bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication class enrichment analysis: a novel algorithm to analyze multiple pharmacologic exposures simultaneously using electronic health record data
Authors: Vajravelu Ravy K , Scott Frank I , Mamtani Ronac , Li Hongzhe , Moore Jason H , Lewis James D 
Published: December 2017

AbstractObjectiveObservational studies analyzing multiple exposures simultaneously have been limited by difficulty distinguishing relevant results from chance associations due to poor specificity. Set-based methods have been successfully used in genomics to improve signal-to-noise ratio. We present and demonstrate medication class enrichment analysis (MCEA), a signal-to-noise enhancement algorithm for observational data inspired by set-based methods.Materials and MethodsWe used The Health Improvement Network database to study medications associated with Clostridium difficile infection (CDI). We performed case-control studies for each medication in The Health Improvement Network to obtain odds ratios (ORs) for association with CDI. We then calculated the association of each pharmacologic class with CDI using logistic regression and MCEA. We also performed simulation studies in which we assessed the sensitivity and specificity of logistic regression compared to MCEA for ORs 0.1–2.0.ResultsWhen analyzing pharmacologic classes using logistic regression, 47 of 110 pharmacologic classes were identified as associated with CDI. When analyzing pharmacologic classes using MCEA, only fluoroquinolones, a class of antibiotics with biologically confirmed causation, and heparin products were associated with CDI. In simulation, MCEA had superior specificity compared to logistic regression across all tested effect sizes and equal or better sensitivity for all effect sizes besides those close to null.DiscussionAlthough these results demonstrate the promise of MCEA, additional studies that include inpatient administered medications are necessary for validation of the algorithm.ConclusionsIn clinical and simulation studies, MCEA demonstrated superior sensitivity and specificity for identifying pharmacologic classes associated with CDI compared to logistic regression.
Itch and neuropathic itch
Authors: Hachisuka Junichi , Chiang Michael C. , Ross Sarah E. 
Published: January 2018

Abstract
Neuropathic itch is a pathological condition that is due to damage within the nervous system. This type of itch can be severe and unrelenting, which has a very negative impact on quality of life. Neuropathic itch is more common than generally appreciated because most types of neuropathic pain have a neuropathic itch counterpart. Unfortunately, much like neuropathic pain, there is a lack of effective treatments for neuropathic itch. Here, we consider the neural basis of itch and then describe how injuries within these neural circuits can lead to neuropathic itch in both animal models and human disease states.
National Imaging Trends of Recurrent Pediatric Urolithiasis
Authors: Barrick Lindsey , Cohen Daniel M. , Schober Megan S. , Schwaderer Andrew 
Published: January 2018

Objectives
The aim of this study was to examine computed tomography (CT) and ultrasound (US) utilization trends in incident and prevalent pediatric emergency department (ED) urolithiasis patients before and after imaging guideline release.

Methods
We reviewed imaging modalities for children with 2 or more ED encounters between January 1, 2006, and September 1, 2013, for urolithiasis using the Pediatric Health Information System database. Z scores compared the proportion of patient encounters receiving CT and US before (January 1, 2006, to December 31, 2010) and after (January 1, 2011, to September 1, 2013) the release of imaging guidelines. McNemar test for paired proportions compared the percentage of US and CT use between initial versus subsequent visits. Piecewise logistic regression was used to determine the probability of US use and CT use over time before and after the implementation of imaging guidance.

Results
Analysis was completed on 2041 patients with 4930 unique encounters for urolithiasis. During 1758 encounters (35.7%), CT was performed initially. Ultrasound was performed 1585 times (32.2%). Fourteen percent fewer CT procedures were performed during first urolithiasis visits after guideline release (P < 0.01), whereas US use increased by 15% (P < 0.01). Fewer CT procedures were performed at later visits compared with the first (P < 0.05), and US was used more during second or later visits than the first (P < 0.05).

Conclusions
Medical providers at large academic pediatric EDs have decreased use of CT and increased use of US over the study time frame to diagnose urolithiasis and are now similar during initial visits (US 36.4% vs CT 36.2%, P = 0.94). Physicians are still more likely to use US as the initial urolithiasis imaging modality during second and later encounters.
Single-cell RNA-Seq Resolves Cellular Heterogeneity and Transcriptional Dynamics in Spermatogonial Stem Cells Establishment
Authors: Liao Jinyue , Ng Shuk Han , Tu Jiajie , Shui Luk Alfred Chun , Qian Yan , Fung Jacqueline , Sang Tang Nelson Leung , Feng Bo , Chan Wai-Yee , Fouchet Pierre , Lee Tin-Lap 
Published: December 2017

