bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonparametric Bayesian inference for mean residual life functions in survival analysis
Authors: Poynor Valerie , Kottas Athanasios
Published: January 2018

Modeling and inference for survival analysis problems typically revolves around different functions related to the survival distribution. Here, we focus on the mean residual life (MRL) function, which provides the expected remaining lifetime given that a subject has survived (i.e. is event-free) up to a particular time. This function is of direct interest in reliability, medical, and actuarial fields. In addition to its practical interpretation, the MRL function characterizes the survival distribution. We develop general Bayesian nonparametric inference for MRL functions built from a Dirichlet process mixture model for the associated survival distribution. The resulting model for the MRL function admits a representation as a mixture of the kernel MRL functions with time-dependent mixture weights. This model structure allows for a wide range of shapes for the MRL function. Particular emphasis is placed on the selection of the mixture kernel, taken to be a gamma distribution, to obtain desirable properties for the MRL function arising from the mixture model. The inference method is illustrated with a data set of two experimental groups and a data set involving right censoring. The supplementary material available at Biostatistics online provides further results on empirical performance of the model, using simulated data examples.
Asymptotic Behaviour and Estimates of Slowly Varying Convolution Semigroups
Authors: Grzywny Tomasz , Ryznar Michał , Trojan Bartosz
Published: December 2017

We study the asymptotic formulas and estimates for the transition densities of isotropic unimodal convolution semigroups of probability measures on $\mathbb{R}^{d}$ under the assumption that its Lévy–Khintchine exponent varies slowly. We derive some new estimates of the transition densities and Green functions.
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

Objective

Observational 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 Methods

We 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.

Results

When 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.

Discussion

Although these results demonstrate the promise of MCEA, additional studies that include inpatient administered medications are necessary for validation of the algorithm.

Conclusions

In clinical and simulation studies, MCEA demonstrated superior sensitivity and specificity for identifying pharmacologic classes associated with CDI compared to logistic regression.
Addressing Implicit Bias to Improve Cross-cultural Care
Authors: PEREDA BRENDA , MONTOYA MARGARET
Published: January 2018

Health disparities cluster around race, ethnicity, education, neighborhoods, and income. Systems of exclusion that correlate with social determinants compound the disproportionate burden of poor health experienced by people of color. By 2056, ~50% of the population is expected to fall into categories currently labeled “under-represented minorities” (URMs), primarily African Americans, Latinxs, and American Indians. Although URMs comprise 30% of the general population, only 9% of medical doctors [Association of American Medical Colleges (AAMC)] are URMs. We can lessen the negative effects of implicit bias and minimize inequities and unequal treatment by medical providers with training in cross-disciplinary diversity knowledge and communication skills.
Itch and neuropathic itch
Authors: Hachisuka Junichi , Chiang Michael C. , Ross Sarah E.
Published: January 2018

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.
Ethical Challenges When Caring for Orthodox Jewish Patients at the End of Life
Authors: Bressler Toby , Popp Beth
Published: January 2018

Dying is a deeply personal process. The personal values, goals, and experiences of a lifetime come to the forefront during the end of life and may be shaped to some degree by the religious and cultural identity of the patient and family. When patients are part of a faith-based, religious, or cultural minority group, it can be particularly challenging for the clinical care team to gain the understanding and insights needed to reconcile disparities between majority and minority values. This article uses a case study to illustrate and review ethical issues, which frequently occur and can be anticipated in the end-of-life care of patients who identify themselves as Orthodox Jews. Although the specifics are unique to this faith-based minority group, the process of identifying, educating, and developing a means to incorporate faith-based and cultural minority beliefs and values in the provision of care can be applied to other such minority groups that the clinical team may encounter in their work.
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

The 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

Brouwer’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

The 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 implementation

TCIApathfinder 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.

