bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures
Authors: Kim Minwook , Steinberg David R. , Burdick Jason A. , Mauck Robert L. 
Published: January 2019

Significance
Coculture is a promising strategy in cartilage tissue engineering given its potential to rejuvenate aged mesenchymal stem cells (MSCs) to promote functional chondrogenesis. Identifying the molecular factors mediating this coculture effect, as well as carriers and delivery mechanisms, will forward the development of therapeutics to promote functional cartilage repair by aged autologous MSCs. This will potentially expand the clinical indications of microfracture and other procedures that rely on aged endogenous stem cell populations.
RIscoper: a tool for RNA–RNA interaction extraction from the literature
Authors: Zhang Yang , Liu Tianyuan , Chen Liqun , Yang Jinxurong , Yin Jiayi , Zhang Yuncong , Yun Zhixi , Xu Hao , Ning Lin , Guo Fengbiao , Jiang Yongshuai , Lin Hao , Wang Dong , Huang Yan , Huang Jian 
Published: January 2019

Abstract

Motivation
Numerous experimental and computational studies in the biomedical literature have provided considerable amounts of data on diverse RNA–RNA interactions (RRIs). However, few text mining systems for RRIs information extraction are available.

Results
RNA Interactome Scoper (RIscoper) represents the first tool for full-scale RNA interactome scanning and was developed for extracting RRIs from the literature based on the N-gram model. Notably, a reliable RRI corpus was integrated in RIscoper, and more than 13 300 manually curated sentences with RRI information were recruited. RIscoper allows users to upload full texts or abstracts, and provides an online search tool that is connected with PubMed (PMID and keyword input), and these capabilities are useful for biologists. RIscoper has a strong performance (90.4% precision and 93.9% recall), integrates natural language processing techniques and has a reliable RRI corpus.

Availability and implementation
The standalone software and web server of RIscoper are freely available at www.rna-society.org/riscoper/.

Supplementary information
Supplementary data are available at Bioinformatics online.
RNF216 is essential for spermatogenesis and male fertility†
Authors: Melnick Ashley F , Gao Yuen , Liu Jiali , Ding Deqiang , Predom Alicia , Kelly Catherine , Hess Rex A , Chen Chen 
Published: January 2019

Abstract
Ring finger protein 216 (RNF216) belongs to the RING family of E3 ubiquitin ligases that are involved in cellular protein degradation. Mutations in human Rnf216 gene have been identified in Gordon Holmes syndrome, which is defined by ataxia, dementia, and hypogonadotropism. However, the gene function of Rnf216 in mammalian species remains unknown. Here, we show that targeted deletion of Rnf216 in mice results in disruption in spermatogenesis and male infertility. RNF216 is not required for female fertility. These findings reveal an essential function of RNF216 in spermatogenesis and male fertility and suggest a critical role for RNF216 in human gonadal development.
Vancomycin Area Under the Curve and Acute Kidney Injury: A Meta-analysis
Authors: Aljefri Doaa M , Avedissian Sean N , Rhodes Nathaniel J , Postelnick Michael J , Nguyen Kevin , Scheetz Marc H 
Published: January 2019

AbstractBackgroundThis study analyzed the relationship between vancomycin area under the concentration-time curve (AUC) and acute kidney injury (AKI) reported across recent studies.MethodsA systematic review of PubMed, Medline, Scopus, and compiled references was conducted. We included randomized cohort and case-control studies that reported vancomycin AUCs and risk of AKI (from 1990 to 2018). The primary outcome was AKI, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on ≥2 consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Primary analyses compared the impact of AUC cutpoint (greater than ~650 mg × hour/L) and AKI. Additional analysis compared AUC vs trough-guided monitoring on AKI incidence.ResultsEight observational studies met inclusion/exclusion criteria with data for 2491 patients. Five studies reported first-24-hour AUCs (AUC0-24) and AKI, 2 studies reported 24- to 48-hour AUCs (AUC24-48) and AKI, and 2 studies reported AKI associated with AUC- vs trough-guided monitoring. AUC less than approximately 650 mg × hour/L was associated with decreased AKI for AUC0-24 (OR, 0.36 [95% CI, .23–.56]) as well as AUC24-48 (OR, 0.45 [95% CI, .27–.75]). AKI associated with the AUC monitoring strategy was significantly lower than trough-guided monitoring (OR, 0.68 [95% CI, .46–.99]).ConclusionsAUCs measured in the first or second 24 hours and lower than approximately 650 mg × hour/L may result in a decreased risk of AKI. Vancomycin AUC monitoring strategy may result in less vancomycin-associated AKI. Additional investigations are warranted.
Energy oversupply to tissues: a single mechanism possibly underlying multiple cancer risk factors
Authors: Wu Daniel J , Aktipis Athena , Pepper John W 
Published: January 2019

