bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clusters of circulating tumor cells traverse capillary-sized vessels
Authors: Au Sam H. , Storey Brian D. , Moore John C. , Tang Qin , Chen Yeng-Long , Javaid Sarah , Sarioglu A. Fatih , Sullivan Ryan , Madden Marissa W. , O’Keefe Ryan , Haber Daniel A. , Maheswaran Shyamala , Langenau David M. , Stott Shannon L. , Toner Mehmet 
Published: April 2016

Significance
Metastasis is responsible for 90% of cancer-related deaths and is driven by tumor cells circulating in blood. However, it is believed that only individual tumor cells can reach distant organs because multicellular clusters are too large to pass through narrow capillaries. Here, we collected evidence by examining clusters in microscale devices, computational simulations, and animals, which suggest that this assumption is incorrect, and that clusters may transit through capillaries by unfolding into single-file chains. This previously unidentified cell behavior may explain why previous experiments reported that clusters were more efficient at seeding metastases than equal numbers of single tumor cells, and has led to a strategy that, if applied clinically, may reduce the incidence of metastasis in patients.
Benefit of transferred mutations is better predicted by the fitness of recipients than by their ecological or genetic relatedness
Authors: Wang Yinhua , Diaz Arenas Carolina , Stoebel Daniel M. , Flynn Kenneth , Knapp Ethan , Dillon Marcus M. , Wünsche Andrea , Hatcher Philip J. , Moore Francisco B.-G. , Cooper Vaughn S. , Cooper Tim F. 
Published: April 2016

Significance
The fitness effect of many mutations depends on the genotype of the individual in which they occur. Are these dependencies predictable? Do dependencies build on existing variation between individuals to promote divergence, or do they act to favor genetic cohesion? We examine these questions by measuring the fitness effect of mutations that conferred a benefit in a laboratory-evolved population when transferred into genetically and phenotypically diverse natural isolates of the same species. We found that fitness effects were predicted by the fitness of the strain to which they were added but not by the genetic or ecological relationship of the recipient strains. This pattern extends findings that the current fitness of strain is a major predictor of its ability to adapt.
Stable aqueous dispersions of optically and electronically active phosphorene
Authors: Kang Joohoon , Wells Spencer A. , Wood Joshua D. , Lee Jae-Hyeok , Liu Xiaolong , Ryder Christopher R. , Zhu Jian , Guest Jeffrey R. , Husko Chad A. , Hersam Mark C. 
Published: April 2016

Significance
Few-layered phosphorene, which is isolated through exfoliation from black phosphorus, has attracted great interest due to its unique electronic and optical properties. Although solution-based exfoliation methods have been developed for black phosphorus, these techniques have thus far used anhydrous organic solvents. This approach minimizes exposure to known oxidizing species, but at the cost of limited exfoliation yield and relatively thick flakes. Here, we overcome these limitations by using stabilizing surfactants in deoxygenated water, which results in phosphorene down to the monolayer limit. The resulting aqueous phosphorene dispersions show layer-dependent photoluminescence and enable high-performance field-effect transistors. Overall, this approach holds promise for the solution-phase production of few-layered phosphorene in emerging large-volume applications including electronics and optoelectronics.
IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline
Authors: Fu Amy K. Y. , Hung Kwok-Wang , Yuen Michael Y. F. , Zhou Xiaopu , Mak Deejay S. Y. , Chan Ivy C. W. , Cheung Tom H. , Zhang Baorong , Fu Wing-Yu , Liew Foo Y. , Ip Nancy Y. 
Published: April 2016