Contact

pamela.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

We 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

Mimicking 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.
NRT1.1-dependent NH4+ toxicity in Arabidopsis is associated with disturbed balance between NH4+ uptake and assimilation
Authors: Jian Shaofen , Liao Qiong , Song Haixing , Liu Qiang , Lepo Joe Eugene , Guan Chunyun , Zhang Jianhua , Zhang Zhenhua
Published: December 2017

The nitrate transporter NRT1.1 is involved in plant NH4+ toxicity; however, its mechanism remains undefined. In this study, wild-type Arabidopsis (Col-0) and NRT1.1 mutants (chl1-1 and chl1-5) were grown hydroponically in NH4NO3 and (NH4)2SO4 media to evaluate NRT1.1 function in NH4+ stress responses. All plants grew normally in mixed N sources, but Col-0 displayed more chlorosis, and lower biomass and photosynthesis than the NRT1.1 mutants in the (NH4)2SO4 condition. Grafting experiments between Col-0 and chl1-5 further confirmed that NH4+ toxicity is NRT1.1-dependent. In (NH4)2SO4 medium, NRT1.1 facilitated the higher expression of NH4+ transporters, increasing NH4+ uptake. Additionally, glutamine synthetase (GS) and glutamate synthetase (GOGAT) in roots of Col-0 plants decreased and soluble sugar accumulated significantly, whereas pyruvate kinase (PK)-mediated glycolysis was not affected, all of which contributed to NH4+ accumulation. In contrast, the NRT1.1 mutants reduced NH4+ accumulation and enhanced NH4+ assimilation through glutamate dehydrogenase (GDH) and glutamate-oxaloacetate transamination (GOT) activity. In addition, the upregulation of genes involved in senescence in Col-0 plants treated with (NH4)2SO4 suggests that ethylene could be involved in NH4+ toxicity responses. Our results indicate that NH4+ toxicity is dependent on NRT1.1 in Arabidopsis, characterized by enhanced NH4+ accumulation and by perturbed NH4+ metabolism, which stimulated ethylene-induced plant senescence.
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

Aims

Non-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 Methods

Murine 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.

Results

Imatinib 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.

Conclusions

Immune-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 Abstract

Electrospinning 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.

We 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

Purpose

This 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/approach

To 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.

Findings

The 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/value

This 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

A 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

Introduction

Spigelian 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.

Methods

A 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.

Results

Four 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.

Conclusion

Laparoscopic 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

Aim

Large‐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.

Location

China.

Methods

Species 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.

Results

Hotspots 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 conclusions

We 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

Kant 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.
Protective effect of fenofibrate against ischemia‐/reperfusion‐induced cardiac arrhythmias in isolated rat hearts
Authors: Bukhari Ishfaq A. , Almotrefi Abdulrahman A. , Mohamed Osama Y. , Al‐Masri Abeer A. , Sheikh Saeed A.
Published: December 2017

Fenofibrate is a peroxisome proliferator‐activated receptor (PPAR)‐α activator that lowers triglycerides and influences cytochrome P‐450 (CYP‐450) epoxygenase‐dependent arachidonic acid (AA) metabolism. CYP‐450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating and cardiac and renal protective properties. Fibrates possess similar properties due to their CYP‐450 epoxygenase‐inducing properties that lead to increase in endogenous EET production. In the current investigations, fenofibrate (100 mg/kg, orally) for 2 weeks decreased ischemia‐/reperfusion (I/R)‐induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) in the isolated rat hearts. Fenofibrate caused marked inhibition of the reperfusion‐induced cardiac arrhythmias. The incidence of reperfusion‐induced VF decreased from 80% in the control vehicle‐treated animals to 33% in the fenofibrate‐treated animals (P < 0.001). PVCs were also significantly (P < 0.01) decreased from 223.2 ± 51 in control vehicle‐treated animals to 136.8 ± 22 in fenofibrate‐treated animals. Total duration of reperfusion‐induced VT decreased from 29.2 ± 6.3 s in control, vehicle‐treated animals to 4.8 ± 1.3 s in fenofibrate‐treated animals, P < 0.001. Heart rate and perfusion pressure were not significantly affected by fenofibrate pretreatment. Diltiazem, a clinically used anti‐arrhythmic agent, produced complete protection against I/R‐induced cardiac arrhythmias in this model reducing the incidence of VF from 80% in control, vehicle‐treated animals to 10% in diltiazem‐treated hearts. These findings indicate that fenofibrate suppresses arrhythmias in isolated rat hearts subjected to I/R‐induced injury.
Three‐dimensional texture of natural pseudotachylyte: Pseudotachylyte formation mechanism in hydrous accretionary complex
Authors: Hamada Yohei , Kimura Gaku , Kameda Jun , Yamaguchi Asuka , Hamahashi Mari , Fukuchi Rina , Kitamura Yujin , Okamoto Shin'ya
Published: January 2018

