bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines
Authors: LaBonte Melissa J , Wilson Peter M , Fazzone William , Groshen Susan , Lenz Heinz-Josef , Ladner Robert D 
Published: December 2009

AbstractBackgroundDespite the significant progress made in colon cancer chemotherapy, advanced disease remains largely incurable and novel efficacious chemotherapies are urgently needed. Histone deacetylase inhibitors (HDACi) represent a novel class of agents which have demonstrated promising preclinical activity and are undergoing clinical evaluation in colon cancer. The goal of this study was to identify genes in colon cancer cells that are differentially regulated by two clinically advanced hydroxamic acid HDACi, vorinostat and LBH589 to provide rationale for novel drug combination partners and identify a core set of HDACi-regulated genes.MethodsHCT116 and HT29 colon cancer cells were treated with LBH589 or vorinostat and growth inhibition, acetylation status and apoptosis were analyzed in response to treatment using MTS, Western blotting and flow cytometric analyses. In addition, gene expression was analyzed using the Illumina Human-6 V2 BeadChip array and Ingenuity®Pathway Analysis.ResultsTreatment with either vorinostat or LBH589 rapidly induced histone acetylation, cell cycle arrest and inhibited the growth of both HCT116 and HT29 cells. Bioinformatic analysis of the microarray profiling revealed significant similarity in the genes altered in expression following treatment with the two HDACi tested within each cell line. However, analysis of genes that were altered in expression in the HCT116 and HT29 cells revealed cell-line-specific responses to HDACi treatment. In addition a core cassette of 11 genes modulated by both vorinostat and LBH589 were identified in both colon cancer cell lines analyzed.ConclusionThis study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets that are modulated by HDACi, providing much-needed information on HDACi mechanism of action and providing rationale for novel drug combination partners. We identified a core signature of 11 genes which were modulated by both vorinostat and LBH589 in a similar manner in both cell lines. These core genes will assist in the development and validation of a common gene set which may represent a molecular signature of HDAC inhibition in colon cancer.
From HIV diagnosis to treatment: evaluation of a referral system to promote and monitor access to antiretroviral therapy in rural Tanzania
Authors: Nsigaye Ray , Wringe Alison , Roura Maria , Kalluvya Samuel , Urassa Mark , Busza Joanna , Zaba Basia 
Published: December 2009

BackgroundIndividuals diagnosed with HIV in developing countries are not always successfully linked to onward treatment services, resulting in missed opportunities for timely initiation of antiretroviral therapy, or prophylaxis for opportunistic infections. In collaboration with local stakeholders, we designed and assessed a referral system to link persons diagnosed at a voluntary counselling and testing (VCT) clinic in a rural district in northern Tanzania with a government‐run HIV treatment clinic in a nearby city.MethodsTwo‐part referral forms, with unique matching numbers on each side were implemented to facilitate access to the HIV clinic, and were subsequently reconciled to monitor the proportion of diagnosed clients who registered for these services, stratified by sex and referral period. Delays between referral and registration at the HIV clinic were calculated, and lists of non‐attendees were generated to facilitate tracing among those who had given prior consent for follow up.Transportation allowances and a “community escort” from a local home‐based care organization were introduced for patients attending the HIV clinic, with supportive counselling services provided by the VCT counsellors and home‐based care volunteers. Focus group discussions and in‐depth interviews were conducted with health care workers and patients to assess the acceptability of the referral procedures.ResultsReferral uptake at the HIV clinic averaged 72% among men and 66% among women during the first three years of the national antiretroviral therapy (ART) programme, and gradually increased following the introduction of the transportation allowances and community escorts, but declined following a national VCT campaign. Most patients reported that the referral system facilitated their arrival at the HIV clinic, but expressed a desire for HIV treatment services to be in closer proximity to their homes. The referral forms proved to be an efficient and accepted method for assessing the effectiveness of the VCT clinic as an entry point for ART.ConclusionThe referral system reduced delays in seeking care, and enabled the monitoring of access to HIV treatment among diagnosed persons. Similar systems to monitor referral uptake and linkages between HIV services could be readily implemented in other settings.
India‐US collaboration to prevent adolescent HIV infection: the feasibility of a family‐based HIV‐prevention intervention for rural Indian youth
Authors: Soletti Asha Banu , Guilamo‐Ramos Vincent , Burnette Denise , Sharma Shilpi , Bouris Alida 
Published: December 2009

