bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescription Opioid Distribution After the Legalization of Recreational Marijuana in Colorado, 2007-2017
Authors: Kropp Amalie K. , Nichols Stephanie D. , Chung Daniel Y. , McCall Kenneth L. , Piper Brian J. 
Published: July 2019

AbstractImportanceOpioid related overdoses and overprescribing continue to be an ongoing issue within the United States. Further consideration of nonopioid alternatives as a substitute to treat chronic noncancer pain and in the treatment of opioid use disorders (OUD) is warranted.ObjectiveTo examine the association between the legalization of Colorado’s recreational marijuana and prescription opioid distribution trends. Two states that have not legalized recreational marijuana were selected for comparison.MethodsThe United States Drug Enforcement Administration’s Automation of Report and Consolidated Orders System (ARCOS) was used to examine nine pain medications: oxycodone, fentanyl, morphine, hydrocodone, hydromorphone, oxymorphone, tapentadol, codeine, meperidine and two OUD medications: methadone and buprenorphine from 2007-2017 in Colorado, Utah, and Maryland. The drug weights were extracted, examined, and graphed. Medications were converted to their oral morphine milligram equivalents (MME) using standard conversion factors.ResultsColorado reached a peak of pain MME weight in 2012 and had an −11.66% reduction from 2007 to 2017. During the same interval, Utah had a +9.64% increase in pain medication distribution and Maryland, a −6.02% reduction. As for medications used for OUD, Colorado, Utah, and Maryland had +19.42% increase, −31.45% reduction, and +66.56% increase, respectively. Analysis of the interval pre (2007-2009) versus post (2013-2017) marijuana legalization was completed. Statistically significant changes were observed for Colorado (P=0.033) and Maryland (P=0.007), but not Utah (P=0.659) for pain medications. Analysis of the OUD medications identified significant changes for Colorado (P=0.0003) and Maryland (P=0.0001), but not Utah (P=0.0935). Over the decade, Colorado’s opioid distribution was predominantly (72.49%) for pain with one-quarter (27.51%) for an OUD. Utah distributed 61.00% for pain and 39.00% for OUD. However, Maryland was one-third (37.89%) for pain but over-three-fifths (62.11%) for an OUD.ConclusionThere has been a significant decrease in the prescription opioid distribution after the legalization of marijuana in Colorado. This finding was particularly notable for opioids indicated predominantly for analgesia such as hydrocodone, morphine and fentanyl. Colorado had a larger decrease in opioid distribution after 2012 than Utah or Maryland. Therefore, marijuana could be considered as an alternative treatment for chronic pain and reducing use of opioids. Also, when combined with other novel research, it may also reduce the overdose death rate. Additional research with more comparison states is ongoing.
A novel lineage of candidate pheromone receptors for sex communication in moths
Authors: Bastin-Héline Lucie , Fouchier Arthur de , Cao Song , Koutroumpa Fotini , Caballero-Vidal Gabriela , Robakiewicz Stefania , Monsempes Christelle , François Marie-Christine , Ribeyre Tatiana , Cian Anne de , Walker William B. , Wang Guirong , Jacquin-Joly Emmanuelle , Montagné Nicolas 
Published: July 2019

AbstractSex pheromone receptors (PRs) are key players in chemical communication between mating partners in insects. In the highly diversified insect order Lepidoptera, male PRs tuned to female-emitted type I pheromones (which make up the vast majority of pheromones identified) form a dedicated subfamily of odorant receptors (ORs). Here, using a combination of heterologous expression and in vivo genome editing methods, we bring functional evidence that at least one moth PR does not belong to this subfamily but to a distantly related OR lineage. This PR, identified in the cotton leafworm Spodoptera littoralis, is over-expressed in male antennae and is specifically tuned to the major sex pheromone component emitted by females. Together with a comprehensive phylogenetic analysis of moth ORs, our functional data suggest two independent apparitions of PRs tuned to type I pheromones in Lepidoptera, opening up a new path for studying the evolution of moth pheromone communication.
Non-apoptotic caspase-dependent regulation of enteroblast quiescence in Drosophila
Authors: Arthurton Lewis , Nahotko Dominik Antoni , Alonso Jana , Baena-Lopez Luis Alberto 
Published: July 2019

