bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Metal Complexes of the Proton Sponge 1,8‐Bis(N,N,N′,N′‐tetramethylguanidino)naphthalene: Syntheses and Properties
Authors: Wild Ute , Hübner Olaf , Maronna Astrid , Enders Markus , Kaifer Elisabeth , Wadepohl Hubert , Himmel Hans‐Jörg
Published: August 2008

In this work we report on the syntheses and properties of the first transition metal complexes of the proton sponge 1,8‐bis(N,N,N′,N′‐tetramethylguanidino)naphthalene (btmgn). Of the three complexes [(btmgn)PdCl2], [(btmgn)PtCl2] and [(btmgn)PtCl2(C2H4)], the first two feature a chelating btmgn ligand that is bound to the metal atom through two nitrogen atoms. Only one metal–N bond is established in [(btmgn)PtCl2(C2H4)]. The molecular structures of [(btmgn)PdCl2] and [(btmgn)PtCl2] show some interesting details. X‐ray crystallographic studies reveal that the naphthyl aromatic systems in both complexes are not planar, the metal atoms reside above the “best‐plane” of the naphthyl systems and the compounds adopt a chiral conformation in the crystalline phase. Several dynamic processes of the two guanidinyl groups in solution were identified by line‐shape analysis of the temperature‐dependent NMR spectra. The complex [(btmgn)PtCl2(C2H4)] eliminates ethylene at elevated temperature to give [(btmgn)PtCl2]. Quantum chemical (DFT) calculations indicate that the ΔG0 value for this reaction is close to zero. Indeed the compound [(btmgbp)PtCl2] {btmgbp = 2,2′‐bis(N,N,N′,N′‐tetramethylguanidino)biphenyl} in which the naphthyl group is replaced by a biphenyl group is not amenable to ethylene elimination. First experiments point to interesting catalytic properties of the new complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
One‐Pot Dual Substitutions of Bromobenzyl Chloride, 2‐Chloromethyl‐6‐halogenoimidazo[1,2‐a]pyridine and ‐[1,2‐b]pyridazine by Suzuki–Miyaura Cross‐Coupling Reactions
Authors: Henry Nicolas , Enguehard‐Gueiffier Cécile , Thery Isabelle , Gueiffier Alain
Published: August 2008

A very simple, mild and inexpensive palladium‐catalyzed cross‐coupling of (hetero)arylboronic acids with benzylic halides occurs in good yield. This method was successfully expanded to two heterocyclic electrophiles and allowed one‐pot dual substitutions of bromobenzyl chloride, 2‐chloromethyl‐6‐halogenoimidazo[1,2‐a]pyridine or ‐[1,2‐b]pyridazine, leading to numerous new unsymmetrical methylene‐linked biaryl systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Motivational correlates of need for cognition
Authors: Steinhart Yael , Wyer Robert S.
Published: August 2008

Need for cognition is usually characterized as an intrinsic desire to engage in challenging intellectual activity. In achievement situations, however, it could be associated with more extrinsic goals such as success or the avoidance of failure. Three experiments examined this possibility. Participants in all studies were led to believe they would perform either an easy or a difficult intellectual task that they were likely to fail. After inducing this expectation, indices of extrinsic motivation were obtained. Participants with high need for cognition became more motivated to avoid negative consequences of their behavior (e.g., failure) when they expected the task they would perform to be difficult. In contrast, participants with low need for cognition were not appreciably affected by these expectancies. The anticipation of engaging in intellectual activity apparently stimulates different motives in people with high and low need for cognition, and the mindset induced by these motives influences their later behavioral decisions. Copyright © 2008 John Wiley & Sons, Ltd.
A mechanical model for elastomeric seismic isolation bearings including the influence of axial load
Authors: Yamamoto Sachie , Kikuchi Masaru , Ueda Masaiki , Aiken Ian D.
Published: August 2008

For the purpose of predicting the large‐displacement response of seismically isolated buildings, an analytical model for elastomeric isolation bearings is proposed. The model comprises shear and axial springs and a series of axial springs at the top and bottom boundaries. The properties of elastomeric bearings vary with the imposed vertical load. At large shear deformations, elastomeric bearings exhibit stiffening behavior under low axial stress and buckling under high axial stress. These properties depend on the interaction between the shear and axial forces. The proposed model includes interaction between shear and axial forces, nonlinear hysteresis, and dependence on axial stress. To confirm the validity of the model, analyses are performed for actual static loading tests of lead–rubber isolation bearings. The results of analyses using the new model show very good agreement with the experimental results. Seismic response analyses with the new model are also conducted to demonstrate the behavior of isolated buildings under severe earthquake excitations. The results obtained from the analyses with the new model differ in some cases from those given by existing models. Copyright © 2008 John Wiley & Sons, Ltd.
Weight limits, estimations of future BMI, subjective pubertal timing and physical appearance comparisons among adolescent girls as precursors of disturbed eating behaviour in a community sample
Authors: Berger Uwe , Weitkamp Katharina , Strauss Bernhard
Published: August 2008

Objective

From a clinical point of view, a high ‘objective’ BMI or an early biological onset of puberty are well‐known risk factors for eating disorders. In contrast, little is known about irrational beliefs and subjective meanings of body weight and pubertal timing.