BackgroundDespite the centrality of family in Indian society, relatively little is known about family‐based communication concerning sexual behaviour and HIV/AIDS in rural Indian families. To date, very few family‐based adolescent HIV‐prevention interventions have been developed for rural Indian youth. This study conducted formative research with youth aged 14 to18 years and their parents in order to assess the feasibility of conducting a family‐based HIV‐prevention intervention for rural Indian adolescents.MethodsEight focus groups were conducted (n = 46) with mothers, fathers, adolescent females and adolescent males (two focus groups were held for each of the four groups). All focus groups consisted of same‐gender participants. Adolescents aged 14 to18 years old and their parents were recruited from a tribal community in rural Maharashtra, India. Focus group transcripts were content analyzed to identify themes related to family perceptions about HIV/AIDS and participation in a family‐based intervention to reduce adolescent vulnerability to HIV infection.ResultsSix primary thematic areas were identified: (1) family knowledge about HIV/AIDS; (2) family perceptions about adolescent vulnerability to HIV infection; (3) feasibility of a family‐based programme to prevent adolescent HIV infection; (4) barriers to participation; (5) recruitment and retention strategies; and (6) preferred content for an adolescent HIV prevention intervention.ConclusionDespite suggestions that family‐based approaches to preventing adolescent HIV infection may be culturally inappropriate, our results suggest that a family‐based intervention to prevent adolescent HIV infection is feasible if it: (1) provides families with comprehensive HIV prevention strategies and knowledge; (2) addresses barriers to participation; (3) is adolescent friendly, flexible and convenient; and (4) is developmentally and culturally appropriate for rural Indian families.
Measurement of tissue cortisol levels in patients with severe burns: a preliminary investigation
Authors: Cohen Jeremy , Deans Renae , Dalley Andrew , Lipman Jeff , Roberts Michael S , Venkatesh Bala 
Published: December 2009

Abstract
Introduction
The assessment of adrenal function in critically ill patients is problematic, and there is evidence to suggest that measurement of tissue glucocorticoid activity may be more useful than estimation of plasma cortisol concentrations. Interstitial cortisol concentrations of cortisol represent the available pool of glucocorticoids able to enter the cell and bind to the glucocorticoid receptor. However the concentrations of plasma cortisol may not accurately reflect interstitial concentrations. We elected to perform a preliminary study into the feasibility of measuring interstitial cortisol by microdialysis, and to investigate the relationship between total plasma cortisol, free plasma cortisol and interstitial cortisol in patients with severe burns.

Methods
A prospective observational study carried out in a tertiary intensive care unit. Ten adult patients with a mean total burn surface area of 48% were studied. Interstitial cortisol was measured by microdialysis from patient-matched burnt and non-burnt tissue and compared with that of 3 healthy volunteers. Plasma sampling for estimations of total and free cortisol concentrations was performed concurrently.

Results
In the burn patients, mean total plasma and free plasma cortisol concentrations were 8.8 +/- 3.9, and 1.7 +/- 1.1 mcg/dL, (p < 0.001), respectively. Mean subcutaneous microdialysis cortisol concentrations in the burn and non-burn tissue were 0.80 +/- 0.31 vs 0.74 +/- 0.41 mcg/dL (p = 0.8), respectively, and were significantly elevated over the mean subcutaneous microdialysis cortisol concentrations in the healthy volunteers. There was no significant correlation between total plasma or free plasma and microdialysis cortisol concentrations. Plasma free cortisol was better correlated with total burn surface area than total cortisol.