AbstractBackground and objectivesSeveral major risk factors for cancer involve vascular oversupply of energy to affected tissues. These include obesity, diabetes and chronic inflammation. Here, we propose a potential mechanistic explanation for the association between energy oversupply and cancer risk, which we call the metabolic cancer suppression hypothesis: We hypothesize that oncogenesis is normally suppressed by organismal physiology that regulates and strictly limits normal energy supply to somatic cells, and that this protection is removed by abnormal oversupply of energy.MethodologyWe evaluate this hypothesis using a computational model of somatic cell evolution to simulate experimental manipulation of the vascular energy supply to a tissue. The model simulates the evolutionary dynamics of somatic cells during oncogenesis.ResultsIn our simulation experiment, we found that under plausible biological assumptions, elevated energy supply to a tissue led to the evolution of elevated energy uptake by somatic cells, leading to the rapid evolution of both defining traits of cancer cells: hyperproliferation, and tissue invasion.Conclusions and implicationsOur results support the hypothesis of metabolic cancer suppression, suggesting that vascular oversupply of energetic resources to somatic cells removes normal energetic limitations on cell proliferation, and that this accelerates cellular evolution toward cancer. Various predictions of this hypothesis are amenable to empirical testing, and have promising implications for translational research toward clinical cancer prevention.
Decreases in length at maturation of Mediterranean fishes associated with higher sea temperatures
Authors: Shapiro Goldberg Daphna , van Rijn Itai , Kiflawi Moshe , Belmaker Jonathan 
Published: January 2019

Abstract
Fish size at maturation influences lifetime reproductive success and is an important parameter in managing stocks. Fish tend to reach maturity at a smaller size in warmer water; however, the generality of this pattern is a matter of controversy. The mechanisms by which temperature influences fish size at maturation are not well understood, particularly in natural populations, but may have broad implications if climate change continues to warm the seas. In this study, we use populations of 16 fish species across the Mediterranean Sea to evaluate the association between different temperature metrics and fish size at maturation, and to understand the variation among species. We found that both mean annual temperature and growing degree days (GDD) were the best supported environmental predictors of fish size at maturation. This suggests that the mechanisms affecting size at maturation may differ from those affecting maximum size, for which maximum temperature was the best predictor. Across species, we found that the effect of temperature is stronger for more active species, while other species-level predictors had limited influence. The correlation of fish size at maturation to specific temperature metrics should help fisheries and conservation programmes better predict the effects of climate change on fish populations.
Gene editing in plants: progress and challenges
Authors: Mao Yanfei , Botella Jose Ramon , Liu Yaoguang , Zhu Jian-Kang 
Published: January 2019

Abstract
The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) genome editing system is a powerful tool for targeted gene modifications in a wide range of species, including plants. Over the last few years, this system has revolutionized the way scientists perform genetic studies and crop breeding, due to its simplicity, flexibility, consistency and high efficiency. Considerable progress has been made in optimizing CRISPR/Cas9 systems in plants, particularly for targeted gene mutagenesis. However, there are still a number of important challenges ahead, including methods for the efficient delivery of CRISPR and other editing tools to most plants, and more effective strategies for sequence knock-ins and replacements. We provide our viewpoint on the goals, potential concerns and future challenges for the development and application of plant genome editing tools.
First Contact and Early Colonization of Brazil
Authors: Schwartz Stuart B. , Rodrigues Aldair 
Published: January 2019

This article covers much of the first century of the history of Brazil. The quincentennial commemorations of the Vasco da Gama voyage (1498) to India and that of Pedro Alvares Cabral (1500), which “discovered” Brazil, stimulated in Portugal and Brazil as well as in the academic communities interested in their histories a surge in research, reeditions of classic accounts, and a rise in the curiosity of, and readership by, the general public. This article includes major works from this recent historiographical boom along with classical studies that have long served as the basis for understanding Brazil’s first century. The article covers the period from 1500 to c. 1580 when a dynastic crisis brought Portugal and its empire under the control of King Phillip II of Spain. At first a number of royally commissioned voyages of exploration visited the Brazilian coast, but, for the most part, contact was in private hands since the Portuguese Crown granted contracts for the extraction of dyewood. In the 16th century, French competitors contested the Portuguese presence on the coast and the relations of the Portuguese with native peoples. By the 1530s, to secure this region from foreign competition, Portugal instituted a system of proprietary captaincies to develop settlements. A few of the captaincies (e.g., Pernambuco, São Vicente) flourished due to the beginnings of a sugar industry, but most of them failed such that, in 1549, to secure the colony, a royal governor and judicial and treasury officers were dispatched along with c. 1,300 men. Jesuit missionaries accompanied them and a capital city was established at Salvador. During the next three decades, the Portuguese settled and took control of the Brazilian coast, eliminating a French attempt at colonization and, in its place, founding the city of Rio de Janeiro in 1565. Meanwhile, relations with Brazil’s indigenous population shifted as missionary efforts, epidemic diseases, and the need for laborers in the growing sugar plantation economy resulted in war, enslavement, and depopulation. By the 1560s, colonists in Brazil had turned to the existing Portuguese slave trade with Africa to augment their supply of workers. By c. 1570 a multiracial society had formed. Although the laws and institutions of Portugal clearly provided governing structures for the colony, the extent to which Brazil’s colonial situation, the influences of indigenous and then African cultures, and the growing importance of slavery distinguished the colony from its metropolis has recently become a central issue of debate about the origins and the nature of early Brazil.
Literati Culture
Authors: Roddy Stephen 
Published: January 2019