Melt‐origin pseudotachylyte is the most reliable seismogenic fault rock. It is commonly believed that pseudotachylyte generation is rare in the plate subduction zone where interstitial fluids are abundant and can trigger dynamic fault‐weakening mechanisms such as thermal pressurization. Some recent studies, however, have discovered pseudotachylyte‐bearing faults in exhumed ancient accretionary complexes, indicating that frictional melting also occurrs during earthquakes in subduction zones. To clarify the pseudotachylyte generation mechanism and the variation of slip behavior in the plate subduction zone, a pseudotachylyte found in the exhumed fossil accretionary complex (the Shimanto Belt, Nobeoka, Japan) was re‐focused and microscopic and three‐dimensional observations of the pseudotachylyte‐bearing fault were performed based on optical, electron, and X‐ray microscope images. Based on the patterns contained in the fragment, the pseudotachylyte is divided into four domains, although no clear domain boundaries or layering structures are not found. Three‐dimensional observation also suggests that the pseudotachylyte were fragmented or isolated by cataclasite or carbonate breccia. The pseudotachylyte was rather injected into the surrounding carbonate breccia, which is composed of angular fragments of the host rock and a matrix of tiny crystalline carbonate. The pseudotachylyte volume was extracted from the X‐ray microscope image and the heat abundance consumed by the pseudotachylyte generation was estimated at 2.18 MJ/m2, which can be supplied during a slip of approximately 0.5 m. These observations and calculations, together with the results of the previous investigations, suggest hydrofracturing and rapid carbonate precipitation that preceded or accompanied the frictional melting. Dynamic hydrofracturing during a slip can be caused by rapid fluid pressurization, and can induce abrupt decrease in fluid pressure while drastically enhancing the shear strength of the shear zone. Consequently, frictional heating would be reactivated and generate the pseudotachylyte. These deformation processes can explain pseudotachylyte generation in hydrous faults with the impermeable wall rock.
P21‐activated kinase 2 is essential in maintenance of peripheral Foxp3+ regulatory T cells
Authors: Choi Jinyong , Pease David Randall , Chen Siqi , Zhang Bin , Phee Hyewon
Published: January 2018

The p21‐activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus‐derived regulatory T (Treg) cells. However, whether Pak2 is required for the functions of various subsets of peripheral T cells, such as naive CD4 and helper T‐cell subsets including Foxp3+ Treg cells, is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen. Temporal deletion of Pak2 greatly reduced the number of Foxp3+ Treg cells, while minimally affecting the homeostasis of naive CD4 T cells. Pak2 was required for proliferation and Foxp3 expression of Foxp3+ Treg cells upon T‐cell receptor and interleukin‐2 stimulation, differentiation of in vitro induced Treg cells, and activation of naive CD4 T cells. Together, Pak2 is essential in maintaining the peripheral Treg cell pool by providing proliferation and maintenance signals to Foxp3+ Treg cells.
Non‐interventional 1‐year follow‐up study of peri‐implant soft tissues following previous soft tissue augmentation and crown insertion in single‐tooth gaps
Authors: Huber Samuel , Zeltner Marco , Hämmerle Christoph H. F. , Jung Ronald E. , Thoma Daniel S.
Published: December 2017

Aim

To assess peri‐implant soft tissue dimensions at implant sites, previously augmented with a collagen matrix (VCMX) or an autogenous subepithelial connective tissue graft (SCTG), between crown insertion and 1 year.