SummaryThe transition of gonocytes to spermatogonia and subsequent differentiation provide the foundation of spermatogenesis. However, systematic understanding on the cellular and molecular basis of this process is still limited, mainly impeded by the asynchrony in development and the lack of stage-specific markers. Using single-cell RNA sequencing on Oct4-GFP+/KIT- cells isolated from PND5.5 mice, we dissected the cellular heterogeneity and established molecular regulations. We demonstrated that gonocyte-spermatogonial transition was characterized by gene expression change related to apoptosis, cell cycle progression, and regulation of migration processes. Pseudotime analysis reconstructed developmental dynamics of the spermatogonial populations and unraveled sequential cellular and molecular transitions. We also identified CD87 as a neonatal stem cell marker which are potentially involved in the intial establishment of SSC pool. Lastly, we uncovered an unexpected subpopulation of spermatogonia primed to differentiation within the undifferentiated compartment, which is characterized by the lack of self-renewal genes and enhanced Oct4 expression and retinoic acid signaling response. Our study thus provides a novel understanding of cellular and molecular changes during spermatogonial establishment.
On a non-trivial application of Algebraic Topology to Molecular Biology
Authors: Braslavsky Ido , Stavans Joel 
Published: December 2017

AbstractBrouwer’s fixed point theorem, a fundamental theorem in algebraic topology proved more than a hundred years ago, states that given any continuous map from a closed, simply connected set into itself, there is a point that is mapped unto itself. Here we point out the connection between a one-dimensional application of Brouwer’s fixed point theorem and a mechanism proposed to explain how extension of single-stranded DNA substrates by recombinases of the RecA superfamily facilitates significantly the search for homologous sequences on long chromosomes.
TCIApathfinder: an R client for The Cancer Imaging Archive REST API
Authors: Russell Pamela , Fountain Kelly , Wolverton Dulcy , Ghosh Debashis 
Published: December 2017

AbstractSummaryThe Cancer Imaging Archive (TCIA) hosts publicly available de-identified medical images of cancer from over 25 body sites and over 30, 000 patients. Over 400 published studies have utilized freely available TCIA images. Image series and metadata are available for download through a web interface or a REST API. We present TCIApathfinder, an R client for the TCIA REST API. TCIApathfinder wraps API access in user-friendly R functions that can be called within an R session or easily incorporated into scripts. Functions are provided to explore the contents of the large database and to download image files.Availability and implementationTCIApathfinder is available under the MIT license as a package on CRAN (https://cran.r-project.org/web/packages/TCIApathfinder/index.html) and at https://github.com/pamelarussell/TCIApathfinder.Contactpamela.russell@ucdenver.edu
Unconsciously Implanted Visuoauditory Memory in the Presence of Cholecystokinin Retrieved in Behavioral Contexts
Authors: Zhang Zicong , Zheng Christine Xuejiao , Peng Yujie , Guo Yiping , Lu Danyi , Li Xiao , Sun Wenjian , Tang Peng , He Sherry Ling , Li Min , Liu Qing , Xu Fuqiang , Ng Gabriel , Chen Xi , He Jufang 
Published: December 2017

SUMMARYWe investigated whether visuoauditory association can be artificially implanted in rodents and then retrieved in a behaviorally relevant context. Rats were trained to approach the left or right hole of a behavioral apparatus to retrieve a reward depending on the side of electrical stimulation of the auditory cortex (EAC) they received and mice were fear-conditioned to EAC. Next, an irrelevant visual stimulus (VS) was repeatedly paired with EAC in the presence of cholecystokinin (CCK) or with activation of terminals of entorhinal CCK neurons in the auditory cortex. In subsequent behavioral testing with VS, rats approached the hole associated with reward availability and mice showed a freezing response to the VS. A CCK antagonist blocked the establishment of visuoauditory association, whereas a CCK agonist rescued the deficit of association. Our findings provide a scientific foundation for “memory implantation” and indicate that CCK is the switching chemical for formation of visuoauditory association.
Outperforming nature: synthetic enzyme built from DNA flips lipids of biological membranes at record rates
Authors: Ohmann Alexander , Li Chen-Yu , Maffeo Christopher , Al Nahas Kareem , Baumann Kevin N. , Göpfrich Kerstin , Yoo Jejoong , Keyser Ulrich F. , Aksimentiev Aleksei 
Published: December 2017

AbstractMimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane’s inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and single-molecule experiments we find the lipid transport rate catalyzed by the DNA nanostructure to exceed 107molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine.
Pharmacological Macrophage Attenuation by Imatinib Reverts Hepatic Steatosis and Inflammation in Obese Mice
Authors: AlAsfoor Shefaa , Rohm Theresa V. , Bosch Angela J. T. , Dervos Thomas , Calabrese Diego , Matter Matthias S. , Weber Achim , Cavelti-Weder Claudia 
Published: December 2017