Method

Mostly using standardised questionnaires, 136 girls with an average age of 12 years were asked to report their eating behaviour, (body) self‐esteem, body dissatisfaction, weight limits, estimations of future BMI, subjective pubertal timing and appearance‐related social comparisons.

Results

Results showed significant correlations between disturbed eating behaviour and the existence of a weight limit, which was reported by 45% of the girls. Twenty two per cent wished to have a future BMI beneath the 10th percentile. In terms of pubertal timing, girls who perceived themselves as either ‘early starters’ or ‘late starters’ reported significantly more risky eating behaviour.

Conclusions

Results are discussed with a focus on the psychotherapeutic use of our findings as well as the opportunity for the development of preventive strategies. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association.
Factors associated with non‐use of antipsychotics among older residents with schizophrenia in long‐term institutional care
Authors: Alanen Hanna‐Mari , Finne‐Soveri Harriet , Leinonen Esa
Published: August 2008

Objective

To investigate factors associated with non‐use of antipsychotics among older schizophrenia residents in long‐term institutional care.

Design

A retrospective study was designed using cross‐sectional data gathered between 1 January and 30 June 2006 in Finland. Data were extracted from the Resident Assessment Instrument (RAI) database, based on Minimum Data Set for long‐term care facilities (MDS‐LC) assessments.

Participants

Residents with schizophrenia 65 years or older were included, giving a total of 356 patient assessments.

Results

The prevalence of older schizophrenia residents not receiving any antipsychotic medication was 18.5%. Factors independently associated with non‐use of antipsychotics in the logistic regression model were: severe degree of functional impairment, severely impaired vision, any diagnosis of dementia and severe underweight. There was a negative association between non‐use of antipsychotics and a factor ‘had arrived from a psychiatric hospital’.

Conclusions

Severe degree of functional impairment and dementia were the main findings associated with non‐use of antipsychotics in this resident group. Copyright © 2008 John Wiley & Sons, Ltd.
What do we know about quality of life in dementia? A review of the emerging evidence on the predictive and explanatory value of disease specific measures of health related quality of life in people with dementia
Authors: Banerjee Sube , Samsi Kritika , Petrie Charles D. , Alvir Jose , Treglia Michael , Schwam Ellias M. , del Valle Megan
Published: August 2008

Objective

Given its complexity, there is growing consensus on the need to measure patient‐rated broad outcomes like health‐related quality of life (HRQL) as well as discrete functions like cognition and behaviour in dementia. This review brings together current data on the distribution, determinants and course of HRQL in dementia to investigate the predictive and explanatory value of measures of HRQL in people with dementia.

Design

A systematic review of papers in English published up to October 2007 to identify data on the use of disease‐specific measures of HRQL in dementia.

Results

There are no clear or consistent associations between socio‐demographic variables and HRQL. There is no convincing evidence that lower cognition or greater activity limitation is associated with lower HRQL. There is a strong suggestion that depression is consistently associated with decreased HRQL in dementia. However, the magnitude of the associations observed is moderate only and the proportion of variance explained is low suggesting that depression and HRQL are different constructs. We currently know almost nothing about the natural history of HRQL in dementia or what attributes or interventions promote or inhibit HRQL life for people with dementia.

Conclusions

While in other illnesses there may be simple association between HRQL and an easily measurable clinical variable, in dementia this is not so. There are now instruments available with which to measure disease‐specific HRQL directly in clinical trials and other studies that can yield informative data. Copyright © 2008 John Wiley & Sons, Ltd.
The association of individual and facility characteristics with psychiatric hospitalization among nursing home residents
Authors: Becker Marion , Andel Ross , Boaz Timothy , Howell Timothy
Published: August 2008

Objective

To examine resident and facility characteristics associated with psychiatric hospitalizations (PH) for Medicaid enrolled nursing home (NH) residents.

Methods

Participants were all Medicaid enrolled NH residents (n = 32,604) from all Medicaid certified nursing homes in Florida (n = 584) with complete data. We used individual demographic and diagnostic characteristics, as well as facility characteristics, to explore risk of psychiatric hospitalization in this dataset.

Results

Using generalized estimating equations, we found that younger age, male gender, poor physical health, serious mental illness, dementia, and drug use disorder were associated with risk of psychiatric hospitalization. Most notably, residents under 65 were more than three times more likely to undergo psychiatric hospitalization and dementia was associated with a three‐fold increase in the risk of psychiatric hospitalization. Predictors of PH differed somewhat for younger and older residents. Among facility characteristics, greater facility size, low proportion of those paying via Medicare and high proportion of residents with serious mental illness were associated with increased risk of psychiatric hospitalization, whereas, low proportion of residents paying via Medicaid, high proportion of residents paying via Medicare, and low proportion of resident with serious mental illness were associated with reduced risk.

Conclusions

Both resident and facility characteristics impact risk for psychiatric hospitalization. Attention to identified predictors may reduce risk and improve outcomes for nursing home residents. Copyright © 2008 John Wiley & Sons, Ltd.
Integrated specialty mental health care among older minorities improves access but not outcomes: results of the PRISMe study
Authors: Areán Patricia A. , Ayalon Liat , Jin Chengshi , McCulloch Charles E. , Linkins Karen , Chen Hongtu , McDonnell‐Herr Betsy , Levkoff Sue , Estes Carroll
Published: August 2008

Objective

In this secondary data analysis of Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRIMSe) study, we hypothesized that older minorities who receive mental health services integrated in primary care settings would have greater service use and better mental health outcomes than older minorities referred to community services.

