bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxycodone‐induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition
Authors: Hill Rob , Dewey William L , Kelly Eamonn , Henderson Graeme 
Published: March 2018

Background and PurposeOxycodone, a prescription opioid, is a major drug of abuse, especially in the USA, and contributes significantly to opioid overdose deaths each year. Overdose deaths result primarily from respiratory depression. We have studied respiratory depression by oxycodone and have characterized how tolerance develops on prolonged exposure to the drug. We have investigated the role of PKC in maintaining tolerance and have examined whether ethanol or pregabalin reverses oxycodone‐induced tolerance.Experimental ApproachRespiration was measured in male CD‐1 mice by whole‐body plethysmography. Mice were preinjected with oxycodone then implanted with mini‐pumps (s.c.) delivering 20, 45 or 120 mg·kg−1·day−1 oxycodone for 6 days and subsequently challenged with oxycodone (3 mg·kg−1, i.p.) or morphine (10 mg·kg−1, i.p.) to assess the level of tolerance.Key ResultsOxycodone‐treated mice developed tolerance to oxycodone and cross tolerance to morphine‐induced respiratory depression. Tolerance was less with 20 mg·kg−1·day−1 than with 45 or 120 mg·kg−1·day−1 oxycodone treatment. At doses that do not depress respiration, ethanol (0.3 g·kg−1), pregabalin (20 mg·kg−1) and calphostin C (45 μg·kg−1) all reversed oxycodone‐induced tolerance resulting in significant respiratory depression. Reversal of tolerance was less in mice treated with oxycodone (120 mg·kg−1·day−1). In mice receiving ethanol and calphostin C or ethanol and pregabalin, there was no greater reversal of tolerance than seen with either drug alone.Conclusion and ImplicationsThese data suggest that oxycodone‐induced tolerance is mediated by PKC and that reversal of tolerance by ethanol or pregabalin may be a contributory factor in oxycodone overdose deaths.
Separating the wheat from the chaff: A disaggregate analysis of the effects of public spending in the US
Authors: Bouakez Hafedh , Larocque Denis , Normandin Michel 
Published: March 2018

AbstractIn this paper, we undertake a systematic disaggregate analysis of the effects of government spending on economic activity in the US. The level of disaggregation we consider is the highest available and is unprecedented in the empirical literature. More specifically, public consumption and public investment are decomposed into various subcategories, which are measured at the levels of the federal (defence and non‐defence), and state and local governments. For each subcategory, we estimate a structural vector autoregression that identifies public spending shocks through the conditional heteroskedasticity of the structural disturbances, thus relaxing the identifying restrictions commonly used in the literature. Our analysis reveals significant heterogeneity in the effects of public spending shocks on output both across subcategories and government levels. Shocks to spending on durables and structures are found to have the largest and most persistent effect on aggregate output, with a peak multiplier that exceeds 1. Our results also suggest that there is little association between the size of a given category of public expenditures and the magnitude of its effect on output.RésuméSéparer le bon grain de l’ivraie : une analyse désagrégée des effets des dépenses publiques aux États‐Unis. Dans ce texte, on entreprend une analyse désagrégée des effets des dépenses gouvernementales sur l’activité économique aux États‐Unis. Le niveau de désagrégation considéré est le plus grand possible et est sans précédent dans la littérature empirique. Plus spécifiquement, la consommation et l’investissement publics sont décomposés en diverses sous‐catégories qui sont mesurées pour le gouvernement fédéral (défense et non‐défense), ainsi que pour les gouvernements des états et locaux. Pour chaque sous‐catégorie, on estime un vecteur autorégressif structurel qui identifie les chocs de dépenses publiques à travers l’hétéroscédastictité conditionnelle des perturbations structurelles, pour ainsi relâcher les restrictions d’identification communément utilisées dans la littérature. L’analyse révèle une hétérogénéité significative dans les effets des chocs de dépenses publiques sur la production agrégée selon les sous‐catégories et les niveaux de gouvernement. Les chocs dans les dépenses sur les biens durables et les structures tendent à avoir les effets les plus grands et les plus persistants sur la production agrégée avec un effet multiplicateur qui excède 1. Les résultats suggèrent qu’il y a peu de rapport entre la taille d’une catégorie donnée dans les dépenses publiques et l’ampleur de l’effet sur la production agrégée.
c‐Src inhibitor selectively inhibits triple‐negative breast cancer overexpressed Vimentin in vitro and in vivo
Authors: Lou Longquan , Yu Ziyi , Wang Yue , Wang Shui , Zhao Yi 
Published: March 2018