AbstractAimsNon-alcoholic fatty liver disease (NAFLD) has become one of the most common liver diseases worldwide. As macrophages play a key role in NAFLD, therapies targeting macrophages have been postulated. Indeed, strategies depleting macrophages or blocking monocyte recruitment into the liver improve NAFLD, however, are not feasible in clinical practice. Our goal was to assess whether attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, and how this impacts NAFLD.Materials and MethodsMurine macrophages were polarized in vitro to different activation states in the presence or absence of imatinib; mice on high fat diet orally treated with imatinib or vehicle; and human monocytes of diabetic patients and healthy controls treated with or without imatinib for translational application.ResultsImatinib specifically attenuated pro-inflammatory murine macrophages in vitro and in vivo. In livers of obese mice, imatinib caused Kupffer cells to adopt an attenuated phenotype via modulation of the TNFα-pathway. This immune-modulation resulted in markedly improved hepatic steatosis along with beneficial effects on liver function, lipids and systemic inflammation. The immune-dampening effect of imatinib also prevailed in human monocytes, indicating translational applicability.ConclusionsImmune-modulation of myeloid cells as exemplified by imatinib may be a novel therapeutic strategy in patients with NAFLD.
Polypyrrole increases branching and neurite extension by Neuro2A cells on PBAT ultrathin fibers
Authors: Granato Alessandro E.C. , Ribeiro André C. , Marciano Fernanda R. , Rodrigues Bruno V. M. , Lobo Anderson O. , Porcionatto Marimelia 
Published: December 2017

Graphical AbstractElectrospinning shows a feasible way to generate hybrid scaffolds from the combination of different materials. This work presented a successful route to prepare ultrathin fibers from hybrid solutions containing a commercial polyester, poly (butylene adipate-co-terephthalate) (PBAT) and a conductive polymer, polypyrrole (PPy). The final material (PBAT/PPy) showed an enhanced potential for neuronal differentiation when compared to neat PBAT. The PPy loading improved branching and neurite extension of Neuro2a cells, which opens a wide range of perspectives where these materials may be applied in regenerative medicine.ABSTRACTWe present a methodology for production and application of electrospun hybrid materials containing commercial polyester (poly (butylene adipate-co-terephthalate; PBAT), and a conductive polymer (polypirrole; PPy) as scaffold for neuronal growth and differentiation. The physical-chemical properties of the scaffolds and optimization of the electrospinning parameters are presented. The electrospun scaffolds are biocompatible and allow proper adhesion and spread of mesenchymal stem cells (MSCs). Fibers produced with PBAT with or without PPy were used as scaffold for Neuro2a mouse neuroblastoma cells adhesion and differentiation. Neuro2a adhered to PBAT and PBAT/PPy2% scaffolds without laminin coating. However, Neuro2a failed to differentiate in PBAT when stimulated by treatment with retinoic acid (RA), but differentiated in PBAT/PPy2% fibers. We hypothesize that PBAT hydrophobicity inhibited proper spreading and further differentiation, and inhibition was overcome by coating the PBAT fibers with laminin. We conclude that fibers produced with the combination of PBAT and PPy can support neuronal differentiation.
The market efficiency of socially responsible investment in Korea
Authors: Ang Wei Rong , Weber Olaf 
Published: January 2018

PurposeThis paper aims to analyze the market efficiency of socially responsible investment in Korea. The authors used the daily price of the Dow Jones Sustainability Index Korea between January 2006 and December 2015.Design/methodology/approachTo analyze the unpredictability of the returns, the authors conducted runs tests, such as the Dickey–Fuller test, the Philip–Perron test, the variance ratio test and autocorrelation tests. These tests investigate whether the future price of socially responsible investment in Korea is dependent on its previous price. If the relationship is dependent, this will violate the theory of weak form of efficient market hypothesis which explains that the past price movements and data do not affect stock prices. Therefore, investors cannot gain any abnormal return by extrapolating the historical data.FindingsThe results suggest that the weak form of the efficient market hypothesis is not valid for the Dow Jones Sustainability Index Korea. This implies that the future price of the index is correlated with past prices. Hence, the future movement of socially responsible investment in Korea can be predicted and enables socially responsible investors to gain abnormal returns.Originality/valueThis is the first study to investigate the market efficiency of socially responsible investment in Korea.
Circulating levels of monocyte chemoattractant protein‐1 as a potential measure of biological age in mice and frailty in humans
Authors: Yousefzadeh Matthew J. , Schafer Marissa J. , Noren Hooten Nicole , Atkinson Elizabeth J. , Evans Michele K. , Baker Darren J. , Quarles Ellen K. , Robbins Paul D. , Ladiges Warren C. , LeBrasseur Nathan K. , Niedernhofer Laura J. 
Published: December 2017