Conclusions
In this preliminary study, interstitial cortisol concentrations measured by microdialysis in burnt and non-burnt skin from patients with severe thermal injury are significantly elevated over those from healthy volunteers. Plasma estimations of cortisol do not correlate with the microdialysis levels, raising the possibility that plasma cortisol may be an unreliable guide to tissue cortisol activity.
Angiotensin II in experimental hyperdynamic sepsis
Authors: Wan Li , Langenberg Christoph , Bellomo Rinaldo , May Clive N 
Published: December 2009

Abstract
Introduction
Angiotensin II (Ang II) is a potential vasopressor treatment for hypotensive hyperdynamic sepsis. However, unlike other vasopressors, its systemic, regional blood flow and renal functional effects in hypotensive hyperdynamic sepsis have not been investigated.

Methods
We performed an experimental randomised placebo-controlled animal study. We induced hyperdynamic sepsis by the intravenous administration of live E. coli in conscious ewes after chronic instrumentation with flow probes around the aorta and the renal, mesenteric, coronary and iliac arteries. We allocated animals to either placebo or angiotensin II infusion titrated to maintain baseline blood pressure.

Results
Hyperdynamic sepsis was associated with increased renal blood flow (from 292 +/- 61 to 397 +/- 74 ml/min), oliguria and a decrease in creatinine clearance (from 88.7 +/- 19.6 to 47.7 +/- 21.0 ml/min, P < 0.0001). Compared to placebo, Ang II infusion restored arterial pressure but reduced renal blood flow (from 359 +/- 81 ml/min to 279 +/- 86 ml/min; P < 0.0001). However, despite the reduction in renal blood flow, Ang II increased urine output approximately 7-fold (364 +/- 272 ml/h vs. 48 +/- 18 ml/h; P < 0.0001), and creatinine clearance by 70% (to 80.6 +/- 20.7 ml/min vs.46.0 +/- 26 ml/min; P < 0.0001). There were no major effects of Ang II on other regional blood flows.

Conclusions
In early experimental hypotensive hyperdynamic sepsis, intravenous angiotensin II infusion decreased renal blood while inducing a marked increase in urine output and normalizing creatinine clearance.
Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study
Authors: Bora Emre , Yucel Murat , Pantelis Christos 
Published: December 2009

BackgroundCognitive functioning in affective psychosis and schizoaffective disorder is much less studied compared with schizophrenia.AimsTo quantitatively undertake a meta-analysis of the available data that directly compares cognitive functioning across schizophrenia, schizoaffective disorder and affective psychosis.MethodFollowing a thorough literature review, 31 studies that compared the performances of people with schizophrenia (1979 participants) with that of those with affective psychosis or schizoaffective disorder (1314 participants) were included. To determine the effect of demographic and clinical confounders, meta-regression and subgroup analyses were conducted.ResultsIn 6 of 12 cognitive domains, people with schizophrenia performed worse than people with schizoaffective disorder or affective psychosis. However, the between-group differences were small and the distribution of effect sizes showed substantial heterogeneity. The between-group differences were driven by a higher percentage of males, more severe negative symptoms and younger age at onset of illness in the schizophrenia samples.ConclusionsNeuropsychological data do not provide evidence for categorical differences between schizophrenia and other groups. However, a subgroup of individuals with schizophrenia who have more severe negative symptoms may be cognitively more impaired than those with affective psychosis/schizoaffective disorder.
Association between extreme autistic traits and intellectual disability: insights from a general population twin study
Authors: Hoekstra R. A. , Happé F. , Baron-Cohen S. , Ronald A. 
Published: December 2009

