bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons learnt recruiting to a multi-site UK cohort study to explore recovery of health and well-being after colorectal cancer (CREW study)
Authors: Fenlon Deborah , Chivers Seymour Kim , Okamoto Ikumi , Winter Jane , Richardson Alison , Addington-Hall Julia , Corner Jessica L , Smith Peter W , May Christine M , Breckons Matthew , Foster Claire 
Published: December 2013

Abstract

Background
The UK leads the world in recruitment of patients to cancer clinical trials, with a six-fold increase in recruitment during 2001–2010. However, there are large variations across cancer centres. This paper details recruitment to a large multi-centre prospective cohort study and discusses lessons learnt to enhance recruitment.

Methods
During CREW (ColoREctal Wellbeing) cohort study set up and recruitment, data were systematically collected on all centres that applied to participate, time from study approval to first participant recruited and the percentage of eligible patients recruited into the study.

Results
30 participating NHS cancer centres were selected through an open competition via the cancer networks. Time from study approval to first participant recruited took a median 124 days (min 53, max 290). Of 1350 eligible people in the study time frame, 78% (n = 1056) were recruited into the study, varying from 30-100% eligible across centres. Recruitment of 1056 participants took 17 months.

Conclusion
In partnership with the National Cancer Research Network, this successful study prioritised relationship building and education. Key points for effective recruitment: pre-screening and selection of centres; nurses as PIs; attendance at study days; frequent communication and a reduced level of consent to enhance uptake amongst underrepresented groups.
Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA175 is associated to clinical protection in the Brazilian Amazon
Authors: Medeiros Márcia M , Fotoran Wesley L , dalla Martha Rosimeire C , Katsuragawa Tony H , Pereira da Silva Luiz Hildebrando , Wunderlich Gerhard 
Published: December 2013

AbstractBackgroundAntibodies have an essential role in the acquired immune response against blood stageP. falciparuminfection. Although several antigens have been identified as important antibody targets, it is still elusive which antigens have to be recognized for clinical protection. Herein, we analyzed antibodies from plasmas from symptomatic or asymptomatic individuals living in the same geographic area in the Western Amazon, measuring their recognition of multiple merozoite antigens.MethodsSpecific fragments of genes encoding merozoite proteins AMA1 and members of MSP and EBL families from circulatingP. falciparumfield isolates present in asymptomatic and symptomatic patients were amplified by PCR. After cloning and expression of different versions of the antigens as recombinant GST-fusion peptides, we tested the reactivity of patients’ plasmas by ELISA and the presence of IgG subclasses in the most reactive plasmas.Results11 out of 24 recombinant antigens were recognized by plasmas from either symptomatic or asymptomatic infections. Antibodies to MSP9 (X2DF=1 = 9.26/p = 0.0047) and MSP5 (X2DF=1 = 8.29/p = 0.0069) were more prevalent in asymptomatic individuals whereas the opposite was observed for MSP1 block 2-MAD20 (X2DF=1 = 6.41/p = 0.0206, Fisher’s exact test). Plasmas from asymptomatic individuals reacted more intensely against MSP4 (U = 210.5,p < 0.03), MSP5 (U = 212,p < 0.004), MSP9 (U = 189.5,p < 0.002) and EBA175 (U = 197, p < 0.014, Mann-Whitney’s U test). IgG1 and IgG3 were predominant for all antigens, but some patients also presented with IgG2 and IgG4. The recognition of MSP5 (OR = 0.112, IC95% = 0.021-0.585) and MSP9 (OR = 0.125, IC95% = 0.030-0.529, cross tab analysis) predicted 8.9 and 8 times less chances, respectively, to present symptoms. Higher antibody levels against MSP5 and EBA175 were associated by odds ratios of 9.4 (IC95% = 1.29-69.25) and 5.7 (IC95% = 1.12-29.62, logistic regression), respectively, with an asymptomatic status.ConclusionsMerozoite antigens were targets of cytophilic antibodies and antibodies against MSP5, MSP9 and EBA175 were independently associated with decreased symptoms.
Maternal infection and risk of intrapartum death: a population based observational study in South Asia
Authors: Iwamoto Azusa , Seward Nadine , Prost Audrey , Ellis Matthew , Copas Andrew , Fottrell Edward , Azad Kishwar , Tripathy Prasanta , Costello Anthony 
Published: December 2013