ABSTRACTCaspase malfunction in stem cells often instigates the appearance and progression of multiple types of cancer, including human colorectal cancer. However, the caspase-dependent regulation of intestinal stem cell properties remains poorly understood. Here, we demonstrate that Dronc, the Drosophila ortholog of caspase-9/2 in mammals, limits the proliferation of intestinal progenitor cells and prevents the premature differentiation of enteroblasts into enterocytes. Strikingly, these unexpected roles of Dronc are non-apoptotic and have been uncovered under experimental conditions without basal epithelial turnover. A novel set of genetic tools have also allowed us to correlate these Dronc functions with its specific accumulation and transient activation in enteroblasts. Finally, we establish that the Dronc-dependent regulation of enteroblast quiescence, largely relies on the fine-tuning of the Notch and Insulin-TOR signalling pathways. Together, this data provides novel insights into the caspase-dependent but non-apoptotic modulation of enteroblast differentiation in non-regenerative conditions. These findings could improve our understanding regarding the origin of caspase-related intestinal malignancies, and the efficacy of therapeutic interventions based on caspase-modulating molecules.
Probabilistic Assessment of Nerve Regeneration with Diffusion MRI: Validation in Rat Models of Peripheral Nerve Trauma
Authors: Manzanera Esteve Isaac V. , Farinas Angel F. , Pollins Alonda C. , Nussenbaum Marlieke E. , Cardwell Nancy L. , Kang Hakmook , Does Mark D. , Thayer Wesley P. , Dortch Richard D. 
Published: July 2019

ABSTRACTNerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham=21, crush=23, cut/repair=19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1-12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD=0.40±0.02) and fractional anisotropy (FA=0.53±0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r=−0.54, p<1e-3; FA: r=0.56, p<1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI can distinguish successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.
Determinants of anemia among pregnant women in northern Ghana
Authors: Adokiya Martin N. , Aryeetey Richmond , Yost Monica , Jones Andrew D. , Wilson Mark L. 
Published: July 2019

ABSTRACTAnemia is a global public health issue affecting half of all pregnant women in developing countries. In 2014, 42% of Ghanaian pregnant women aged 15-49 years were anemic (<11.0g/dl) but information on the determinants of anemia, particularly dietary diversity during the critical third trimester of pregnancy is limited. We assessed the association between determinants and anemia among pregnant women in northern Ghana.We employed a cross-sectional design involving 624 pregnant women (≥20 weeks of gestation) attending four antenatal care (ANC) health facilities ~25 kilometres north of Tamale, Ghana between July and August 2017. Hemoglobin concentration (measured using Hemocue HB 301) was classified as severe, moderate, or mild. Other data included socio-demographic characteristics, malaria prevention, deworming, and iron/folate tablet use. The FAO Minimum Dietary Diversity (MDD-W) metric was used to categorize women into “inadequate” (MDD-W <5 food groups) and “adequate” (MDD-W ≥5). Logistic regression models were used to determine the association between moderate/severe anemia (Hb<9.0g/dl) and mild anemia (9.0-10.9g/dl), or with ‘no anemia’ (≥11.0g/dl) using STATA 14 software.Of 624 women sampled, hemoglobin data were available for 601. The mean age was 27.81±0.25 years, gestational age was 31.93±0.13 weeks, ANC attendance was 3.89±0.07; Hb concentration was 9.73g/dl±0.07, and MDD-W index for ten food groups was 5.33±0.04. Anemia (Hb<11.0g/dl) was observed in 74.8% of women (moderate/severe anemia=33.4% and mild anemia=41.4%). Using adjusted logistic regression, women who received deworming medication had lesser odds of being moderate/severe anemic (aOR=0.51, P=0.021). While women who were engaged in other occupation (herdsmen) and no previous parity had higher odds of being moderate/severe anemic (aOR=2.90, P=0.042) and (aOR=2.13, P=0.004) respectively. Moderate/severe anemia was not statistically associated with MDD-W, nor with socioeconomic status/wealth index. Conclusion, anemia in pregnancy was nearly twice that of Ghana as a whole. Deworming medication was found to be protective intervention for anemia during pregnancy.
Lung Tumour Cell-derived Exosomes Promote the Expansion of MDSC Through miR-21a/PDCD4/IL-6/STAT3 Pathway
Authors: Zhang Xingju , Li Fei , Zhang Jiale , Tang Ying , Xiao Bin , Wan Ying , Jiang Shan 
Published: July 2019