BackgroundAutism is associated with intellectual disability. The strength and origin of this association is unclear.AimsTo investigate the association between extreme autistic traits and intellectual disability in children from a community-based sample and to examine whether the association can be explained by genetic factors.MethodChildren scoring in the extreme 5% on measures of autistic traits, IQ and academic achievement were selected from 7965 7/8-year-old and 3687 9-year-old twin pairs. Phenotypic associations between extreme autistic traits and intellectual disability were compared with associations among the full-range scores. Genetic correlations were estimated using bivariate DeFries–Fulker extremes analyses.ResultsExtreme autistic traits were modestly related to intellectual disability; this association was driven by communication problems characteristic of autism. Although this association was largely explained by genetic factors, the genetic correlation between autistic traits and intellectual disability was only modest.ConclusionsExtreme autistic traits are substantially genetically independent of intellectual disability.
Genetic and environmental contributions to depression in Sri Lanka
Authors: Ball Harriet A. , Sumathipala Athula , Siribaddana Sisira H. , Kovas Yulia , Glozier Nick , McGuffin Peter , Hotopf Matthew 
Published: December 2009

BackgroundSusceptibility to depression results from genetic and non-familially shared environmental influences in high-income, Western countries. Environments may play a different role for populations in different contexts.AimsTo examine heritability of depression in the first large, population-based twin study in a low-income country.MethodLifetime depression and a broader measure of depression susceptibility (D-probe) were assessed in 3908 adult twins in Sri Lanka (the CoTASS study).ResultsThere were gender differences for the broad definition (D-probe), with a higher genetic contribution in females (61%) than males (4%). Results were similar for depression, but the prevalence was too low to estimate heritability for males.ConclusionsGenetic influences on depression in women appear to be at least as strong in this Sri Lankan sample as in higher-income countries. Conclusions are less clear for men but suggest a larger role for environments rather than genes. The nature as well as the magnitude of environmental influences may also differ across populations.
High-potency cannabis and the risk of psychosis
Authors: Di Forti Marta , Morgan Craig , Dazzan Paola , Pariante Carmine , Mondelli Valeria , Marques Tiago Reis , Handley Rowena , Luzi Sonija , Russo Manuela , Paparelli Alessandra , Butt Alexander , Stilo Simona A. , Wiffen Ben , Powell John , Murray Robin M. 
Published: December 2009

BackgroundPeople who use cannabis have an increased risk of psychosis an effect attributed to the active ingredient δ9-tetrahydrocannabinol (Δ9-THC). There has recently been concern over an increase in the concentration of Δ9-THC in the cannabis available in many countries.AimsTo investigate whether people with a first episode of psychosis were particularly likely to use high-potency cannabis.MethodWe collected information on cannabis use from 280 cases presenting with a first episode of psychosis to the South London & Maudsley National Health Service (NHS) Foundation Trust, and from 174 healthy controls recruited from the local population.ResultsThere was no significant difference between cases and controls in whether they had ever taken cannabis, or age at first use. However, those in the cases group were more likely to be current daily users (OR = 6.4) and to have smoked cannabis for more than 5 years (OR = 2.1). Among those who used cannabis, 78% of the cases group used high-potency cannabis (sinsemilla, ‘skunk’) compared with 37% of the control group (OR 6.8).ConclusionsThe finding that people with a first episode of psychosis had smoked higher-potency cannabis, for longer and with greater frequency, than a healthy control group is consistent with the hypothesis that Δ9-THC is the active ingredient increasing risk of psychosis. This has important public health implications, given the increased availability and use of high-potency cannabis.
Meta-Analysis of Breast Cancer Outcomes in Adjuvant Trials of Aromatase Inhibitors Versus Tamoxifen
Authors: Dowsett Mitch , Cuzick Jack , Ingle Jim , Coates Alan , Forbes John , Bliss Judith , Buyse Marc , Baum Michael , Buzdar Aman , Colleoni Marco , Coombes Charles , Snowdon Claire , Gnant Michael , Jakesz Raimund , Kaufmann Manfred , Boccardo Francesco , Godwin Jon , Davies Christina , Peto Richard 
Published: December 2009

