bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual‐orientation differences in alcohol use trajectories and disorders in emerging adulthood: results from a longitudinal cohort study in the United States
Authors: Coulter Robert W. S. , Jun Hee‐Jin , Calzo Jerel P. , Truong Nhan L. , Mair Christina , Markovic Nina , Charlton Brittany M. , Silvestre Anthony J. , Stall Ron , Corliss Heather L. 
Published: April 2018

AbstractAimsWe estimated sexual‐orientation differences in alcohol use trajectories during emerging adulthood, and tested whether alcohol use trajectories mediated sexual‐orientation differences in alcohol use disorders (AUDs).DesignLongitudinal self‐reported survey data from the Growing Up Today Study.SettingUnited States.ParticipantsA total of 12 493 participants aged 18–25 during the 2003, 2005, 2007 or 2010 surveys.MeasurementsStratified by gender, longitudinal latent class analyses estimated alcohol use trajectories (using past‐year frequency, quantity and binge drinking from 2003 to 2010). Multinomial logistic regression tested differences in trajectory class memberships by sexual orientation [comparing completely heterosexual (CH) participants with sexual‐minority subgroups: mainly heterosexual (MH), bisexual (BI) and gay/lesbian (GL) participants]. Modified Poisson regression and mediation analyses tested whether trajectories explained sexual‐orientation differences in AUDs (past‐year DSM‐IV abuse/dependence in 2010).FindingsSix alcohol use trajectory classes emerged for women and five for men: these included heavy (23.5/36.9% of women/men), moderate (31.8/26.4% of women/men), escalation to moderately heavy (9.7/12.0% of women/men), light (17.0% for women only), legal (drinking onset at age 21; 11.1/15.7% of women/men) and non‐drinkers (7.0/9.1% of women/men). Compared with CH women, MH and BI women had higher odds of being heavy, moderate, escalation to moderately heavy and light drinkers versus non‐drinkers (odds ratios = 2.02–3.42; P‐values < 0.01–0.04). Compared with CH men, MH men had higher odds of being heavy, moderate and legal drinkers versus non‐drinkers (odds ratios = 2.24–3.34; P‐values < 0.01–0.01). MH men and women, BI women and GLs had higher risk of AUDs in 2010 than their same‐gender CH counterparts (risk ratios = 1.34–2.17; P‐values < 0.01). Alcohol use trajectories mediated sexual‐orientation differences in AUDs for MH and GL women (proportion of effect mediated = 30.8–31.1%; P‐values < 0.01–0.02), but not for men.ConclusionsIn the United States, throughout emerging adulthood, several sexual‐minority subgroups appear to have higher odds of belonging to heavier alcohol use trajectories than completely heterosexuals. These differences partially explained the higher risk of alcohol use disorders among mainly heterosexual and gay/lesbian women but not among sexual‐minority men.
Randomized clinical trial of the effects of azithromycin use in the treatment of peri‐implantitis
Authors: Gershenfeld L , Kalos A , Whittle T , Yeung S 
Published: April 2018

AbstractBackgroundThe aim of this clinical trial was to establish a proof of concept that the adjunctive use of systemic azithromycin (AZM) in conjunction with mechanical debridement has an increased benefit in reducing soft tissue inflammation in the treatment of peri‐implantitis.MethodsIn a randomized, double‐blind, clinical trial, the treatment group (nine patients) received AZM as well as mechanical debridement in a single course of treatment, whereas the control group (eight patients) received a placebo and mechanical debridement. The primary outcome variables studied were bleeding on probing, suppuration, pocket probing depth and gingival recession. The secondary variables studied were gingival index, plaque index, microbiological and interleukin‐1β status. The observation period was 6 months.ResultsOver the 6 months’ observation period, the treatment patients showed a consistently greater reduction of gingival inflammation and an improvement in soft tissue healing than the control patients.ConclusionsThe adjunctive use of a single course of systemic azithromycin can assist in the control of peri‐implant mucositis in the treatment of peri‐implantitis.
Intraoral frostbite and Leidenfrost effect
Authors: Divya VC , Saravanakarthikeyan B 
Published: April 2018