Significance
Dysfunction of the innate immune system is involved in the pathogenesis of Alzheimer’s disease (AD); however, the pathophysiological mechanisms underlying these dysfunctions are unclear. Here we report that stimulation of IL-33/ST2 signaling rescues memory deficits and reduces the accumulation of β-amyloid in APP/PS1 mice that exhibit select pathologies associated with AD. Although impaired IL-33/ST2 signaling is associated with early progression of AD, IL-33 injection rescues contextual memory deficits and reduces the accumulation of β-amyloid in APP/PS1 mice. IL-33 skews the microglia toward an alternative activation state with enhanced Aβ phagocytic capacity and elevated antiinflammatory gene expression, which results in a decreased proinflammatory response in the brain. Thus, this study suggests that IL-33 can be developed as a new therapeutic intervention for AD.
Durable antitumor responses to CD47 blockade require adaptive immune stimulation
Authors: Sockolosky Jonathan T. , Dougan Michael , Ingram Jessica R. , Ho Chia Chi M. , Kauke Monique J. , Almo Steven C. , Ploegh Hidde L. , Garcia K. Christopher 
Published: April 2016

SignificanceTherapeutic antitumor antibodies are widely used clinically. CD47 is an antiphagocytic ligand expressed by tumors that binds the inhibitory receptor signal regulatory protein alpha (SIRPα) on phagocytic cells. Interruption of CD47–SIRPα interactions in immunodeficient mice bearing human tumors enhances therapeutic antitumor antibody responses by promoting phagocytosis of antibody-bound tumor cells. Here, we use a novel anti-CD47 single domain antibody, derived from an alpaca, in an immunocompetent mouse model of melanoma and find that, in contrast to immunodeficient models, CD47 blockade alone is insufficient to enhance the effects of antimelanoma antibodies. However, when combined with blockade of programmed death-ligand 1 (PD-L1), an immune receptor that inhibits antitumor T cell responses, we find synergistic activity, suggesting a role for both innate and adaptive inhibitory pathways in the response to therapeutic antibodies.
Predation by Northern Pikeminnow and Tiger Muskellunge on Juvenile Salmonids in a High‐Head Reservoir: Implications for Anadromous Fish Reintroductions
Authors: Sorel Mark H. , Hansen Adam G. , Connelly Kristin A. , Wilson Andrew C. , Lowery Erin D. , Beauchamp David A. 
Published: April 2016

AbstractThe feasibility of reintroducing anadromous salmonids into reservoirs above high‐head dams is affected by the suitability of the reservoir habitat for rearing and the interactions of the resident fish with introduced fish. We evaluated the predation risk to anadromous salmonids considered for reintroduction in Merwin Reservoir on the North Fork Lewis River in Washington State for two reservoir use‐scenarios: year‐round rearing and smolt migration. We characterized the role of the primary predators, Northern Pikeminnow Ptychocheilus oregonensis and tiger muskellunge (Northern Pike Esox lucius × Muskellunge E. masquinongy), by using stable isotopes and stomach content analysis, quantified seasonal, per capita predation using bioenergetics modeling, and evaluated the size and age structures of the populations. We then combined these inputs to estimate predation rates of size‐structured population units. Northern Pikeminnow of FL ≥ 300 mm were highly cannibalistic and exhibited modest, seasonal, per capita predation on salmonids, but they were disproportionately much less abundant than smaller, less piscivorous, conspecifics. The annual predation on kokanee Oncorhynchus nerka (in biomass) by a size‐structured unit of 1,000 Northern Pikeminnow having a FL ≥ 300 mm was analogous to 16,000–40,000 age‐0 spring Chinook Salmon O. tshawytscha rearing year‐round, or 400–1,000 age‐1 smolts migrating April–June. The per capita consumption of salmonids by Northern Pikeminnow having a FL ≥ 200 mm was relatively low, due in large part to spatial segregation during the summer and the skewed size distribution of the predator population. Tiger muskellunge fed heavily on Northern Pikeminnow, other nonsalmonids, and minimally on salmonids. In addition to cannibalism within the Northern Pikeminnow population, predation by tiger muskellunge likely contributed to the low recruitment of larger (more piscivorous) Northern Pikeminnow, thereby decreasing the risk of predation to salmonids. This study highlights the importance of evaluating trophic interactions within reservoirs slated for reintroduction with anadromous salmonids, as they can be functional migration corridors and may offer profitable juvenile‐rearing habitats despite hosting abundant predator populations.Received September 3, 2015; accepted December 7, 2015 Published online April 19, 2016
Factors Influencing Stream Fish Species Composition and Functional Properties at Multiple Spatial Scales in the Sand Hills of the Southeastern United States
Authors: Paller Michael H. , Prusha Blair A. , Fletcher Dean E. , Kosnicki Ely , Sefick Stephen A. , Jarrell Miller S. , Sterrett Sean C. , Grosse Andrew M. , Tuberville Tracey D. , Feminella Jack W. 
Published: April 2016

