bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid Pairwise Likelihood Analysis of Animal Behavior Experiments
Authors: Cattelan Manuela , Varin Cristiano 
Published: October 2013

Summary
The study of the determinants of fights between animals is an important issue in understanding animal behavior. For this purpose, tournament experiments among a set of animals are often used by zoologists. The results of these tournament experiments are naturally analyzed by paired comparison models. Proper statistical analysis of these models is complicated by the presence of dependence between the outcomes of fights because the same animal is involved in different contests. This paper discusses two different model specifications to account for between-fights dependence. Models are fitted through the hybrid pairwise likelihood method that iterates between optimal estimating equations for the regression parameters and pairwise likelihood inference for the association parameters. This approach requires the specification of means and covariances only. For this reason, the method can be applied also when the computation of the joint distribution is difficult or inconvenient. The proposed methodology is investigated by simulation studies and applied to real data about adult male Cape Dwarf Chameleons.
Early changes, attrition, and dose–response in low intensity psychological interventions
Authors: Delgadillo Jaime , McMillan Dean , Lucock Mike , Leach Chris , Ali Shehzad , Gilbody Simon 
Published: October 2013

ObjectivesTo investigate if early symptom changes in brief low intensity psychological interventions (guided self‐help and psycho‐education using cognitive behavioural therapy principles) are predictive of final treatment outcome.DesignRetrospective cohort data analysis.MethodClinical records for 1,850 patients who screened positive for depression and/or an anxiety disorder were analysed. Reliable and clinically significant improvement (RCSI) on depression (Patient Health Questionnaire‐9: PHQ‐9) or anxiety (generalized anxiety disorder‐7: GAD‐7) outcome measures after treatment was the primary outcome. Change scores ≥6 on PHQ‐9 and ≥5 on GAD‐7 were taken as indicative of reliable improvement (RI). The model assumed that RI in the earliest treatment sessions would be predictive of RCSI post‐treatment. Predictive accuracy was assessed by calculating the area under the curve (AUC), as well as positive and negative predictive values. Diagnostic odds ratios were also estimated, adjusting for confounders such as baseline severity, use of medication, and pre‐treatment symptom change.ResultsThe AUC estimates for session‐to‐session change scores ranged between .62 and .88, indicative of modest to high predictive reliability. Predictive accuracy was higher for patients who had four or more treatment sessions, with more than 70% of patients with RCSI being accurately identified as early as sessions 1–3. Attrition rates were significantly associated with poor outcomes. Results suggest that at least four therapy sessions are necessary to achieve more than 50% RCSI rates, and the dose–response effect appears to decline in treatments longer than six sessions.ConclusionsPatients showing RI early in treatment were at least twice as likely to fully recover compared to those without early RI.Practitioner points

Patients showing early response to low intensity therapy are at least twice as likely to recover at the end of treatment.

Dropout from treatment is associated with poor clinical outcomes.

Optimal recovery rates were observed for treatments with a total length of between four and six sessions; the dose–response declined in lengthier treatments.

Randomization to different treatment lengths is necessary to confirm this dose–response effect with greater certainty.
A person‐centred analysis of teacher–child relationships in early childhood
Authors: Hughes Kathleen , Bullock Amanda , Coplan Robert J. 
Published: October 2013

BackgroundPreviously, the nature of teacher–child relationships (TCRs) has been explored through dimensions of close, conflicted, and dependent. However, this variable‐centred approach is limited, as many relationships can be characterized by more than one characteristic or trait. A person‐centred approach would allow for a greater understanding of the types of relationships that are formed and improved interpretation of the students' socio‐emotional outcomes associated with that relationship.AimsThe primary goal of this study was to examine the socio‐emotional functioning of young children who formed distinct types of TCRs.SampleParticipants were n = 202 kindergarten children (98 girls, 104 boys, Mage = 64.12 months, SD = 4.86).MethodMulti‐source assessment was employed with data collected from parent ratings, teacher reports, child interviews, and naturalistic observations in the classroom. Using quartile cut‐offs, we identified children who formed conflicted, dependent, and ‘combined’ (conflicted and dependent) TCRs.ResultsResults indicated distinct patterns of socio‐emotional functioning for each TCR group. For example, whereas children in conflicted TCRs evidenced greater externalizing difficulties, children with dependent TCRs had greater internalizing difficulties. Children who evidenced high levels of both conflicted and dependent TCRs displayed the most pervasive socio‐emotional difficulties.ConclusionsChildren who form TCRs characterized by high levels of both conflict and dependency displayed the most pervasive adjustment difficulties. Further investigation is needed to improve our understanding of this group and to assess the plausibility of early intervention strategies.
Transformed non‐Hodgkin lymphoma in the rituximab era: analysis of the NCCN outcomes database
Authors: Ban‐Hoefen Makiko , Vanderplas Ann , Crosby‐Thompson Allison L. , Abel Gregory A. , Czuczman Myron S. , Gordon Leo I. , Kaminski Mark S. , Kelly Jennifer , Millenson Michael , Nademanee Auayporn P. , Rodriguez Maria A. , Zelenetz Andrew D. , Niland Joyce , LaCasce Ann S. , Friedberg Jonathan W. 
Published: October 2013

