bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Changes in Prescription Opioids from 2006 to 2017 in Texas
Authors: Ighodaro Ebuwa T , McCall Kenneth L , Chung Daniel Y , Nichols Stephanie D , Piper Brian J 
Published: August 2019

AbstractStudy ObjectiveThe US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic non-cancer pain and subsequent escalation to heroin or illicit fentanyl. As Texas was reported to be among the lowest in the US for opioid use and misuse, further examination of this state is warranted.Study DesignThis study was conducted to quantify prescription opioid use in Texas.Data SourceData was obtained from the publically available US Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) which monitors controlled substances transactions from manufacture to commercial distribution.Measurement and Main ResultsData for 2006-2017 from Texas for ten prescription opioids including eight primarily used to relieve pain (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, oxycodone, oxymorphone) and two (buprenorphine and methadone) for the treatment of an Opioid Use Disorder (OUD) were examined. The change in Morphine Mg Equivalent (MME) of all opioids (+23.3%) was only slightly greater than the state’s population gains (21.1%). Opioids used to treat an OUD showed pronounced gains (+90.8%) which were four-fold faster than population growth. Analysis of individual agents revealed pronounced elevations in codeine (+387.5%), hydromorphone (+106.7%), and oxycodone (+43.6%) and a reduction in meperidine (−80.3%) in 2017 relative to 2006. Methadone in 2017 accounted for a greater portion (39.5%) of the total MME than hydrocodone, oxycodone, morphine, hydromorphone, oxymorphone, and meperidine, combined. There were differences between urban and rural areas in the changes in hydrocodone and buprenorphine.ConclusionsCollectively, these findings indicate that continued vigilance is needed in Texas to appropriately treat pain and an OUD while minimizing the potential for prescription opioid diversion and misuse. Texas may lead the US in a return to pre opioid crisis prescription levels.
Impact of overfishing on density and test-diameter size of the sea urchinTripneustes gratillaat Wakatobi Archipelago, south-eastern Sulawesi, Indonesia
Authors: Nane La 
Published: August 2019

AbstractSea urchinTripneustes gratillais one of an economic important fisheries resources product for localities at Wakatobi archipelago. High demands for sea urchin gonad have intensified high fishing activity. We hypothesize that sea urchins at Wakatobi have overfished. To answer that hypothesizes; we measure the density and its test diameter size at two different sites. They are Pulau Tomia (inhabited area) and Pulau Sawa (uninhabited area and very distant from the localities). The results show that sea urchin density and its test diameter is significantly different. The densities (mean ± SE) Tripneustes gratilla at Pulau Sawa and Pulau Tomia are 10 ± 0.6 (ind./m2) and 2.7 ± 0.9 ind./m2, respectively. Moreover, the test diameter at Pulau Sawa and Pulau Tomia are 69.7 ± 2.1 mm (mean ± SE), and 58.5 ± 1.7 mm (mean ± SE), respectively. These results have indeed shown that overfishing has occurred. Therefore, sea urchin with test diameter 66–75 mm, 76–85 mm, and 86–95 mm have disappeared at Pulau Tomia. Our conclusion reveals that fishing of sea urchin Tripneustes gratilla at Pulau Tomia has overfished.
“Integrative Genomic Analysis for the Bioprospection of Regulators and Accessory Enzymes Associated with Cellulose Degradation in a Filamentous Fungus (Trichoderma harzianum)”
Authors: Filho Jaire A. Ferreira , Horta Maria Augusta C. , dos Santos Clelton A. , Almeida Deborah A. , Murad Natália F. , Mendes Juliano S. , Sforça Danilo A. , Silva Claudio Benício C. , Crucello Aline , de Souza Anete P. 
Published: August 2019

