bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of gossypol biosynthetic pathway
Authors: Tian Xiu , Ruan Ju-Xin , Huang Jin-Quan , Yang Chang-Qing , Fang Xin , Chen Zhi-Wen , Hong Hui , Wang Ling-Jian , Mao Ying-Bo , Lu Shan , Zhang Tian-Zhen , Chen Xiao-Ya 
Published: May 2018

SignificanceCotton is an important crop, and terpenoids form the largest group of natural products. Gossypol and related sesquiterpene aldehydes in cotton function as phytoalexins against pathogens and pests but pose human health concerns, as cotton oil is still widely used as vegetable oil. We report the isolation and identification of four enzymes and the recharacterization of one previously reported P450. We are now close to the completion of the gossypol pathway, an important progress in agricultural and plant sciences, and the data are beneficial to improving food safety. Among the six compounds (intermediates) isolated following gene silencing, one affected plant disease resistance significantly. Thus, these “hidden natural products” harbor interesting biological activities worthy of exploration.
Students’ Reparticularization of Chinese Language and Culture at the University of Rwanda Confucius Institute
Authors: Stambach Amy , Wamalwa Kevin 
Published: May 2018

AbstractThis article examines the reparticularization of Chinese language and culture in a teaching-learning context at the University of Rwanda. It critiques models of dissemination that suggest direct inscription of semiotic value onto local contexts of use. Ethnographically, the article demonstrates that students’ uptake of what their teachers deem real or authentic is in fact a metapragmatic reconstrual of teachers’ lexemic tokens “real” and “original” that teachers enact in their teaching activities. Students’ reconstrual incrementally alters teachers’ sign values and links their users to one other. Students’ reparticularized sign values, in turn, link their users to distinct activity routines beyond learning Chinese and kung fu in the classroom. The article argues that language and kung fu classes for students are one phase segment of larger sets of activities students undertake to become competitive in a challenging job market.
Apple, Acaricide Evaluation, 1986
Authors: Beers E. H. , Baird R. J. , Eisner E. A. 
Published: May 2018

Abstract
This test was conducted in a commercial orchard containing mixed ages of trees with under-tree irrigation. The block had a history of reduced effectiveness of control with Plictran. A randomized complete block design was used, with 4 single-tree replicates per treatment. Materials were applied on 6 Jun as a dilute spray to the point of drip with a handgun sprayer operating at 400-500 psi. Per acre rates were based on 400 gal/acre. Mites were sampled weekly. Twenty-five leaves were collected from each tree (100 per treatment), brushed with a mite brushing machine, and mites of each species counted.
Institutional review of glial tumors treated with chemotherapy: the first description of PCV-related pseudoprogression
Authors: Sharma Ankur M , Willcock Michael , Bucher Oliver , Amaratunga Thelina , Khan M Nazir , Loewen Shaun K , Quon Harvey , Essig Marco , Pitz Marshall 
Published: May 2018

Abstract

Background
Pseudoprogression refers to areas of enhancement on MRI postadjuvant chemoradiation that arise as a result of treatment-related effects. Pseudoprogression has been well described with temozolomide-based chemoradiation but has not been studied in the setting of procarbazine, lomustine, and vincristine (PCV) chemotherapy. We reviewed patients treated with PCV to investigate the occurrence of pseudoprogression.

Methods
Adults diagnosed with World Health Organization grade II or III gliomas between 2010 and 2015 and treated with PCV or temozolomide were identified. Patient, tumor, treatment, and MRI data were retrospectively collected and analyzed. Pseudoprogression was defined as new enhancement seen on MRI within 6 months of completion of adjuvant radiotherapy or concurrent chemoradiation, which improved or remained stable on subsequent scans without therapeutic intervention. If MRI showed areas of new enhancement outside the 6-month post-treatment window, which resolved or remained stable without treatment, or in patients who did not receive adjuvant treatment, it was referred to as “atypical pseudoprogression.”

Results
Fifty-seven patients were identified. Nine (16%) patients were identified as having pseudoprogression on MRI. Two (4%) of these patients were treated with PCV and 7 (12%) were treated with temozolomide. Seventeen (30%) patients had atypical pseudoprogression: 8 (14%) treated with temozolomide, 8 (14%) treated with PCV, and 1 (2%) treated with both types of chemotherapy.

