bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jurisdictional differences in opioid use, other licit and illicit drug use, and harms associated with substance use among people who tamper with pharmaceutical opioids
Authors: Peacock Amy , Bruno Raimondo , Cama Elena , Kihas Ivana , Larance Briony , Lintzeris Nick , Hordern Antonia , White Nancy , Ali Robert , Degenhardt Louisa 
Published: June 2015

AbstractIntroduction and AimsThe harms associated with non‐medical use of pharmaceutical opioid analgesics are well established; however, less is known about the characteristics and drug‐use patterns of the growing and hidden populations of people using pharmaceutical opioids illicitly, including the frequency of pharmaceutical opioid injection. This paper aimed to undertake a detailed examination of jurisdictional differences in patterns of opioid use among a cohort of people who regularly tamper with pharmaceutical opioids in Australia.Design and MethodsData were drawn from the National Opioid Medications Abuse Deterrence study. The cohort was recruited from New South Wales (NSW; n = 303), South Australia (SA; n = 150) and Tasmania (TAS; n = 153) to participate in face‐to‐face structured interviews collecting data on use of pharmaceutical opioids, benzodiazepines, other sedative drugs and illicit substances, as well as the harms associated with substance use.ResultsTAS participants reported greater use and injection of certain pharmaceutical opioids (particularly morphine and methadone tablets), and limited heroin use, with lower rates of engagement in opioid substitution treatment, compared with NSW participants. NSW participants were more socially disadvantaged and more likely to report risky injecting behaviours and injecting‐related injuries and diseases compared with SA and TAS participants. SA participants reported greater rates of pain conditions, greater use of pain‐based services, as well as broader use of pharmaceutical opioids in regards to forms and route of administration, compared with NSW participants.Discussion and ConclusionsDistinct jurisdictional profiles were evident for people who tamper with pharmaceutical opioids, potentially reflecting jurisdictional differences in prescribing regulatory mechanisms and addiction treatment models [Peacock A, Bruno R, Cama E, Kihas I, Larance B, Lintzeris N, Hordern A, White N, Ali R, Degenhardt L. Jurisdictional differences in opioid use, other licit and illicit drug use, and harms associated with substance use among people who tamper with pharmaceutical opioids. Drug Alcohol Rev 2015;34:611–22]
Sexual identity and its relationship to injecting in a sample of disadvantaged young drug users
Authors: Wilson Hannah , Bryant Joanne , Ellard Jeanne , Howard John , Treloar Carla 
Published: June 2015

AbstractIntroduction and aimsPeople who are new to injecting are at the highest risk of acquiring blood‐borne viruses, and certain other characteristics, such as sexual identity, have been known to further heighten this risk. We investigate whether disadvantaged drug‐using young people who are gay, lesbian, bisexual or who identify as other sexual identity (GLBO) are more likely to have ever injected drugs compared with their heterosexual peers.Design and MethodsConvenience sampling was employed across 15 youth services in metropolitan Sydney. Respondents were required to be 16–24 years of age, to have used an illicit drug, to have been exposed to injecting through social networks and been socially disadvantaged in the past 12 months. Participants self‐completed a survey using touch screen laptops.ResultsIn a sample of 250 young people, GLBO participants more commonly reported ever injecting drugs [37.1%, confidence interval (CI) 21.5–55.1% vs. 12.3%, CI 8.1–17.4%] or injecting drugs in the past 12 months [31.4%, CI 16.9–49.3% vs. 5.7%, CI 2.9–9.6%] compared with participants who identified as heterosexual.Discussion and ConclusionsThe higher rates of injecting among GLBO young people found in this sample advocates for the development of targeted prevention strategies for this group. Utilising existing networks in GLBO communities could be one strategy to limit the transition to injecting drug use and reduce the risk of drug‐related harms among this group. [Wilson H, Bryant J, Ellard J, Howard J, Treloar C. Sexual identity and its relationship to injecting in a sample of disadvantaged young drug users. Drug Alcohol Rev 2016;35:218–22]
Treatment satisfaction in people with type 2 diabetes mellitus treated with once‐weekly dulaglutide: data from the AWARD‐1 and AWARD‐3 clinical trials
Authors: Reaney M. , Yu M. , Lakshmanan M. , Pechtner V. , van Brunt K. 
Published: June 2015

