bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo
Authors: Kozina Elena , Sadasivan Shankar , Jiao Yun , Dou Yuchen , Ma Zhijun , Tan Haiyan , Kodali Kiran , Shaw Timothy , Peng Junmin , Smeyne Richard J 
Published: March 2018

Abstract
Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene result in late-onset Parkinson’s disease. The incomplete penetrance of LRRK2 mutations in humans and LRRK2 murine models of Parkinson’s disease suggests that the disease may result from a complex interplay of genetic predispositions and persistent exogenous insults. Since neuroinflammation is commonly associated with the pathogenesis of Parkinson’s disease, we examine a potential role of mutant LRRK2 in regulation of the immune response and inflammatory signalling in vivo. Here, we show that mice overexpressing human pathogenic LRRK2 mutations, but not wild-type mice or mice overexpressing human wild-type LRRK2 exhibit long-term lipopolysaccharide-induced nigral neuronal loss. This neurodegeneration is accompanied by an exacerbated neuroinflammation in the brain. The increased immune response in the brain of mutant mice subsequently has an effect on neurons by inducing intraneuronal LRRK2 upregulation. However, the enhanced neuroinflammation is unlikely to be triggered by dysfunctional microglia or infiltrated T cells and/or monocytes, but by peripheral circulating inflammatory molecules. Analysis of cytokine kinetics and inflammatory pathways in the peripheral immune cells demonstrates that LRRK2 mutation alters type II interferon immune response, suggesting that this increased neuroinflammatory response may arise outside the central nervous system. Overall, this study suggests that peripheral immune signalling plays an unexpected—but important—role in the regulation of neurodegeneration in LRRK2-associated Parkinson’s disease, and provides new targets for interfering with the onset and progression of the disease.
Piggy: a rapid, large-scale pan-genome analysis tool for intergenic regions in bacteria
Authors: Thorpe Harry A , Bayliss Sion C , Sheppard Samuel K , Feil Edward J 
Published: March 2018

Abstract

Background
The concept of the “pan-genome,” which refers to the total complement of genes within a given sample or species, is well established in bacterial genomics. Rapid and scalable pipelines are available for managing and interpreting pan-genomes from large batches of annotated assemblies. However, despite overwhelming evidence that variation in intergenic regions in bacteria can directly influence phenotypes, most current approaches for analyzing pan-genomes focus exclusively on protein-coding sequences.

Findings
To address this we present Piggy, a novel pipeline that emulates Roary except that it is based only on intergenic regions. A key utility provided by Piggy is the detection of highly divergent (“switched”) intergenic regions (IGRs) upstream of genes. We demonstrate the use of Piggy on large datasets of clinically important lineages of Staphylococcus aureus and Escherichia coli.

Conclusions
For S. aureus, we show that highly divergent (switched) IGRs are associated with differences in gene expression and we establish a multilocus reference database of IGR alleles (igMLST; implemented in BIGSdb).
Integration of physical abuse clinical decision support into the electronic health record at a Tertiary Care Children’s Hospital
Authors: Suresh Srinivasan , Saladino Richard A , Fromkin Janet , Heineman Emily , McGinn Tom , Richichi Rudolph , Berger Rachel P 
Published: March 2018

Abstract

Objective
To evaluate the effect of a previously validated electronic health record-based child abuse trigger system on physician compliance with clinical guidelines for evaluation of physical abuse.

Methods
A randomized controlled trial (RCT) with comparison to a preintervention group was performed. RCT-experimental subjects’ providers received alerts with a direct link to a physical abuse-specific order set. RCT-control subjects’ providers had no alerts, but could manually search for the order set. Preintervention subjects’ providers had neither alerts nor access to the order set. Compliance with clinical guidelines was calculated.

Results
Ninety-nine preintervention subjects and 130 RCT subjects (73 RCT-experimental and 57 RCT-control) met criteria to undergo a physical abuse evaluation. Full compliance with clinical guidelines was 84% pre-intervention, 86% in RCT-control group, and 89% in RCT-experimental group. The physical abuse order set was used 43 times during the 7-month RCT. When the abuse order set was used, full compliance was 100%. The proportion of cases in which there was partial compliance decreased from 10% to 3% once the order set became available (P = .04). Male gender, having &gt;10 years of experience and completion of a pediatric emergency medicine fellowship were associated with increased compliance.