AbstractCurrent lifestyle trends encouraging the rise in use of liquid nitrogen in food and beverages may eventually increase the episodes of injuries reported as well. Here, we report the first case of intraoral frostbite as a result of direct injury to the tissues due to ingestion of liquid nitrogen. The mechanism of injury to the oral mucosa in the absence of any injury to the gastric mucosa is explained correlating it to the Leidenfrost phenomenon. Awareness and proper regulations for the use of liquid nitrogen are unavailable and must be created in order to avoid any potential mortality. The diagnostician must consider the possibility of a chemical agent such as liquid nitrogen, which is so widely being used in the food and beverage industry, as a possible aetiological factor of oral mucosal injury.
Functional traits reveal environmental constraints on amphibian community assembly in a subtropical dry forest
Authors: Lescano Julián N. , Miloch Daniela , Leynaud Gerardo C. 
Published: April 2018

AbstractThe relationships between functional traits and environmental gradients are useful to identify different community assembly processes. In this work, we used an approach based on functional traits to analyse if changes in hydroperiod and tree covers of ponds are relevant for local amphibian community assembly processes. Ephemeral ponds with low vegetation cover are expected to impose constraints on different species with particular trait combinations and, therefore, to exhibit communities with lower functional diversity than more stable ponds with greater tree cover. Sampling was conducted in 39 temporary ponds located along vegetation and hydroperiod gradients in the most arid portion of the Chaco ecoregion. Seven functional traits were measured in each species present in the regional pool. Associations between these traits and environmental gradients were detected using multivariate ordination techniques and permutation test (RLQand fourth‐corner analyses respectively). Functional diversity indices were then calculated and related to variations in the environmental gradients. The results obtained allowed us to identify different sets of traits associated with hydroperiod and tree cover, suggesting that these environmental variables are relevant for structuring amphibian communities according to interspecific variations in functional traits from both, larval and adult stages. Contrary to our expectations, communities associated with more stable ponds and with greater tree cover exhibited lower functional diversity than expected by chance (and were the ponds with highest species richness). This result indicates that the reduction in relative importance of environmental restrictions imposed by a very short hydroperiod and the lack of tree cover, favours different species of the regional pool that are similar in several functional traits. Accordingly, communities associated with stable ponds with high tree cover exhibited high functional redundancy.
Model predicting the microvascular invasion and satellite lesions of hepatocellular carcinoma after hepatectomy
Authors: Shen Junyi , Wen Tianfu , Chen Weixia , Lu Changli , Yan Lvnan , Yang Jiayin 
Published: April 2018

BackgroundMicrovascluar invasion and satellite lesion (MS), important unfavourable pathological factors, significantly contribute to tumour recurrence and impair the prognosis in hepatocellular carcinoma. We aimed to construct a model for the prediction of MS in order to plan treatment better.MethodsA total of 1135 consecutive patients with hepatocellular carcinoma who received radical hepatectomy at West China Hospital were randomly assigned to a training set and a validation set. Multivariate analysis was preformed to identify independent risk factors of MS in the training set, and a nomogram was then constructed based on the risk factors. The concordance index (C‐index) and a calibration curve were used to assess the predictive performance of the model.ResultsThe occurrence rate of MS was about 36.5%. Based on the multivariate analysis, the following six variables were incorporated into the nomogram: age (hazard ratio (HR): 0.531), alpha fetoprotein (HR: 1.327), neutrophil‐to‐lymphocyte ratio (>2.8, HR: 1.732), international normalized ratio (>1.07, HR: 1.702), tumour size (HR: 1.116) and tumour number (HR: 1.842). The model showed satisfactory discrimination abilities, with a C‐index of 0.721 for the training set and 0.704 for the validation set. The receiver operating characteristic curve confirmed the predictive power. Meanwhile, the calibration curve presented a goodness of fit between prediction of the model and actual observations.ConclusionsThe user‐friendly model may be useful for prediction of the occurrence of MS and to plan treatment more rationally preoperatively.
Is magnetic resonance imaging‐targeted biopsy a useful addition to systematic confirmatory biopsy in men on active surveillance for low‐risk prostate cancer? A systematic review and meta‐analysis
Authors: Schoots Ivo G. , Nieboer Daan , Giganti Francesco , Moore Caroline M. , Bangma Chris H. , Roobol Monique J. 
Published: April 2018