AimsTo compare treatment satisfaction among people with type 2 diabetes receiving dulaglutide 1.5 mg and dulaglutide 0.75 mg (a once‐weekly, long‐acting, glucagon‐like peptide‐1 receptor agonist) with those receiving either exenatide or placebo (AWARD‐1 study) or metformin (AWARD‐3 study) over 52 weeks.MethodsThe Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and change version (DTSQc) were used to evaluate total treatment satisfaction and perceived frequency of hyperglycaemia and hypoglycaemia.ResultsIn the AWARD‐1 study, significant improvements from baseline were observed in total DTSQs score for both dulaglutide doses (26 and 52 weeks) and exenatide (26 weeks). The improvement was significantly greater with both dulaglutide doses compared with placebo (26 weeks) and exenatide (26 and 52 weeks). The perceived frequency of hyperglycaemia was lower for all groups at 26 and 52 weeks compared with baseline. The improvement was greater with both dulaglutide doses and exenatide compared with placebo at 26 weeks, and was also greater with both dulaglutide doses compared with exenatide at 26 and 52 weeks. The exenatide group had an increase in perceived frequency of hypoglycaemia at 26 and 52 weeks. In the AWARD‐3 study, significant improvements from baseline were observed for total DTSQs scores in all groups at 26 and 52 weeks. Perceived frequency of hyperglycaemia was lower for all groups at 26 and 52 weeks compared with baseline, and this improvement was greater with both dulaglutide doses compared with metformin at 52 weeks.ConclusionsDulaglutide was associated with improvements in treatment satisfaction and a decrease in perceived frequency of hyperglycaemia.
Sponge erosion under acidification and warming scenarios: differential impacts on living and dead coral
Authors: Stubler Amber D. , Furman Bradley T. , Peterson Bradley J. 
Published: June 2015

AbstractOcean acidification will disproportionately impact the growth of calcifying organisms in coral reef ecosystems. Simultaneously, sponge bioerosion rates have been shown to increase as seawater pH decreases. We conducted a 20‐week experiment that included a 4‐week acclimation period with a high number of replicate tanks and a fully orthogonal design with two levels of temperature (ambient and +1 °C), three levels of pH (8.1, 7.8, and 7.6), and two levels of boring sponge (Cliona varians, present and absent) to account for differences in sponge attachment and carbonate change for both living and dead coral substrate (Porites furcata). Net coral calcification, net dissolution/bioerosion, coral and sponge survival, sponge attachment, and sponge symbiont health were evaluated. Additionally, we used the empirical data from the experiment to develop a stochastic simulation of carbonate change for small coral clusters (i.e., simulated reefs). Our findings suggest differential impacts of temperature, pH and sponge presence for living and dead corals. Net coral calcification (mg CaCO3 cm−2 day−1) was significantly reduced in treatments with increased temperature (+1 °C) and when sponges were present; acidification had no significant effect on coral calcification. Net dissolution of dead coral was primarily driven by pH, regardless of sponge presence or seawater temperature. A reevaluation of the current paradigm of coral carbonate change under future acidification and warming scenarios should include ecologically relevant timescales, species interactions, and community organization to more accurately predict ecosystem‐level response to future conditions.
FBXO21 mediates the ubiquitylation and proteasomal degradation of EID1
Authors: Watanabe Koki , Yumimoto Kanae , Nakayama Keiichi I. 
Published: June 2015

Although identification of substrates for ubiquitin ligase (E3) is important for understanding its biological functions, detection of the interaction between an E3 and its substrates has remained challenging. We recently developed a new approach, termed differential proteomics‐based identification of ubiquitylation substrates (DiPIUS), for the discovery of substrates of a given E3 ligase. We have now applied this approach to an uncharacterized human F‐box protein, FBXO21, which serves as the substrate‐recognition subunit of a SKP1‐CUL1‐F‐box protein (SCF)‐type E3, thereby identifying EID1 (EP300‐interacting inhibitor of differentiation 1) as a candidate substrate. The central and COOH‐terminal portion of FBXO21 was found to interact with the COOH‐terminal region of EID1 in transfected cells. Over‐expression of FBXO21 resulted in the down‐regulation of EID1, whereas disruption of the FBXO21 gene with the CRISPR/Cas9 system stabilized EID1 and led to its accumulation in both the cytoplasm and nucleus. An in vitro ubiquitylation assay showed that EID1 is a direct substrate of SCFFBXO21. Collectively, our results suggest that EID1 is a bona fide substrate of FBXO21 and that the control of EID1 abundance by SCFFBXO21 might affect the transcriptional repression activity of EID1.
Accurate Classification of Chronic Migraine via Brain Magnetic Resonance Imaging
Authors: Schwedt Todd J. , Chong Catherine D. , Wu Teresa , Gaw Nathan , Fu Yinlin , Li Jing 
Published: June 2015