AbstractThe percentage of MDSC population in peripheral blood is significantly increased in lung cancer patients. The accumulation of MDSC contributes to the development of a tumour-associated immune suppressive environment. But the mechanism mediating MDSC accumulation in lung cancer patients is elusive. We found that exosomes from Lewis lung cancer cells (LLC-Exo) can be taken up by the mice bone marrow cells and then promote MDSC expansion, which enhance tumour growth. Mechanistically, during the induction of MDSC from the bone marrow cells, miR-21a from LLC-Exo can stimulate BM cells to produce more IL-6 by inhibitingpdcd4expression post-transcriptionally. Autocrine IL-6 induces tyrosine 705(Y705) of STAT3 to be phosphorylated during MDSC expansion. LLC-Exo with miR-21a deletion lost its ability to stimulate IL-6 production, STAT3 activation and MDSC expansion. These results demonstrate that lung cancer cell-derived exosomes promote functional MDSC expansion through activation of miR-21a/PDCD4/IL-6/STAT3 pathway.
A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division
Authors: Stojic Lovorka , Lun Aaron T L , Mascalchi Patrice , Ernst Christina , Redmond Aisling M , Mangei Jasmin , Barr Alexis R , Bousgouni Vicky , Bakal Chris , Marioni John C , Odom Duncan T , Gergely Fanni 
Published: July 2019

ABSTRACTGenome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture and faithfully segregate chromosomes into daughter cells. The role of long noncoding RNAs (lncRNAs) in controlling these processes however remains largely unexplored. To identify lncRNAs with mitotic functions, we performed a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs. By investigating major hallmarks of cell division such as chromosome segregation, mitotic duration and cytokinesis, we discovered numerous lncRNAs with functions in each of these processes. The chromatin-associated lncRNA,linc00899,was selected for in-depth studies due to the robust mitotic delay observed upon its depletion. Transcriptome analysis oflinc00899-depleted cells together with gain-of-function and rescue experiments across multiple cell types identified the neuronal microtubule-binding protein,TPPP/p25,as a target oflinc00899.Linc00899binds the genomic locus ofTPPP/p25and suppresses its transcription through acis-acting mechanism. In cells depleted oflinc00899,the consequent upregulation ofTPPP/p25alters microtubule dynamics and is necessary and sufficient to delay mitosis. Overall, our comprehensive screen identified several lncRNAs with roles in genome stability and revealed a new lncRNA that controls microtubule behaviour with functional implications beyond cell division.
NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system
Authors: Sánchez-Martín Pablo , Sou Yu-shin , Kageyama Shun , Komatsu Masaaki 
Published: July 2019

Abstractp62/SQSTM1 is a multivalent protein that has an ability to cause a liquid-liquid phase separation and serves as a receptor protein that participates in cargo isolation during selective autophagy. This protein is also involved in the non-canonical activation of the Keap1-Nrf2 system, a major oxidative stress response pathway. Here we show a role of Neighbor of BRCA1 gene 1 (NBR1), an autophagy receptor structurally similar to p62/SQSTM1, in the p62-liquid droplet formation and the Keap1-Nrf2 pathway. The overexpression of NBR1 blocked selective degradation of p62/SQSTM1 through autophagy and promoted the accumulation and phosphorylation of p62/SQSTM1 in liquid-like bodies, which is required for the activation of Nrf2. NBR1 was induced in response to oxidative stress, and then the p62-mediated Nrf2 activation was up-regulated. Conversely, loss of Nbr1 suppresses not only the formation of p62/SQSTM1-liquid droplets but also p62-dependent Nrf2 activation during oxidative stress. Taken together, our results show that NBR1 mediates p62/SQSTM1-liquid droplet formation to activate the Keap1-Nrf2 pathway.
Identifying hetero-protein complexes in the nuclear envelope
Authors: Hennen J. , Hur K.H. , Kohler J. , Karuka S.R. , Angert I. , Luxton G.W.G. , Mueller J.D. 
Published: July 2019

