bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the royal marsden hospital prognostic score in patients treated in the phase I clinical trials program at the MD Anderson Cancer Center
Authors: Garrido‐Laguna Ignacio , Janku Filip , Vaklavas Christos , Falchook Gerald S. , Fu Siqing , Hong David S. , Naing Aung , Tsimberidou Apostolia M. , Wen Sijin , Kurzrock Razelle 
Published: August 2011

AbstractBACKGROUND:The authors validated the Royal Marsden Hospital (RMH) prognostic score in patients with advanced lung, pancreatic, and head and neck cancers who were enrolled on phase 1 trials in the MD Anderson Cancer Center Phase I Clinical Trials Program.METHODS:The RMH score uses albumin (≥3.5 g/dL vs <3.5 g/dL), lactate dehydrogenase (less than or equal to the upper limit of normal [≤ULN] vs >ULN), and the number of metastatic sites (≤2 sites vs ≥3 sites) to predict patient survival in phase 1 trials. The authors of this report retrospectively reviewed the outcomes of 229 consecutive patients with lung, pancreatic, and head and neck tumors who were treated on 57 phase 1 trials.RESULTS:Two hundred twenty‐nine consecutive patients with lung cancer (N = 85), pancreatic cancer (N = 83), and head and neck tumors (N = 61) were treated. The median patient age was 60 years (range, 26‐85 years), and 63% of the patients were men. Patients with a good RMH prognostic score (0‐1) at baseline had a longer median survival than patients with a poor prognostic score (2‐3; 33.9 weeks vs 21.1 weeks; P < .0001). The RMH score was an independent variable that predicted survival in multivariate analysis. Other independent variables that predicted better survival were hemoglobin level (≥10.5 g/dL), Eastern Cooperative Oncology Group performance status (0‐1), and tumor type. Patients who were treated on first‐in‐human trials did not fare worse compared with those who were not treated on first‐in‐human trials.CONCLUSIONS:For patients with lung, pancreatic, and head and neck tumors who were treated on phase 1 trials, survival was predicted accurately by the RMH prognostic score. Cancer 2012;. © 2011 American Cancer Society.
Intranasal but not intravenous delivery of the adjuvant α‐galactosylceramide permits repeated stimulation of natural killer T cells in the lung
Authors: Courtney Amy N. , Thapa Prakash , Singh Shailbala , Wishahy Ameerah M. , Zhou Dapeng , Sastry Jagannadha 
Published: August 2011

AbstractEfficient induction of antigen‐specific immunity is achieved by delivering multiple doses of vaccine formulated with appropriate adjuvants that can harness the benefits of innate immune mediators. The synthetic glycolipid α‐galactosylceramide (α‐GalCer) is a potent activator of NKT cells, a major innate immune mediator cell type effective in inducing maturation of DCs for efficient presentation of co‐administered antigens. However, systemic administration of α‐GalCer results in NKT cell anergy in which the cells are unresponsive to subsequent doses of α‐GalCer. We show here that α‐GalCer delivered as an adjuvant by the intranasal route, as opposed to the intravenous route, enables repeated activation of NKT cells and DCs, resulting in efficient induction of cellular immune responses to co‐administered antigens. We show evidence that after intranasal delivery,α‐GalCer is selectively presented by DCs for the activation of NKT cells, not B cells. Furthermore, higher levels of PD‐1 expression, a potential marker for functional exhaustion of the NKT cells when α‐GalCer is delivered by the intravenous route, are not observed after intranasal delivery. These results support a mucosal route of delivery for the utility of α‐GalCer as an adjuvant for vaccines, which often requires repeated dosing to achieve durable protective immunity.
B lymphocytes that migrate to tuberculous pleural fluid via the SDF‐1/CXCR4 axis actively respond to antigens specific for Mycobacterium tuberculosis
Authors: Feng Lian , Li Li , Liu Yun , Qiao Dan , Li Qin , Fu Xiaoying , Wang Hui , Lao Suihua , Wu Changyou 
Published: August 2011