AbstractAn understanding of how fish communities differ among river basin, watershed, and stream reach spatial scales and the factors that influence these differences can help in the design of effective conservation programs and the development of reference models that appropriately represent biota under relatively undisturbed conditions. We assessed the heterogeneity among fish assemblages in first‐ to fourth‐order stream sites from four river basins (Savannah, Chattahoochee, Cape Fear, and Pee Dee rivers) within the Sand Hills ecoregion of the southeastern USA and compared it with the heterogeneity associated with watershed and stream reach spatial scales. Fifty‐five species of fish representing 15 families were collected by electrofishing, with the most speciose families being Cyprinidae, Centrarchidae, Percidae, Ictaluridae, and Catostomidae. Constrained ordination identified clearly demarcated species assemblages among river basins as well as subbasin environmental variables that affected fish species composition; the amounts of variance attributable to basin, watershed, and stream reach spatial scales were roughly equivalent. Prominent differences occurred between Gulf of Mexico coast and Atlantic coast river basins, but differences among Atlantic coast basins were also apparent. Key variables at the watershed scale included watershed size, relief, extent of anthropogenic disturbance, and forest cover; key variables at the stream reach scale included instream habitat quality, proximity to a larger stream, and stream width. Fish assemblage collective and functional properties were more strongly influenced by variables acting at watershed and stream reach spatial scales than by differences among basins. Species richness peaked at intermediate levels of habitat quality as a likely result of biotic homogenization, indicating that the least disturbed sites within the region do not necessarily possess the highest species richness. Failure to consider this may lead to the overrating of moderately disturbed sites and the underrating of minimally disturbed sites, thus contributing to false conclusions about fish assemblage integrity.Received September 15, 2015; accepted December 15, 2015 Published online April 19, 2016
Dialogue and the development of ideas in the political and social sciences: from critical realism to problem-solving via Colin Hay and the rejection of the epistemic fallacy
Authors: Cruickshank Justin 
Published: April 2016

ABSTRACT
Colin Hay’s extensive work on politics helps illustrate that ideas can have significant traction of their own which inhibits change. Therefore, accounts of conceptual development in the political and social sciences should examine the possibility of slow dialogue, as a form of communication hospitable to innovation. For critical realism, justified explanations must avoid the ‘epistemic fallacy’ of conflating ontological questions about what reality is with epistemological questions about how we know reality; it prefers basing explanations on an ontology of structure and agency. I argue, using Popper and Lakatos’s problem-solving epistemology, that the critical-realist construction of the epistemic fallacy is untenable, and that attempts at justification entail what I call ‘speedy’ dialogue, with putatively ‘unjustified’ positions being simply rejected; unlike the slow dialogue that problem-solving demands. I also use Hay to show how problem-solving needs to include ontological references, once they are separated from the attempt to justify ideas.
A short proof of the Dimension Conjecture for real hypersurfaces in ℂ²
Authors: Isaev Alexander , Kruglikov Boris 
Published: April 2016

Recently, I. Kossovskiy and R. Shafikov settled the so-called Dimension Conjecture, which characterizes spherical hypersurfaces in

C

2

\mathbb {C}^2

via the dimension of the algebra of infinitesimal CR-automorphisms. In this note, we propose a short argument for obtaining their result.
Conceptualizing Medieval Book Collections
Authors: Hinton Thomas 
Published: April 2016