BackgroundThe International Classification of Headache Disorders provides criteria for the diagnosis and subclassification of migraine. Since there is no objective gold standard by which to test these diagnostic criteria, the criteria are based on the consensus opinion of content experts. Accurate migraine classifiers consisting of brain structural measures could serve as an objective gold standard by which to test and revise diagnostic criteria. The objectives of this study were to utilize magnetic resonance imaging measures of brain structure for constructing classifiers: (1) that accurately identify individuals as having chronic vs episodic migraine vs being a healthy control; and (2) that test the currently used threshold of 15 headache days/month for differentiating chronic migraine from episodic migraine.MethodsStudy participants underwent magnetic resonance imaging for determination of regional cortical thickness, cortical surface area, and volume. Principal components analysis combined structural measurements into principal components accounting for 85% of variability in brain structure. Models consisting of these principal components were developed to achieve the classification objectives. Tenfold cross validation assessed classification accuracy within each of the 10 runs, with data from 90% of participants randomly selected for classifier development and data from the remaining 10% of participants used to test classification performance. Headache frequency thresholds ranging from 5‐15 headache days/month were evaluated to determine the threshold allowing for the most accurate subclassification of individuals into lower and higher frequency subgroups.ResultsParticipants were 66 migraineurs and 54 healthy controls, 75.8% female, with an average age of 36 +/− 11 years. Average classifier accuracies were: (1) 68% for migraine (episodic + chronic) vs healthy controls; (2) 67.2% for episodic migraine vs healthy controls; (3) 86.3% for chronic migraine vs healthy controls; and (4) 84.2% for chronic migraine vs episodic migraine. The classifiers contained principal components consisting of several structural measures, commonly including the temporal pole, anterior cingulate cortex, superior temporal lobe, entorhinal cortex, medial orbital frontal gyrus, and pars triangularis. A threshold of 15 headache days/month allowed for the most accurate subclassification of migraineurs into lower frequency and higher frequency subgroups.ConclusionsClassifiers consisting of cortical surface area, cortical thickness, and regional volumes were highly accurate for determining if individuals have chronic migraine. Furthermore, results provide objective support for the current use of 15 headache days/month as a threshold for dividing migraineurs into lower frequency (ie, episodic migraine) and higher frequency (ie, chronic migraine) subgroups.
Linear ubiquitination signals in adaptive immune responses
Authors: Ikeda Fumiyo 
Published: June 2015

SummaryUbiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three‐dimensional topology, functioning as a tag to attract specific signaling molecules, which are so‐called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head‐to‐tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best‐characterized tumor necrosis factor (TNF)‐induced canonical nuclear factor‐κB (NF‐κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF‐induced signaling pathways.
The E3 ligase Itch in immune regulation and beyond
Authors: Aki Daisuke , Zhang Wen , Liu Yun‐Cai 
Published: June 2015

SummaryItch or itchy E3 ubiquitin ligase was initially discovered by genetic studies on the mouse coat color changes, and its deletion results in an itchy phenotype with constant skin scratching and multi‐organ inflammation. It is a member of the homologous to E6‐associated protein C‐terminus (HECT)‐type family of E3 ligases, with the protein‐interacting WW‐domains for the recruitment of substrate and the HECT domain for the transfer of ubiquitin to the substrate. Since its discovery, numerous studies have demonstrated that Itch is involved in the control of many aspects of immune responses including T‐cell activation and tolerance and T‐helper cell differentiation. Itch is also implicated in other biological contexts such as tumorigenesis, development, and stress responses. Many signaling pathways are regulated by Itch‐promoted ubiquitylation of diverse target proteins. Itch is also involved in human diseases. Here, we discuss the major progress in understanding the biological significance of Itch‐promoted protein ubiquitylation in the immune and other systems and in Itch‐mediated regulation of signal transduction.
Kinase inhibition, competitive binding and proteasomal degradation: resolving the molecular function of the suppressor of cytokine signaling (SOCS) proteins
Authors: Linossi Edmond M. , Nicholson Sandra E. 
Published: June 2015

SummaryThe suppressor of cytokine signaling (SOCS) family of proteins are key negative regulators of cytokine and growth factor signaling. They act at the receptor complex to modulate the intracellular signaling cascade, preventing excessive signaling and restoring homeostasis. This regulation is critical to the normal cessation of signaling, highlighted by the complex inflammatory phenotypes exhibited by mice deficient in SOCS1 or SOCS3. These two SOCS proteins remain the best characterized of the eight family members (CIS, SOCS1‐7), and in particular, we now possess a sound understanding of the mechanism of action for SOCS3. Here, we review the mechanistic role of the SOCS proteins and identify examples where clear, definitive data have been generated and discuss areas where the information is less clear. From this functional viewpoint, we discuss how the SOCS proteins achieve exquisite and specific regulation of cytokine signaling and highlight outstanding questions regarding the function of the less well‐studied SOCS family members.
Roles of linear ubiquitinylation, a crucial regulator of NF‐κB and cell death, in the immune system
Authors: Sasaki Katsuhiro , Iwai Kazuhiro 
Published: June 2015