Abstract

Background
Approximately 1.2 million stillbirths occur in the intrapartum period, and a further 717,000 annual neonatal deaths are caused by intrapartum events, most of which occur in resource poor settings. We aim to test the ‘double-hit’ hypothesis that maternal infection in the perinatal period predisposes to neurodevelopmental sequelae from an intrapartum asphyxia insult, increasing the likelihood of an early neonatal death compared with asphyxia alone. This is an observational study of singleton newborn infants with signs of intrapartum asphyxia that uses data from three previously conducted cluster randomized controlled trials taking place in rural Bangladesh and India.

Methods
From a population of 81,778 births in 54 community clusters in rural Bangladesh and India, we applied mixed effects logistic regression to data on 3890 singleton infants who had signs of intrapartum asphyxia, of whom 769 (20%) died in the early neonatal period. Poor infant condition at five minutes post-delivery was our proxy measure of intrapartum asphyxia. We had data for two markers of maternal infection: fever up to three days prior to labour, and prolonged rupture of membranes (PROM). Cause-specific verbal autopsy data were used to validate our findings using previously mentioned mixed effect logistic regression methods and the outcome of a neonatal death due to intrapartum asphyxia.

Results
Signs of maternal infection as indicated by PROM, combined with intrapartum asphyxia, increased the risk of an early neonatal death relative to intrapartum asphyxia alone (adjusted odds ratio (AOR) 1.28, 95% CI 1.03 – 1.59). Results from cause-specific verbal autopsy data verified our findings where there was a significantly increased odds of a early neonatal death due to intrapartum asphyxia in newborns exposed to both PROM and intrapartum asphyxia (AOR: 1.52, 95% CI 1.15 – 2.02).

Conclusions
Our data support the double-hit hypothesis for signs of maternal infection as indicated by PROM. Interventions for pregnant women with signs of infection, to prevent early neonatal deaths and disability due to asphyxia, should be investigated further in resource-poor populations where the chances of maternal infection are high.
Mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean patients with lung cancer
Authors: Ji Wonjun , Choi Chang-Min , Rho Jin Kyung , Jang Se Jin , Park Young Soo , Chun Sung-Min , Kim Woo Sung , Lee Jung-Shin , Kim Sang-We , Lee Dae Ho , Lee Jae Cheol 
Published: December 2013

Abstract

Background
Despite an initial good response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), resistance to treatment eventually develops. Although several resistance mechanisms have been discovered, little data exist regarding Asian patient populations.

Methods
Among patients at a tertiary referral hospital in Korea who initially responded well to gefitinib and later acquired resistance to treatment, we selected those with enough tissues obtained before EGFR-TKI treatment and after the onset of resistance to examine mutations by mass spectrometric genotyping technology (Asan-Panel), MET amplification by fluorescence in situ hybridization (FISH), and analysis of AXL status, epithelial-to-mesenchymal transition (EMT) and neuroendocrine markers by immunohistochemistry.

Results
Twenty-six patients were enrolled, all of whom were diagnosed with adenocarcinoma with EGFR mutations (19del: 16, L858R: 10) except one (squamous cell carcinoma with 19del). Secondary T790M mutation was detected in 11 subjects (42.3%) and four of these patients had other co-existing resistance mechanisms; increased AXL expression was observed in 5/26 patients (19.2%), MET gene amplification was noted in 3/26 (11.5%), and one patient acquired a mutation in the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) gene. None of the patients exhibited EMT; however, increased CD56 expression suggesting neuroendocrine differentiation was observed in two patients. Interestingly, conversion from L858R-mutant to wild-type EGFR occurred in one patient. Seven patients (26.9%) did not exhibit any known resistance mechanisms. Patients with a T790M mutation showed a more favorable prognosis.