Method

We identified 2,022 (48% minorities) primary care patients 65 years and older, who met study inclusion criteria and had either alcohol misuse, depression, and/or anxiety. They were randomized to receive treatment for these disorders in the primary care clinic or to a brokerage case management model that linked patients to community‐based services. Service use and clinical outcomes were collected at baseline, three months and six months post randomization on all participants.

Results

Access to and participation in mental health /substance abuse services was greater in the integrated model than in referral; there were no treatment by ethnicity effects. There were no treatment effects for any of the clinical outcomes; Whites and older minorities in both integrated and referral groups failed to show clinically significant improvement in symptoms and physical functioning at 6 months.

Conclusions

While providing services in primary care results in better access to and use of these services, accessing these services is not enough for assuring adequate clinical outcomes. Copyright © 2008 John Wiley & Sons, Ltd.
Single session educational programme for caregivers of psychogeriatric in‐patients – results from a randomised controlled pilot study
Authors: Aakhus Eivind , Engedal Knut , Aspelund Tom , Selbæk Geir
Published: August 2008

Background

Family caregivers of patients with psychiatric or medical disorders are at risk of developing psychological distress. Studies including family caregivers of patients with dementia have shown that psychoeducative programmes reduce distress and postpone institutionalisation. Little is known about the effect of psychoeducation of relatives of psychogeriatric patients. The aim of this study was to investigate the effect of a single‐session educational intervention of relatives of psychogeriatric in‐patients.

Methods

A randomised controlled intervention study was carried out with 16 relatives in the intervention group and 14 in the control group. The intervention was carried out as a single session programme. Primary outcome measures were psychological well‐being and depression as measured by means of General Health Questionnaire (GHQ‐30), Impact of Event Scale (IES) and Geriatric Depression Scale (GDS). Outcome measures were performed at baseline, at discharge and at 3‐month follow‐up.

Results

Psychological distress was high. Daughters were more depressed and distressed than spouses. Patients' diagnoses did not seem to exert influence on the relatives' well‐being. There was a significant worsening of psychological distress in the intervention group as measured by GHQ‐30.

Conclusions

The study is small and results must be interpreted with caution. Distress among relatives was high regardless of patient's diagnosis. The results of the intervention might lead us to conclude that single‐session interventions towards this specific group of relatives do not improve psychological stress and might, in some aspects, even worsen it. Copyright © 2008 John Wiley & Sons, Ltd.
A valid instrument for measuring informal care time for people with dementia
Authors: Neubauer Simone , Holle Rolf , Menn Petra , Gräßel Elmar
Published: August 2008

Objective

An economic evaluation of dementia‐related interventions from a societal perspective should take account of informal caregiving. We assessed informal caregiving time and report our findings on the validity and stability of our results.

Methods

Within the German IDA study (‘Dementia Care Initiative in Primary Practice’), informal care time for people with dementia living at home is assessed. We applied a German adaptation of the Resource Utilization in Dementia (RUD) questions on informal care, which distinguishes three categories of informal care activities: Activities of Daily Living (ADL), Instrumental ADL (IADL), and supervision. In contrast to the original version, we included the time of all informal caregivers who are involved in caring for the patient. The questionnaire was completed as a computer‐assisted telephone interview at baseline and after 1 year. To test the plausibility of the questionnaire, we proposed seven hypotheses about the reported informal care time.

Results

Nearly all results confirmed our hypotheses. Informal care time as well as changes over time correlated with the physical and mental health status of the patient. Considering the time of other informal caregivers led to slightly higher correlations (not significant). The results indicate that interviewees seem to underestimate particularly the time of supervision of other informal caregivers.

Conclusion

In sum, the instrument gives plausible results and is suited for measuring informal care time, as well as changes over time. If it is not possible to directly interview each caregiver involved, it is of great importance to identify and interview the primary informal caregiver in order to prevent an underestimation of total informal care time. Copyright © 2008 John Wiley & Sons, Ltd.
Does dementia predict adverse hospitalization outcomes? A prospective study in aged inpatients
Authors: Zekry Dina , Herrmann François R. , Grandjean Raphael , Vitale Ana‐Maria , De Pinho Maria‐Fatima , Michel Jean‐Pierre , Gold Gabriel , Krause Karl‐Heinz
Published: August 2008

Background

Dementia is often considered a predictor of adverse hospitalization outcomes. However, the relative contributions of dementia and other risk factors remain unclear.

Objective

To assess, in a prospective study, the relative value of dementia for predicting hospitalization outcomes, taking into account comorbidity, functional and nutritional status in 435 inpatients (age 85.3 ± 6.7; 207 cognitively normal, 48 with mild cognitive impairment and 180 demented) from the acute and rehabilitation geriatric hospital of Geneva. Hospitalization outcomes (death in hospital, length of stay, institutionalisation and formal home care needs) were predicted using logistic regression models with sociodemographic characteristics, cognitive status, comorbid Charlson index‐CCI, functional and nutritional status as independent variables.