Although the term literati culture (wenren wenhua) entered the Chinese lexicon only in the late 20th century, the aesthetic, moral, and intellectual pursuits it encompasses can be traced back nearly two millennia to the Wei-Jin era (220–420 ce). In its narrowest sense, it denotes the “four arts” (siyi) associated with cultured, literate males (wenren): music (especially the qin or guqin), the game of go (weiqi), calligraphy, and painting, as well as poetry and lyrical essays (especially xiaopin) associated with them. Literati culture is also usually construed to include connoisseurship of various categories of material objects, including tea and its implements, antique paintings and specimens of calligraphy, celebrated or rare manuscripts and book editions, rubbings taken from steles, ancient bronze vessels, and objets d’art associated with writing, such as ink stones or seals. During the mature phase of literati culture in the late Ming and Qing dynasties, this repertoire of practices further widened to include, inter alia, the collecting of any manner of rare or prized objects (both natural and man-made), garden design and architecture, the connoisseurship of the theater and its actors or other entertainers, and the espousal of philosophical ideals associated with leisure or reclusion. Given this expansive scope, scholarship has tended to treat this array of arts and avocations either through disciplinary lenses such as art history and material culture, or in terms of their associations with the principal intellectual vocations—literature (the so-called wenyuan or Garden of Literature) and textual scholarship (rulin or Forest of Scholarship)—that marked literati status. As the relatively elastic conception of literati culture has gained currency, however, cultural historians have increasingly studied these arts within the continuum of socioeconomic practices that marked membership in the elite, and also in light of the position of these arts in relation to more-demotic (tongsu) cultural forms. The growth of literati avocations and the writings about them after c. 1500 was stimulated by the surfeit of first- and second-tier examination holders, along with opportunities for patronage by wealthy merchants in the Yangzi delta region. Also evident in the late Ming and throughout the Qing is the influence of philological scholarship (kaozheng) on the classification or cataloguing of objects of various kinds. Finally, the statecraft-oriented (jingshi) scholarship and letters that flourished during the last century of Qing rule, and critiques of literati social preeminence relative to other vocations and social categories, stimulated the rethinking of the social and cultural institutions that perpetuated their dominance, which extended to the arts associated with the literati as well.
Antidepressant Use Among People Prescribed Opioids for Chronic Noncancer Pain
Authors: Gisev Natasa , Nielsen Suzanne , Campbell Gabrielle , Santo Thomas , Mant Andrea , Bruno Raimondo , Cohen Milton , Hall Wayne D , Larance Briony , Lintzeris Nicholas , Farrell Michael , Degenhardt Louisa 
Published: January 2019

Abstract

Objective
Although depression and chronic pain often coexist, few studies have examined antidepressant use among people with pain. This study examines the prevalence and characteristics associated with antidepressant use among people prescribed opioids for chronic noncancer pain (CNCP).

Design
Baseline data from a prospective cohort study.

Setting
Australian community.

Subjects
A total of 1166 people prescribed opioids for CNCP.

Methods
Baseline data collection consisted of a self-completed seven-day medication diary and telephone interview to collect information on sociodemographic characteristics and mental/physical health using validated questionnaires. Logistic regression was used to examine characteristics associated with antidepressant use, reporting adjusted odds ratios (AORs) and 95% confidence intervals (CIs).

Results
Of the 1166 participants, 668 (57.3%) were female, and the median (interquartile range) age was 59 (49–68) years. About half the cohort (N = 637, 54.6%) used antidepressants. Of these, 329 (51.7%) reported moderate to severe depression. Amitriptyline was the most commonly used antidepressant (17.3%). Factors independently associated with antidepressant use were being female (AOR = 1.47, 95% CI = 1.13–1.92), more years lived in pain (AOR = 1.01, 95% CI = 1.00–1.02), and use of nonopioid analgesics (AOR = 1.34, 95% CI = 1.01–1.78), benzodiazepines and related drugs (AOR = 1.84, 95% CI = 1.36–2.49), antiepileptics (AOR = 1.86, 95% CI = 1.38–2.51), and antipsychotics (AOR = 2.15, 95% CI = 1.22–3.77).