AbstractThe nucleus is delineated by the nuclear envelope (NE), which is a double membrane barrier composed of the inner and outer nuclear membranes as well as a ~40 nm wide lumen. In addition to its barrier function, the NE acts as a critical signaling node for a variety of cellular processes which are mediated by protein complexes within this subcellular compartment. While fluorescence fluctuation spectroscopy (FFS) is a powerful tool for characterizing protein complexes in living cells, it was recently demonstrated that conventional FFS methods are not suitable for applications in the NE because of the presence of slow nuclear membrane undulations. We previously addressed this challenge by developing time-shifted mean-segmented Q (tsMSQ) analysis and applied it to successfully characterize protein homo-oligomerization in the NE. However, many NE complexes, such as the linker of the nucleoskeleton and cytoskeleton (LINC) complex, are formed by heterotypic interactions, which single-color tsMSQ is unable to characterize. Here, we describe the development of dual-color (DC) tsMSQ to analyze NE hetero-protein complexes built from proteins that carry two spectrally distinct fluorescent labels. Experiments performed on model systems demonstrate that DC tsMSQ properly identifies hetero-protein complexes and their stoichiometry in the NE by accounting for spectral crosstalk and local volume fluctuations. Finally, we applied DC tsMSQ to study the assembly of the LINC complex, a hetero-protein complex composed of Klarsicht/ANC-1/SYNE homology (KASH) and Sad1/UNC-84 (SUN) proteins, in the NE of living cells. Using DC tsMSQ, we demonstrate the ability of the SUN protein SUN2 and the KASH protein nesprin-2 to form a hetero-complexin vivo. Our results are consistent with previously publishedin vitrostudies and demonstrate the utility of the DC tsMSQ technique for characterizing NE hetero-protein complexes.Statement of SignificanceProtein complexes found within the nuclear envelope (NE) play a vital role in regulating cellular functions ranging from gene expression to cellular movement. However, the assembly state of these complexes within their native environment remains poorly understood, which is compounded by a general lack of fluorescence techniques suitable for quantifying the oligomeric state of NE protein complexes. This study aims at addressing this issue by introducing dual-color time-shifted mean-segmented Q analysis as a fluorescence fluctuation method specifically designed to identify the average oligomeric state of hetero-protein complexes within the NE of living cells.
Interaction Between Ploidy, Breeding System, and Lineage Diversification
Authors: Zenil-Ferguson Rosana , Burleigh J. Gordon , Freyman William A. , Igić Boris , Mayrose Itay , Goldberg Emma E. 
Published: July 2019

AbstractIf particular traits consistently affect rates of speciation and extinction, broad macroevolutionary patterns can be understood as consequences of selection at high levels of the biological hierarchy. Identifying traits associated with diversification rate differences is complicated by the wide variety of characters under consideration and the statistical challenges of testing for associations from comparative phylogenetic data. Ploidy (diploid vs. polyploid states) and breeding system (self-incompatible vs. self-compatible states) have been repeatedly suggested as possible drivers of differential diversification. We investigate the connections of these traits, including their interaction, to speciation and extinction rates in Solanaceae. We show that the effect of ploidy on diversification can be largely explained by its correlation with breeding system and that additional unknown factors, alongside breeding system, influence diversification rates. These results are largely robust to allowing for diploidization. Finally, we find that the most common evolutionary pathway to polyploidy in Solanaceae occurs via direct breakdown of self-incompatibility by whole genome duplication, rather than indirectly via breakdown followed by polyploidization.
Neural evidence for the prediction of animacy features during language comprehension: Evidence from MEG and EEG Representational Similarity Analysis
Authors: Wang Lin , Wlotko Edward , Alexander Edward , Schoot Lotte , Kim Minjae , Warnke Lena , Kuperberg Gina R. 
Published: July 2019