Results

Moderate and severe dementia and poor physical function strongly predicted longer hospital stay, institutionalization and greater home care needs in univariate analyses. CCI was the best single predictor, with a four‐fold difference in mortality rates between the highest and lowest scores. In multivariate analysis, the best predictor of institutionalisation was dementia, whereas the best predictor of death in hospital or longer hospital stay was higher comorbidity score, regardless of cognitive status. Functional status was the best predictor of greater home care needs.

Conclusions

Dementia in very old medically ill inpatients was predictive only of discharge to a nursing home. Higher levels of comorbidity and poor functional status were more predictive than dementia for the other three hospitalization outcomes. Thus, comorbid medical conditions, functional and nutritional status should be considered, together with cognitive assessment, when predicting hospitalization outcome. Copyright © 2008 John Wiley & Sons, Ltd.
Functional decoupling of BOLD and gamma‐band amplitudes in human primary visual cortex
Authors: Muthukumaraswamy Suresh D. , Singh Krish D.
Published: August 2008

Although functional magnetic resonance imaging is an important tool for measuring brain activity, the hemodynamic blood oxygenation level dependent (BOLD) response is only an indirect measure of neuronal activity. Converging evidence obtained from simultaneous recording of hemodynamic and electrical measures suggest that the best correlate of the BOLD response in primary visual cortex is gamma‐band oscillations (∼40 Hz). Here, we examined the coupling between BOLD and gamma‐band amplitudes measured with magntoencephalography (MEG) in human primary visual cortex in 10 participants. In Experiment A, participants were exposed to grating stimuli at two contrast levels and two spatial frequencies and in Experiment B square and sine wave stimuli at two spatial frequencies. The amplitudes of both gamma‐band oscillations and BOLD showed tuning with stimulus contrast and stimulus type; however, gamma‐band oscillations showed a 300% increase across two spatial frequencies, whereas BOLD exhibited no change. This functional decoupling demonstrates that increased amplitude of gamma‐band oscillations as measured with MEG is not sufficient to drive the subsequent BOLD response. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Runoff modelling of the glacierized Alpine Upper Salzach basin (Austria): multi‐criteria result validation
Authors: Koboltschnig Gernot R. , Schöner Wolfgang , Zappa Massimiliano , Kroisleitner Christine , Holzmann Hubert
Published: August 2008

Snow cover and glaciers are the most important long‐term forms of water storage and, hence, the main sources of runoff during the ablation period for many alpine headwater basins. We therefore investigated the application of the conceptual, distributed hydrological precipitation runoff evapotranspiration hydrological response unit model (PREVAH) to the alpine glacierized headwater basin of the Upper Salzach (593 km2, 5% glacierized) river in Austria. Hourly meteorological data from 17 stations for a 6‐year period were available for the calibration and validation of the hourly runoff simulations. Multi‐criteria validation included hourly discharge, snow covered area (SCA), and glacier mass balances. SCA maps were generated from optical satellite images for six dates. These maps were compared to simulated maps of SCA to (1) calculate differences in SCA, (2) calculate altitudinal differences, and (3) show the ability to accurately model snow cover on different aspects. The differences between observed and simulated SCA for glacierized areas were between 1 and 9% during June and July, and between 10 and 36% during August and September observations. In general, the model overestimated SCA, which is the result of PREVAH not including redistribution of snow by wind or avalanches. The temporal variability of the simulated mass balance agreed well with observations from surrounding glaciers. Nash‐Sutcliffe Efficiency Criteria (R2) of the hourly discharge simulations were between 0·83 and 0·89 with the exception of the extreme summer of 2003 which had an R2 of 0·74. Contributions of glacier melt (firn/ice melt) to annual total runoff were between 1 and 4%. Again, the exception was 2003, when glaciers contributed 15% of the annual runoff and 60% to the August runoff alone. Copyright © 2008 John Wiley & Sons, Ltd.
Multifractal detrended fluctuation analysis of streamflow series of the Yangtze River basin, China
Authors: Zhang Qiang , Xu Chong‐Yu , Chen Yongqin David , Yu Zuguo
Published: August 2008

Scaling and multifractal properties of the hydrological processes of the Yangtze River basin were explored by using a multifractal detrended fluctuation analysis (MF‐DFA) technique. Long daily mean streamflow series from Cuntan, Yichang, Hankou and Datong stations were analyzed. Using shuffled streamflow series, the types of multifractality of streamflow series was also studied. The results indicate that the discharge series of the Yangtze River basin are non‐stationary. Different correlation properties were identified within streamflow series of the upper, the middle and the lower Yangtze River basin. The discharge series of the upper Yangtze River basin are characterized by short memory or anti‐persistence; while the streamflow series of the lower Yangtze River basin is characterized by long memory or persistence. h(q) vs q curves indicate multifractality of the hydrological processes of the Yangtze River basin. h(q) curves of shuffled streamflow series suggest that the multifractality of the streamflow series is mainly due to the correlation properties within the hydrological series. This study may be of practical and scientific importance in regional flood frequency analysis and water resource management in different parts of the Yangtze River basin. Copyright © 2008 John Wiley & Sons, Ltd.
Intratumoral rhIL‐12 administration in head and neck squamous cell carcinoma patients induces B cell activation
Authors: van Herpen Carla M.L. , van der Voort Robbert , van der Laak Jeroen A.W.M. , Klasen Ina S. , de Graaf Aniek O. , van Kempen Léon C.L. , de Vries I. Jolanda M. , Boer Tjitske Duiveman‐de , Dolstra Harry , Torensma Ruurd , van Krieken Johan H. , Adema Gosse J. , De Mulder Pieter H.M.
Published: August 2008