AbstractBackgroundUnveiling fungal genome structure and function reveals the potential biotechnological use of fungi.Trichoderma harzianumis a powerful CAZyme-producing fungus. We studied the genomic regions inT. harzianumIOC3844 containing CAZyme genes, transcription factors and transporters.ResultsWe used bioinformatics tools to mine theT. harzianumgenome for potential genomics, transcriptomics, and exoproteomics data and coexpression networks. The DNA was sequenced by PacBio SMRT technology for multi-omics data analysis and integration. In total, 1676 genes were annotated in the genomic regions analyzed; 222 were identified as CAZymes inT. harzianumIOC3844. When comparing transcriptome data under cellulose or glucose conditions, 114 genes were differentially expressed in cellulose, with 51 CAZymes. CLR2, a transcription factor physically and phylogenetically conserved inT. harzianumspp., was differentially expressed under cellulose conditions. The genes induced/repressed under cellulose conditions included those important for plant biomass degradation, including CIP2 of the CE15 family and a copper-dependent LPMO of the AA9 family.ConclusionsOur results provide new insights into the relationship between genomic organization and hydrolytic enzyme expression and regulation inT. harzianumIOC3844. Our results can improve plant biomass degradation, which is fundamental for developing more efficient strains and/or enzymatic cocktails for the production of hydrolytic enzymes.
Bypass of an epigenetic S-phase transcriptional module by convergent nutrient stress signals
Authors: Delaby Marie , Panis Gaël , Fumeaux Coralie , Degeorges Laurence , Viollier Patrick H. 
Published: August 2019

AbstractThe signals feeding into bacterial S-phase transcription are poorly understood. Cellular cycling in the alpha-proteobacteriumCaulobacter crescentusis driven by a complex circuit of at least three transcriptional modules that direct sequential promoter firing during the G1, early and late S cell cycle phases. In alpha-proteobacteria, the transcriptional regulator GcrA and the CcrM methyltransferase epigenetically activate promoters of cell division and polarity genes that fire in S-phase. By evolvingCaulobacter crescentuscells to cycle and differentiate in the absence of the GcrA/CcrM module, we discovered that phosphate deprivation and (p)ppGpp alarmone stress signals converge on S-phase transcriptional activation. The cell cycle oscillations of the CtrA protein, the transcriptional regulator that implements G1 and late S-phase transcription, are essential in our evolved mutants, but not in wild-type cells, showing that the periodicity in CtrA abundance alone can sustain cellular cycling without GcrA/CcrM. While similar nutritional sensing occurs in other alpha-proteobacteria, GcrA and CcrM are not encoded in the reduced genomes of obligate intracellular relatives. We thus propose that the nutritional stress response induced during intracellular growth obviated the need for an S-phase transcriptional regulator.
Preservation of stemness in high-grade serous ovarian cancer organoids requires low Wnt environment
Authors: Hoffmann Karen , Berger Hilmar , Kulbe Hagen , Thillainadarasan Sukanija , Mollenkopf Hans-Joachim , Zemojtel Tomasz , Taube Eliane , Darb-Esfahani Silvia , Mangler Mandy , Sehouli Jalid , Chekerov Radoslav , Braicu Elena , Meyer Thomas F. , Kessler Mirjana 
Published: August 2019

SummaryHigh-grade serous ovarian cancer (HGSOC) likely originates from the fallopian tube (FT) epithelium. Here, we established 15 organoid lines from HGSOC primary tumor deposits that closely match the parental tumor mutational profile and phenotype. We found that Wnt pathway activation leads to growth arrest of these cancer organoids. Moreover, active BMP signaling is almost always required for generation of HGSOC organoids, while healthy FT organoids depend on BMP suppression by Noggin. Interestingly, FT organoids modified by stable shRNA knockdown (KD) of p53, PTEN, and Retinoblastoma (RB), also require a low Wnt environment for long-term growth, while FT organoid medium triggers growth arrest. Thus, early changes in the stem cell niche environment are needed to support outgrowth of these genetically altered cells. Indeed, comparative analysis of gene expression pattern and phenotype of normal and KD organoids confirmed that depletion of tumor suppressors triggers changes in the regulation of stemness and differentiation.
The giant pouched rat (Cricetomys ansorgei) olfactory receptor repertoire
Authors: Freeman Angela R. , Ophir Alexander G. , Sheehan Michael J. 
Published: August 2019