Abstract
This article argues for a conceptual distinction between the practices and ideologies of institutional learning on the one hand (whose natural vehicle was Latin, the language of formal education) and those of a vernacular written culture that both challenges and models itself on the former. The garden, used as a figure for the ideal library by Richard de Fournival in the thirteenth century, creates order through the institutionalization of knowledge and the exclusion of undesirable elements. By contrast, the forest is deployed by medieval and modern thinkers to embody a wild, unsorted chaos apparently inimical to learning. And yet the forest in medieval literature functions as a margin always in contact with civilization, whose illicit danger is matched by its attractiveness as a space for unplanned encounters and reconfigurations of hierarchy and authority. As I demonstrate, an analogous concern with the potential for book collections to lead readers to unexpected discoveries is a recurrent theme of vernacular authors from Benoît de Sainte-Maure to Chaucer. This conceptual approach to the function and cultural value of medieval libraries offers a supplementary perspective to more traditional ‘book archaeology’, one which may be especially fruitful for making sense of the often fragmentary and vague records of private ownership.
A Model for Catalyzing Educational and Clinical Transformation in Primary Care: Outcomes From a Partnership Among Family Medicine, Internal Medicine, and Pediatrics
Authors: Eiff M. Patrice , Green Larry A. , Holmboe Eric , McDonald Furman S. , Klink Kathleen , Smith David Gary , Carraccio Carol , Harding Rose , Dexter Eve , Marino Miguel , Jones Sam , Caverzagie Kelly , Mustapha Mumtaz , Carney Patricia A. 
Published: April 2016

Purpose
To report findings from a national effort initiated by three primary care certifying boards to catalyze change in primary care training.

Method
In this mixed-method pilot study (2012–2014), 36 faculty in 12 primary care residencies (family medicine, internal medicine, pediatrics) from four institutions participated in a professional development program designed to prepare faculty to accelerate change in primary care residency training by uniting them in a common mission to create effective ambulatory clinical learning environments. Surveys administered at baseline and 12 months after initial training measured changes in faculty members’ confidence and skills, continuity clinics, and residency training programs. Feasibility evaluation involved assessing participation. The authors compared quantitative data using Wilcoxon signed-rank and Bhapkar tests. Observational field notes underwent narrative analysis.

Results
Most participants attended two in-person training sessions (92% and 72%, respectively). Between baseline and 12 months, faculty members’ confidence in leadership improved significantly for 15/19 (79%) variables assessed; their self-assessed skills improved significantly for 21/22 (95%) competencies. Two medical home domains (“Continuity of Care,” “Support/Care Coordination”) improved significantly (P < .05) between the two time periods. Analyses of qualitative data revealed that interdisciplinary learning communities formed during the program and served to catalyze transformational change.

Conclusions
Results suggest that improvements in faculty perceptions of confidence and skills occurred and that the creation of interdisciplinary learning communities catalyzed transformation. Lengthening the intervention period, engaging other professions involved in training the primary care workforce, and a more discriminating evaluation design are needed to scale this model nationally.
Feedback to Supervisors: Is Anonymity Really So Important?
Authors: Dudek Nancy L. , Dojeiji Suzan , Day Kathleen , Varpio Lara 
Published: April 2016

Purpose
Research demonstrates that physicians benefit from regular feedback on their clinical supervision from their trainees. Several features of effective feedback are enabled by nonanonymous processes (i.e., open feedback). However, most resident-to-faculty feedback processes are anonymous given concerns of power differentials and possible reprisals. This exploratory study investigated resident experiences of giving faculty open feedback, advantages, and disadvantages.

Method
Between January and August 2014, nine graduates of a Canadian Physiatry residency program that uses open resident-to-faculty feedback participated in semistructured interviews in which they described their experiences of this system. Three members of the research team analyzed transcripts for emergent themes using conventional content analysis. In June 2014, semistructured group interviews were held with six residents who were actively enrolled in the program as a member-checking activity. Themes were refined on the basis of these data.

Results
Advantages of the open feedback system included giving timely feedback that was acted upon (thus enhancing residents’ educational experiences), and improved ability to receive feedback (thanks to observing modeled behavior). Although some disadvantages were noted, they were often speculative (e.g., “I think others might have felt …”) and were described as outweighed by advantages. Participants emphasized the program’s “feedback culture” as an open feedback enabler.