The objectives of this study were to investigate the effects of intratumorally (i.t.) administered recombinant human interleukin‐12 (rhIL‐12) on the distribution and function of B cells in the primary tumors, the locoregional lymph nodes and peripheral blood of head and neck squamous cell carcinoma (HNSCC) patients. The initial characterization of the patients participating in the phase Ib and phase II studies has previously been reported. After rhIL‐12 treatment, fewer secondary follicles with a broader outer region of the mantle zones and an increase in interfollicular B‐blasts were seen in the enlarged lymph nodes compared with control HNSCC patients. The size of the germinal center (GC) was diminished, partly due to a decrease in the number of CD57+ GC cells that have been associated with immune suppression. These changes did not correlate with signs of apoptosis or CXCR5 expression by B cells. Strikingly, in 3 out of 4 IL‐12 treated patients, increased IFN‐γ mRNA expression by B cells was detected. In addition, a highly significant IgG subclass switch was seen in the plasma with more IgG1, less IgG2 and more IgG4, indicating a switch to T helper 1 phenotype. Finally, peritumoral B cell infiltration was a positive prognostic sign for overall survival in the 30 HNSCC patients investigated, irrespective of IL‐12 treatment. In conclusion, these data indicate that after i.t. IL‐12 treatment in HNSCC, significant activation of the B cell and the B cell compartment occurred and that the presence of tumor infiltrating B cells correlated with overall survival of HNSCC patients. © 2008 Wiley‐Liss, Inc.
Diet diversity and the risk of squamous cell esophageal cancer
Authors: Lucenteforte Ersilia , Garavello Werner , Bosetti Cristina , Talamini Renato , Zambon Paola , Franceschi Silvia , Negri Eva , La Vecchia Carlo
Published: August 2008

A varied diet may have a favorable role against digestive tract cancers. We analyzed the relationship between diet diversity (i.e. measured by the number of different foods consumed at least once per week) and the risk of esophageal cancer. We considered data from a case–control study conducted between 1992 and 1997 in northern Italy on 304 squamous cell esophageal cancer cases below age 78 years and 743 controls admitted to hospital for acute, nonneoplastic conditions, unrelated to tobacco or alcohol consumption. There was a significant inverse association for total diet diversity: the multivariate odds ratio (OR), adjusted for age, sex, area of residence, education, tobacco smoking, alcohol drinking and non‐alcohol energy intake was 0.42 (95% confidence interval, CI: 0.25–0.71) for subjects in the highest versus those in the lowest quartile of diversity. Inverse relations were also found for diversity within vegetables (OR = 0.34, 95% CI: 0.21–0.55) and fruits (OR = 0.51, 95% CI: 0.33–0.80). No significant association was found for meat and cereal diversity. These results add epidemiological support to the dietary guidelines recommending a more varied diet, particularly in fruit and vegetables, for esophageal cancer prevention. © 2008 Wiley‐Liss, Inc.
Measures of cutaneous human papillomavirus infection in normal tissues as biomarkers of HPV in corresponding nonmelanoma skin cancers
Authors: Rollison Dana E. , Pawlita Michael , Giuliano Anna R. , Iannacone Michelle R. , Sondak Vernon K. , Messina Jane L. , Cruse C. Wayne , Fenske Neil Alan , Glass Lewis Frank , Kienstra Matthew , Michael Kristina M. , Waterboer Tim , Gheit Tarik , Tommasino Massimo
Published: August 2008

Cutaneous human papillomavirus (HPV) may be associated with the development of nonmelanoma skin cancer (NMSC), as suggested by reports of HPV DNA in NMSC tumors. HPV has also been investigated as an NMSC risk factor in epidemiologic studies, although findings vary across studies that used different biomarkers of HPV infection in normal tissues. To identify appropriate biomarkers for use in future epidemiologic studies, we conducted a sampling validation study. NMSC tumor tissue was obtained from 20 patients with pathology‐confirmed basal or squamous cell carcinoma of the skin, in addition to several normal tissues, including eyebrow hairs, normal skin swabs obtained using multiple techniques, normal skin punch and shave biopsies, and serum for antibody measurement. Presence of cutaneous HPV DNA in tissues was measured with multiplex PCR using HPV type‐specific primers and array primer extension (APEX) for HPV typing. Antibody detection was based on glutathione‐S‐transferase capture ELISA in combination with fluorescent bead technology. Using HPV DNA in tumor tissues as a gold standard, sensitivity and specificity were calculated for each measure of HPV infection in normal tissues. β‐Papillomavirus DNA was observed in tumor tissues in 60% of patients. The normal skin punch biopsy demonstrated optimal sensitivity (75%) and specificity (75%). Biomarkers obtained using less‐invasive techniques demonstrated poor specificity when considered individually, although specificity improved when biomarkers were combined. Based on the current case series, the combinations of antibodies+eyebrow hairs or antibodies+eyebrow hairs+Dacron swabs are the optimal, minimally invasive markers of cutaneous HPV infection for use in epidemiologic studies. © 2008 Wiley‐Liss, Inc.
CCAAT/enhancer binding protein‐alpha polymorphisms occur more frequently than mutations in acute myeloid leukemia and exist across all cytogenetic risk groups and leukemia subtypes
Authors: Leecharendkeat Amporn , Tocharoentanaphol Chintana , Auewarakul Chirayu U.
Published: August 2008