AbstractFor rodents, olfaction is essential for locating food, recognizing mates and competitors, avoiding predators, and navigating their environment. It is thought that rodents may have expanded olfactory receptor repertoires in order to specialize in olfactory behavior. Despite being the largest clade of mammals and depending on olfaction relatively little work has documented olfactory repertoires outside of the conventional laboratory mice and rats. Here we report the olfactory receptor repertoire of the African giant pouched rat (Cricetomys ansorgei), a Muroid rodent distantly related to mice and rats. The African giant pouched rat is notable for its large cortex and olfactory bulbs relative to its body size compared to other sympatric rodents, which suggests anatomical elaboration of olfactory capabilities. We hypothesized that in addition to anatomical elaboration for olfaction, these pouched rats might also have an expanded olfactory receptor repertoire to enable their olfactory behavior. We examined the composition of the olfactory receptor repertoire to better understand how their sensory capabilities have evolved. We identified 1145 functional olfactory genes, and 260 additional pseudogenes within 301 subfamilies from the African giant pouched rat genome. This repertoire is similar to mice and rats in terms of size, pseudogene percentage and number of subfamilies. Analyses of olfactory receptor gene trees revealed that the pouched rat has 6 expansions in different subfamilies compared to mice, rats and squirrels. We identified 99 orthologous genes conserved among 4 rodent species and an additional 167 conserved genes within the Muroid rodents. The orthologous genes shared within Muroidea suggests that there may be a conserved Muroid-specific olfactory receptor repertoire. We also note that the description of this repertoire can serve as a complement to other studies of rodent olfaction, as the pouched rat is an outgroup within Muroidea. Thus, our data suggest that African giant pouched rats are capable of both natural and trained olfactory behaviors with a typical Muriod olfactory receptor repertoire.
Immunosuppression, rather than inflammation, is a salient feature of sepsis in an Indian cohort
Authors: Mukhopadhyay Samanwoy , Thatoi Pravat K , Das Bidyut K , Mohapatra Saroj K 
Published: August 2019

1AbstractSepsis remains a lethal ailment with imprecise treatment and ill-understood biology. A clinical transcriptomic analysis of sepsis patients was performed for the first time in India and revealed large-scale change in blood gene expression in patients of severe sepsis and septic shock admitted to ICU. Three biological processes were quantified using scores derived from the corresponding transcriptional modules. Comparison of the module scores revealed that genes associated with immune response were more suppressed compared to the inflammation-associated genes. These findings will have great implication in the treatment and prognosis of severe sepsis/septic shock if it can be translated into a bedside tool.
How structural brain network topologies associate with cognitive abilities in a value-based decision-making task
Authors: Bañuelos Cristina , Verstynen Timothy 
Published: August 2019

Value-based decision-making relies on effective communication across disparate brain networks. Given the scale of the networks involved in adaptive decision-making, variability in how they communicate should impact behavior; however, precisely how the topological pattern of structural connectivity of individual brain networks influences individual differences in value-based decision-making remains unclear. Using diffusion MRI, we measured structural connectivity networks in a sample of community dwelling adults (N=124). We used standard graph theoretic measures to characterize the topology of the networks in each individual and correlated individual differences in these topology measures with differences in the Iowa Gambling Task. A principal components regression approach revealed that individual differences in brain network topology associate with differences in optimal decision-making, as well as associate with differences in each participant’s sensitivity to high frequency rewards. These findings show that aspects of structural brain network organization can constrain how information is used in value-based decision-making.AbbreviationsMRI - Magnetic Resonance Imaging; IGT – Iowa Gambling Task; DWI – Diffusion Weighted Imaging; QSDR – Q-Space Diffeomorphic Reconstruction; PCA – Principal Components Analysis; GLM – Generalized Linear Models
The IRE1α stress signaling axis is a key regulator of neutrophil antimicrobial effector function
Authors: Abuaita B. H. , Sule G. J. , Schultz T. L. , Gao F. , Knight J. S. , O’Riordan M. X. 
Published: August 2019