AbstractB‐cell biology has been largely uncharacterized in the field of tuberculosis (TB). In this study, we investigated the immunophenotypical and functional characteristics of B cells obtained from the pleural fluid (PF) and peripheral blood of patients with tuberculous pleuritis (TP). Our results indicated that the total numbers of B cells, CD27+ memory B cells and plasmablasts were clearly lower in the PF than in peripheral blood. Furthermore, we found significantly higher expression of CXCR4 on B cells in the PF, and a chemotaxis assay showed that B cells in the PF were more responsive to stromal cell‐derived factor‐1 (SDF‐1) than B cells from peripheral blood. In addition, SDF‐1 levels in PF were remarkably high compared with SDF‐1 levels in plasma, suggesting that the SDF‐1/CXCR4 axis might facilitate the migration of circulating B cells into tuberculous pleural space. Importantly, we observed that significantly more antibodies were produced by B cells in the PF following stimulation with BCG, early secretory antigenic target (ESAT‐6)/culture filtrate protein‐10 (CFP‐10) or ESAT‐6 protein. Collectively, these data demonstrate that Mycobacterium tuberculosis‐specific B cells exist at local sites of infection in TP patients and this localization might influence the immune response to M. tuberculosis.
Regiospecific C(naphthyl)–H Bond Activation by Platinum(II) – Isolation, Characterization, Reactivity and TD‐DFT Study of the Cycloplatinate Complexes
Authors: Biswas Achintesh Narayan , Das Purak , Bagchi Vivek , Choudhury Amitava , Bandyopadhyay Pinaki 
Published: August 2011

AbstractThe regiospecific activation of C(naphthyl)–H bonds in a group of naphthylazo‐2′‐hydroxyarene ligands (H2L) has been achieved by platinum(II) compounds under different reaction conditions, and stable cycloplatinates [PtIIL(D)] have been isolated in presence of neutral Lewis bases (D). Structures of the cycloplatinate complexes of platinum(II) have been established by single‐crystal X‐ray crystallography. The platinum(II) centres are surrounded by a C,N,O‐terdentate ligand frame (L) and Lewis base (D) in a distorted square planar fashion. These cycloplatinate species have been found to react with halogens and methyl iodide undergoing metal‐centered two electron oxidation affording platinum(IV) cycloplatinates with distorted octahedral geometry. In the reactions with halogens and methyl iodide, trans oxidative addition has been found for [Pt(L)D] (D = 4‐picoline), whereas cis addition has been observed for [Pt(L)D] where D is a more sterically demanding triphenylphosphane. Structures of two representative platinum(IV) cycloplatinate species have been determined by single‐crystal X‐ray crystallography. A time dependent (TD)‐DFT study of representative cycloplatinate compounds has been performed. Optical absorption spectra of the cycloplatinate compounds in dichloromethane have been simulated using the TD‐DFT method, and the experimental spectra are in very good agreement.
Direct Carboxylation of Zincocene Cp*2Zn
Authors: Schulz Stephan , Schmidt Sarah , Bläser Dieter , Wölper Christoph 
Published: August 2011

AbstractThe reaction of zincocene Cp*2Zn with CO2 proceeds with the formation of [Zn4(μ4‐O)(O2CCp*)6] (1), which was characterized by NMR (1H, 13C) and IR spectroscopy as well as by elemental analysis and single‐crystal X‐ray diffraction. The solid‐state structure of 1 is comparable to that previously observed for basic zinc acetate. In contrast to many previously reported CO2 activation reactions, the formation of 1 occurred without the use of any additional transmetalation catalyst.
Recognition of Peptides by Cyclodextrin Trimers
Authors: Christensen Helena Staunstrup , Sigurskjold Bent W. , Frihed Tobias Gylling , Marinescu Lavinia G. , Pedersen Christian M. , Bols Mikael 
Published: August 2011