Conclusions
We describe the first 2 cases of PCV-related pseudoprogression and 17 cases of atypical pseudoprogression. As the re-emergence of adjuvant PCV occurs in clinical practice, the occurrence of classical and atypical pseudoprogression could have a significant impact on clinical decision making.
Macrovascular Decompression of Facial Nerve With Anteromedial Transposition of a Dolichoectatic Vertebral Artery: 3-Dimensional Operative Video
Authors: Tabani Halima , Yousef Sonia , Burkhardt Jan-Karl , Gandhi Sirin , Benet Arnau , Lawton Michael T 
Published: May 2018

Abstract
Most cranial nerve compression syndromes (ie, trigeminal neuralgia and hemifacial spasm) are caused by small arteries impinging on a nerve and are relieved by microvascular decompression. Rarely, cranial nerve compression syndromes can be caused by large artery impingement and can be relieved by macrovascular decompression. When present, this compression often occurs in association with degenerative atherosclerosis in the vertebral arteries (VA) and basilar artery. Conservative treatment is recommended for mild forms, but surgical transposition of the VA away from the root entry zone (REZ) can be considered. This video demonstrates macrovascular decompression of a dolichoectatic VA in a 74-yr-old female with refractory left hemifacial spasm. After obtaining IRB approval, patient consent was sought for the procedure. With the patient in three-quarter-prone position, a far-lateral craniotomy was performed. The dentate ligament was cut to free the VA, and the suprahypoglossal portion of the vagoaccessory triangle was widened. VA compressed the REZ of the facial nerve, but was mobilized anteromedially off the REZ. A muslin sling was wrapped around the VA and its tail brought down to the clival dura, which was punctured with a 19-gauge needle and enlarged with a dissector. The sling was pulled anteromedially to this puncture site and secured to the dura with an aneurysm clip, relieving the REZ of all compression. The patient tolerated the procedure with mild, transient hoarseness and her hemifacial spasm resolved completely. This case demonstrates the macrovascular decompression technique with anteromedial transposition of the vertebrobasilar artery, which can also be used for trigeminal neuralgia.
Neuroendocrine Regulation of Air Pollution Health Effects: Emerging Insights
Authors: Snow Samantha J , Henriquez Andres R , Costa Daniel L , Kodavanti Urmila P 
Published: May 2018

Abstract
Air pollutant exposures are linked to cardiopulmonary diseases, diabetes, metabolic syndrome, neurobehavioral conditions, and reproductive abnormalities. Significant effort is invested in understanding how pollutants encountered by the lung might induce effects in distant organs. The role of circulating mediators has been predicted; however, their origin and identity have not been confirmed. New evidence has emerged which implicates the role of neuroendocrine sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenal (HPA) stress axes in mediating a wide array of systemic and pulmonary effects. Our recent studies using ozone exposure as a prototypical air pollutant demonstrate that increases in circulating adrenal-derived stress hormones (epinephrine and cortisol/corticosterone) contribute to lung injury/inflammation and metabolic effects in the liver, pancreas, adipose, and muscle tissues. When stress hormones are depleted by adrenalectomy in rats, most ozone effects including lung injury/inflammation are diminished. Animals treated with antagonists for adrenergic and glucocorticoid receptors show inhibition of the pulmonary and systemic effects of ozone, whereas treatment with agonists restore and exacerbate the ozone-induced injury/inflammation phenotype, implying the role of neuroendocrine activation. The neuroendocrine system is critical for normal homeostasis and allostatic activation; however, chronic exposure to stressors may lead to increases in allostatic load. The emerging mechanisms by which circulating mediators are released and are responsible for producing multiorgan effects of air pollutants insists upon a paradigm shift in the field of air pollution and health. Moreover, since these neuroendocrine responses are linked to both chemical and nonchemical stressors, the interactive influence of air pollutants, lifestyle, and environmental factors requires further study.
Systemic Acquired Resistance and Salicylic Acid: Past, Present, and Future
Authors: Klessig Daniel F. , Choi Hyong Woo , Dempsey D’Maris Amick 
Published: May 2018