AbstractActivation of the endoplasmic reticulum stress sensor, IRE1α, is required for effective immune responses against bacterial infection and is associated with human inflammatory diseases where neutrophils are a key immune component. However, the specific role of IRE1α in regulating neutrophil effector function has not been studied. Here we show that infection-induced IRE1α activation licenses neutrophil antimicrobial capacity, including IL-1β production, NET formation, and MRSA killing. Inhibition of IRE1α diminished production of mitochondrial reactive oxygen species (mROS) and decreased CASPASE-2 activation, which both contributed to neutrophil antimicrobial activity. Mice deficient in Caspase-2 were highly susceptible to MRSA infection and failed to form NETs in a subcutaneous abscess. IRE1α activation enhanced calcium influx and citrullination of histone H3 (Cit-H3) independently of mROS production, suggesting that IRE1α coordinates multiple pathways required for NET formation. Our data demonstrate that the IRE1α-Caspase-2 axis is a major driver of neutrophil activity against MRSA infection and highlight the importance of IRE1α in neutrophil antibacterial function.One Sentence SummaryIRE1α controls neutrophil antimicrobial defenses
Stochastic Models for Revealing the Dynamics of the Growth of Small Tumor Populations
Authors: Johnson Kaitlyn E. , Brock Amy 
Published: August 2019

AbstractThe widely accepted model of tumor growth assumes tumors grow exponentially at a constant rate during early tumorigenesis when populations are small. The possibility that tumors might exhibit altered slower growth dynamics or even net cell death below a critical tumor size has yet to be fully explored. Deterministic growth models are capable of describing larger populations because population variation becomes small compared with the average, but when the population being modeled is small, the inherent stochasticity of the birth and death process produces significant variation. Recent advances in high throughput data collection allow for precise and sufficiently large data sets needed to capture this variation. Therefore, we present a stochastic modeling framework to describe and test the potential for altered growth dynamics at small tumor populations.
Assortative mating by population of origin in a mechanistic model of admixture
Authors: Goldberg Amy , Rastogi Ananya , Rosenberg Noah A 
Published: August 2019

AbstractPopulations whose mating pairs have levels of similarity in phenotypes or genotypes that differ systematically from the level expected under random mating are described as experiencing assortative mating. Excess similarity in mating pairs is termed positive assortative mating, and excess dissimilarity is negative assortative mating. In humans, empirical studies suggest that mating pairs from various admixed populations—whose ancestry derives from two or more source populations—possess correlated ancestry components that indicate the occurrence of positive assortative mating on the basis of ancestry. Generalizing a two-sex mechanistic admixture model, we devise a model of one form of ancestry-assortative mating that occurs through preferential mating based on source population. Under the model, we study the moments of the admixture fraction distribution for different assumptions about mating preferences, including both positive and negative assortative mating by population. We consider the special cases of assortative mating by population that involve a single admixture event and that consider a model of constant contributions to the admixed population over time. We demonstrate that whereas the mean admixture under assortative mating is equivalent to that of a corresponding randomly mating population, the variance of admixture depends on the level and direction of assortative mating. In contrast to standard settings in which positive assortment increases variation within a population, certain assortative mating scenarios allow the variance of admixture to decrease relative to a corresponding randomly mating population: with the three populations we consider, the variance-increasing effect of positive assortative mating within a population might be overwhelmed by a variance-decreasing effect emerging from mating preferences involving other pairs of populations. The effect of assortative mating is smaller on the X chromosome than the autosomes because inheritance of the X in males depends only on the mother’s ancestry, not on the mating pair. Because the variance of admixture is informative about the timing of admixture and possibly about sex-biased admixture contributions, the effects of assortative mating are important to consider in inferring features of population history from distributions of admixture values. Our model provides a framework to quantitatively study assortative mating under flexible scenarios of admixture over time.
A novel fully-human potency-matched dual cytokine-antibody fusion protein targets carbonic anhydrase IX in renal cell carcinomas
Authors: De Luca Roberto , Gouyou Baptiste , Ongaro Tiziano , Villa Alessandra , Ziffels Barbara , Sannino Alessandro , Buttinoni Gianluca , Galeazzi Simone , Mazzacuva Mirko , Neri Dario 
Published: August 2019

