binary contrast prosodic system in Chinese regulated-style verse. Victor Mair and Tsu-lin Mei have further argued that the rules of the “eight defects” and the concept of ping-ze contrast were designed by Shen Yue under the influence of Sanskrit prosodic theory. The most challenging puzzle that remains for scholars in the field is to understand why Shen Yue and the other Six dynasties poets failed to follow their own prosodic theory in their composition practices. The rise of regulated-style verse in the history of Chinese literature still remains something of a mystery. Through a case study of Shen Yue's poems, this essay aims to solve the puzzle by exploring: (1) the nature of poetic prosody, (2) tonal prosodic patterns in Chinese regulated verse, (3) problems with the Sanskrit origins hypothesis of Chinese tonal prosody, and (4) the pathways of Chinese poetic metricalization from the Six dynasties (222–589) to the Tang dynasty (618–907).
Emerging Indications for Fractionated Gamma Knife Radiosurgery
Authors: McTyre Emory , Helis Corbin A. , Farris Michael , Wilkins Lisa , Sloan Darrell , Hinson William H. , Bourland J. Daniel , Dezarn William A. , Munley Michael T. , Watabe Kounosuke , Xing Fei , Laxton Adrian W. , Tatter Stephen B. , Chan Michael D. 
Published: March 2016

Abstract

BACKGROUND: Gamma Knife radiosurgery (GKRS) allows for the treatment of intracranial tumors with a high degree of dose conformality and precision. There are, however, certain situations wherein the dose conformality of GKRS is desired, but single-session treatment is contraindicated. In these situations, a traditional pin-based GKRS head frame cannot be used, because it precludes fractionated treatment.

OBJECTIVE: To report our experience in treating patients with fractionated GKRS using a relocatable, noninvasive immobilization system.

METHODS: Patients were considered candidates for fractionated GKRS if they had 1 or more of the following indications: a benign tumor >10 cc in volume or abutting the optic pathway, a vestibular schwannoma with the intent of hearing preservation, or a tumor previously irradiated with single-fraction GKRS. The immobilization device used for all patients was the Extend system (Leksell Gamma Knife Perfexion, Elekta, Kungstensgatan, Stockholm).

RESULTS: We identified 34 patients treated with fractionated GKRS between August 2013 and February 2015. There were a total of 37 tumors treated including 15 meningiomas, 11 pituitary adenomas, 6 brain metastases, 4 vestibular schwannomas, and 1 hemangioma. At last follow-up, all 21 patients treated for perioptic tumors had stable or improved vision and all 4 patients treated for vestibular schwannoma maintained serviceable hearing. No severe adverse events were reported.

CONCLUSION: Fractionated GKRS was well tolerated in the treatment of large meningiomas, perioptic tumors, vestibular schwannomas with intent of hearing preservation, and reirradiation of previously treated tumors.
Mesial Extratemporal Lobe Epilepsy: Clinical Features and Surgical Strategies
Authors: Theys Tom , Minotti Lorella , Tassi Laura , Lo Russo Giorgio , Benabid Alim-Louis , Kahane Philippe , Chabardès Stephan 
Published: March 2016

Abstract

BACKGROUND: Extratemporal lobe epilepsy surgery remains a diagnostic and therapeutic challenge. Scalp electroencephalography (EEG) correlates, clinical semiology, and imaging findings are often ambiguous or difficult to interpret, necessitating the need for invasive recordings. This is particularly true for those extratemporal lobe epilepsy cases in which seizures develop from the midline.

OBJECTIVE: The aim of this study was to examine the clinical features and surgical strategies in mesial extratemporal lobe epilepsy.

METHODS: A retrospective study reviewing clinical and surgical characteristics was conducted in 30 patients who underwent epilepsy surgery in mesial extratemporal areas at our institution between 1991 and 2011.

RESULTS: Although the location of the epileptogenic zone was associated with specific seizure types, semiology proved to be heterogeneous. Although scalp EEG was of good lateralizing value, it was poor for localizing the epileptogenic zone, necessitating a frequent need for invasive electroencephalographic recordings.

CONCLUSION: Surgical resections in mesial extratemporal regions were found to be safe and resulted in satisfactory seizure outcomes.