bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cocaine‐specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse
Authors: Contreras‐Rodríguez Oren , Albein‐Urios Natalia , Perales José C. , Martínez‐Gonzalez José M. , Vilar‐López Raquel , Fernández‐Serrano María J. , Lozano‐Rojas Oscar , Verdejo‐García Antonio 
Published: July 2015

AbstractAimsTo contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting‐state functional connectivity approach; and to determine the association between cocaine dependence‐related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse.DesignCross‐sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed‐up for 12 weeks to measure drug relapse.Setting and ParticipantsCD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain).MeasurementsSeed‐based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay‐discounting questionnaire, the reversal‐learning task and a dichotomous measure of cocaine relapse indicated with self‐report and urine tests.FindingsCD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre‐frontal cortex and the dorsal putamen seed and insula (P ≤ 0.001, kE = 108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P ≤ 0.001, kE = 108) and cocaine relapse (P ≤ 0.005, kE = 34).ConclusionsCocaine dependence‐related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.
Measuring coping style following acquired brain injury: A modification of the Coping Inventory for Stressful Situations Using Rasch analysis
Authors: Simblett Sara K. , Gracey Fergus , Ring Howard , Bateman Andrew 
Published: July 2015

ObjectiveThe importance of coping style factors in the process of emotional adjustment following acquired brain injury (ABI) has been gaining increased attention. To assess ways of coping with distress accurately, clear conceptual definitions and measurement precision is vital. The purpose of this study was to investigate the psychometric properties of a well‐known measure of coping, the Coping Inventory for Stressful Situations (CISS), for people who have experienced an ABI; and to modify the CISS, where necessary, to create a more reliable and valid measurement tool for this clinical group.MethodsPsychometric properties were investigated using Rasch analysis of responses from a sample of adults with ABI (n = 207). The internal consistency reliability and construct validity of the scale were examined.ResultsAll originally proposed subscales were not valid or reliable and, as such, were incapable of interval‐level measurement within this sample – Task: χ2(32, N = 207) = 105.1, p < .001; Emotion: χ2(32, N = 204) = 121.9, p < .001; Avoidance: χ2(32, N = 207) = 66.7, p < .001. Three valid and reliable subscales were derived measuring emotion‐, task‐, and avoidance‐oriented coping styles by removing items that provided the most unreliable information and exploring fit to the Rasch model.ConclusionsThe original version of the CISS may not be a valid and reliable measure of coping style following ABI. Modified subscales of the three distinct coping domains have been proposed that would help to improve measurement of coping style following ABI in future research and clinical practice.Practitioner points

How people cope with difficulties following an ABI has been shown to impact upon emotional outcomes and functional recovery.

The original version of the CISS was found to be an imprecise measure of coping following ABI.

A modified version of the CISS was found to be a valid and reliable measure of three styles of coping (task‐focused, emotion‐focused, and avoidance‐focused) that conforms to the properties of interval‐level measurement as represented by the Rasch model. This structure is in keeping with previous theoretical models of coping.

We advise caution about including items (1, 6, 7, 22, 24, 28, 29, 33, 34, and 46) that were found to diverge from the expectations of the Rasch measurement model in total subscale scores for measuring change in coping style.

A conversion table for the three modified subscales is included in this paper to convert total raw scores into Rasch transformed logit values.

Identifying strengths and weaknesses in coping style could be a means of guiding psychological intervention to promote good recovery following ABI.

The sample included mainly people who had experienced non‐traumatic brain injuries (e.g., a stroke).

This research could be extended to include broader sample of people with differing brain injury aetiologies and neurological disorders.
‘Judging a book by its cover’: An experimental study of the negative impact of a diagnosis of borderline personality disorder on clinicians’ judgements of uncomplicated panic disorder
Authors: Lam Danny C. K. , Salkovskis Paul M. , Hogg Lorna I. 
Published: July 2015

ObjectivesDiagnosis is ubiquitous in Psychiatry, and whilst it does bring benefits; adverse effects of ‘labelling’ may also be possible. This study aimed to evaluate experimentally whether clinicians’ judgements about a patient with panic disorder were influenced by an inappropriately suggested diagnosis of comorbid borderline personality disorder (BPD).DesignAn experimental design was used to evaluate clinician's judgements when the nature of the information they were given was varied to imply BPD comorbidity.MethodsTwo hundred and sixty‐five clinicians watched a video‐recorded assessment of a woman describing her experience of uncomplicated ‘panic disorder’ and then rated her present problems and likely prognosis. Prior to watching the video recording, participants were randomly allocated to one of three conditions with written information including the following: (1) her personal details and general background; (2) the addition of a behavioural description consistent with BPD; and (3) the further addition of a ‘label’ (past BPD diagnosis).ResultsThe BPD label was associated with more negative ratings of the woman's problems and her prognosis than both information alone and a behavioural description of BPD ‘symptoms’.ConclusionsRegardless of potential actuarial value of such diagnoses, it is concluded that clinicians can be overly influenced by past diagnostic labels in the context of an apparent current comorbid problem, although such biases appear to be less likely if a description of the relevant behaviours is used instead. Thus, the label, rather than the behaviour it denotes, may be stigmatizing in mental health professionals.Practitioner points