AbstractThe efficient synthesis of a new class of cyclodextrin trimers has been carried out by using a click chemistry strategy. The cyclodextrin trimers were subsequently investigated for molecular recognition of peptides with aromatic side chains. Binding affinities for the self‐assembly of different peptides to cyclodextrin trimers were determined by using real‐time bimolecular interaction analyses with plasmon surface resonance. Peptides were prepared and immobilized on the sensor surface. The association constants were obtained by titration with different solutions of the cyclodextrin trimers and they were in the range of 103 M–1. The selectivity of molecular recognition of nonapeptides favored cyclodextrin trimers over unmodified cyclodextrin.
The Synthesis of Stereodefined Trisubstituted Olefins From Olefin Templates Using Pd Catalysis – Synthesis of the Antihypertensive Isbogrel
Authors: Rogers Lawrence R. , Konstantinou Zissis , Reddy Madhav , Organ Michael G. 
Published: August 2011

AbstractA collection of highly functionalized, trisubstituted olefin building blocks (templates) have been developed for their Pd‐catalyzed elaboration into more complex structures, including natural products and compounds of medicinal chemistry interest. The Pd‐mediated transformations involve a combination of allylic substitution and cross‐coupling reactions. The templates have been designed such that these processes proceed not only with a high degree of regio‐ and stereoselectivity, but the transformations can all be conducted sequentially in the same flask using the same catalyst.
History of Eating Disorder in Mothers of Children with Early Onset Eating Disorder or Disturbance
Authors: Watkins Beth , Cooper Peter J , Lask Bryan 
Published: August 2011

AbstractThe literature suggests that there is significant familial aggregation of eating disorders. A specific association has also been reported between childhood feeding problems and maternal eating disorder. This study investigates whether subgroups of children with early onset eating disturbance are distinguished by maternal eating disorder history. The mothers of 66 children with either anorexia nervosa (AN), food avoidance emotional disorder (FAED) or selective eating (SE) were interviewed to ascertain eating disorder history. Seventeen per cent of mothers reported a history of eating disorder, compared with 3%–5% reported for community samples. A history of eating disorder was reported by 5.9% of mothers of children with SE, 12.9% of mothers of children with AN and 33.3% of mothers of children with FAED. The findings, based on this small sample, suggest that children with FAED are especially likely to have grown up in a dysfunctional food environment. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Do Men with Eating Disorders Differ from Women in Clinics, Psychopathology and Personality?
Authors: Núñez‐Navarro Araceli , Agüera Zaida , Krug Isabel , Jiménez‐Murcia Susana , Sánchez Isabel , Araguz Noemí , Gorwood Phillip , Granero Roser , Penelo Eva , Karwautz Andreas , Moragas Laura , Saldaña Sandra , Treasure Janet , Menchón José Manuel , Fernández‐Aranda Fernando 
Published: August 2011

AbstractObjectiveTo determine if male and female eating disorders differ in clinics, psychopathology and personality traits when compared with a healthy group.MethodsSixty male and 60 female eating disorder individuals (16% anorexia nervosa, 42% bulimia nervosa and 42% eating disorder not otherwise specified), matched for age and diagnostic, were compared with 120 healthy‐eating participants (60 male and 60 female participants). All were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Assessment measures included Eating Disorder Inventory—2, Symptom Checklist—Revised and Temperament and Character Inventory—Revised, as well as other clinical and psychopathological indices.ResultsMale eating disorder participants reported significant lower laxative abuse (p = 0.020) and significant higher vomiting episodes (p = 0.019) than female eating disorder participants. Differences on drive for thinness, body dissatisfaction and some Symptom Checklist—Revised scales were found across genders in eating disorder participants. Male eating disorder participants scored significantly lower than female participants with eating disorders on harm avoidance, reward dependence and cooperativeness.ConclusionsAlthough eating disorder clinical features were similar across genders, male eating disorder participants had less body image concern and general psychopathology than female eating disorder participants. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Unraveling driving factors for large rock–ice avalanche mobility
Authors: Schneider D. , Huggel C. , Haeberli W. , Kaitna R. 
Published: August 2011