Methods

Twenty patients with single‐tooth implants received soft tissue augmentation prior to abutment connection randomly using VCMX or SCTG. Following abutment connection 3 months later, final reconstructions were fabricated and inserted (baseline). Patients were recalled at 6 months (6M) and at 1 year (FU‐1). Measurements included clinical data, soft tissue thickness, volumetric outcomes and patient‐reported outcome measures (PROMs).

Results

The buccal soft tissue thickness showed a median decrease of −0.5 mm (−1.0;0.3) (VCMX) and 0.0 mm (−0.5;1.0) (SCTG) (p = .243) up to FU‐1. The soft tissue volume demonstrated a median decrease between BL and FU‐1 of −0.1 mm (−0.2;0.0) (p = .301) for VCMX and a significant decrease of −0.2 mm (−0.4; −0.1) (p = .002) for SCTG, respectively. Intergroup comparisons did not reveal any significant differences between the groups for peri‐implant soft tissue dimensions and changes up to FU‐1 (p > .05). PROMs did not show any significant changes over time nor differences between the groups.

Conclusion

Between crown insertion and 1 year, the buccal peri‐implant soft tissue dimensions remained stable without relevant differences between sites that had previously been grafted with VCMX or SCTG.
Prominence of scientific publications towards peri‐implant complications in implantology: A bibliometric analysis using the H‐classics method
Authors: Chiang H. ‐S. , Huang R. ‐Y. , Weng P. ‐W. , Mau L. ‐P. , Tsai Y. ‐W. C. , Chung M. ‐P. , Chung C. ‐H. , Yeh H. ‐W. , Shieh Y. ‐S. , Cheng W. ‐C.
Published: January 2018

Current bibliometric analyses of the evolving trends in research scope category across different time periods using the H‐classics method in implantology are considerably limited. The purpose of this study was to identify the classic articles in implantology to analyse bibliometric characteristics and associated factors in implantology for the past four decades. H‐Classics in implantology were identified within four time periods between 1977 and 2016, based on the h‐index from the Scopus® database. For each article, the principal bibliometric parameters of authorship, geographic origin, country origin, and institute origin, collaboration, centralisation, article type, scope of study and other associated factors were analysed in four time periods. A significant increase in mean numbers of authors per H‐Classics was found across time. Both Europe and North America were the most productive region/country and steadily dominated this field in each time period. Collaborations of author, internationally and inter‐institutionally had significantly increased across time. A significant decentralisation in authorships, institutes and journals was noted in past four decades. The journal of Clinical Oral Implant Researches has raised its importance for almost 30 years (1987‐2016). Research on Complications, peri‐implant infection/pathology/therapy had been increasing in production throughout each period. This is the first study to evaluate research trends in implantology in the past 40 years using the H‐classics method, which through analysing via principle bibliometric characteristics reflected a historical perspective on evolutionary mainstream in the field. Prominence of research regarding complications may forecast innovative advancements in future.
Fatigue Behavior of Crystalline‐Reinforced Glass‐Ceramics
Authors: Vicari Carolina Barbosa , Magalhães Bárbara de Oliveira , Griggs Jason Alan , Borba Márcia
Published: January 2018

Purpose

To evaluate the fatigue behavior of two crystalline‐reinforced ceramics: leucite‐reinforced (VL) and lithium disilicate‐based (VD) glass‐ceramics.

Materials and Methods

Bar‐shaped specimens (16 × 4 × 1.2 mm) were produced for each ceramic using prefabricated CAD/CAM blocks. For each group, 30 specimens were subjected to a three‐point flexural strength test in a universal testing machine. For VL and VD, 36 and 41 specimens were subjected to a cyclic fatigue test, respectively. The cyclic fatigue test was performed with a pneumatic mechanical cycling machine (1 Hz; 37°C distilled water). Specimens were tested at two stress levels for each preset lifetime (103 and 104 cycles for VL; 104 and 105 cycles for VD) following the boundary technique. Fractography was performed with a scanning electron microscope. Data were analyzed with Weibull analysis.