Discussion/Conclusion
A child abuse clinical decision support system comprised of a trigger system, alerts and a physical abuse order set was quickly accepted into clinical practice. Use of the physical abuse order set always resulted in full compliance with clinical guidelines. Given the high baseline compliance at our site, evaluation of this alert system in hospitals with lower baseline compliance rates will be more valuable in assessing the efficacy in adherence to clinical guidelines for the evaluation of suspected child abuse.
Cancer Incidence and Multilevel Measures of Residential Economic and Racial Segregation for Cancer Registries
Authors: Krieger Nancy , Feldman Justin M , Kim Rockli , Waterman Pamela D 
Published: March 2018

AbstractBackgroundThe handful of studies (<30) on cancer and residential segregation have focused on racial segregation, primarily at the city/town level. We tested a priori hypotheses about choice of measure and level by extending use of the Index of Concentration at the Extremes (ICE) to quantify both economic and racial residential segregation, singly and combined, and conducted analyses for the total population and stratified by race/ethnicity.MethodsOutcomes comprised Massachusetts incidence rates (2010–2014) for invasive breast, cervical, and lung cancer, analyzed in relation to census tract and city/town ICE measures for income, race/ethnicity, race/ethnicity + income, and the federal poverty line. Multilevel Poisson regression modeled observed counts of incident cases.ResultsBoth choice of metric and level mattered. As illustrated by cervical cancer, in models including both the census tract and city/town levels, the rate ratio for the worst to best quintile for the total population was greatest at the census tract level for the ICE for racialized economic segregation (3.0, 95% confidence interval [CI] = 2.1 to 4.3) and least for the poverty measure (1.9, 95% CI = 1.4 to 2.6), with null associations at the city/town level. In analogous models with both levels for lung cancer, however, for the non-Hispanic black and Hispanic populations, the rate ratios for, respectively, the ICE and poverty measures, were larger (and excluded 1) at the city/town compared with the census tract level.ConclusionsOur study suggests that the ICE for racialized economic segregation, at multiple levels, can be used to improve monitoring and analysis of cancer inequities.
Surgical Treatment of Extratemporal Epilepsy: Results and Prognostic Factors
Authors: Delev Daniel , Oehl Bernhard , Steinhoff Bernhard J , Nakagawa Julia , Scheiwe Christian , Schulze-Bonhage Andreas , Zentner Josef 
Published: March 2018

Abstract

BACKGROUND
Surgery is a widely accepted option for the treatment of pharmacoresistant epilepsies of extratemporal origin.

OBJECTIVE
To analyze clinical and epileptological results and to provide prognostic factors influencing seizure outcome.

METHODS
This retrospective single-center study comprises a consecutive series of 383 patients, most of whom had an identifiable lesion on MRI, who underwent resective surgery for extratemporal epilepsy. Data including diagnostic modalities, surgical treatment, histopathology, prognostic factors, and epileptological outcome were analyzed.

RESULTS
Resective procedures were located as follows: frontal (n = 183), parietal (n = 44), occipital (n = 24), and insular (n = 24). In 108 cases resection included more than 1 lobe. Histopatholological evaluation revealed focal cortical dysplasias (n = 178), tumors (n = 110), cavernomas (n = 27), gliosis (n = 42), and nonspecific findings (n = 36). A distinct epileptogenic lesion was detected in 338 (88.7%) patients. After a mean follow-up of 54 mo, 227 (62.5%) patients remained free from disabling seizures (Engel class I), and 178 (49%) were completely seizure free (Engel class Ia). There was no perioperative mortality. Permanent morbidity was encountered in 46 cases (11.8%). The following predictors were significantly associated with excellent seizure outcome (Engel I): lesion visible on magnetic resonance imaging (MRI; P = .02), noneloquent location (P = .01), complete resection of the lesion (P = .001), absence of epileptic activity postoperatively (P = .001), circumscribed histological findings (P = .001), lower age at surgery (P = .008), and shorter duration of epilepsy (P = .02).