Diagnostic labels can have an inappropriately negative effect on clinicians’ judgements not only of treatment variables such as engagement and response but also risk issues and interpersonal effectiveness.

Diagnostic labels can have a greater effect on clinicians’ judgements than a behavioural description or clinical presentation.

Clinicians should therefore be cautious both in the use of diagnostic labels to describe patients and ensure that these are still valid, and also be mindful of the influence that such labels can have on their own clinical judgements and constantly seek to challenge these.

Behavioural descriptions of difficulties are less likely to result in such negative judgements and predictions.
Theory of mind selectively predicts preschoolers’ knowledge‐based selective word learning
Authors: Brosseau‐Liard Patricia , Penney Danielle , Poulin‐Dubois Diane 
Published: July 2015

Children can selectively attend to various attributes of a model, such as past accuracy or physical strength, to guide their social learning. There is a debate regarding whether a relation exists between theory‐of‐mind skills and selective learning. We hypothesized that high performance on theory‐of‐mind tasks would predict preference for learning new words from accurate informants (an epistemic attribute), but not from physically strong informants (a non‐epistemic attribute). Three‐ and 4‐year‐olds (N = 65) completed two selective learning tasks, and their theory‐of‐mind abilities were assessed. As expected, performance on a theory‐of‐mind battery predicted children's preference to learn from more accurate informants but not from physically stronger informants. Results thus suggest that preschoolers with more advanced theory of mind have a better understanding of knowledge and apply that understanding to guide their selection of informants. This work has important implications for research on children's developing social cognition and early learning.
Role for engagement of β‐arrestin2 by the transactivated EGFR in agonist‐specific regulation of δ receptor activation of ERK1/2
Authors: Zhang Le‐Sha , Wang Yu‐Jun , Ju Yun‐Yue , Zan Gui‐Ying , Xu Chi , Hong Min‐Hua , Wang Yu‐Hua , Chi Zhi‐Qiang , Liu Jing‐Gen 
Published: July 2015

Background and Purposeβ‐Arrestins function as signal transducers linking GPCRs to ERK1/2 signalling either by scaffolding members of ERK1/2s cascades or by transactivating receptor tyrosine kinases through Src‐mediated release of transactivating factor. Recruitment of β‐arrestins to the activated GPCRs is required for ERK1/2 activation. Our previous studies showed that δ receptors activate ERK1/2 through a β‐arrestin‐dependent mechanism without inducing β‐arrestin binding to the δ receptors. However, the precise mechanisms involved remain to be established.Experimental ApproachERK1/2 activation by δ receptor ligands was assessed using HEK293 cells in vitro and male Sprague Dawley rats in vivo. Immunoprecipitation, immunoblotting, siRNA transfection, intracerebroventricular injection and immunohistochemistry were used to elucidate the underlying mechanism.Key ResultsWe identified a new signalling pathway in which recruitment of β‐arrestin2 to the EGFR rather than δ receptor was required for its role in δ receptor‐mediated ERK1/2 activation in response to H‐Tyr–Tic–Phe–Phe–OH (TIPP) or morphine stimulation. Stimulation of the δ receptor with ligands leads to the phosphorylation of PKCδ, which acts upstream of EGFR transactivation and is needed for the release of the EGFR‐activating factor, whereas β‐arrestin2 was found to act downstream of the EGFR transactivation. Moreover, we demonstrated that coupling of the PKCδ/EGFR/β‐arrestin2 transactivation pathway to δ receptor‐mediated ERK1/2 activation was ligand‐specific and the Ser363 of δ receptors was crucial for ligand‐specific implementation of this ERK1/2 activation pathway.Conclusions and ImplicationsThe δ receptor‐mediated activation of ERK1/2 is via ligand‐specific transactivation of EGFR. This study adds new insights into the mechanism by which δ receptors activate ERK1/2.
δ Subunit‐containing GABAA receptors are preferred targets for the centrally acting analgesic flupirtine
Authors: Klinger Felicia , Bajric Mirnes , Salzer Isabella , Dorostkar Mario M. , Khan Deeba , Pollak Daniela D. , Kubista Helmut , Boehm Stefan , Koenig Xaver 
Published: July 2015