Results

There were significant differences among groups for characteristic strength (σ0) and Weibull modulus (m), as the confidence intervals did not overlap. The VD group presented the highest values of σ0, but the lowest Weibull modulus. Both groups showed a reduction of approximately 60% of the initial flexural strength (σf) after cycling for 104 cycles. For VD tested in fatigue, there was no degradation of σf when the number of cycles was increased from 104 to 105. The VL group showed an 18% decrease in σf when the number of cycles increased from 103 to 104. Flexural strength values estimated for a 5% probability of failure were 36 MPa for VL and 55 MPa for VD, after 104 cycles.

Conclusion

Both glass‐ceramics showed similar strength degradation (60%) after a lifetime of 104 cycles, despite their distinct mechanical properties. Mechanical cycling in humid conditions proved to be an important factor for the degradation of the mechanical properties of crystalline‐reinforced glass‐ceramics.
Macroalgal–bacterial interactions: Role of dimethylsulfoniopropionate in microbial gardening by Ulva (Chlorophyta)
Authors: Kessler Ralf W. , Weiss Anne , Kuegler Stefan , Hermes Cornelia , Wichard Thomas
Published: December 2017

The marine macroalga Ulva mutabilis (Chlorophyta) develops into callus‐like colonies consisting of undifferentiated cells and abnormal cell walls under axenic conditions. Ulva mutabilis is routinely cultured with two bacteria, the Roseovarius sp. MS2 strain and the Maribacter sp. MS6 strain, which release morphogenetic compounds and ensure proper algal morphogenesis. Using this tripartite community as an emerging model system, we tested the hypothesis that the bacterial–algal interactions evolved as a result of mutually taking advantage of signals in the environment. Our study aimed to determine whether cross‐kingdom crosstalk is mediated by the attraction of bacteria through algal chemotactic signals. Roseovarius sp. MS2 senses the known osmolyte dimethylsulfoniopropionate (DMSP) released by Ulva into the growth medium. Roseovarius sp. is attracted by DMSP and takes it up rapidly such that DMSP can only be determined in axenic growth media. As DMSP did not promote bacterial growth under the tested conditions, Roseovarius benefited solely from glycerol as the carbon source provided by Ulva. Roseovarius quickly catabolized DMSP into methanethiol (MeSH) and dimethylsulphide (DMS). We conclude that many bacteria can use DMSP as a reliable signal indicating a food source and promote the subsequent development and morphogenesis in Ulva.
Hypocritical Blame, Fairness, and Standing
Authors: Roadevin Cristina
Published: January 2018

This paper argues that hypocritical blame renders blame inappropriate. Someone should not express her blame if she is guilty of the same thing for which she is blaming others, in the absence of an admission of fault. In failing to blame herself for the same violations of norms she condemns in another, the hypocrite evinces important moral faults, which undermine her right to blame. The hypocrite refuses or culpably fails to admit her own mistakes, while at the same time demands that others admit theirs. The paper argues that this lack of reciprocity—expecting others to take morality seriously by apologizing for their faults, without one doing the same in return—is what makes hypocritical blame unfair.
Challenges in developing mucosal vaccines and antibodies against infectious diarrhea in children
Authors: Tokuhara Daisuke
Published: December 2017

Infectious diarrhea in children can be life‐threatening and imposes a large economic burden on healthcare systems, therefore more effective prophylactic and therapeutic drugs are needed urgently. Because most of the pathogens responsible for childhood diarrhea infect the gastrointestinal mucosa, providing protective immunity at the mucosal surface is an ideal way to control pathogen invasion and toxic activity. Mucosal (e.g. oral, nasal) vaccines are superior to systemic (subcutaneous or intramuscular) vaccination for conferring both mucosal and systemic pathogen‐specific immune responses. Therefore, great efforts has been focused on the development of cost‐effective mucosal vaccines for the past 50 years. Recent progress in plant genetic engineering has revolutionized the production of inexpensive and safe recombinant vaccine antigens. For example, rice plant biotechnology has facilitated the development of a cold‐chain‐free rice‐based oral subunit vaccine against Vibrio cholerae. Furthermore, this technology has led to the creation of a rice‐based oral antibody for prophylaxis and treatment of rotavirus gastroenteritis. This review summarizes current perspectives regarding the mucosal immune system and the development of mucosal vaccines and therapeutic antibodies, particularly rice‐based products, and discusses future prospects regarding mucosal vaccines for children.
Breast‐feeding regulates immune system development via transforming growth factor‐β in mice pups
Authors: Sakaguchi Keita , Koyanagi Akemi , Kamachi Fumitaka , Harauma Akiko , Chiba Asako , Hisata Ken , Moriguchi Toru , Shimizu Toshiaki , Miyake Sachiko
Published: December 2017