ObjectiveTo systematically review and meta‐analyse evidence regarding the additional value of magnetic resonance imaging (MRI) and MRI‐targeted biopsies to confirmatory systematic biopsies in identifying high‐grade prostate cancer in men with low‐risk disease on transrectal ultrasonography (TRUS) biopsy, as active surveillance (AS) of prostate cancer is recommended for men with Gleason 3 + 3 on standard TRUS‐guided biopsy. Confirmatory assessment can include repeat standard TRUS‐guided biopsy, and/or MRI with targeted biopsy when indicated.MethodsA systematic review of the Embase, Medline, Web‐of‐science, Google scholar, and Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)‐2 criteria. Studies reporting men with Gleason 3 + 3 prostate cancer who had chosen AS based on transrectal systematic biopsy findings and had undergone MRI with systematic ± targeted biopsy at confirmatory assessment were included. The primary outcome was detection of any Gleason pattern ≥4.ResultsIncluded reports (six) of men on AS (n = 1 159) showed cancer upgrading (Gleason ≥3 + 4) in 27% (95% confidence interval [CI] 22–34%) using a combined approach of MRI‐targeted biopsies and confirmatory systematic biopsies. MRI‐targeted biopsies alone would have missed cancer upgrading in 10% (95% CI 8–14%) and standard biopsies alone would have missed cancer upgrading in 7% (95% CI 5–10%). No pathway was more favourable than the other (relative risk [RR] 0.92, 95% CI 0.79–1.06). In all, 35% (95% CI 27–43%) of men with a positive MRI were upgraded, compared to 12% (95% CI 8–18%) of men with a negative MRI being upgraded (RR 2.77, 95% CI 1.76–4.38).ConclusionsA pre‐biopsy MRI should be performed before confirmatory systematic TRUS‐guided biopsies in men on AS, together with MRI‐targeted biopsies when indicated. A combined approach maximises cancer detection, although other factors within multivariate risk prediction can be used to aid the decision to biopsy in these men.
Novel inhibitors of the cellular renin‐angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/β‐catenin pathway against renal fibrosis
Authors: Wang Ming , Chen Dan‐Qian , Chen Lin , Cao Gang , Zhao Hui , Liu Dan , Vaziri Nosratola D , Guo Yan , Zhao Ying‐Yong 
Published: April 2018

Background and PurposeTubulo‐interstitial fibrosis is the final pathway in the progression of chronic kidney disease (CKD) to kidney failure. The renin‐angiotensin system (RAS) plays a major role in CKD progression. Hence, we determined the efficacy of novel RAS inhibitors isolated from Poria cocos against renal fibrosis.Experimental ApproachEffects of three novel tetracyclic triterpenoid compounds, poricoic acid ZC (PZC), poricoic acid ZD (PZD) and poricoic acid ZE (PZE), were investigated on TGFβ1‐ and angiotensin II (AngII)‐treated HK‐2 cells and unilateral ureteral obstruction (UUO) in mice. Immunofluorescence staining, quantitative real‐time PCR, siRNA, co‐immunoprecipitation and Western blot analyses were used to evaluate expression of key molecules in RAS, Wnt/β‐catenin and TGFβ/Smad pathways.Key ResultsAddition of the above compounds to culture media and their administration to UUO mice: (i) significantly attenuated epithelial‐to‐mesenchymal transition and extracellular matrix production in TGFβ1‐ and AngII‐treated HK‐2 cells and UUO mice by inhibiting Wnt/β‐catenin pathway activation and Smad3 phosphorylation; (ii) selectively inhibited Smad3 phosphorylation by blocking the interaction of TGFBR1 with Smad3; and (iii) specifically inhibited Smad3 activation. PZC and PZD showed a strong inhibitory effect on all RAS components, and PZE showed a strong inhibitory effect on renin. Furthermore, the secolanostane tetracyclic triterpenoids, PZC and PZD, showed a stronger inhibitory effect than the lanostane tetracyclic triterpenoid PZE. Therefore, compounds with secolanostance skeleton showed stronger bioactivity than those with lanostance skeleton.Conclusion and ImplicationsThe secolanostane tetracyclic triterpenoids effectively blocked RAS by simultaneously targeting multiple RAS components and lanostane tetracyclic triterpenoids inhibited renin and protected against tubulo‐interstitial fibrosis.
The role of autoimmune reactivity induced by heat shock protein 70 in the pathogenesis of essential hypertension
Authors: Rodriguez‐Iturbe Bernardo , Lanaspa Miguel A , Johnson Richard J 
Published: April 2018