Oncogene c‐Src has been found to be a potential target for the treatment of triple‐negative breast cancer (TNBC). However, the therapeutic effects of the c‐Src inhibitor on TNBC patients are controversial compared to those on cell lines. The molecular mechanisms of the inhibitory effects of the c‐Src inhibitor on TNBC remain unclear. Herein, we showed that a specific c‐Src inhibitor, PP2, was effective in inhibiting phosphorylation of c‐Src in 4 cell lines: T‐47D, SK‐BR‐3, SUM1315MO2, and MDA‐MB‐231, regardless of hormone receptors and human epidermal growth factor receptor 2 (HER2) expression levels. Giving PP2 preferentially reduced the S phase of cell cycles and inhibited colony formation in SUM1315MO2 and MDA‐MB‐231, but not in SK‐BR‐3 and T‐47D cells. Furthermore, PP2 effectively blocked cell migration/invasion and epithelial‐mesenchymal transition (EMT) in TNBC cell lines, SUM1315MO2 and MDA‐MB‐231. An EMT biomarker, vimentin, was highly expressed in 2 TNBC cell lines when they were compared with SK‐BR‐3 and T‐47D cells. Further depletion of vimentin by shRNA remarkably attenuated the inhibitory effects of the c‐Src inhibitor on TNBC cells in vitro and in vivo, indicating a crucial action of vimentin to affect the function of c‐Src in TNBC. This study provides an important rationale for the clinic to precisely select TNBC patients who would benefit from c‐Src inhibitor treatment. This finding suggests that traditional markers for TNBC are not sufficient to precisely define this aggressive type of cancer. Vimentin is identified as an important biomarker to enable categorization of TNBC.
3‐Aminomethyl pyridine chalcone derivatives: Design, synthesis, DNA binding and cytotoxic studies
Authors: Durgapal Sunil Dutt , Soni Rina , Umar Shweta , Suresh Balakrishnan , Soman Shubhangi S. 
Published: March 2018

Herein we report design, synthesis, and anticancer activity of compounds 6a–h and 11a–j. Compounds 6a–f were designed based on 3‐aminomethyl pyridine attached to different acetamide derivatives and in compounds 6g–h it was attached to coumarin moiety. Coumarin containing compounds 6g–h showed very poor anticancer activity against both A549 (Lungs cancer cell line), and MCF‐7 (Breast cancer cell line) cell lines in MTT assay. Compounds 11a–j were designed as derivatives of 3‐aminomethyl pyridine and 4‐amino chalcones. A series of chalcone derivatives of 3‐aminomethyl pyridine 11a–j have been synthesized and screened for their in vitro anticancer activity and DNA binding affinity. Most of the compounds showed very good antimitotic activity against A549 cell line as compared to fluorouracil. Compounds 11g and 11i were selected for DNA‐binding studies as they showed excellent activity against cancer cell lines in MTT assay. CT‐DNA binding affinity of compounds 11g and 11i have been investigated by UV based DNA titration and fluorescence emission study against DNA‐EtBr complex. Interestingly, compound 11i has displayed excellent antiproliferative activity, with IC50 0.0067 ± 0.0002 μm, against MCF‐7 cell line. Compound 11i has been studied for its cytotoxicity using MTT, LDH, as well as EtBr/AO assay and was found to induce apoptosis in the cancerous cell line.
Our Buddies, Ourselves: The Role of Sexual Homophily in Adolescent Friendship Networks
Authors: Trinh Sarah L. , Lee Jaemin , Halpern Carolyn T. , Moody James 
Published: March 2018