CCAAT/enhancer binding protein‐alpha (CEBPA) belongs to a family of leucine zipper transcription factors necessary for late differentiation events of many cell types. CEBPA gene has recently been recognized as the target of genetic alterations in acute myeloid leukemia (AML). CEBPA mutations and polymorphisms were determined in a large series of Southeast Asian AML (n = 247) using polymerase chain reaction and direct sequencing. Chromosome and FLT3 mutation analyses were also undertaken. Thirty‐two distinct types of nucleotide changes (7 known and 25 novel mutations) were identified in 34 cases (13.8%). Three types of polymorphisms were found in 60 cases (24.3%) including a novel nt1401C>T polymorphism. All polymorphisms were located at the C‐terminal region whereas the majority of mutations (62.5%) occurred at the N‐terminal region. The most common polymorphism was the nt1175_1180dup resulting in the predicted P194_H195 duplication protein in 50 cases. Although CEBPA mutations were predominantly associated with a normal karyotype (76%), 15.7% of patients with an unfavorable risk and 4.3% of patients with a favorable risk also had the mutations. Moreover, CEBPA polymorphisms were similarly found across all cytogenetic risk groups and occurred in all leukemia subtypes. FLT3 mutations were comparably discovered among patients with CEBPA mutations, polymorphisms and wild‐type (26–30%). In conclusion, CEBPA polymorphisms occurred more frequently than CEBPA mutations and could be identified across all prognostic risk groups. The high occurrence of CEBPA polymorphisms should be recognized in order not to include this group of patients with CEBPA polymorphisms for prognostic evaluation of CEBPA mutations in any clinical trials. © 2008 Wiley‐Liss, Inc.
Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis
Authors: Kundu Samrat T. , Gosavi Prajakta , Khapare Nileema , Patel Rachana , Hosing Amol S. , Maru Girish B. , Ingle Arvind , DeCaprio James A. , Dalal Sorab N.
Published: August 2008

Plakophilin3 is a desmosomal plaque protein whose levels are reduced in poorly differentiated tumors of the oropharyngeal cavity and in invasive colon carcinomas. To test the hypothesis that plakophilin3 loss stimulates neoplastic progression, plakophilin3 expression was inhibited by DNA vector driven RNA interference in 3 epithelial cell lines, HCT116, HaCaT and fetal buccal mucosa. The plakophilin3‐knockdown clones showed a decrease in cell–cell adhesion as assessed in a hanging drop assay, which was accompanied by an increase in cell migration. The HCT116 plakophilin3‐knockdown clones showed a decrease in desmosome size as revealed by electron microscopy. These altered desmosomal properties were accompanied by colony formation in soft agar and growth to high density in culture. The HCT116‐derived clones showed accelerated tumor formation in nude mice and increased metastasis to the lung, a phenotype consistent with the increased migration observed in vitro and is consistent with data from human tumors that suggests that plakophililn3 is lost in invasive and metastatic tumors. These data indicate that plakophilin3 loss leads to a decrease in cell–cell adhesion leading to the stimulation of neoplastic progression and metastasis. © 2008 Wiley‐Liss, Inc.
Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries
Authors: Chuang Shu‐Chun , Scelo Ghislaine , Tonita Jon M. , Tamaro Sharon , Jonasson Jon G. , Kliewer Erich V. , Hemminki Kari , Weiderpass Elisabete , Pukkala Eero , Tracey Elizabeth , Friis Soren , Pompe‐Kirn Vera , Brewster David H. , Martos Carmen , Chia Kee‐Seng , Boffetta Paolo , Brennan Paul , Hashibe Mia
Published: August 2008

The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population‐based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person‐years of follow‐up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person‐years and the age‐, sex‐ and calendar period‐specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83–1.90) and the 20‐year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20‐year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking. © 2008 Wiley‐Liss, Inc.
Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer
Authors: Leung Elaine Y.L. , Crozier Joseph E.M. , Talwar Dinesh , O'Reilly Denis St. J. , McKee Ruth F. , Horgan Paul G. , McMillan Donald C.
Published: August 2008