This article is part of the Distinguished Review Article Series in Conceptual and Methodological Breakthroughs in Molecular Plant-Microbe Interactions. Salicylic acid (SA) is a critical plant hormone that regulates numerous aspects of plant growth and development as well as the activation of defenses against biotic and abiotic stress. Here, we present a historical overview of the progress that has been made to date in elucidating the role of SA in signaling plant immune responses. The ability of plants to develop acquired immunity after pathogen infection was first proposed in 1933. However, most of our knowledge about plant immune signaling was generated over the last three decades, following the discovery that SA is an endogenous defense signal. During this timeframe, researchers have identified i) two pathways through which SA can be synthesized, ii) numerous proteins that regulate SA synthesis and metabolism, and iii) some of the signaling components that function downstream of SA, including a large number of SA targets or receptors. In addition, it has become increasingly evident that SA does not signal immune responses by itself but, rather, as part of an intricate network that involves many other plant hormones. Future efforts to develop a comprehensive understanding of SA-mediated immune signaling will therefore need to close knowledge gaps that exist within the SA pathway itself as well as clarify how crosstalk among the different hormone signaling pathways leads to an immune response that is both robust and optimized for maximal efficacy, depending on the identity of the attacking pathogen.
Designer human tissue: coming to a lab near you
Authors: Hay David C. , O'Farrelly Cliona 
Published: May 2018

Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology ‘in a dish’ or immune-matched cell-based therapies for the clinic. This special issue will guide the reader through stem cell self-renewal, pluripotency and differentiation. The first articles focus on improving cell fidelity, understanding the innate immune system and the importance of materials chemistry, biofabrication and bioengineering. These are followed by articles that focus on industrial application, commercialization and label-free assessment of tissue formation. The special issue concludes with an article discussing human liver cell-based therapies past, present and future.
This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Pluripotent stem cells: induction and self-renewal
Authors: Abu-Dawud R. , Graffmann N. , Ferber S. , Wruck W. , Adjaye J. 
Published: May 2018

Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewalin vitroand their ability to differentiate into cell types representative of the three embryonic germ layers—mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells. This understanding serves two purposes: first, to enable efficient, reliable and cost-effective production of excellent quality induced PSCs and, second, to enable the derivation of safe, good manufacturing practice-grade transplantable donor cells. Here, we review the reprogramming process of somatic cells into induced PSCs and associated mechanisms with emphasis on self-renewal, epigenetic control, mitochondrial bioenergetics, sub-states of pluripotency, naive ground state, naive and primed. A meta-analysis identified genes expressed exclusively in the inner cell mass and in the naive but not in the primed pluripotent state. We propose these as additional biomarkers defining naive PSCs.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Three-dimensional cell culture: from evolution to revolution
Authors: Alhaque Sharmin , Themis Michael , Rashidi Hassan 
Published: May 2018

Recent advances in the isolation of tissue-resident adult stem cells and the identification of inductive factors that efficiently direct differentiation of human pluripotent stem cells along specific lineages have facilitated the development of high-fidelity modelling of several tissuesin vitro. Many of the novel approaches have employed self-organizing three-dimensional (3D) culturing of organoids, which offer several advantages over conventional two-dimensional platforms. Organoid technologies hold great promise for modelling diseases and predicting the outcome of drug responsesin vitro. Here, we outline the historical background and some of the recent advances in the field of three-dimensional organoids. We also highlight some of the current limitations of these systems and discuss potential avenues to further benefit biological research using three-dimensional modelling technologies.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Intestinal organoids for modelling intestinal development and disease
Authors: Fair Kathryn L. , Colquhoun Jennifer , Hannan Nicholas R. F. 
Published: May 2018

Gastrointestinal diseases are becoming increasingly prevalent in developed countries. Immortalized cells and animal models have delivered important but limited insight into the mechanisms that initiate and propagate these diseases. Human-specific models of intestinal development and disease are desperately needed that can recapitulate structure and function of the gutin vitro. Advances in pluripotent stem cells and primary tissue culture techniques have made it possible to culture intestinal epithelial cells in three dimensions that self-assemble to form ‘intestinal organoids'. These organoids allow for new, human-specific models that can be used to gain insight into gastrointestinal disease and potentially deliver new therapies to treat them. Here we review currentin vitromodels of intestinal development and disease, considering where improvements could be made and potential future applications in the fields of developmental modelling, drug/toxicity testing and therapeutic uses.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you'.
Innate immunity in stem cell-derived hepatocytes
Authors: Fischer Lena , Hay David C. , O'Farrelly Cliona 
Published: May 2018

Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host–pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs. IFN expression in HLCs is characterized by strong expression of type III IFN and low expression of type I IFN which is also a characteristic of primary hepatocytes. The response to IFN differs in HLCs with lower interferon-stimulated gene (ISG)-expression levels than in primary hepatocytes. Tumour necrosis factor-alpha (TNF-α) signalling is less studied in HLCs, but appears to be functional. Expression of toll-like receptors (TLR) 2–5, 7 and 9 has been reported in primary hepatocytes but has been poorly studied in HLCs. In summary, although they retain some immature features, HLCs are in many ways superior to hepatoma cell lines for cell-based modelling. In this review, we will provide an overview of innate immune signalling in HLCs and how this compares with primary hepatocytes.
This article is part of the themed issue ‘Designer human tissue: coming to a lab near you’.
Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine
Authors: Skeldon Gregor , Lucendo-Villarin Baltasar , Shu Wenmiao 
Published: May 2018

Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of ‘bio-inks’ and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.
This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Developing defined substrates for stem cell culture and differentiation
Authors: Hagbard Louise , Cameron Katherine , August Paul , Penton Christopher , Parmar Malin , Hay David C. , Kallur Therése 
Published: May 2018

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation processin vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune theirin vitrodifferentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell–matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Effects of line orientation in visual evoked potentials. Spatial dynamics, and gender differences of neural oblique effect
Authors: Mikhailova Elena S. , Gerasimenko Natalia Yu. , Slavutskaya Anna V. 
Published: May 2018

ABSTRACTThe aim of the study was to investigate neural mechanisms of orientation discrimination in humans by recording the 128-channel event-related potentials (ERPs) of the brain. Stimuli were black-and-white gratings having four orientations: horizontal, vertical, and oblique 45 and 135 deg. from vertical. Thirty-five healthy subjects (16 males, 19 females) participating in the experiments were asked to differentiate the orientations and push the button. The results showed that the orientation processing consists of two main stages. In the occipital, parietal and temporal areas the P100 and N150 components reflecting the early perceptual stage of processing showed amplitudes greater for oblique orientations than for cardinal ones - “inverse” oblique effect. Further, in the central-parietal and frontal areas the P300 and N400 components reflecting the later cognitive stage of processing showed the “classic” oblique effect with greater amplitudes for cardinal orientations. Females demonstrated lower ERP amplitudes and less pronounced differences between responses elicited by cardinal and oblique orientations. The results suggest that in humans the orientation discrimination occurs in a distributed neural network involving the early sensory as well as higher anterior cortical areas. The classic behavioral oblique effect might be controlled by later processing in the anterior cortical areas. The insufficient neural orientation selectivity observed in females may be considered as the biological basis of their poorer visuospatial abilities.
A double-blinded randomised placebo-controlled phase II trial to evaluate high dose rifampicin for tuberculous meningitis: a dose finding study
Authors: Dian S , Yunivita V , Ganiem AR , Pramaesya T , Chaidir L , Wahyudi K , Achmad TH , Colbers A , te Brake L , van Crevel R , Ruslami R , Aarnoutse R 
Published: May 2018

ABSTRACTBackgroundHigh doses of rifampicin may help tuberculous meningitis (TBM) patients to survive. Pharmacokinetic-pharmacodynamic evaluations suggested that rifampicin doses higher than 13 mg/kg intravenously or 20 mg/kg orally (as previously studied) are warranted to maximize treatment response.MethodsIn a double-blinded, randomised, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg or 1350 mg (10, 20 and 30 mg/kg) oral rifampicin combined with other TB drugs for 30 days. Endpoints included pharmacokinetic measures, adverse events and survival.ResultsA double and triple dose of oral rifampicin led to three and five-fold higher geometric mean total exposures in plasma in the critical early days (2±1) of treatment (AUC0-24h: 53·5 mg.h/L vs 170·6 mg.h/L vs. 293·5 mg.h/L, p<0·001), with proportional increases in CSF concentrations and without an increase in the incidence of grade 3/4 adverse events. Six-month mortality was 7/20 (35%, 9/20 (45%) and 3/20 (15%) in the 10, 20 and 30 mg/kg groups, respectively (p=0·12).ConclusionsTripling the standard dose caused a large increase in rifampicin exposure in plasma and CSF and was safe. Survival benefit with this dose should now be evaluated in a larger phase III clinical trial.