SummaryA serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early‐onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. Here, we identified MCP‐1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating monocyte chemoattractant protein‐1 (MCP‐1) levels increased in an age‐dependent manner in wild‐type (WT) mice. That age‐dependent increase was accelerated in Ercc1−/Δ and Bubr1H/H mouse models of progeria. Genetic and pharmacologic interventions that slow aging of Ercc1−/Δ and WT mice lowered serum MCP‐1 levels significantly. Finally, in elderly humans with aortic stenosis, MCP‐1 levels were significantly higher in frail individuals compared to nonfrail. These data support the conclusion that MCP‐1 can be used as a measure of mammalian biological age that is responsive to interventions that extend healthy aging.
Elective laparoscopic totally extraperitoneal repair for Spigelian hernia: A case series of four patients
Authors: Law Tsz Ting , Ng Ka Kin , Ng Lily , Wong Kin Yuen 
Published: January 2018

AbstractIntroductionSpigelian hernia (SH) is uncommon. Clinical diagnosis may be difficult, but computed tomography (CT) can help to establish the diagnosis. Laparoscopic repair is increasingly performed because it is associated with low morbidity rates. Laparoscopic approaches include transabdominal preperitoneal (TAPP), intraperitoneal onlay mesh (IPOM), and totally extraperitoneal (TEP). Here, we report our experiences of TEP repair for SH.MethodsA retrospective review was performed on all patients with SH who underwent elective laparoscopic TEP repair from 2007 to 2017 at Tung Wah Hospital, Hong Kong.ResultsFour patients with SH were identified in the study period: three with a preoperative diagnosis of SH confirmed by CT scan and one diagnosed incidentally during TEP repair for inguinal hernia. The patients' mean age was 66.8 years (range, 55.0–82.0 years). The mean BMI was 22.8 kg/m2 (range, 20.8–23.6 kg/m2). The mean size of the SH defect was 2.0 cm (range, 0.5–3.0 cm). The mean operative time was 59 min (range, 40–86 min). Concomitant direct inguinal hernia was found in one patient and repaired simultaneously. All patients were discharged on postoperative day 1. One patient developed seroma, which subsided on conservative management. At a mean follow‐up of 36 months (range, 2–108 months), there was no recurrence.ConclusionLaparoscopic repair for SH is preferred over the open approach as it is associated with a low morbidity rate and a short hospital stay. In our experience, TEP technique is safe and effective in laparoscopic SH repair.
Geographical gradients in the biodiversity of Chinese freshwater molluscs: Implications for conservation
Authors: Cai Yongjiu , Zhang Min , Xu Jun , Heino Jani 
Published: January 2018

AbstractAimLarge‐scale diversity patterns are generated by different but not mutually exclusive mechanisms. However, understanding of multiple facets of diversity and their determinants in the freshwater realm remains limited. Here, we characterized the geographical gradients, hotspots and spatial congruence of three facets of freshwater molluscan diversity and evaluated the relative importance of three different underlying mechanisms related to the energy, area/environmental heterogeneity and dispersal/historical hypotheses.LocationChina.MethodsSpecies richness (SR), functional richness (FR) and taxonomic distinctness (TD, a proxy of phylogenetic diversity) were calculated for 212 drainage basins with a total of 313 molluscan species. Spatial congruence between the diversity facets was evaluated with Pearson correlation coefficient and overlap among hotspots. Multiple linear regression models and variation partitioning were used to assess the relative importance of different mechanisms.ResultsHotspots of SR and FR were mainly concentrated in the Yangtze River and Huai River basins, while high TD values were patchily distributed across China. We found extremely low spatial congruence between TD and both SR and FR, while there was relatively high concordance between SR and FR. All diversity facets were best explained by the dispersal/historical hypothesis with strong unique effects, followed by the factors related to the energy hypothesis. The area/ environmental heterogeneity hypothesis was only weakly supported.Main conclusionsWe found a potentially strong influence of dispersal limitation and evolutionary history on the geographical diversity gradients of Chinese molluscs. This finding contrasts with the general finding that energy‐related factors are the strongest correlates of diversity patterns at large spatial scales. Moreover, our results do not support the idea that using any one diversity component as a surrogate of the others in developing conservation strategies. Instead, an integrative approach embracing multiple facets of diversity should be adopted in the conservation of freshwater biodiversity.
Kant's principles of modality
Authors: Blecher Ian 
Published: January 2018

AbstractKant presents three principles of modality in theCritique of Pure Reason. Historically, commentators have mostly disregarded them; a few have rejected them outright. In recent years, however, a consensus has begun to develop around the idea that the role of these principles is to rule out certain metaphysical doctrines. I argue that this understates their importance. Rather, the principles of modality are essential conditions of the possibility of experience. I conclude by examining the question of their truth, which, I argue, can only be grasped by considering them as postulates—i.e., aspracticalpropositions of a certain kind.