AbstractCertain cytokines synergize in activating anti-cancer immunity at the site of disease and it may be desirable to generate biopharmaceutical agents, capable of simultaneous delivery of cytokine pairs to the tumor. In this article, we have described the cloning, expression and characterization of IL2-XE114-TNFmut, a dual-cytokine biopharmaceutical featuring the sequential fusion of interleukin-2 (IL2) with the XE114 antibody in scFv format and a tumor necrosis factor mutant (TNFmut). The fusion protein recognized the cognate antigen (carbonic anhydrase IX, a marker of hypoxia and of renal cell carcinoma) with high affinity and specificity. IL2-XE114-TNFmut formed a stable non-covalent homotrimeric structure, displayed cytokine activity in in vitro tests and preferentially localized to solid tumors in vivo. The product exhibited a partial growth inhibition of murine CT26 tumors transfected for carbonic anhydrase IX. When administered to Cynomolgus monkey as intravenous injection, IL2-XE114-TNFmut showed the expected plasma concentration of ~1500 ng/ml at early time points, indicating the absence of any in vivo trapping events, and a half-life of ~2 hours. IL2-XE114-TNFmut may thus be considered as a promising biopharmaceutical for the treatment of metastatic clear-cell renal cell carcinoma, since these tumors are known to be sensitive to IL2 and to TNF.Contribution to the fieldThere is a growing interest in the antibody-based targeted delivery of pro-inflammatory cytokines for tumor therapy, which may be complementary or alternative to immune checkpoint inhibitors for immunotherapeutic applications. In this article, we have described a novel fusion protein, featuring antibody moieties specific to carbonic anhydrase IX, as well as interleukin-2 and tumor necrosis factor as pro-inflammatory cytokines, which combines the ability to recognize a tumor-associated antigen on the surface of renal cell carcinomas with the simultaneous display of two potent therapeutic payloads. The newly developed product (termed IL2-XE114-TNFmut) exhibited favorable biochemical characteristics, the ability to preferentially localize at the tumor site, a cancer growth inhibition activity and a suitable pharmacokinetic profile in Cynomolgus monkey. IL2-XE114-TNFmut may therefore represent an attractive candidate for the immunotherapy of renal cell carcinoma.
LINC complexes are mechanotransducers that discriminate Epithelial-Mesenchymal Transition programs
Authors: Déjardin Théophile , Carollo Pietro Salvatore , Davidson Patricia M. , Seiler Cynthia , Cuvelier Damien , Cadot Bruno , Sykes Cecile , Gomes Edgar R. , Borghi Nicolas 
Published: August 2019

AbstractLINC complexes are transmembrane protein assemblies that physically connect the nucleo- and cytoskeletons through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes in these contexts are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in LINC complex proteins of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that LINC complex proteins experience tension generated by the cytoskeleton and act as mechanical sensors of cell packing. Moreover, the LINC complex discriminates between inductions of partial and complete epithelial-mesenchymal transitions (EMT). We identify the implicated mechanisms, which associate nesprin tension sensing with α-catenin capture at the nuclear envelope, thereby regulating β-catenin transcription. Our data thus implicate that LINC complexes are mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the Epithelial-Mesenchymal Transition program.
Effects of map design characteristics on users’ search performance and cognitive load
Authors: Al-Samarraie Hosam , Eldenfria Atef , Price Melissa Lee , Zaqout Fahed , Fauzy Wan Mohamad 
Published: August 2019

Purpose
This paper aims to investigate the influence of map design characteristics on users’ cognitive load and search performance. Two design conditions (symbolic vs non-symbolic) were used to evaluate users’ ability to locate a place of interest.

Design/methodology/approach
A total of 19 students (10 male and 9 female, 20-23 years old) participated in this study. The time required for subjects to find a place in the two conditions was used to estimate their searching performance. An electroencephalogram (EEG) device was used to examine students’ cognitive load using event-related desynchronization percentages of alpha, beta and theta brain wave rhythms.

Findings
The results showed that subjects needed more time to find a place in the non-symbolic condition than the symbolic condition. The EEG data, however, revealed that users experienced higher cognitive load when searching for a place in the symbolic condition. The authors found that the design characteristics of the map significantly influenced users’ brain activity, thus impacting their search performance.

Originality/value
Outcomes from this study can be used by cartographic designers and scholars to understand how certain design characteristics can trigger cognitive activity to improve users' searching experience and efficiency.