Background

Breast milk contains important nutrients and immunoregulatory factors that are essential for newborn infants. Recently, epidemiological studies suggested that breast‐feeding prevents a wide range of infectious diseases and lowers the incidence of infant allergic diseases.

Methods

To examine the effects of breast milk on immunological development in infancy, we established an artificial rearing system for hand‐feeding mice and compared mouse pups fed with either breast milk or milk substitute. All mice were killed at 14 days of age and immune cells in the thymus, spleen, and small intestine were examined on flow cytometry.

Results

The number of thymocytes was higher whereas that of total immune cells of peripheral lymphoid tissues was lower in mice fed breast milk compared with milk substitute‐fed mice. In peripheral lymphoid tissues, the proportion of B cells was higher and that of CD8+ T cells, macrophages, dendritic cells, and granulocytes was significantly lower in breast milk‐fed mice. The same alteration in immune cells of the thymus and peripheral lymphoid tissues in milk substitute‐fed mice was also observed in pups reared by mother mice treated with anti‐transforming growth factor‐β (anti‐TGF‐β) monoclonal antibody.

Conclusions

Breast milk regulates the differentiation and expansion of innate and adaptive immune cells partly due to TGF‐β. Hence, TGF‐β in breast milk may be a new therapeutic target for innate immune system‐mediated diseases of infancy.
Alexithymia, depression and anxiety in parents of children with neurodevelopmental disorder: Comparative study of autistic disorder, pervasive developmental disorder not otherwise specified and attention deficit–hyperactivity disorder
Authors: Durukan İbrahim , Kara Koray , Almbaideen Mahmoud , Karaman Dursun , Gül Hesna
Published: December 2017

Background

Recent studies have shown that individuals with neurodevelopmental disorders and their relatives have problems expressing and recognizing emotions, but there is a lack of studies on alexithymia, and the relationship between parental alexithymia and depression–anxiety symptoms in these groups. The aim of this study was therefore to measure alexithymia, depression, and anxiety levels in parents of children with pervasive developmental disorders and attention deficit–hyperactivity disorder (ADHD), and determine whether there is a positive correlation between the child's neurodevelopmental problem severity and parent scores.

Methods

Parents of 29 autistic disorder (AD), 28 pervasive developmental disorder not otherwise specified (PDD‐NOS) and 29 ADHD children were recruited into the study, and completed a demographic information form, as well as the Toronto Alexithymia Scale (TAS‐20), Beck Depression Inventory, and State–Trait Anxiety Inventory.

Results

Alexithymia symptoms were higher in parents of children with AD than in others but unexpectedly, also these symptoms were higher in ADHD parents than in PDD‐NOS groups. In addition, there were unexpected differences according to alexithymia subtype, while only the difference in maternal TAS‐1 scores (difficulty in describing feelings) were statistically significant. Parental depression and state anxiety scores were increased as the child's symptom severity increased, but trait anxiety symptoms were higher in the AD and ADHD group than in the PDD‐NOS group. In all groups, maternal depression and anxiety scores were higher than paternal scores, and differences were significant for depression and anxiety types in AD, and for only anxiety types in ADHD parents. The AD group had the strongest correlation between parental depression–anxiety and alexithymia.

Conclusion

The possibility of alexithymia, depression and anxiety should be kept in mind when working with parents of children with neurodevelopmental disorders.