AbstractIt has been proposed that people can generate probabilistic predictions at multiple levels of representation during language comprehension. We used Magnetoencephalography (MEG) and Electroencephalography (EEG), in combination with Representational Similarity Analysis (RSA), to seek neural evidence for the prediction of animacy features. In two studies, MEG and EEG activity was measured as human participants (both sexes) read three-sentence scenarios. Verbs in the final sentences constrained for either animate or inanimate semantic features of upcoming nouns, and the broader discourse context constrained for either a specific noun or for multiple nouns belonging to the same animacy category. We quantified the similarity between spatial patterns of brain activity following the verbs until just before the presentation of the nouns. The MEG and EEG datasets revealed converging evidence that the similarity between spatial patterns of neural activity following animate constraining verbs was greater than following inanimate constraining verbs. This effect could not be explained by lexical-semantic processing of the verbs themselves. We therefore suggest that it reflected the inherent difference in the semantic similarity structure of the predicted animate and inanimate nouns. Moreover, the effect was present regardless of whether a specific word could be predicted, providing strong evidence for the prediction of coarse-grained semantic features that goes beyond the prediction of individual words.Significance statementLanguage inputs unfold very quickly during real-time communication. By predicting ahead we can give our brains a “head-start”, so that language comprehension is faster and more efficient. While most contexts do not constrain strongly for a specific word, they do allow us to predict some upcoming information. For example, following the context, “they cautioned the…”, we can predict that the next word will be animate rather than inanimate (we can caution a person, but not an object). Here we used EEG and MEG techniques to show that the brain is able to use these contextual constraints to predict the animacy of upcoming words during sentence comprehension, and that these predictions are associated with specific spatial patterns of neural activity.
BIRD: Identifying Cell Doublets via Biallelic Expression from Single cells
Authors: Wainer-Katsir Kerem , Linial Michal 
Published: July 2019

ABSTRACTMotivationCurrent technologies for single-cell transcriptomics allow thousands of cells to be analyzed in a single experiment. The increased scale of these methods led to a higher risk of cell doublets’ contamination. Available tools and algorithms for identifying doublets and estimating their occurrence in single-cell expression data focus on cell doublets from different species, cell types or individuals.ResultsIn this study, we analyze transcriptomic data from single cells having an identical genetic background. We claim that the ratio of monoallelic to biallelic expression provides a discriminating power towards doublets’ identification. We present a pipeline called BIRD (BIallelic Ratio for Doublets) that relies on heterologous genetic variations extracted from single-cell RNA-seq (scRNA-seq). For each dataset, doublets were artificially created from the actual data and used to train a predictive model. BIRD was applied on Smart-Seq data from 163 primary fibroblasts. The model achieved 100% accuracy in annotating the randomly simulated doublets. Bonafide doublets from female-origin fibroblasts were verified by the unexpected biallelic expression from X-chromosome. Data from 10X Genomics microfluidics of peripheral blood cells analyzed by BIRD achieved in average 83% (± 3.7%) accuracy with an area under the curve of 0.88 (± 0.04) for a collection of ∼13,300 single cells.ConclusionsBIRD addresses instances of doublets which were formed from cell mixtures of identical genetic background and cell identity. Maximal performance is achieved with high coverage data. Success in identifying doublets is data specific which varies according to the experimental methodology, genomic diversity between haplotypes, sequence coverage, and depth.
Conjunctive representation of what and when in monkey hippocampus and lateral prefrontal cortex during an associative memory task
Authors: Cruzado Nathanael A. , Tiganj Zoran , Brincat Scott L. , Miller Earl K. , Howard Marc W. 
Published: July 2019

AbstractAdaptive memory requires the organism to form associations that bridge between events separated in time. Many studies show interactions between hippocampus (HPC) and prefrontal cortex (PFC) during formation of such associations. We analyze neural recording from monkey HPC and PFC during a memory task that requires the monkey to associate stimuli separated by about a second in time. After the first stimulus was presented, large numbers of units in both HPC and PFC fired in sequence. Many units fired only when a particular stimulus was presented at a particular time in the past. These results indicate that both HPC and PFC maintain a temporal record of events that could be used to form associations across time. This temporal record of the past is a key component of the temporal coding hypothesis, a hypothesis in psychology that memory not only encodes what happened, but when it happened.