bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering
Authors: Liang Fan , Leland Hyuma , Jedrzejewski Breanna , Auslander Allyn , Maniskas Seija , Swanson Jordan , Urata Mark , Hammoudeh Jeffrey , Magee William 
Published: February 2018

Abstract
Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft.
A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well.
Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), β-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL.
The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most promise in alveolar cleft reconstruction.
Nasal Cavity Actinomycosis Mimicking Rhinolith
Authors: Kim Sung-Dong , Kim Deok-Soo , Choi Kyung-Un , Cho Kyu-Sup 
Published: February 2018

Abstract
Actinomycosis is a subacute-to-chronic bacterial infection caused by filamentous, gram-positive, non-acid-fast, anaerobic-to-microaerophilic bacteria. It is characterized by continuous spread, suppurative and granulomatous inflammation, and formation of multiple abscesses and sinus tracts that may discharge sulfur granules. Although the most common clinical forms of actinomycosis are cervicofacial, involvement of the nose and paranasal sinuses are extremely rare. Furthermore, nasal cavity actinomycosis mimicking rhinolith has not been reported in the literature previously. This article reports a patient of nasal cavity actinomycosis causing symptoms similar to those of a rhinolith, which was successfully treated by surgical debridement and antibiotic therapy.
Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients
Authors: Liang Emily C. , Rossetti Maura , Sidwell Tiffany , Groysberg Victoria , Sunga Gema , Korin Yael , Vangala Sitaram , Abdalla Basmah , Lum Erik , Bunnapradist Suphamai , Pham Phuong-Thu , Danovitch Gabriel , Reed Elaine F. , Schaenman Joanna 
Published: February 2018

Background
The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via “inflamm-aging.” Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes.

Methods
Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression.

Results
Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16−) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients.

Conclusions
In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation.
Tradeoffs and cultural diversity
Authors: Karin Omer , Alon Uri 
Published: February 2018

AbstractCulture is humanity’s prime adaptation. Which cultural traits contribute to adaptive value, and how they do so, is, however, unclear and debated. Here, we apply an approach from systems biology, known as Pareto task inference (ParTI), to bring a fresh perspective to these questions. ParTI considers systems that need to perform multiple tasks. No system can be optimal at all tasks at once, leading to a fundamental tradeoff. Such tradeoffs constrain evolution, because adaptive change for one task may be prevented because it compromises other tasks. These constraints result in specific polygon patterns in multivariate trait data. ParTI detects these polygons and their vertices, in order to infer the number of adaptive tasks and their nature. Here, we applied ParTI to two datasets of human cultural traits, on Austronesian cultures and modern hunter-gatherers, adjusting for phylogeny and spatial diffusion effects. We find that these independent datasets show the hallmarks of a tradeoff between the same three tasks: resource defense, resource competition, and mobility/exchange. Specific combinations of cultural traits are adaptive for each of these tasks. We thus suggest that part of the diversity of human cultural traits is constrained by tradeoffs between key tasks.
Occipitotemporal Representations Reflect Individual Differences in Conceptual Knowledge
Authors: Braunlich K. , Love B. C. 
Published: February 2018

AbstractThrough selective attention, decision-makers can learn to ignore behaviorally-irrelevant stimulus dimensions. This can improve learning and increase the perceptual discriminability of relevant stimulus information. To account for this effect, popular contemporary cognitive models of categorization typically include of attentional parameters, which provide information about the importance of each stimulus dimension in decision-making. The effect of these parameters on psychological representation is often described geometrically, such that perceptual differences over relevant psychological dimensions are accentuated (or stretched), and differences over irrelevant dimensions are down-weighted (or compressed). In sensory and association cortex, representations of stimulus features are known to covary with their behavioral relevance. Although this implies that neural representational space might closely resemble that hypothesized by formal categorization theory, to date, attentional effects in the brain have been demonstrated through powerful experimental manipulations (e.g., contrasts between relevant and irrelevant features). This approach sidesteps the role of idiosyncratic conceptual knowledge in guiding attention to useful information sources. To bridge this divide, we used formal categorization models, which were fit to behavioral data, to make inferences about the concepts and strategies used by individual participants during decision-making. We found that when greater attentional weight was devoted to a particular visual feature (e.g., “color”), its value (e.g., “red”) was more accurately decoded from occipitotemporal cortex. We additionally found that this effect was sufficiently sensitive to reflect individual differences in conceptual knowledge. The results indicate that occipitotemporal stimulus representations are embedded within a space closely resembling that proposed by classic categorization models.
Information use during movement regulates how fragmentation and loss of habitat affect body size
Authors: Hillaert Jasmijn , Vandegehuchte Martijn L. , Hovestadt Thomas , Bonte Dries 
Published: February 2018