The present study tests the assumption that peers wield sufficient influence to induce sexual homophily (i.e., similarities in sexual experiences). Because girls face greater stigma for their sexual experiences than do boys, sexual homophily may be greater in girls' friendship networks than in boys'. Stochastic actor‐based models were used to analyze network data (n = 2,566; ages 14–18) from two high schools in the National Longitudinal Study of Adolescent to Adult Health. Sexual homophily was present in friendship networks. Girls and boys were equally susceptible to their friends' influence, but the former exhibited a stronger preference for befriending same sexual debut status peers than the latter. The findings suggest that adolescents—particularly girls—“curate” their networks to minimize peer ostracism.
Sensitization to minor cat allergen components is associated with type‐2 biomarkers in young asthmatics
Authors: Tsolakis N. , Malinovschi A. , Nordvall L. , Mattsson L. , Lidholm J. , Pedroletti C. , Janson C. , Borres M. P. , Alving K. 
Published: March 2018

SummaryBackgroundCat allergy is a major trigger of asthma world‐wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied.ObjectiveTo investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type‐2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals.MethodsPatients with asthma (age 10‐35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE‐antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B‐Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders.ResultsThe level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with Β‐Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23‐.51).ConclusionsLevels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type‐2 biomarkers and total IgE in young asthmatics.Clinical relevanceWe suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects.
Treatment for moderate to severe atopic dermatitis in alpine and moderate maritime climates differentially affects helper T cells and memory B cells in children
Authors: Heeringa J. J. , Fieten K. B. , Bruins F. M. , van Hoffen E. , Knol E. F. , Pasmans S. G. M. A. , van Zelm M. C. 
Published: March 2018

SummaryBackgroundTreatment of atopic dermatitis (AD) is focused on topical anti‐inflammatory therapy, epidermal barrier repair and trigger avoidance. Multidisciplinary treatment in both moderate maritime and alpine climates can successfully reduce disease activity in children with AD. However, it remains unclear whether abnormalities in B cell and T cell memory normalize and whether this differs between treatment strategies.ObjectiveTo determine whether successful treatment in maritime and alpine climates normalizes B‐ and T lymphocytes in children with moderate to severe AD.MethodsThe study was performed in the context of a trial (DAVOS trial, registered at Current Controlled Trials ISCRTN88136485) in which eighty‐eight children with moderate to severe AD were randomized to 6 weeks of treatment in moderate maritime climate (outpatient setting) or in the alpine climate (inpatient setting). Before and directly after treatment, disease activity was determined with SA‐EASI and serum TARC, and T cell and B cell subsets were quantified in blood.ResultsBoth treatment protocols achieved a significant decrease in disease activity, which was accompanied by a reduction in circulating memory Treg, transitional B cell and plasmablast numbers. Alpine climate treatment had a significantly greater effect on disease activity and was accompanied by a reduction in blood eosinophils and increases in memory B cells, CD8+ TemRO, CD4+ Tcm and CCR7+ Th2 subsets.Conclusions and clinical relevanceClinically successful treatment of AD induces changes in blood B‐ and T cell subsets reflecting reduced chronic inflammation. In addition, multidisciplinary inpatient treatment in the alpine climate specifically affects memory B cells, CD8+ T cells and Th2 cells. These cell types could represent good markers for treatment efficacy.
Simultaneously elevated FeNO and blood eosinophils relate to asthma morbidity in asthmatics from NHANES 2007‐12
Authors: Mogensen I. , Alving K. , Jacinto T. , Fonseca J. , Janson C. , Malinovschi A. 
Published: March 2018