Conclusion
The mechanisms and frequency of acquired EGFR-TKI resistance in Koreans are comparable to those observed in Western populations; however, more data regarding the mechanisms that drive EGFR-TKI resistance are necessary.
Bifractionated CPT-11 with LV5FU2 infusion (FOLFIRI-3) in combination with bevacizumab: clinical outcomes in first-line metastatic colorectal cancers according to plasma angiopoietin-2 levels
Authors: Kim Stefano , Dobi Erion , Jary Marine , Monnien Franck , Curtit Elsa , NGuyen Thierry , Lakkis Zaher , Heyd Bruno , Fratte Serge , Cléau Denis , Lamfichekh Najib , Nerich Virginie , Guiu Boris , Demarchi Martin , Borg Christophe 
Published: December 2013

Abstract

Background
Optimization of chemotherapy effectiveness in metastatic colorectal cancers (mCRC) is a major endpoint to enhance the possibility of curative intent surgery. FOLFIRI3 has shown promising results as second-line chemotherapy for mCRC patients previously exposed to oxaliplatin. The clinical efficacy of FOLFIRI3 was never determined in association with bevacizumab in non-previously treated mCRC patients.

Methods
We conducted a phase II clinical trial to characterize the response rate and toxicity profile of FOLFIRI3-bevacizumab as initial treatment for mCRC. Sixty-one patients enrolled in 3 investigation centers were treated with FOLFIRI3-bevacizumab (median of 10 cycles) followed by a maintenance therapy combining bevacizumab and capecitabine. Levels of plasma angiopoietin-2 (Ang-2) were measured by enzyme-linked immunosorbent assay at baseline.

Results
Overall response rate (ORR) was 66.7% (8% of complete and 58% of partial responses). The disease control rate was 91.7%. After a median time of follow-up of 46.7 months, 56 patients (92%) had progressed or died. The median progression free survival (PFS) was 12.7 months (95% confidence interval (CI) 9.7-15.8 months). The median overall survival (OS) was 24.5 months (95% CI: 10.6-38.3 months). Twenty-one patients underwent curative intent-surgery including 4 patients with disease initially classified as unresectable. Most common grade III-IV toxicities were diarrhea (15%), neutropenia (13%), asthenia (10%), and infections (4%). Hypertension-related medications needed to be increased in 3 patients. In multivariate analysis, surgery of metastases and Ang-2 levels were the only independent prognostic factors for PFS and OS. Indeed, baseline level of Ang-2 above 5 ng/mL was confirmed as an independent prognostic factor for progression free survival (HR = 0.357; 95% CI: 0.168-0.76, p = 0.005) and overall survival (HR = 0.226; 95% CI: 0.098-0.53, p = 0.0002).

Conclusions
As front-line therapy, FOLFIRI-3-bevacizumab is associated with an acceptable toxicity and induced promising objective response rates. However, unfavorable clinical outcomes were observed in patients with high levels of angiopoietin-2.
Patterns and trends of medical student research
Authors: Wickramasinghe Dakshitha Praneeth , Perera Chamila Sudarshi , Senarathna Supun , Samarasekera Dharmabandhu Nandadeva 
Published: December 2013

AbstractBackgroundOur study describes the change in the research output, trends and content of published research involving medical students over the last century.MethodsPubmed® and Scopus® were searched for keywords ‘Medical Student’ in the affiliation field. The search results were combined in Endnote® and duplicate entries removed and the multiple variables described below were assessed.ResultsThe combined searches after excluding duplicates yielded 416 results and 66 articles were excluded. There was an exponential increase in medical student research from 1980–2010. Medical student was the first author in 170 (48.6%) studies and 55 studies were authored by a single medical student. The 3 most common areas of research in descending order were Psychiatry (n = 26, 7.4%), General Medicine (n = 24, 6.9%) and Medical Education (n = 21, 6%). The commonest type of articles, in descending order were review articles (n = 48, 13.7%), Cross sectional studies (n = 47, 13.4%) and Case reports (n = 43, 12.3. The majority of these articles (n = 207, 59.1%) have never been cited subsequently. The trend of increasing number of articles was seen equally among all article types, fields and countries.ConclusionsThere is an exponential increase in articles by medical students but the majority of articles have not been cited. The numbers of medical student authors per publication have remained static while the total numbers of authors have increased. The proportions in the type of articles, fields of study and country of origin have largely remained static. Publishers and authors should strive to enhance the quality and quantity of data available in indexing services.
Patterns, determinants and barriers of health and social service utilization among young urban crack users in Brazil
Authors: Santos Cruz Marcelo , Andrade Tarcisio , Bastos Francisco I , Leal Erotildes , Bertoni Neilane , Lipman Lara , Burnett Chantal , Fischer Benedikt 
Published: December 2013

Abstract

Background
Crack use is prevalent across the Americas, and specifically among marginalized urban street drug users in Brazil. Crack users commonly feature multiple physical and mental health problems, while low rates of and distinct barriers to help service use have been observed in these populations. This study examined profiles and determinants of social and health service utilization, and unmet service needs, in a two-city sample of young (18–24 years), marginalized crack users in Brazil.