AbstractAn individual's body size is central to its behavior and physiology, and tightly linked to its dispersal ability. The spatial arrangement of resources and a consumer's capacity to locate them are therefore expected to exert strong selection on consumer body size.We investigated the evolutionary impact of both the fragmentation and loss of habitat on consumer body size and its feedback effects on resource distribution, under varying levels of information use during the settlement phase of dispersal. We developed a mechanistic, individual-based, spatially explicit model, including several allometric rules for key consumer traits. Our model reveals that as resources become more fragmented and scarce, informed settlement selects for larger body sizes while random settlement promotes small sizes. Information use may thus be an overlooked explanation for the observed variation in body size responses to habitat fragmentation. Moreover, we find that resources can accumulate and aggregate if information on resource abundance is incomplete. Informed movement results in stable resource-consumer dynamics and controlled resources across space. However, habitat fragmentation and loss destabilize local dynamics and disturb resource suppression by the consumer. Considering information use during movement is thus critical to understand the eco-evolutionary dynamics underlying the functioning and structuring of consumer communities.
A Highly Efficient and Faithful MDS Patient-Derived Xenotransplantation Model for Pre-Clinical Studies
Authors: Song Yuanbin , Rongvaux Anthony , Taylor Ashley , Jiang Tingting , Tebaldi Toma , Balasubramanian Kunthavai , Bagale Arun , Terzi Yunus Kasim , Gbyli Rana , Wang Xiaman , Zhao Jun , Podoltsev Nikolai , Xu Mina , Neparidze Natalia , Wong Ellice , Torres Richard , Bruscia Emanuela M. , Kluger Yuval , Manz Markus G. , Flavell Richard A. , Halene Stephanie 
Published: February 2018

AbstractComprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. We developed a novel MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that for the first time provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and functionin vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.
The DNA repair associated protein Gadd45γ regulates the temporal coding of immediate early gene expression and is required for the consolidation of associative fear memory
Authors: Li Xiang , Marshall Paul R. , Leighton Laura J. , Zajaczkowski Esmi L. , Bredy Timothy W. , Wei Wei 
Published: February 2018

AbstractVisual abstractWe have identified a member of the Growth arrest and DNA damage (Gadd45) family, Gadd45γ, which is known to be involved in the regulation of DNA repair, as a key player in the formation of associative fear memory. Gadd45γ regulates the temporal dynamics of learning-induced immediate early gene (IEG) expression in the prelimbic prefrontal cortex through its interaction with DNA double-strand break (DSB)-mediated changes in DNA methylation. Our findings suggest a two-hit model of experience-dependent IEG activity and learning that comprises 1) a first wave of IEG expression governed by DSBs followed by an increase in DNA methylation, and 2) a second wave of IEG expression associated with Gadd45γ and active DNA demethylation at the same site, which is necessary for memory consolidation.Significance statementHow does the pattern of immediate early gene (IEG) transcription in the brain relate to the storage and accession of information, and what controls these patterns? This paper explores how GADD45γ, a gene that is known to be involved with DNA modification and repair, regulates the temporal coding of IEGs underlying associative learning and memory. We reveal that, during fear learning, GADD45γ serves to act as a coordinator of IEG expression and subsequent memory consolidation by directing temporally specific changes in active DNA demethylation at the promoter of plasticity-related IEGs.
Variation among intact tissue samples reveals the core transcriptional features of human CNS cell classes
Authors: Kelley Kevin W. , Inoue Hiromi , Molofsky Anna V. , Oldham Michael C. 
Published: February 2018

AbstractIt is widely assumed that cells must be physically isolated to study their molecular profiles. However, intact tissue samples naturally exhibit variation in cellular composition, which drives covariation of cell-class-specific molecular features. By analyzing transcriptional covariation in 7221 intact CNS samples from 840 individuals representing billions of cells, we reveal the core transcriptional identities of major CNS cell classes in humans. By modeling intact CNS transcriptomes as a function of variation in cellular composition, we identify cell-class-specific transcriptional differences in Alzheimer’s disease, among brain regions, and between species. Among these, we show that PMP2 is expressed by human but not mouse astrocytes and significantly increases mouse astrocyte size upon ectopic expression in vivo, causing them to more closely resemble their human counterparts. Our work is available as an online resource (http://oldhamlab.ctec.ucsf.edu) and provides a generalizable strategy for determining the core molecular features of cellular identity in intact biological systems.
A functional landscape of chronic kidney disease entities from public transcriptomic data
Authors: Tajti Ferenc , Kuppe Christoph , Antoranz Asier , Ibrahim Mahmoud M. , Kim Hyojin , Ceccarelli Francesco , Holland Christian , Olauson Hannes , Floege Jürgen , Alexopoulos Leonidas G. , Kramann Rafael , Saez-Rodriguez Julio 
Published: February 2018