Background and PurposeThe Kv7 channel activator flupirtine is a clinical analgesic characterized as ‘selective neuronal potassium channel opener’. Flupirtine was found to exert comparable actions at GABAA receptors and Kv7 channels in neurons of pain pathways, but not in hippocampus.Experimental ApproachExpression patterns of GABAA receptors were explored in immunoblots of rat dorsal root ganglia, dorsal horns and hippocampi using antibodies for 10 different subunits. Effects of flupirtine on recombinant and native GABAA receptors were investigated in patch clamp experiments and compared with the actions on Kv7 channels.Key ResultsImmunoblots pointed towards α2, α3, β3 and γ2 subunits as targets, but in all γ2‐containing receptors the effects of flupirtine were alike: leftward shift of GABA concentration‐response curves and diminished maximal amplitudes. After replacement of γ2S by δ, flupirtine increased maximal amplitudes. Currents through α1β2δ receptors were more enhanced than those through Kv7 channels. In hippocampal neurons, flupirtine prolonged inhibitory postsynaptic currents, left miniature inhibitory postsynaptic currents (mIPSCs) unaltered and increased bicuculline‐sensitive tonic currents; penicillin abolished mIPSCs, but not tonic currents; concentration‐response curves for GABA‐induced currents were shifted to the left by flupirtine without changes in maximal amplitudes; in the presence of penicillin, maximal amplitudes were increased; GABA‐induced currents in the presence of penicillin were more sensitive towards flupirtine than K+ currents. In dorsal horn neurons, currents evoked by the δ‐preferring agonist THIP (gaboxadol) were more sensitive towards flupirtine than K+ currents.Conclusions and ImplicationsFlupirtine prefers δ‐containing GABAA receptors over γ‐containing ones and over Kv7 channels.
DDX5 promotes proliferation and tumorigenesis of non‐small‐cell lung cancer cells by activating β‐catenin signaling pathway
Authors: Wang Zhendong , Luo Zhonghua , Zhou Lin , Li Xiaofei , Jiang Tao , Fu Enqing 
Published: July 2015

The DEAD‐box‐protein DDX5 is an ATP‐dependent RNA helicase that is frequently overexpressed in various cancers and acts as a transcriptional co‐activator of several transcription factors, including β‐catenin. DDX5 is reported to be involved in cancer progression by promoting cell proliferation and epithelial–mesenchymal transition. However, the clinical significance and biological role of DDX5 in non‐small‐cell lung cancer (NSCLC) remain largely unknown. In this study, we examined the expression of DDX5 in clinical NSCLC samples, investigated its role in regulating NSCLC cell proliferation and tumorigenesis, and explored the possible molecular mechanism. We found that DDX5 was significantly overexpressed in NSCLC tissues as compared with the matched normal adjacent tissues. In addition, overexpression of DDX5 was associated with advanced clinical stage, higher Ki67 index, and shorter overall survival in NSCLC patients. Upregulation of DDX5 promoted proliferation of NSCLC cells in vitro and growth of NSCLC xenografts in vivo, whereas downregulation of DDX5 showed the opposite effects. Furthermore, DDX5 directly interacted with β‐catenin, promoted its nuclear translocation, and co‐activated the expression of cyclin D1 and c‐Myc. β‐catenin silencing significantly abrogated DDX5‐induced cyclin D1 and c‐Myc expression and proliferation in NSCLC cells. Interestingly, DDX5 and cyclin D1 expression followed positive correlation in the same set of NSCLC samples. These findings indicated that DDX5 played an important role in the proliferation and tumorigenesis of NSCLC cells by activating the β‐catenin signaling pathway. Therefore, DDX5 may serve as a novel prognostic marker and potential therapeutic target in the treatment of NSCLC.
Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors
Authors: Yu Man , Lee Carol , Wang Marina , Tannock Ian F. 
Published: July 2015

Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration‐dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors.
Immunological evaluation of peptide vaccination for cancer patients with the HLA‐A26 allele
Authors: Sakamoto Shinjiro , Matsueda Satoko , Takamori Shinzo , Toh Uhi , Noguchi Masanori , Yutani Shigeru , Yamada Akira , Shichijo Shigeki , Yamada Teppei , Suekane Shigetaka , Kawano Kouichiro , Sasada Tetsuro , Hattori Noboru , Kohno Nobuoki , Itoh Kyogo 
Published: July 2015