CONCLUSION
Surgical treatment of extratemporal epilepsy provides satisfying epileptological results with an acceptable morbidity. Best results can be achieved in younger patients with circumscribed MRI lesions, which can be resected completely.
Pediatric Pontine Cavernous Malformations: The Presigmoid, Posterior Petrosal Approach
Authors: Kulwin Charles G , Payner Troy D , Nelson Rick F , Ackerman Laurie L , Fulkerson Daniel H 
Published: March 2018

Abstract

BACKGROUND
Brainstem cavernous malformations (cavernomas) in children have a high risk of hemorrhage and neurological deterioration. This risk is magnified if the child has a genetic predisposition for cavernoma formation. The surgical management is challenging and carries a significant risk of morbidity.

OBJECTIVE
To describe the feasibility of a posterior petrosal approach to brainstem cavernomas in a pediatric population.

METHODS
A single institution operative experience with this technique was reviewed; 2 cases were identified and are technically described here with supportive figures and illustrations, as well as a focused literature review.

RESULTS
Two pediatric cases with multiple symptomatic hemorrhages from large expanding pontine cavernomas were identified. Both cavernomas were resected through a presigmoid posterior petrosal approach. While this approach is well described in the adult literature for ventral brainstem lesions, its description for the treatment of pontine cavernomas in the pediatric populations is scarce.

CONCLUSION
This study demonstrates the utility and feasibility of the posterior petrosal approach in two pediatric patients at different points in cranial base development.
Cerebral Hyperperfusion Syndrome by the Numbers: Transient Focal Neurological Deficit, Imaging-Proven Focal Hyperperfusion, and High Graft Flow Rate Following Superficial Temporal Artery-Middle Cerebral Artery bypass in a Patient With Symptomatic Carotid Occlusion—Case Report
Authors: Rahme Ralph , Sudhakar Tejaswi D , Alimi Marjan , White Timothy G , Ortiz Rafael A , Langer David J 
Published: March 2018

Abstract

BACKGROUND AND IMPORTANCE
Cerebral hyperperfusion syndrome (CHS) is a well-known complication of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass for ischemic cerebrovascular disease. While this argues against “low flow” in the bypass construct, flow rates in the graft have not been previously quantified in the setting of CHS.

CLINICAL PRESENTATION
A 58-yr-old man presented with recurrent left hemispheric ischemic strokes and fluctuating right hemiparesis and aphasia. Vascular imaging revealed left cervical internal carotid artery occlusion and perfusion imaging confirmed left hemispheric hypoperfusion. After failing to respond to maximal medical therapy, the patient underwent single-barrel STA-MCA bypass. Postoperatively, his symptoms resolved and blood pressure (BP) was strictly controlled within normal range. However, 2 d later, he developed severe expressive aphasia. CTA demonstrated a patent bypass graft and SPECT showed focal hyperperfusion in Broca's speech area. Seizure activity was ruled out. A high graft flow rate of 52 mL/min was documented by quantitative magnetic resonance angiography (MRA). Thus, the diagnosis of CHS was made and managed with strict BP control. The patient exhibited complete recovery of speech over a period of days and was discharged home. Repeat SPECT at 4 mo showed resolution of hyperperfusion and quantitative MRA demonstrated reduction of graft flow rate to 34 mL/min.

CONCLUSION
This is the first case of perfusion imaging-proven CHS after STA-MCA bypass, where high graft flow rates are objectively documented. Our observations constitute irrefutable evidence challenging the classic belief that the STA-MCA bypass is a low-flow construct.
Analysis of Surgical Freedom Variation Across the Basilar Artery Bifurcation: Towards a Deeper Insight Into Approach Selection for Basilar Apex Aneurysms
Authors: Tayebi Meybodi Ali , Benet Arnau , Rodriguez Rubio Roberto , Yousef Sonia , Lawton Michael T 
Published: March 2018

Abstract

BACKGROUND
The orbitozygomatic approach is generally advocated over the pterional approach for basilar apex aneurysms. However, the impact of the extensions of the pterional approach on the obtained maneuverability over multiple vascular targets (relevant to basilar apex surgery) has not been studied before.