ABSTRACTLarge rock–ice avalanches have attracted attention from scientists for decades and some of these events have caused high numbers of fatalities. A relation between rock slope instabilities in cold high mountain areas and climate change is currently becoming more evident and questions about possible consequences and hazard scenarios in densely populated high mountain regions leading beyond historical precedence are rising. To improve hazard assessment of potential rock–ice avalanches, their mobility is a critical factor. This contribution is an attempt to unravel driving factors for the mobility of large rock–ice avalanches by synthesizing results from physical laboratory experiments and empirical data from 64 rock–ice avalanches with volumes >1x106 m3 from glacierized high mountain regions around the world. The influence of avalanche volume, water and ice content, low‐friction surfaces, and topography on the apparent coefficient of friction (as a measure of mobility) is assessed. In laboratory experiments granular ice in the moving mass was found to reduce bulk friction up to 20% while water led to a reduction around 50% for completely saturated material compared with dry flows. Evidence for the effects of water as a key driving factor to enhance mobility was also found in the empirical data, while the influence of the ice content could not be confirmed to be of much relevance in nature. Besides liquefaction, it was confirmed that mobility increases with volumes and that frictional surface characteristics such as flow paths over glaciers are also dominant variables determining mass movement mobility. Effects of the topography along the flow path as well as channeling are assumed to be other critical factors. The results provide an empirical basis to roughly account for different path and flow characteristics of large rock–ice avalanches and to find appropriate ranges for friction parameters for scenario modeling and hazard assessments. Copyright © 2011 John Wiley & Sons, Ltd.
Look at me, I'll remember you
Authors: Conty Laurence , Grèzes Julie 
Published: August 2011

AbstractBeing looked at by a person enhances the subsequent memorability of her/his identity. Here, we tested the specificity of this effect and its underlying brain processes. We manipulated three social cues displayed by an agent: Gaze Direction (Direct/Averted), Emotional Expression (Anger/Neutral), and Pointing gesture (Presence/Absence). Our behavioral experiment showed that direct as compared with averted gaze perception enhanced subsequent retrieval of face identity. Similar effect of enhanced retrieval was found when pointing finger was absent as compared with present but not for anger as compared with neutral expression. The fMRI results revealed amygdala activity for both Anger and Direct gaze conditions, suggesting emotional arousal. Yet, the right hippocampus, known to play a role in self‐relevant memory processes, was only revealed during direct gaze perception. Further investigations suggest that right hippocampal activity was maximal for the most self‐relevant social event (i.e. actor expressing anger and pointing toward the participant with direct gaze). Altogether, our results suggest that the perception of self‐relevant social cues such as direct gaze automatically prompts “self‐relevant memory” processes. Hum Brain Mapp 33:2428–2440, 2012. © 2011 Wiley Periodicals, Inc.
Memory training impacts short‐term changes in aging white matter: A Longitudinal Diffusion Tensor Imaging Study
Authors: Engvig Andreas , Fjell Anders M. , Westlye Lars T. , Moberget Torgeir , Sundseth Øyvind , Larsen Vivi Agnete , Walhovd Kristine B. 
Published: August 2011

AbstractA growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging‐ and training‐related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract‐based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI‐scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10‐week interval. Further, group analysis demonstrated positive effects of training on the short‐term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin‐related processes in WM plasticity. Hum Brain Mapp 33:2390–2406, 2012. © 2011 Wiley Periodicals, Inc.
Longitudinal patterns of benzodiazepine consumption in a German cohort of methadone maintenance treatment patients
Authors: Specka Michael , Bonnet Udo , Heilmann Martin , Schifano Fabrizio , Scherbaum Norbert 
Published: August 2011