Conclusions
Antidepressant use is common among people with CNCP prescribed opioids. Those using antidepressants were more likely to use other psychotropic medicines concurrently, highlighting that they are a high-risk population requiring comprehensive assessment to optimize outcomes and reduce potential harms from polypharmacy.
Medicaid Expansion and Prescription Trends
Authors: Cher Benjamin A.Y. , Morden Nancy E. , Meara Ellen 
Published: January 2019

Background:
Opioid overdose deaths in the United States have climbed since 1999. In 2014, the Affordable Care Act prompted some states to expand Medicaid programs, providing low-cost prescription access to millions of Americans. Some have questioned whether Medicaid expansion might worsen the opioid crisis.

Objective:
To test the association between the expansion of state Medicaid programs and Medicaid-paid prescriptions of opioid pain relievers and opioid addiction therapies.

Research Design:
We analyzed the 2010–2016 Medicaid State Drug Utilization Data using a difference-in-differences regression approach, comparing prescriptions per enrollee between states that expanded Medicaid in 2014 and states that did not. We compared opioid pain relievers and opioid addiction therapies to 5 other commonly prescribed drug types important to the Medicaid expansion population (antidepressants, antihypertensives, diabetes medications, cholesterol treatments, and contraceptives) and to overall prescription volume. A secondary analysis compared opioid pain relievers and opioid addiction therapies, between states with high and low overdose death rates.

Results:
We found overall prescription use per enrollee was higher after 2014. Relative growth in opioid pain reliever prescriptions was modest compared with growth in medications for depression, hypertension, diabetes, and high cholesterol. Growth in prescriptions used to treat opioid use disorder greatly outpaced other drugs, suggesting important gains in access to addiction treatments; growth was higher in states with higher pre-2014 overdose death rates.

Conclusions:
Our results suggest Medicaid expansion benefited a population with unique needs, and that Medicaid expansion could be a valuable tool in addressing the opioid overdose epidemic.
Conscious perception of natural images is constrained by category-related visual features
Authors: Lindh Daniel , Sligte Ilja G. , Assecondi Sara , Shapiro Kimron L. , Charest Ian 
Published: January 2019

AbstractConscious perception is crucial for adaptive behaviour yet access to consciousness varies for different types of objects. The visual system comprises regions with widely distributed category information and exemplar-level representations that cluster according to category. Does this categorical organisation in the brain provide insight into object-specific access to consciousness? We address this question using the Attentional Blink (AB) approach with visual objects as targets. We find large differences across categories in the AB then employ activation patterns extracted from a deep convolutional neural network (DCNN) to reveal that these differences depend on mid- to high-level, rather than low-level, visual features. We further show that these visual features can be used to explain variance in performance across trials. Taken together, our results suggest that the specific organisation of the higher-tier visual system underlies important functions relevant for conscious perception of differing natural images.
Genetic Landscape of Electron Transport Chain Complex I Dependency in Acute Myeloid Leukemia
Authors: Baccelli Irène , Gareau Yves , Lehnertz Bernhard , Gingras Stéphane , Spinella Jean-François , Beautrait Alexandre , Corneau Sophie , Mayotte Nadine , Boivin Isabel , Girard Simon , MacRae Tara , Frechette Mélanie , Leveillé Koryne , Krosl Jana , Thiollier Clarisse , Lavallée Vincent-Philippe , Kanshin Evgeny , Bertomeu Thierry , Coulombe-Huntington Jasmin , St-Denis Corinne , Bordeleau Marie-Eve , Boucher Geneviève , Roux Philippe P. , Lemieux Sébastien , Tyers Mike , Thibault Pierre , Hébert Josée , Marinier Anne , Sauvageau Guy 
Published: January 2019

AbstractInhibition of oxidative phosphorylation (OXPHOS) is a promising therapeutic strategy in Acute Myeloid Leukemia (AML), but patients respond heterogeneously. Through chemically interrogation of 200 sequenced specimens, we identified Mubritinib as a strongin vitroandin vivoanti-leukemic compound, acting through ubiquinone-dependent inhibition of Electron Transport Chain complex I (ETC1). ETC1 targeting showed selective toxicity against a subgroup of chemotherapy-resistant leukemias exhibiting OXPHOS hyperactivity, high expression of mitochondrial activity-related genes, and mutations affectingNPM1, FLT3andDNMT3A. Altogether, our work thus identifies a novel ETC1 inhibitor with high clinical potential and reveals the landscape of OXPHOS dependency in AML.