Methods
N = 160 study participants were recruited by community-based methods from impoverished neighborhoods in the cities of Rio de Janeiro (n = 81) and Salvador (n = 79). A mixed methods protocol was used. Participants’ drug use, health, and social and health service utilization characteristics were assessed by an anonymous interviewer-administered questionnaire completed in a community setting; descriptive statistics on variables of interest were computed. Service needs and barriers were further assessed by way of several focus groups with the study population; narrative data were qualitatively analyzed. The study protocol was approved by institutional ethics review boards; data were collected between November 2010 and June 2011.

Results
The majority of the sample was male, without stable housing, and used other drugs (e.g., alcohol, marijuana). About half the sample reported physical and mental health problems, yet most had not received medical attention for these problems. Only small minorities had utilized locally available social or health services; utilization appeared to be influenced by sex, race and housing characteristics in both sites. Participants cited limited service resources, lack of needs-specific professional skills, bureaucratic barriers and stigma as obstacles to better service access. However, most respondents stated strong interest and need for general social, health and treatment services designed for the study population, for which various key features were emphasized as important.

Conclusions
The study contributes substantive evidence to current discussions about the development and utilization of health and treatment interventions for crack use in Brazil. Based on our data, crack users’ social, service needs are largely unmet; these gaps appear to partly root in systemic barriers of access to existing services, while improved targeted service offers for the target population seem to be needed also.
Lavender (Lavandula stoechas L.) essential oils attenuate hyperglycemia and protect against oxidative stress in alloxan-induced diabetic rats
Authors: Sebai Hichem , Selmi Slimen , Rtibi Kais , Souli Abdelaziz , Gharbi Najoua , Sakly Mohsen 
Published: December 2013

Abstract

Background
The present study described the phytochemical profile of Lavandula stoechas essential oils, collected in the area of Ain-Draham (North-West of Tunisia), as well as their protective effects against alloxan-induced diabetes and oxidative stress in rat.

Methods
Essential oils samples were obtained from the aerial parts of the plant by hydrodistillation and analyzed by GC–MS. Rats were divided into four groups: Healthy Control (HC); Diabetic Control (DC); Healthy + Essential Oils (H + EO) and Diabetic + Essential Oils (D + EO).
Antidiabetic and antioxidant activities were evaluated after subacute intraperitoneally injection of Lavandula stoechas essential oils (50 mg/kg b.w., i.p.) to rats during 15 days.

Results
The principal compounds detected are: D-Fenchone (29.28%), α-pinene (23.18%), Camphor (15.97%), Camphene (7.83%), Eucapur (3.29%), Limonene, (2.71%) Linalool, (2.01%) Endobornyl Acetate (1.03%). The essential oils also contained smaller percentages of Tricyclene, Cymene, Delta-Cadinene, Selina-3,7(11)-diene. Furthermore, we found that Lavandula stoechas essential oils significantly protected against the increase of blood glucose as well as the decrease of antioxidant enzyme activities induced by aloxan treatment. Subacute essential oils treatment induced a decrease of lipoperoxidation as well as an increase of antioxidant enzyme activities.

Conclusions
These findings suggested that lavandula stoechas essential oils protected against diabetes and oxidative stress induced by alloxan treatment. These effects are in partly due to its potent antioxidant properties.
Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in down syndrome
Authors: Jones Meaghan J , Farré Pau , McEwen Lisa M , MacIsaac Julia L , Watt Kim , Neumann Sarah M , Emberly Eldon , Cynader Max S , Virji-Babul Naznin , Kobor Michael S 
Published: December 2013

Abstract

Background
The presence of an extra whole or part of chromosome 21 in people with Down syndrome (DS) is associated with multiple neurological changes, including pathological aging that often meets the criteria for Alzheimer’s Disease (AD). In addition, trisomies have been shown to disrupt normal epigenetic marks across the genome, perhaps in response to changes in gene dosage. We hypothesized that trisomy 21 would result in global epigenetic changes across all participants, and that DS patients with cognitive impairment would show an additional epigenetic signature.