SummaryHistological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non‐Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy‐confirmed indolent lymphoma and subsequent biopsy‐confirmed HT were identified. Treatments for HT included autologous stem‐cell transplant (auto‐SCT) (n = 50), allogeneic SCT (allo‐SCT) (n = 18), and treatment without transplant (n = 50). The 2‐year overall survival (OS) for the entire cohort was 68%. For auto‐SCT patients aged ≤60 years (n = 24), the 2‐year OS was 74%. For non‐transplanted patients aged ≤60 years (n = 19), the 2‐year OS was 59%. The 2‐year OS of patients naïve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0·03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era.
Genetics on a WHIM
Authors: Al Ustwani Omar , Kurzrock Razelle , Wetzler Meir 
Published: October 2013

SummaryWe initially described the WHIM syndrome based on the combination of Warts, Hypogammaglobulinaemia, Infections and Myelokathexis (neutrophil retention in the bone marrow). Translational research led to the discovery that this rare immunodeficiency disease is caused by a heterozygous mutation in the CXCR4 gene. Recently, Plerixafor has been suggested as a treatment for WHIM syndrome due to its efficacy as a CXCR4 antagonist, closing the translational research loop. In this review, we will focus on the clinical manifestations, pathophysiology, diagnosis and possible therapies for this rare entity.
An investigation into the relevance of action planning, theory of planned behaviour concepts, and automaticity for fruit intake action control
Authors: de Bruijn Gert‐Jan , Wiedemann Amelie , Rhodes Ryan E. 
Published: October 2013

ObjectivesIn the action control framework, intention–behaviour discordance is studied around public health guidelines. Although this framework has been applied to physical activity behaviours, it has only seen very limited attention regarding fruit intake. The purpose of this study was therefore to investigate distributions and predictors of fruit intake intention–behaviour discordance.DesignProspective correlational design.MethodsData were obtained from undergraduate students (n = 413) using validated questionnaires. Variables from the theory of planned behaviour, automaticity, and action planning were assessed at baseline, and fruit intake was assessed 2 weeks later. Data were analysed using discriminant function analyses and analyses of variance.ResultsThe proportion of unsuccessful intenders ranged from 39.2% to 80.8%. There was a larger proportion of fruit intake intenders amongst those who reported strong automatic fruit intake. Action control was predicted by fruit intake automaticity and affective attitudes, but the strongest predictor was perceived behavioural control. No action planning items were related to fruit intake action control.ConclusionsThere is considerable asymmetry in the intention–fruit intake relationship. An application of the action control framework may stimulate debate on the applicability of intention‐based models at the public health level.Statement of contribution

What is already known on this subject?

Intention is theorized to be a key construct in fruit intake.

Studies in the physical activity domain indicate that nearly half of the people with positive intentions fail to subsequently act.

What does this study add?

The proportion of unsuccessful intenders ranged from 39.2% to 80.8%.

Holding positive intentions is not sufficient to consume fruit at suggested public health guidelines.

Perceived behavioural control is the most important predictor of fruit intake action control.
Urinary saturation: casual or causal risk factor in urolithiasis?
Authors: Rodgers Allen L. 
Published: October 2013

Objective
To assess (i) the extent to which urinary supersaturation (SS) has successfully discriminated between stone formers and healthy individuals (N), (ii) whether absolute SS has diagnostic worth and (iii) whether high SS is the fundamental cause of stone formation per se.
Materials and Methods
Google Scholar was used to identify studies in which urinary compositional data had been determined.
In those cases where SS values were not given, or where other risk indices had been reported, they were (re‐)calculated.
Collected data were termed ‘global’ but were then ‘filtered’ according to stone type and protocols used for SS calculations.
SS distribution plots for calcium oxalate, brushite and uric acid were constructed.
Data were statistically analysed using the unpaired t‐test and Mann–Whitney test.
Results
In all, 47 studies yielded 123 SS values for healthy individuals and 122 values for stone formers.
The mean and median SS values were significantly greater in stone formers compared with healthy individuals in all but one of the comparisons.
Wide variations in SS occurred for healthy individuals and stone formers. The two groups could not be separated.
Conclusions
Absolute SS has no diagnostic worth. It is impossible to quantify the meaning of a ‘high’ SS value. Urines cannot be identified as originating from healthy individuals or stone formers based on their SS.
SS should be determined in clinical and research settings for relative comparisons during the assessment of treatment efficacies.
This study provides a compelling argument for SS being a casual factor rather than a causal one.
Plasminogen‐stimulated airway smooth muscle cell proliferation is mediated by urokinase and annexin A2, involving plasmin‐activated cell signalling
Authors: Stewart A G , Xia Y C , Harris T , Royce S , Hamilton J A , Schuliga M 
Published: October 2013