Autoimmunity is increasingly recognized as having a central role in essential hypertension. Heat shock proteins (HSPs) are immunodominant molecules with high interspecies homology and autoimmune reactivity directed against HSP70 may play a role in the pathogenesis of hypertension. Autoimmunity to HSP70 may result from molecular mimicry between human HSP and bacterial HSP or, alternatively, as a response to HSP70–peptide complexes generated during cellular stress and delivered to the major histocompatibility complex by antigen‐presenting cells. HSP70 is increased in the circulation and kidney of hypertensive patients, and genetic polymorphisms of HSP70 are associated with essential hypertension. Depending on the route and conditions of administration, HSP70 may induce or suppress immune‐related inflammation. Renal inflammation induced by immunity to HSP70 causes hypertension in laboratory animals, and administration of specific peptide sequences of HSP70 results in a protective anti‐inflammatory response that prevents and corrects salt‐induced hypertension. Potential therapeutic uses of HSP70 in essential hypertension deserve to be investigated.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Prostaglandin FP receptor antagonists: discovery, pharmacological characterization and therapeutic utility
Authors: Sharif Najam A , Klimko Peter G 
Published: April 2018

In contrast to the availability of potent and selective antagonists of several prostaglandin receptor types (including DP1, DP2, EP and TP receptors), there has been a paucity of well‐characterized, selective FP receptor antagonists. The earliest ones included dimethyl amide and dimethyl amine derivatives of PGF2α, but these have failed to gain prominence. The fluorinated PGF2α analogues, AL‐8810 and AL‐3138, were subsequently discovered as competitive and non‐competitive FP receptor antagonists respectively. Non‐prostanoid structures, such as the thiazolidinone AS604872, the D‐amino acid‐based oligopeptide PDC31 and its peptidomimic analogue PDC113.824 came next, but the latter two are allosteric inhibitors of FP receptor signalling. AL‐8810 has a sub‐micromolar in vitro potency and ≥2 log unit selectivity against most other PG receptors when tested in several cell‐ and tissue‐based functional assays. Additionally, AL‐8810 has demonstrated therapeutic efficacy as an FP receptor antagonist in animal models of stroke, traumatic brain injury, multiple sclerosis, allodynia and endometriosis. Consequently, it appears that AL‐8810 has become the FP receptor antagonist of choice.Linked ArticlesThis article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc
Identification and structure elucidation of the pro‐resolving mediators provides novel leads for resolution pharmacology
Authors: Dalli Jesmond , Serhan Charles N 
Published: April 2018

Inflammatory diseases are a major socio‐economic burden, with the incidence of such conditions on the rise, especially in western societies. For decades, the primary treatment paradigm for many of these conditions was to develop drugs that inhibit or antagonize the production and biological actions of molecules that were thought to be the culprits in propagating disease; these include cytokines and eicosanoids. This approach is effective in controlling disease propagation; however, long‐term exposure to these anti‐inflammatories is also associated with many side effects, some of which are severe, including immune‐suppression. The discovery that termination of self‐limited acute inflammation is an active process orchestrated by endogenous mediators, including the essential fatty acid‐derived resolvins, protectins and maresins, has provided novel opportunities for the design of therapeutics that control inflammation with a lower burden of side effects. This is because at variance to anti‐inflammatories, pro‐resolving mediators do not completely inhibit inflammatory responses; instead, these mediators reprogramme the immune response to accelerate the termination of inflammation, facilitating the regain of function. The scope of this review is to highlight the biological actions of these autacoids and their potential utility as lead compounds in developing resolution pharmacology‐based therapeutics.Linked ArticlesThis article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc
New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism
Authors: Vecchio Elizabeth A , Baltos Jo‐Anne , Nguyen Anh T N , Christopoulos Arthur , White Paul J , May Lauren T 
Published: April 2018