Methods
We therefore examined whole-genome DNA methylation in buccal epithelial cells of 10 adults with DS and 10 controls to determine whether patterns of DNA methylation were correlated with DS and/or cognitive impairment. In addition we examined DNA methylation at the APP gene itself, to see whether there were changes in DNA methylation in this population. Using the Illumina Infinium 450 K Human Methylation Array, we examined more than 485,000 CpG sites distributed across the genome in buccal epithelial cells.

Results
We found 3300 CpGs to be differentially methylated between the groups, including 495 CpGs that overlap with clusters of differentially methylated probes. In addition, we found 5 probes that were correlated with cognitive function including two probes in the TSC2 gene that has previously been associated with Alzheimer’s disease pathology. We found no enrichment on chromosome 21 in either case, and targeted analysis of the APP gene revealed weak evidence for epigenetic impacts related to the AD phenotype.

Conclusions
Overall, our results indicated that both Trisomy 21 and cognitive impairment were associated with distinct patterns of DNA methylation.
Evaluation of six different DNA extraction methods for detection of Mycobacterium tuberculosis by means of PCR-IS6110: preliminary study
Authors: de Almeida Isabela Neves , da Silva Carvalho Wânia , Rossetti Maria Lúcia , Costa Elis Regina Dalla , de Miranda Silvana Spindola 
Published: December 2013

Abstract

Background
Developments in molecular detection and strain differentiation of members of Mycobacterium tuberculosis complex have proved to be useful. The DNA extraction method influences the amplification efficiency, causing interference on the sensitivity and respective inhibitors. The aim of this study was to standardize a simple and fast DNA extraction method, providing DNA amplification by IS6110-PCR effectively free from undue interferences.

Findings
The efficiency of the six different protocols tested in M. tuberculosis cultures has varied from 75% to 92.5%. This preliminary study evaluating the IS6110 PCR sensitivity and specificity was developed in DNA extracted from microscope slides, and achieved 100% of efficiency.

Conclusions
DNA extraction by Chelex + NP-40 method from both, cultures of M. tuberculosis and smear slides, resulted in good quantity of interference free DNA, especially in samples with low concentrations of genetic material; therefore, such technique may be used for the molecular diagnosis of tuberculosis.
Optimizing Ventana chromogenic dual in-situ hybridization for mucinous epithelial ovarian cancer
Authors: Li Xinyun , Chew Sung-Hock , Chay Wen-Yee , Lim-Tan Soo-Kim , Goh Liang-Kee 
Published: December 2013

Abstract

Background
Dual in-situ hybridization (DISH) assay is a relatively new assay for evaluating Human Epidermal Growth Factor Receptor 2 (HER2) genomic amplification. Optimization protocol for the assay is not yet well established, especially for archival tissues. Although there is a recommended nominal protocol, it is not suited for formalin-fixed and paraffin-embedded (FFPE) samples that were archived for long periods.

Findings
In a study on local population of mucinous epithelial ovarian cancer, we developed a series of optimization protocols based on the age of samples to improve success of the DISH assay. A decision workflow was generated to facilitate individualization of further optimization protocols. The optimizations were evaluated on 92 whole tissue sections of FFPE mucinous ovarian tumors dating from 1990 to 2011. Overall, 79 samples were successfully assayed for DISH using the series of optimization protocols. We found samples older than 1 year required further optimization beyond the nominal protocol recommended. Thirteen samples were not further assayed after first DISH assay due to inadequately preserved nuclear morphology with no ISH signals throughout the tissue section.

Conclusion
The study revealed age of samples and storage conditions were major factors in successful DISH assays. Samples that were ten years or less in age, and archived in-house were successfully optimized, whereas older samples, which were also archived off-site, have a higher frequency of unsuccessful optimizations. The study provides practical and important guidelines for the new DISH assay which can facilitate successful HER2 evaluation in ovarian cancers and possibly other cancers as well.