Both the tumour growth and progression and the systemic inflammatory response have the potential to increase oxidative stress. We therefore examined the relationship between lipid‐soluble antioxidant vitamins, lipid peroxidation, the systemic inflammatory response and survival in patients with primary operable (n = 53) and advanced inoperable (n = 53) colorectal cancer. Compared with those patients with primary operable colorectal cancer, patients with unresectable liver disease had significantly lower median concentrations of α‐tocopherol (p < 0.001), lutein (p < 0.001), lycopene (p < 0.001), α‐carotene (p < 0.01) and β‐carotene (p < 0.001) and higher malondialdehyde concentrations. An elevated systemic inflammatory response (Glasgow prognostic score, mGPS) was associated with a greater proportion of females (p < 0.05) and more advanced tumour stage (p < 0.05), lower circulating levels of retinol (p < 0.01), lutein (p < 0.01), lycopene (p < 0.01) and α‐ (p < 0.01) and β‐carotene but not MDA (p = 0.633). In the liver metastases group 41 patients died of their cancer and a further 1 patient died of intercurrent disease on follow‐up. On univariate survival analysis, mGPS (p < 0.01), retinol (p < 0.001), α‐tocopherol (p < 0.05) and α‐carotene (p < 0.05) were associated significantly with cancer‐specific survival. On multivariate survival analysis of these significant variables, only mGPS (p < 0.01) and retinol (p < 0.001) were independently associated with cancer‐specific survival. The results of the present study showed that the systemic inflammatory response was associated with a reduction of lipid‐soluble antioxidant vitamins, whereas advanced tumour stage was associated with increased lipid peroxidation in patients with colorectal cancer. Of the antioxidant vitamins measured, only retinol was independently associated with cancer‐specific survival. © 2008 Wiley‐Liss, Inc.
Gene silencing of β‐catenin in melanoma cells retards their growth but promotes the formation of pulmonary metastasis in mice
Authors: Takahashi Yuki , Nishikawa Makiya , Suehara Tetsuya , Takiguchi Naomi , Takakura Yoshinobu
Published: August 2008

Altered expression of β‐catenin, a key component of the Wnt signaling pathway, is involved in a variety of cancers because increased levels of β‐catenin protein are frequently associated with enhanced cellular proliferation. Although our previous study demonstrated that gene silencing of β‐catenin in melanoma B16‐BL6 cells by plasmid DNA (pDNA) expressing short‐hairpin RNA targeting the gene (pshβ‐catenin) markedly suppressed their growth in vivo, gene silencing of β‐catenin could promote tumor metastasis by the rearranging cell adhesion complex. In this study, we investigated how silencing of β‐catenin affects metastatic aspects of melanoma cells. Transfection of B16‐BL6 cells with pshβ‐catenin significantly reduced the amount of cadherin protein, a cell adhesion molecule binding to β‐catenin, with little change in its mRNA level. Cadherin‐derived fragments were detected in culture media of B16‐BL6 cells transfected with pshβ‐catenin, suggesting that cadherin is shed from the cell surface when the expression of β‐catenin is reduced. The mobility of B16‐BL6 cells transfected with pshβ‐catenin was greater than that of cells transfected with any of the control pDNAs. B16‐BL6 cells stably transfected with pshβ‐catenin (B16/pshβ‐catenin) formed less or an equal number of tumor nodules in the lung than cells stably transfected with other plasmids when injected into mice via the tail vein. However, when subcutaneously inoculated, B16/pshβ‐catenin cells formed more nodules in the lung than the other stably transfected cells. These results raise concerns about the gene silencing of β‐catenin for inhibiting tumor growth, because it promotes tumor metastasis by reducing the amount of cadherin in tumor cells. © 2008 Wiley‐Liss, Inc.
Targeting the methionine cycle for melanoma therapy with 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐epicatechin
Authors: Sánchez‐del‐Campo Luís , Rodríguez‐López José Neptuno
Published: August 2008

The higher expression of methionine cycle genes in melanoma cells than in normal melanocytes may be related with increased protein synthesis and transmethylation reactions and the subsequent need for high levels of methionine. 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐epicatechin (TMECG), a trimethoxy derivative of epicatechin‐3‐gallate (ECG), effectively suppressed proliferation of melanoma cells in cultures by inducing apoptosis. TMECG modulates the expression of genes involved in methionine metabolism, cellular methylation and glutathione synthesis in melanoma cells. TMECG treatment of melanoma cells resulted in the downregulation of antiapoptotic Bcl‐2, the upregulation of proapoptotic Bax and the activation of caspase‐3; however, it did not induce the expression of the apoptosis protease‐activating factor‐1 (Apaf‐1). Having elucidated the effects of TMECG on the melanoma methionine cycle, we designed therapeuthical strategies to increase its effectiveness. Combinations of TMECG withS‐adenosylmethionine or compounds that modulate the intracellular concentration of adenosine strongly increase the antiproliferative effects of TMECG. The ability of TMECG to target multiple aspects related with melanoma survival, with a high degree of potency, points to its clinical value in melanoma therapy. © 2008 Wiley‐Liss, Inc.
Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine‐based chemotherapy: Evidence from 24 studies
Authors: Qiu Li‐Xin , Tang Qi‐Yun , Bai Jian‐Ling , Qian Xiao‐Ping , Li Ru‐Tian , Liu Bao‐Rui , Zheng Ming‐Hua
Published: August 2008