SummaryLinear ubiquitinylation, a newly identified post‐translational modification, is catalyzed by the linear ubiquitin assembly complex (LUBAC), which is composed of three different subunits, HOIL‐1L (heme‐oxidized IRP2 ligase 1L), HOIP (HOIL‐1 interacting protein), and SHARPIN (SHANK‐associated RH domain‐interacting protein). LUBAC plays a critical role in the activation of nuclear factor‐κB (NF‐κB) signaling triggered by a variety of stimuli, including tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and pathogen‐derived components, and in the protection from cell death. Loss of function of SHARPIN in mice triggers chronic inflammation in multiple organs including the skin, as well as immunodeficiency. In humans, mutations in the gene encoding HOIL‐1L cause chronic hyperinflammation and immunodeficiency, which are both associated with decreased levels of LUBAC. The linear ubiquitinylation activity of LUBAC is indispensable for B‐cell function in mice, and hyperactivation of LUBAC is associated with oncogenesis in certain forms of B‐cell lymphoma. In this review, the current understanding of the biochemistry of LUBAC‐mediated linear ubiquitinylation and its involvement in the immune system are discussed.
Linear ubiquitination in immunity
Authors: Shimizu Yutaka , Taraborrelli Lucia , Walczak Henning 
Published: June 2015

SummaryLinear ubiquitination is a post‐translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types.
Targeting signaling factors for degradation, an emerging mechanism for TRAF functions
Authors: Yang Xiao‐Dong , Sun Shao‐Cong 
Published: June 2015

SummaryTumor necrosis factor receptor (TNFR)‐associated factors (TRAFs) form a family of proteins that are best known as signaling adapters of TNFRs. However, emerging evidence suggests that TRAF proteins, particularly TRAF2 and TRAF3, also regulate signal transduction by controlling the fate of intracellular signaling factors. A well‐recognized function of TRAF2 and TRAF3 in this aspect is to mediate ubiquitin‐dependent degradation of nuclear factor‐κB (NF‐κB)‐inducing kinase (NIK), an action required for the control of NIK‐regulated non‐canonical NF‐κB signaling pathway. TRAF2 and TRAF3 form a complex with the E3 ubiquitin ligase cIAP (cIAP1 or cIAP2), in which TRAF3 serves as the NIK‐binding adapter. Recent evidence suggests that the cIAP‐TRAF2‐TRAF3 E3 complex also targets additional signaling factors for ubiquitin‐dependent degradation, thereby regulating important aspects of immune and inflammatory responses. This review provides both historical aspects and new insights into the signaling functions of this ubiquitination system.
Sensor‐Based Electromagnetic Navigation (Mediguide®): How Accurate Is It? A Phantom Model Study
Authors: BOURIER FELIX , REENTS TILKO , AMMAR‐BUSCH SONIA , BUIATTI ALESSANDRA , GREBMER CHRISTIAN , TELISHEVSKA MARTA , BRKIC AMIR , SEMMLER VERENA , LENNERZ CARSTEN , KAESS BERNHARD , KOTTMAIER MARC , KOLB CHRISTOF , DEISENHOFER ISABEL , HESSLING GABRIELE 
Published: June 2015

Accuracy of MediGuide® NavigationBackgroundData about localization reproducibility as well as spatial and visual accuracy of the new MediGuide® sensor‐based electroanatomic navigation technology are scarce. We therefore sought to quantify these parameters based on phantom experiments.Methods and ResultsA realistic heart phantom was generated in a 3D‐Printer. A CT scan was performed on the phantom. The phantom itself served as ground‐truth reference to ensure exact and reproducible catheter placement. A MediGuide® catheter was repeatedly tagged at selected positions to assess accuracy of point localization. The catheter was also used to acquire a MediGuide®‐scaled geometry in the EnSite Velocity® electroanatomic mapping system. The acquired geometries (MediGuide®‐scaled and EnSite Velocity®‐scaled) were compared to a CT segmentation of the phantom to quantify concordance. Distances between landmarks were measured in the EnSite Velocity®‐ and MediGuide®‐scaled geometry and the CT dataset for Bland–Altman comparison. The visualization of virtual MediGuide® catheter tips was compared to their corresponding representation on fluoroscopic cine‐loops. Point localization accuracy was 0.5 ± 0.3 mm for MediGuide® and 1.4 ± 0.7 mm for EnSite Velocity®. The 3D accuracy of the geometries was 1.1 ± 1.4 mm (MediGuide®‐scaled) and 3.2 ± 1.6 mm (not MediGuide®‐scaled). The offset between virtual MediGuide® catheter visualization and catheter representation on corresponding fluoroscopic cine‐loops was 0.4 ± 0.1 mm.ConclusionsThe MediGuide® system shows a very high level of accuracy regarding localization reproducibility as well as spatial and visual accuracy, which can be ascribed to the magnetic field localization technology. The observed offsets between the geometry visualization and the real phantom are below a clinically relevant threshold.