To develop a peptide vaccine for cancer patients with the HLA‐A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA‐A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide‐specific IgG responses in pre‐vaccination plasma were selected from the four peptide candidates applicable for HLA‐A26+/A26+ cancer patients and administered s.c. Peptide‐specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA‐A26 genotypes were HLA‐A26:01 (n = 24), HLA‐A26:03 (n = 10), and HLA‐A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide‐specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide‐specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA‐A26+ advanced cancer patients because of their safety and higher rates of immunological responses.
Molecular Modeling, Synthesis, and Anti‐HIV Activity of Novel Isoindolinedione Analogues as Potent Non‐nucleoside Reverse Transcriptase Inhibitors
Authors: Kumari Garima , Singh Ramendra K. 
Published: July 2015

Different isoindolinedione derivatives bearing imine, amide, thioamide, and sulfonamide linkages have been designed in silico using discovery studio software (BIOVIA, San Diego, CA, USA), synthesized, and evaluated for their anti‐HIV activity. SAR studies revealed that the linkages in these molecules did affect their anti‐HIV activity and the molecules having sulfonamide linkages were the most potent HIV‐RT inhibitors as the S=O bonds of the sulfonamide moiety interacted with Lys103 (NH or carbonyl or both) and Pro236; the NH part of the sulfonamide linkage formed bond with carbonyl of Lys101. blood–brain barrier (BBB) plots were also studied, and it was found that all the designed molecules have potential to cross BBB, a very vital criteria for anti‐HIV drugs. In vitro screening was performed using HIV‐1 strain IIIB in MT‐4 cells using the MTT assay, and it was seen that some of these molecules were effective inhibitors of HIV‐1 replication at nanomolar concentration with selectivity indices ranging from 33.75 to 73.33 under in vitro conditions. Some of these molecules have shown good anti‐HIV activity at 3–4 nm concentrations. These derivatives have potential to be developed as lead molecules effective against HIV‐1.Novel isoindolinedione derivatives as probable NNRTIs have been synthesized and characterized. Some of these molecules have shown good anti‐HIV activity at 3–4 nm concentrations.
Effect of interferon-β1b on CXCR4-dependent chemotaxis in T cells from multiple sclerosis patients
Authors: Wostradowski T , Gudi V , Pul R , Gingele S , Lindquist J A , Stangel M , Lindquist S 
Published: July 2015

SummaryMultiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease triggered by infiltration of activated T cells into the central nervous system. Interferon (IFN)-β is an established, safe and effective treatment for patients with relapsing–remitting MS (RRMS). The cytokine can inhibit leucocyte infiltration into the central nervous system; however, little is known about the precise molecular mechanisms. Previously, in vitro application of IFN-β1b was shown to reduce CXCL12/CXCR4-mediated monocyte migration. Here, we analysed the effects of IFN-β1b on CXCR4-dependent T cell function. In vitro exposure to IFN-β1b (1000 U/ml) for 20 h reduced CXCR4-dependent chemotaxis of primary human T cells from healthy individuals and patients with RRMS. Investigating the IFN-β1b/CXCR4 signalling pathways, we found no difference in phosphorylation of ZAP70, ERK1/2 and AKT despite an early induction of the negative regulator of G-protein signalling, RGS1 by IFN-β1b. However, CXCR4 surface expression was reduced. Quantitative real time-PCR revealed a similar reduction in CXCR4-mRNA, and the requirement of several hours' exposure to IFN-β1b supports a transcriptional regulation. Interestingly, T cells from MS patients showed a lower CXCR4 expression than T cells from healthy controls, which was not reduced further in patients under IFN-β1b therapy. Furthermore, we observed no change in CXCL12-dependent chemotaxis in RRMS patients. Our results demonstrate clearly that IFN-β1b can impair the functional response to CXCR4 by down-regulating its expression, but also points to the complex in vivo effects of IFN-β1b therapy.
Participation in sport and physical activity in head and neck cancer survivors: associations with quality of life
Authors: Sammut L. , Fraser L.R. , Ward M.J. , Singh T. , Patel N.N. 
Published: July 2015

BackgroundHead and neck cancer (HNC), and its treatment, is associated with significant side‐effects which can affect quality of life (QOL). Physical activity (PA) is known to improve a number of QOL measures. We aimed to determine the prevalence of PA pre‐ and post‐treatment of HNC and to determine associations with QOL.MethodsA questionnaire‐based survey of 172 patients pre‐ and post‐treatment for HNC.ResultsA total of 62.2% of patients met current UK PA guidelines pre‐treatment, reducing to 40.1% following treatment. There was a significant decrease in Metabolic equivalent task minutes/week post‐treatment, with 71% of participants reporting less PA after diagnosis (P < 0.001). Swimming and cycling remained the two most practiced sports. There was a positive correlation between the post‐treatment PA and QOL (P < 0.001).ConclusionThese data suggest that PA may improve QOL following treatment for HNC. We believe that further studies are warranted.