Conclusions
The relationship between the feedback giver and recipient has been described as influencing the uptake of feedback. Findings suggest that nonanonymous practices can enable a positive relationship in resident-to-faculty feedback. The benefits of an open system for resident-to-faculty feedback can be reaped if a “feedback culture” exists.
Patients, Nurses, and Physicians Working Together to Develop a Discharge Entrustable Professional Activity Assessment Tool
Authors: Meade Lauren B. , Suddarth Kathleen Heist , Jones Ronald R. , Zaas Aimee K. , Albanese Terry , Yamazaki Kenji , O’Malley Cheryl W. 
Published: April 2016

Problem
The Accreditation Council for Graduate Medical Education milestones were written by physicians and thus may not reflect all the behaviors necessary for physicians to optimize their performance as a key member of an interprofessional team.

Approach
From April to May 2013, the authors, Educational Research Outcomes Collaborative leaders, assembled interprofessional team discussion groups, including patients or family members, nurses, physician trainees, physician educators, and other staff (optional), at 11 internal medicine (IM) programs. Led by the site’s principal investigator, the groups generated a list of physician behaviors related to the entrustable professional activity (EPA) of a safe and effective discharge of a patient from the hospital, and prioritized those behaviors.

Outcomes
A total of 182 behaviors were listed, with lists consisting of between 10 and 29 behaviors. Overall, the site principal investigators described all participants as emerging from the activity with a new understanding of the complexity of training physicians for the discharge EPA. The authors batched behaviors into six components of a safe and effective discharge: medication reconciliation, discharge summary, patient/caregiver communication, team communication, active collaboration, and anticipation of posthospital needs. Specific, high-priority behavior examples for each component were identified, and an assessment tool for direct observation was developed for the discharge EPA.

Next Steps
The authors are currently evaluating trainee and educator perceptions of the assessment tool after implementation in 15 IM programs. Additional next steps include developing tools for other EPAs, as well as a broader evaluation of patient outcomes in the era of milestone-based assessment.
Mechanical Construct Characteristics Predisposing to Non-union After Locked Lateral Plating of Distal Femur Fractures
Authors: Rodriguez Edward K. , Zurakowski David , Herder Lindsay , Hall Amber , Walley Kempland C. , Weaver Mike J. , Appleton Paul T. , Vrahas Mark 
Published: April 2016

Objectives:
To identify discrete construct characteristics related to overall construct rigidity that may be independent predictors of nonunion after lateral locked plate (LLP) fixation of distal femur fractures.

Design:
Retrospective case–control study.

Setting:
Three level-1 urban trauma centers.

Patients/Participants:
Two hundred and seventy-one supracondylar femoral fractures treated with LLP at 3 affiliated level 1 urban trauma centers between August 2004 and December 2010.

Methods:
Nonunion was defined as a secondary procedure for poor healing. Construct variables included: (1) combined plate design and material variable, (2) Plate length, (3) # screws proximal to fracture, (4) total screw density (TSD), (5) proximal screw density (PSD), (6) presence of a screw crossing the main fracture, and (7) rigidity score multivariable analysis was performed using logistic regression to identify independent risk factors for nonunion.

Intervention:
LLP fixation.

Main Outcome Measure:
Nonunion.

Results:
Nonunion rate was 13.3% (n = 36). There was a significant association between plate design/material and nonunion with 41% of stainless constructs and 10% of titanium constructs resulting in a nonunion (P < 0.001). Rigidity scores reached significance (P = 0.001) with constructs resulting in a nonunion having higher scores. No significant univariate differences with respect to number of proximal screws, plate length, total screw density, or proximal screw density were observed between healed fractures and those with nonunion. Results of the multivariate analysis confirmed that the primary significant independent predictor of nonunion was plate design/material (odds ratio, 6.8; 95% CI, 2.9–16.1; P < 0.001).

Conclusions:
When treating distal femur fractures with LLP, combined plate design and material variable has a highly significant influence on the risk of nonunion independent of any other construct variable.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.