Background and PurposeThe conversion of plasminogen into plasmin by interstitial urokinase plasminogen activator (uPA) is potentially important in asthma pathophysiology. In this study, the effect of uPA‐mediated plasminogen activation on airway smooth muscle (ASM) cell proliferation was investigated.Experimental ApproachHuman ASM cells were incubated with plasminogen (0.5–50 μg·mL−1) or plasmin (0.5–50 mU·mL−1) in the presence of pharmacological inhibitors, including UK122, an inhibitor of uPA. Proliferation was assessed by increases in cell number or MTT reduction after 48 h incubation with plasmin(ogen), and by earlier increases in [3H]‐thymidine incorporation and cyclin D1 expression.Key ResultsPlasminogen (5 μg·mL−1)‐stimulated increases in cell proliferation were attenuated by UK122 (10 μM) or by transfection with uPA gene‐specific siRNA. Exogenous plasmin (5 mU·mL−1) also stimulated increases in cell proliferation. Inhibition of plasmin‐stimulated ERK1/2 or PI3K/Akt signalling attenuated plasmin‐stimulated increases in ASM proliferation. Furthermore, pharmacological inhibition of cell signalling mediated by the EGF receptor, a receptor trans‐activated by plasmin, also reduced plasmin(ogen)‐stimulated cell proliferation. Knock down of annexin A2, which has dual roles in both plasminogen activation and plasmin‐signal transduction, also attenuated ASM cell proliferation following incubation with either plasminogen or plasmin.Conclusions and ImplicationsPlasminogen stimulates ASM cell proliferation in a manner mediated by uPA and involving multiple signalling pathways downstream of plasmin. Targeting mediators of plasminogen‐evoked ASM responses, such as uPA or annexin A2, may be useful in the treatment of asthma.
Effects of 3,4‐methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats
Authors: Schindler Charles W , Thorndike Eric B , Blough Bruce E , Tella Srihari R , Goldberg Steven R , Baumann Michael H 
Published: October 2013

Background and PurposeThe cardiovascular effects produced by 3,4‐methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats.Experimental ApproachRadiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats.Key ResultsMDMA (1–20 mg·kg−1) produced dose‐related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N‐demethylated metabolite, 3,4‐methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4‐dihydroxymethamphetamine (HHMA; 1–10 mg·kg−1) increased HR more potently and to a greater extent than MDMA, whereas 3,4‐dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4‐hydroxy‐3‐methoxymethamphetamine (HMMA) and 4‐hydroxy‐3‐methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β‐adrenoceptor antagonist propranolol.Conclusions and ImplicationsOur results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study.
The expression and function of histamine H3 receptors in pancreatic beta cells
Authors: Nakamura T , Yoshikawa T , Noguchi N , Sugawara A , Kasajima A , Sasano H , Yanai K 
Published: October 2013

Background and PurposeHistamine and its receptors in the CNS play important roles in energy homeostasis. Here, we have investigated the expression and role of histamine receptors in pancreatic beta cells, which secrete insulin.Experimental ApproachThe expression of histamine receptors in pancreatic beta cells was examined by RT‐PCR, Western blotting and immunostaining. Insulin secretion assay, ATP measurement and calcium imaging studies were performed to determine the function and signalling pathway of histamine H3 receptors in glucose‐induced insulin secretion (GIIS) from MIN6 cells, a mouse pancreatic beta cell line. The function and signalling pathway of H3 receptors in MIN6 cell proliferation were examined using pharmacological assay and Western blotting.Key ResultsHistamine H3 receptors were expressed in pancreatic beta cells. A selective H3 receptor agonist, imetit, and a selective inverse H3 receptor agonist, JNJ‐5207852, had inhibitory and facilitatory effects, respectively, on GIIS in MIN6 cells. Neither imetit nor JNJ‐5207852 altered intracellular ATP concentration, or intracellular calcium concentration stimulated by glucose and KCl, indicating that GIIS signalling was affected by H3 receptor signalling downstream of the increase in intracellular calcium concentration. Moreover, imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The phosphorylation of cAMP response element‐binding protein (CREB), which facilitated beta cell proliferation, was inhibited, though not significantly, by imetit, indicating that activated H3 receptors inhibited MIN6 cell proliferation, possibly by decreasing CREB phosphorylation.Conclusions and ImplicationsHistamine H3 receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation.
Mitochondrial protein quality control in health and disease
Authors: Baker Michael J , Palmer Catherine S , Stojanovski Diana 
Published: October 2013