SummaryBackgroundFraction of exhaled nitric oxide (FeNO) and blood eosinophil (B‐Eos) count are biomarkers for type 2 inflammation. However, they signal different inflammatory pathways. Simultaneously elevated, they are related to more asthma events in a general population and among younger asthmatics.ObjectiveTo investigate if simultaneously elevated FeNO and B‐Eos relate to asthma outcomes and lung function among subjects with asthma at a wide age span, and how different cut‐offs for the markers affect these relations.MethodFeNO, B‐Eos and forced expiratory volume in 1 second (FEV1) were assessed in 1419 subjects with asthma, aged 6‐79 years old, from the National Health and Nutrition Examination Survey (NHANES) 2007‐12. Elevated levels were defined as FeNO ≥20 p.p.b. for children <12 years and ≥25 p.p.b. for subjects ≥12 years and B‐Eos count ≥300 cells/μL. Additional analyses were performed for the cut‐offs FeNO >35/30 and >50/35 p.p.b., and for B‐Eos ≥400 and ≥ 500 cells/μL, as well as for different age subgroups (6‐17, 18‐44, >44 years old). Asthma events during the past year were self‐reported.ResultsSubjects with simultaneously elevated FeNO and B‐Eos compared with normal levels of both markers had a higher adjusted odds ratio (aOR (95%CI)) for having FEV1 <80% of predicted (2.15 (1.28‐3.59), wheeze disturbing sleep (1.88 (1.27, 2.78)) but did not differ regarding asthma attacks past year. Elevated B‐Eos, but not FeNO, was related to higher aOR for asthma attack (1.57 (1.14, 2.18) or emergency room (ER) visit due to asthma (1.88 (1.33, 2.64) when elevated FeNO and elevated B‐Eos were studied as independent predictors.ConclusionSimultaneously elevated FeNO and B‐Eos related to reduced lung function in asthmatics, wheezing symptoms, but not to a history of asthma attacks. Asthma attacks and ER‐visit due to asthma were related to increased B‐Eos levels.
Outcome of pregnancies in a large cohort of women with acromegaly
Authors: Jallad R.S. , Shimon I. , Fraenkel M. , Medvedovsky V. , Akirov A. , Duarte F.H. , Bronstein M.D. 
Published: March 2018

SummaryObjectiveTo assess the outcome of pregnancies in a large cohort of women with acromegaly.Design and methodsThis is a retrospective analysis of 31 pregnancies in 20 patients with acromegaly.ResultsTwenty‐seven pregnancies resulted in healthy offspring, and 4 resulted in abortion. Three patients underwent transsphenoidal surgery during pregnancy. IGF‐1 levels remained elevated during pregnancy in 4 pregnancies and normalized in 23 cases. Fifteen cases were followed during pregnancy without any medical or surgical treatment, and 13 of these exhibited normal IGF‐1 levels. Before or during pregnancy, somatostatin receptor ligands usage was not associated with higher risk for adverse outcomes. Arterial hypertension worsening (45%) and impairment of glucose levels (32%) were the most common complications during pregnancies. There were no maternal or neonatal deaths. One woman delivered twins. Two cases of congenital malformations and one with foetal macrosomia were observed. Caesarean delivery was performed in sixteen cases.ConclusionOur study confirms the impact of gestation on IGF‐1 levels. However, it also indicates that acromegaly still holds an increased risk for worsening of comorbidities, especially in uncontrolled patients.
Association between site‐specific bone mineral density and glucose homeostasis and anthropometric traits in healthy men and women
Authors: Kim Se‐Min , Cui Jinrui , Rhyu Jane , Guo Xiuqing , Chen Yii‐Der I. , Hsueh Willa A. , Rotter Jerome I. , Goodarzi Mark O. 
Published: March 2018

SummaryObjectivePatients with type 2 diabetes mellitus have an increased risk of fracture despite normal or increased bone mineral density (BMD). Studies on the relationship of glucose homeostasis with BMD phenotypes have been inconclusive because distinguishing the roles of insulin resistance and hyperglycaemia in bone remodelling is challenging. In this study, we sought to define the relationship of site‐specific BMD with glucose homeostasis traits and anthropometric traits.Design/Patients/MeasurementsIn a cross‐sectional study, we examined 787 subjects from the Mexican‐American Coronary Artery Disease (MACAD) cohort who had undergone euglycaemic‐hyperinsulinaemic clamps, oral glucose tolerance testing and dual X‐ray absorptiometry. Glucose homeostasis traits included insulinogenic index (IGI30), insulin sensitivity (M value), insulin clearance (MCRI), fasting insulin, fasting glucose and 2‐hour glucose. Univariate and multivariate analyses were performed to assess the association of glucose homeostasis and anthropometric traits with site‐specific BMD.ResultsTwo‐hour glucose was negatively associated with arm BMD in women, which remained significant in multivariate analysis (β = −.15, P = .0015). Positive correlations between fasting insulin and BMD at weight‐bearing sites, including pelvis (β = .22, P < .0001) and legs (β = .17, P = .001) in women and pelvis (β = .33, P < .0001) in men, lost significance after multivariate adjustment. Lean mass exhibited strong independent positive associations with BMD at multiple sites in both sexes.ConclusionOur findings suggest that (i) anabolic effects of insulin might work via mechanical loading from lean mass; (ii) a direct negative effect of increasing glucose might be more prominent at cortical‐bone‐rich sites in women; and (iii) lean mass is a strong positive predictor of bone mass.
The effect of implant‐abutment junction position on crestal bone loss: A systematic review and meta‐analysis
Authors: Saleh Muhammad H. A. , Ravidà Andrea , Suárez‐López del Amo Fernando , Lin Guo‐Hao , Asa'ad Farah , Wang Hom‐Lay 
Published: March 2018