Adenosine receptors are a family of GPCRs containing four subtypes (A1, A2A, A2B and A3 receptors), all of which bind the ubiquitous nucleoside adenosine. These receptors play an important role in physiology and pathophysiology and therefore represent attractive drug targets for a range of conditions. The theoretical framework surrounding drug action at adenosine receptors now extends beyond the notion of prototypical agonism and antagonism to encompass more complex pharmacological concepts. New paradigms include allostery, in which ligands bind a topographically distinct receptor site from that of the endogenous agonist, homomeric or heteromeric interactions across receptor oligomers and biased agonism, that is, ligand‐dependent differential intracellular signalling. This review provides a concise overview of allostery, oligomerization and biased agonism at adenosine receptors and outlines how these paradigms may enhance future drug discovery endeavours focussed on the development of novel therapeutic agents acting at adenosine receptors.Linked ArticlesThis article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc
PPARs and pain
Authors: Okine Bright N , Gaspar Jessica C , Finn David P 
Published: April 2018

Chronic pain is a common cause of disability worldwide and remains a global health and socio‐economic challenge. Current analgesics are either ineffective in a significant proportion of patients with chronic pain or associated with significant adverse side effects. The PPARs, a family of nuclear hormone transcription factors, have emerged as important modulators of pain in preclinical studies and therefore a potential therapeutic target for the treatment of pain. Modulation of nociceptive processing by PPARs is likely to involve both transcription‐dependent and transcription‐independent mechanisms. This review presents a comprehensive overview of preclinical studies investigating the contribution of PPAR signalling to nociceptive processing in animal models of inflammatory and neuropathic pain. We examine current evidence from anatomical, molecular and pharmacological studies demonstrating a role for PPARs in pain control. We also discuss the limited evidence available from relevant clinical studies and identify areas that warrant further research.Linked ArticlesThis article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
Antinociception by the anti‐oxidized phospholipid antibody E06
Authors: Mohammadi Milad , Oehler Beatrice , Kloka Jan , Martin Corinna , Brack Alexander , Blum Robert , Rittner Heike L 
Published: April 2018

Background and PurposeROS and their downstream molecules such as oxidized phospholipids (OxPL) and 4‐hydroxynonenal activate TRPA1 and TRPV1 (vanilloid 1) cation channels in vivo and in vitro shaping thermal and mechanical hypersensitivity in inflammatory pain. E06/T15 is a monoclonal autoantibody against oxidized phosphatidylcholine (OxPC) used in diagnostics in arteriosclerosis. Recently, we provided evidence that E06 also ameliorates inflammatory pain. Here, we studied E06 for local treatment against hypersensitivity evoked by endogenous and exogenous agonists of TRPA1 or TRPV1 channels.Experimental ApproachWe utilized a combination of reflexive and complex behavioural pain measurements, live‐cell calcium imaging and OxPC‐binding assays. The lipid peroxidation metabolite 4‐hydroxynonenal, hydrogen peroxide as a source of ROS, allyl isothiocyanate and capsaicin were used to activate their respective receptors.Key ResultsAll irritants induced thermal and mechanical hypersensitivity, spontaneous nocifensive and affective‐motivational behaviour, as well as calcium influx in HEKTRPA1‐ or HEKTRPV1‐cells and dorsal root ganglion neurons. E06 prevented prolonged mechanical hypersensitivity induced by all irritants except for H2O2. E06 did not alter immediate irritant‐induced nocifensive or affective motivational behaviour. In vitro, E06 blocked only 4‐hydroxynonenal‐induced calcium influx although this compound did not bind to E06. After 1–3 h, all tested irritants elicited formation of OxPC in paw tissue.Conclusions and ImplicationsE06 ameliorates not only inflammatory pain but also prolonged hypersensitivity due to formation of OxPC. This supports the view that neutralizing certain OxPL as endogenous activators of TRPA1 or TRPV1 channels may be valuable for pain therapy.