Purpose To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2). Materials and Methods Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided. Results Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P < .00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal treatment), AI therapy was associated with an absolute 3.1% (SE = 0.6%) decrease in recurrence (5.0% for AI v 8.1% for tamoxifen since divergence; 2P < .00001) and an absolute 0.7% (SE = 0.3%) decrease in breast cancer mortality (1.7% for AI v 2.4% for tamoxifen since divergence; 2P = .02). There was no convincing heterogeneity in the proportional recurrence reduction with respect to age, nodal status, tumor grade, or progesterone receptor status and no indication of an increase in nonbreast deaths with AIs in either cohort. Conclusion AIs produce significantly lower recurrence rates compared with tamoxifen, either as initial monotherapy or after 2 to 3 years of tamoxifen. Additional follow-up will provide clearer information on long-term survival.
Use of Video to Facilitate End-of-Life Discussions With Patients With Cancer: A Randomized Controlled Trial
Authors: El-Jawahri Areej , Podgurski Lisa M. , Eichler April F. , Plotkin Scott R. , Temel Jennifer S. , Mitchell Susan L. , Chang Yuchiao , Barry Michael J. , Volandes Angelo E. 
Published: December 2009

PurposeTo determine whether the use of a goals-of-care video to supplement a verbal description can improve end-of-life decision making for patients with cancer.MethodsFifty participants with malignant glioma were randomly assigned to either a verbal narrative of goals-of-care options at the end of life (control), or a video after the same verbal narrative (intervention) in this randomized controlled trial. The video depicts three levels of medical care: life-prolonging care (cardiopulmonary resuscitation [CPR], ventilation), basic care (hospitalization, no CPR), and comfort care (symptom relief). The primary study outcome was participants' preferences for end-of-life care. The secondary outcome was participants' uncertainty regarding decision making (score range, 3 to 15; higher score indicating less uncertainty). Participants' comfort level with the video was also measured.ResultsFifty participants were randomly assigned to either the verbal narrative (n = 27) or video (n = 23). After the verbal description, 25.9% of participants preferred life-prolonging care, 51.9% basic care, and 22.2% comfort care. In the video arm, no participants preferred life-prolonging care, 4.4% preferred basic care, 91.3% preferred comfort care, and 4.4% were uncertain (P < .0001). The mean uncertainty score was higher in the video group than in the verbal group (13.7 v 11.5, respectively; P < .002). In the intervention arm, 82.6% of participants reported being very comfortable watching the video.ConclusionCompared with participants who only heard a verbal description, participants who viewed a goals-of-care video were more likely to prefer comfort care and avoid CPR, and were more certain of their end-of-life decision making. Participants reported feeling comfortable watching the video.
(Looking) Back to the Future: Using Space—Time Patterns to Better Predict the Location of Street Crime
Authors: Tompson Lisa , Townsley Michael 
Published: December 2009

Crime analysts attempt to identify regularities in police recorded crime data with a central view of disrupting the patterns found. One common method for doing so is hotspot mapping, focusing attention on spatial clustering as a route to crime reduction (Chainey & Ratcliffe, 2005; Clarke & Eck, 2003). Despite the widespread use of this analytical technique, evaluation tools to assess its ability to accurately predict spatial patterns have only recently become available to practitioners (Chainey, Tompson, & Uhlig, 2008). Crucially, none has examined this issue from a spatio-temporal standpoint. Given that the organisational nature of policing agencies is shift based, it is common-sensical to understand crime problems at this temporal sensitivity, so there is an opportunity for resources to be deployed swiftly in a manner that optimises prevention and detection. This paper tests whether hotspot forecasts can be enhanced when time-of-day information is incorporated into the analysis. Using street crime data, and employing an evaluative tool called the Predictive Accuracy Index (PAI), we found that the predictive accuracy can be enhanced for particular temporal shifts, and this is primarily influenced by the degree of spatial clustering present. Interestingly, when hotspots shrank (in comparison with the all-day hotspots), they became more concentrated, and subsequently more predictable. This is meaningful in practice; for if crime is more predictable during specific time-frames, then response resources can be used intelligently to reduce victimisation.