The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine‐based chemotherapy seemed inconclusive. To derive a more precise estimation of the relationship, a metaanalysis was performed. Studies have been identified by searching PubMed and Embase. Inclusion criteria were advanced CRC patients, received fluoropyrimidine‐based chemotherapy and evaluation of TS expression and overall response rate (ORR). The relative ratio (RR) for ORR in patients with low‐TS expression over those with high‐TS expression with 95% confidence interval (CI) was calculated for each study as an estimation of the predictive effect of TS. A total of 24 studies including 1,112 patients were involved in this metaanalysis. The overall RR was 2.20 (95% CI, 1.82–2.66;p= 0.000). For studies evaluating TS expression in metastatic lesions, the pooled RR was 3.23 (95% CI, 2.27–4.59;p= 0.000); for studies testing TS expression in primary lesions, a pooled RR of 1.89 (95% CI, 1.45–2.48;p= 0.000) was estimated. Focusing the analysis on immunohistochemistry (IHC)‐based or RTPCR‐based assessments, the pooled RR was 1.83 (95% CI, 1.44–2.34;p= 0.000) and 2.96 (95% CI, 2.07–4.22;p= 0.000), respectively. The results indicated that low‐TS expression tumors in advanced CRC patients were more sensitive to fluoropyrimidine‐based chemotherapy. Subgroup analyses indicated that the predictive value of TS expression evaluated in metastases was more prominent than that of primary lesions, and that TS expression tested by RTPCR was also of greater predictive value than by IHC. © 2008 Wiley‐Liss, Inc.
Optical detection and grading of lung neoplasia by Raman microspectroscopy
Authors: Jess Phillip R.T. , Mazilu Michael , Dholakia Kishan , Riches Andrew C. , Herrington C. Simon
Published: August 2008

The aim of this study was to investigate whether Raman spectroscopy could be used to identify and potentially grade lung neoplasia in cell samples. Normal human bronchial epithelial cells (HBEpCs) were analyzed by Raman spectroscopy and compared with (i) HBEpCs expressing human papillomavirus (HPV) type 16 E7 or CDK4; (ii) the immortalized bronchial epithelial cell line BEP2D and (iii) its asbestos‐transformed derivative AsbTB2A. Overall, Raman spectroscopy, in combination with a linear discriminant analysis algorithm, was able to identify abnormal cells with a sensitivity of 91% and a specificity of 75%. Subdivision of the cell types into 3 groups, representing normal cells (HBEpCs), cells with extended lifespan (HBEpCs expressing HPV 16 E7 or CDK4) and immortalized/transformed cells (BEP2D and AsbTB2A) showed that Raman spectroscopy identifies cells in these categories correctly with sensitivities of 75, 79 and 87%, and specificities of 91, 85 and 96%, respectively. In conclusion, Raman spectroscopy can, with high sensitivity, detect the presence of neoplastic development in lung cells and identify the stage of this development accurately, suggesting that this minimally invasive optical technology has potential for lung cancer diagnosis. © 2008 Wiley‐Liss, Inc.
Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patients
Authors: Ding Yi , Chen Bin , Wang Shuang , Zhao Liang , Chen Juanzhi , Ding Yanqing , Chen Longhua , Luo Rongcheng
Published: August 2008

Little research has been done to test the usefulness of T‐lymphoma invasion and metastasis 1 (Tiam1) as a prognostic marker for hepatocellular carcinoma (HCC). In this study, we investigated Tiam1 expression and its prognostic value for HCC. HCC surgical tissue samples were taken from 152 HCC patients who had been followed up for 5 years. Overexpression of Tiam1 (Tiam1 2+ to 3+) was shown in 63.8% of the cases. The Tiam1 expression level did not correlate with any clinicopathological parameters. However, survival analysis showed that the Tiam1 overexpression group had a significantly shorter overall survival time than the Tiam1 downexpression group (p = 0.008). Multivariate analysis showed that Tiam1 expression was a significant and independent prognostic parameter (p = 0.042) for HCC patients. Tiam1 expression may be a novel and independent predictor for the prognosis of HCC patients. © 2008 Wiley‐Liss, Inc.
Increased risk of esophageal squamous cell carcinoma in patients with gastric atrophy: Independent of the severity of atrophic changes
Authors: de Vries Annemarie C. , Capelle Lisette G. , Looman Caspar W.N. , van Blankenstein Mark , van Grieken Nicole C.T. , Casparie Mariël K. , Meijer Gerrit A. , Kuipers Ernst J.
Published: August 2008

An association between gastric atrophy and esophageal squamous cell carcinomas (ESCC) has been described. However, the mechanism of this association is unknown. In this study, we aimed to examine this relationship in a cohort of patients with varying grades of gastric atrophy to increase the understanding about the causality of the association. Patients diagnosed with gastric atrophy between 1991 and 2005 were identified in the Dutch nationwide histopathology registry (PALGA). The incidence of ESCC and, presumably unrelated, small cell lung carcinomas (SCLC) observed in these patients was compared with that in the general Dutch population. Relative risks (RRs) and 95% confidence intervals were calculated by a Poisson model. At baseline histological examination, 97,728 patients were diagnosed with gastric atrophy, of whom 23,278 with atrophic gastritis, 65,934 with intestinal metaplasia and 8,516 with dysplasia. During follow‐up, 126 patients were diagnosed with ESCC and 263 with SCLC (overall rates 0.19, respectively 0.39/1,000 person‐years at risk). Compared with the general Dutch population, patients with gastric atrophy ran a RR of developing ESCC of 2.2 [95% CI 1.8–2.6] and of SCLC of 1.8 [95% CI 1.6–2.1]. The risk of ESCC did not increase with increasing severity of gastric atrophy (p = 0.90). In conclusion, this study found an association between gastric atrophy and both ESCC and SCLC, but the risk of ESCC did not increase with the severity of gastric atrophy. Therefore, a causal relationship seems unlikely. Confounding factors, such as smoking, may explain both associations. © 2008 Wiley‐Liss, Inc.