OBJECTIVE
To analyze the patterns of surgical freedom change across the basilar bifurcation between the pterional, orbitopterional, and orbitozygomatic approaches.

METHODS
Surgical freedom was assessed for 3 vascular targets important in basilar apex aneurysm surgery (ipsilateral and contralateral P1-P2 junctions, and basilar apex), and compared between the pterional, orbitopterional, and orbitozygomatic approaches in 10 cadaveric specimens.

RESULTS
Transitioning from the pterional to orbitopterional approach, the surgical freedom increased significantly at all 3 targets (P < .05). However, the gain in surgical freedom declined progressively from the most superficial target (60% for ipsilateral P1-P2 junction) to the deepest target (35% for contralateral P1-P2 junction). Conversely, transitioning from the orbitopterional to the orbitozygomatic approach, the gain in surgical freedom was minimal for the ipsilateral P1-P2 and basilar apex (<4%), but increased dramatically to 19% at the contralateral P1-P2 junction.

CONCLUSION
The orbitopterional approach provides a remarkable increase in surgical maneuverability compared to the pterional approach for the basilar apex target and the relevant adjacent arterial targets. However, compared to the orbitopterional, the orbitozygomatic approach adds little maneuverability except for the deepest target (ie, contralateral P1-P2 junction). Therefore, the orbitozygomatic approach may be most efficacious with larger basilar apex aneurysms limiting the control over of the contralateral P1 PCA.
Stereotypes and Evidentiality
Authors: Wood Michael 
Published: March 2018

AbstractEvidentiality and stereotyping are two highly productive concepts that have recently generated interesting, and in the case of stereotypes, often politically intense, research agendas. This paper initially outlines how some of this productivity relies on a certain indeterminacy concerning the key terms. After outlining debates about the key characteristics of evidentiality and stereotypes the paper considers recent work that links evidentiality to stereotypes. Such works are found primarily in linguistics rather than in other discipline and analytical emphasis is on evidentiality rather than stereotyping. Reluctant to make claims based on ‘Western’ psychology, the linguists approach stereotyping primarily as a social process. Supporting such an approach this review highlights the need for greater analysis of the interactional contexts that deploy both evidentials and pejorative social categories. In addition, there is a need to further investigate the histories of changes in local use of evidentials and stereotypes understood as interrelated social processes.
Extragrammatical Expression of Information Source
Authors: Squartini Mario 
Published: March 2018

AbstractThis chapter reviews some selected lexical items expressing various semantic functions connected to the expression of information source. By focusing on a comparative analysis of what is expressed by lexical items and what can be expressed by grammatical markers of evidentiality, this survey aims to assess to what extent a comprehensive treatment of lexical and grammatical expressions of information source might shed additional light on both domains. Particular attention is paid to the interplay between external sensory evidence and subjective evaluation in verbs of direct perception and verbs of appearance (‘SEEM-verbs’). The role of the speaker as a ‘mediating filter’ between epistemic estimation and source of evidence is also discussed with respect to verbs of belief.
Evidentiality in Nambikwara Languages
Authors: Eberhard David M. 
Published: March 2018

AbstractThis chapter describes evidentiality as it is expressed within the Nambikwara language family of west central Brazil, a loosely related affiliation of seventeen language communities living close to the Brazil-Bolivia border. This overview limits its scope to the four varieties where evidentiality has been documented (Mamaindê, Lakondê, Sabanê, and a generic variety of Southern Nambikwara). All four of these languages share several traits that could be considered characteristics of Nambikwara evidential systems. These are: a large set of evidentials (between four and eight); sets that include inferred and reported; forms that link evidentials and tense; and the use of ‘multiple perspective’ as a way of referencing the singular or plural nature of the ‘knower’. It is this latter trait that constitutes the most salient feature of evidentiality within the family as a whole, one that deserves further attention.
Evidentiality in Boran and Witotoan Languages
Authors: Wojtylak Katarzyna I. 
Published: March 2018