AbstractTo develop efficient therapies and identify novel early biomarkers for chronic kidney disease an understanding of the molecular mechanisms orchestrating it is essential. We here set out to understand how differences in CKD origin are reflected in gene expression. To this end, we integrated publicly available human glomerular microarray gene expression data for nine kidney disease entities that account for a majority of CKD worldwide. We included data from five distinct studies and compared glomerular gene expression profiles to that of non-tumor parts of kidney cancer nephrectomy tissues. A major challenge was the integration of the data from different sources, platforms and conditions, that we mitigated with a bespoke stringent procedure. This allowed us to perform a global transcriptome-based delineation of different kidney disease entities, obtaining a landscape of their similarities and differences based on the genes that acquire a consistent differential expression between each kidney disease entity and nephrectomy tissue. Furthermore, we derived functional insights by inferring activity of signaling pathways and transcription factors from the collected gene expression data, and identified potential drug candidates based on expression signature matching. We validated representative findings by immunostaining in human kidney biopsies indicating e.g. that the transcription factor FOXM1 is significantly and specifically expressed in parietal epithelial cells in RPGN whereas not expressed in control kidney tissue. These results provide a foundation to comprehend the specific molecular mechanisms underlying different kidney disease entities, that can pave the way to identify biomarkers and potential therapeutic targets. To facilitate this, we provide our results as a free interactive web application:https://saezlab.shinyapps.io/ckd_landscape/.Translational StatementChronic kidney disease is a combination of entities with different etiologies. We integrate and analyse transcriptomics analysis of glomerular from different entities to dissect their different pathophysiology, what might help to identify novel entity-specific therapeutic targets.
Uncertainty and Exploration
Authors: Gershman Samuel J. 
Published: February 2018

AbstractIn order to discover the most rewarding actions, agents must collect information about their environment, potentially foregoing reward. The optimal solution to this “explore-exploit” dilemma is often computationally challenging, but principled algorithmic approximations exist. These approximations utilize uncertainty about action values in different ways. Somerandomexploration algorithms scale the level of choice stochasticity with the level of uncertainty. Otherdirectedexploration algorithms add a “bonus” to action values with high uncertainty. Random exploration algorithms are sensitive tototaluncertainty across actions, whereas directed exploration algorithms are sensitive torelativeuncertainty. This paper reports a multi-armed bandit experiment in which total and relative uncertainty were orthogonally manipulated. We found that humans employ both exploration strategies, and that these strategies are independently controlled by different uncertainty computations.
A Model for Resource Competition in CRISPR-Mediated Gene Repression
Authors: Chen Pin-Yi , Qian Yili , Vecchio Domitilla Del 
Published: February 2018

AbstractCRISPR-mediated gene regulation is known for its ability to control multiple targets simultaneously due to its modular nature: the same dCas9 effector can target different genes simply by changing the associated gRNA. However, multiplexing requires the sharing of limited amounts of dCas9 proteins among multiple gRNAs, leading to resource competition. In turn, competition between gRNAs for the same resource may hamper network function. In this work, we develop a general model that takes into account the sharing of a limited amount of dCas9 protein for arbitrary CRISPR-mediated gene repression networks. We demonstrate that, as a result of resource competition, hidden interactions appear, that modify the intended network regulations. As a case study, we analyze the effects of these hidden interactions in repression cascades. In particular, we illustrate that perfect adaptation to resource fluctuations can be achieved in cascades with an even number of repressors. In contrast, cascades with an odd number of repressors are substantially impacted by resource competition.
Asset concentration in the US agricultural balance sheet: a relative information approach
Authors: Onel Gulcan , Kropp Jaclyn , Moss Charles B. 
Published: February 2018

Purpose
Over the past four decades, real values of farm real estate and the share of assets on farmers’ balance sheets attributed to farm real estate have increased. The purpose of this paper is to examine the factors that explain the concentration of the US agricultural balance sheet around a particular asset, farm real estate, and the extent to which the degree of asset concentration varies across United States Department of Agriculture production regions.

Design/methodology/approach
State-level data from 48 states and entropy-based inequality measures are used to examine changes in asset distributions (real estate vs non-real estate assets) both within and between regions over time.

Findings
The agricultural balance sheet is found to concentrate into real estate in the USA over the period 1960-2003 with the rate of concentration varying across production regions. In some regions, the concentration is mainly due to changes in real estate prices, while in other regions concentration is also driven by changes in real estate holdings or changes in total factor productivity.

Originality/value
This study formally estimates the degree to which the concentration of balance sheet items can be explained by the observed changes in farm real estate prices relative to observed changes in agricultural factor productivity or changes in farm real estate holdings. The computed regional differences in asset concentration and its main drivers have implications for changes in equity and solvency positions of farmers as well as agricultural lenders’ risk exposure.