ObjectiveCross‐sectional studies show that considerable proportions of opiate dependents in methadone maintenance treatment (MMT) consume benzodiazepines (BZD). The longitudinal patterns of BZD use over time were described here.MethodsAfter admission to MMT, patients from two outpatient MMT clinics (n = 345) were observed for up to 2 years whilst in treatment. The use of BZD, cannabis, opiates and cocaine was assessed by urine sampling carried out twice a month.ResultsFor the whole sample, the mean BZD‐positive urine specimen rate was 0.36 during the first 3 months. Rates slightly decreased during the first year and remained stable afterwards (last observation carried forward). For study completers (n = 152), the rate decreased over time, from 0.31 (first 3‐month period) to 0.19 (last period; p < 0.001). According to a longitudinal cluster analysis, 26% of all patients showed a pattern of constantly high BZD‐positivity rates, mostly in combination with other substances. Inpatient detoxifications from BZD (carried out in 18% of cases) did not have a sustained effect on levels of BZD use.ConclusionsBZD consumption in MMT is often part of a polydrug consumption pattern and is associated with poorer treatment retention. It is necessary to further investigate the reasons for BZD use in MMT patients and to develop effective interventions to reduce levels of BZD consumption. Copyright © 2011 John Wiley & Sons, Ltd.
Effects of alcohol on highway driving in the STISIM driving simulator
Authors: Mets Monique A. J. , Kuipers Esther , de Senerpont Domis Lieke M. , Leenders Maartje , Olivier Berend , Verster Joris C. 
Published: August 2011

ObjectiveThe STISIM driving simulator is widely used. To enhance its usefulness in pharmacological research, a calibration study was performed to test a standardized highway driving test scenario after administration of three different dosages of alcohol and placebo.MethodsTwenty‐seven healthy young adults (14 men and 13 women; mean age (SD) = 22.8 (1.4)) participated in this randomized, single‐blind crossover trial. Subjects received alcohol to gain a blood alcohol concentration (BAC) of 0.05%, 0.08%, and 0.11%, or placebo–alcohol. In each condition, subjects completed a 100‐km highway driving simulator test. The standard deviation of lateral position, the weaving of the car, was the primary parameter of the test.ResultsAlcohol produced dose‐dependent driving impairment. Standard deviation of lateral position and standard deviation of speed were significantly increased relative to placebo (p < 0.05). Subjective driving assessments were in line with the objective driving measurements.ConclusionThe STISIM highway driving simulator test is able to differentiate dose‐dependent impairment after administration of alcohol. The highway driving test scenario is suitable for future psychopharmacological research. Copyright © 2011 John Wiley & Sons, Ltd.
The role of focal adhesion kinase catalytic activity on the proliferation and migration of squamous cell carcinoma cells
Authors: Serrels Alan , McLeod Kenneth , Canel Marta , Kinnaird Andrew , Graham Kathryn , Frame Margaret C , Brunton Valerie G 
Published: August 2011

AbstractFocal adhesion kinase (FAK) is upregulated in several epithelial tumours and there has been considerable interest in developing small molecule kinase inhibitors of FAK. However, FAK also has important adaptor functions within the cell, integrating signals from both integrins and growth factors. To investigate the role of FAKs kinase domain, we generated fak‐deficient squamous cell carcinoma (SCC) cell lines. Re‐expression of a wild type or kinase dead FAK allowed us to delineate its kinase dependent functions. In addition, we used the novel FAK kinase inhibitor PF‐562,271. The kinase activity of FAK was important for tumour cell migration and polarity but more striking was its requirement for the anchorage independent 3 dimensional (3D) proliferation of SCC cells and their growth as xenografts in mice. Inhibition of FAK activity and prevention of growth in 3D correlated with Src inhibition. We further identified a mechanism whereby FAK regulates proliferation in 3D via regulation of the kinase activity of Src. This was dependent on the kinase activity of FAK and its resulting phosphorylation on Y397 that provides a high affinity binding site for Src. These data support the further development of FAK kinase inhibitors as agents that have the potential to inhibit both tumour cell migration and proliferation.