AbstractPurposeTo investigate the effect of the apico‐coronal implant position on early and late crestal bone loss (CBL), in bone and tissue level implants.Materials and methodsElectronic and manual literature searches were conducted for controlled clinical trials reporting on CBL before and after functional loading of implants. Random effects meta‐analyses were applied to analyze the weighted mean difference (WMD) and meta‐regression was conducted to investigate any potential influences of select confounding factors.ResultsFourteen articles were included in the systematic review and 12 were included in the quantitative synthesis. For bone level implants, WMD comparing early CBL in equi and subcrestal placement was 0.15 mm (P = .18). For analyses of late CBL in bone level implants, equi and subcrestal placement revealed a 0.03 mm WMD (P = .88). Where in supra and subcrestal placement, WMD was 0.04 mm (P = .86). The comparison presented considerable heterogeneity between these two arms, where the P value for chi‐square test presented as .006. Finally, for CBL between supra and equicrestal placement, WMD was −0.64 mm (P < .0001), favoring the supracrestal group. For tissue level implants, WM of early and late CBL in implants placed equi‐crestally was 0.68 ± 0.12 mm and 0.69 ± 0.54 mm, respectively, where for implants placed sub‐crestally, the WM of CBL was 1.72 ± 0.15 mm and 2.26 ± 0.63 mm, respectively.ConclusionWithin the limitations of this study, it is recommended to place tissue level implants equicrestally, and bone level implants subcrestally.
A randomized controlled clinical trial to assess crestal bone remodeling of four different implant designs
Authors: Glibert Maarten , Vervaeke Stijn , Jacquet Wolfgang , Vermeersch Kim , Östman Pär‐Olov , De Bruyn Hugo 
Published: March 2018

AbstractBackgroundIt is claimed that bone remodeling is limited when the implant neck has microthreads and an internal abutment connection. However, comparative studies, excluding confounding factors, are scarce.AimThis RCT aims to assess whether a coronal microthreaded design and an internal abutment connection affects crestal bone loss, up to one year of function.Materials and MethodsTwenty‐one maxillary edentulous patients were consecutively treated for a bar supported maxillary overdenture on four different implants with respectively: internal connection and microthreads on the implant neck (I MT); internal connection, no microthreads (I NMT), external connection, with microthreads (E MT), and external connection, without microthreads (E NMT). Other design features, s.a. width, surface topography, platform switch as well as surgical placement and prosthetic protocol were consistent. Implant survival and crestal bone loss in relation to the implant type were considered the main variables and a Friedman test for ordered alternatives was used to assess the difference in crestal bone loss between the different study implants.ResultsTwenty‐one patients received 83 study implants. Three implants failed within three months and required replacement. The total survival rate was 96.39% after one year and based on 21 patients and 80 implants a mean crestal bone loss of 0.25 mm (SD: 0.38; range: 0‐1.48) was measured. After a follow‐up of 3, 6, 12, and 21 months no statistically significant differences in crestal bone loss between the different study implants or the different time intervals could be identified.ConclusionsFrom this RCT, it is concluded that the implant‐abutment connection and a microthreaded external thread configuration have limited influence on crestal bone remodeling. The latter can be considered a multifactorial process and is more dependent on other factors such as biologic considerations than on implant design.
GeX: an automated tool for generating XYD files for analysis of endemicity using VNDM
Authors: Santos Charles Morphy D. , Fuhlendorf Max 
Published: March 2018

AbstractIn the last decade, a method widely used to delimit areas of endemism is the analysis of endemicity (AE), a non‐hierarchical and grid‐dependent algorithm implemented through the package NDM/VNDM. Its input files are based on lists of georeferenced taxa, and any mistakes in their preparation will influence the results of the analyses. We describe here a free online automated tool for generating the input files for VNDM from simple spreadsheets.