AbstractThis chapter is the first attempt to explore how evidentiality is expressed in two neighbouring language families spoken in northwest Amazonia, Boran, and Witotoan. The evidentiality systems in Boran and Witotoan languages are not as complex as those found in languages spoken in vicinity of the Vaupés area to the north. Marking of evidentiality is more elaborate in Boran languages, with three choices available in Bora, while evidentiality distinctions in Witotoan languages are less expressive, with only two terms available in Murui. Although evidentiality choices can differ even within a single language family, a reported evidential is present in all Boran and Witotoan languages without exception. In addition to marking evidentiality, all languages show some type of optional marking that is related to expressing speaker’s certainty regarding an assertion.
Evidentials and Person
Authors: Sun Jackson T.-S. 
Published: March 2018

AbstractThis chapter presents an overview of salient issues regarding the correlation between evidentiality and person. A synthesis of research findings is provided and illustrated by empirical data. The person category relevant for evidentiality is shown to be the ‘speaking person’, which translates into various grammatical persons depending on the grammatical construction. The person-sensitive distribution of evidential forms is attributable to features like control, observability, and access to knowledge, and may be creatively manipulated along an evidential directness cline, such that an evidential value reserved for the speaking person may be employed to assert intimate knowledge about another person, and conversely, a reduced evidential value may be selected in self-reports to tone down first-person involvement, exhibiting ‘first-person effects’. Also elucidated herein is how the addressee’s perspective, another critical person factor in evidentiality, shapes evidential formation and selection.
Non-Propositional Evidentiality
Authors: Jacques Guillaume 
Published: March 2018

AbstractThis chapter deals with non-propositional evidentiality, i.e. evidential-like distinctions on markers whose scope is limited to a noun phrase. First, it presents the different types of non-propositional evidential markers, the most common of which are demonstrative pronouns and determiners. Second, it shows how non-propositional evidential markers can encode morphosyntactic parameters such as case or topicality in addition to evidentiality. Then, it describes attested non-propositional evidential categories, focusing on sensory (visual, auditory, non-visual) evidentials, as non-sensory non-propositional evidentials are extremely rare. Finally, it discusses how non-propositional evidentiality and nominal tense can interact in some languages and presents some general observations on commonalities and differences between propositional and non-propositional evidential systems.
Many Worlds Colliding
Authors: Behrens Joanna , Swanepoel Natalie 
Published: March 2018

AbstractThe character of historical archaeology in South Africa has been cast by the geography of its development and the historical roots of its subject matter. Arising in the south-western Cape, where Europeans collided with the nomadic Khoe and Bushmen, research agendas meshed with broader sub-disciplinary goals for a global, comparative archaeology of the last 500 years. In practice, this led to a focus on sites associated with European colonists. Investigations issuing from the ‘other side’ of these encounters were rare. In this chapter we acknowledge the important precedents set by pioneer researchers and explore how historical archaeologies in the interior offer new directions. Here encroaching colonists met established farming groups, encounters that set in motion complex and historically situated long-term entanglements. Recent and developing research in these areas signals a growing maturity within the field, enhanced by increasing collaboration among archaeologists of different sub-disciplinary persuasions, and between archaeologists and historians.
Politics and Power
Authors: Collis John , Karl Raimund 
Published: March 2018

Abstract
Reconstruction of Iron Age social and political structures relies initially on written sources, but classical texts are both biased in how they describe institutions, especially among other peoples, and patchy in time and space. From the mid-first millennium BC, we get details on how polities such as Athens, Sparta, and Rome functioned, but these are not representative of other Greek and Italian peoples, let alone non-Mediterranean societies. The second source of information is archaeology, especially burials, but also settlements. The chapter discusses social and political development using both a core–periphery (Mediterranean societies were more complex than those in the north) and an evolutionary model, though not one which necessarily assumes increasing complexity. The varying nature of individual power bases is also considered. A major area of contention (including between the authors) is the extent to which we can back-project documented societies into the past or into other contexts.