Progressive mitochondrial dysfunction is linked with the onset of many age‐related pathologies and neurological disorders. Mitochondrial damage can come in many forms and be induced by a variety of cellular insults. To preserve organelle function during biogenesis or times of stress, multiple surveillance systems work to ensure the persistence of a functional mitochondrial network. This review provides an overview of these processes, which collectively contribute to the maintenance of a healthy mitochondrial population, which is critical for cell physiology and survival.Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Unravelling mitochondrial pathways to Parkinson's disease
Authors: Celardo I , Martins L M , Gandhi S 
Published: October 2013

Mitochondria are essential for cellular function due to their role in ATP production, calcium homeostasis and apoptotic signalling. Neurons are heavily reliant on mitochondrial integrity for their complex signalling, plasticity and excitability properties, and to ensure cell survival over decades. The maintenance of a pool of healthy mitochondria that can meet the bioenergetic demands of a neuron, is therefore of critical importance; this is achieved by maintaining a careful balance between mitochondrial biogenesis, mitochondrial trafficking, mitochondrial dynamics and mitophagy. The molecular mechanisms that underlie these processes are gradually being elucidated. It is widely recognized that mitochondrial dysfunction occurs in many neurodegenerative diseases, including Parkinson's disease. Mitochondrial dysfunction in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress, is observed in several Parkinson's disease models. However, identification of the recessive genes implicated in Parkinson's disease has revealed a common pathway involving mitochondrial dynamics, transport, turnover and mitophagy. This body of work has led to the hypothesis that the homeostatic mechanisms that ensure a healthy mitochondrial pool are key to neuronal function and integrity. In this paradigm, impaired mitochondrial dynamics and clearance result in the accumulation of damaged and dysfunctional mitochondria, which may directly induce neuronal dysfunction and death. In this review, we consider the mechanisms by which mitochondrial dysfunction may lead to neurodegeneration. In particular, we focus on the mechanisms that underlie mitochondrial homeostasis, and discuss their importance in neuronal integrity and neurodegeneration in Parkinson's disease.Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Platelet P2Y12 receptors are involved in the haemostatic effect of notoginsenoside Ft1, a saponin isolated from Panax notoginseng
Authors: Gao B , Huang L , Liu H , Wu H , Zhang E , Yang L , Wu X , Wang Z 
Published: October 2013

Background and PurposeSaponins isolated from Panax notoginseng (Burk.) F.H. Chen have been shown to relieve thrombogenesis and facilitate haemostasis. However, it is not known which saponin accounts for this haemostatic effect. Hence, in the present study we aimed to identify which saponins contribute to its haemostatic activity and to elucidate the possible underlying mechanisms.Experimental ApproachPlatelet aggregation was analysed using a platelet aggregometer. Prothrombin time, activated partial thromboplastin time and thrombin time were measured using a blood coagulation analyser, which was further corroborated with bleeding time and thrombotic assays. The interaction of notoginsenoside Ft1 with the platelet P2Y12 receptor was determined by molecular docking analysis, cytosolic Ca2+ and cAMP measurements, and phosphorylation of PI3K and Akt assays.Key ResultsAmong the saponins examined, Ft1 was the most potent procoagulant and induced dose‐dependent platelet aggregation. Ft1 reduced plasma coagulation indexes, decreased tail bleeding time and increased thrombogenesis. Moreover, it potentiated ADP‐induced platelet aggregation and increased cytosolic Ca2+ accumulation, effects that were attenuated by clopidogrel. Molecular docking analysis suggested that Ft1 binds to platelet P2Y12 receptors. The increase in intracellular Ca2+ evoked by Ft1 in HEK293 cells overexpressing P2Y12 receptors could be blocked by ticagrelor. Ft1 also affected the production of cAMP and increased phosphorylation of PI3K and Akt downstream of P2Y12 signalling pathways.Conclusion and ImplicationsFt1 enhanced platelet aggregation by activating a signalling network mediated through P2Y12 receptors. These novel findings may contribute to the effective utilization of this compound in the therapy of haematological disorders.