bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avian influenza A (H9N2): computational molecular analysis and phylogenetic characterization of viral surface proteins isolated between 1997 and 2009 from the human population
Authors: Butt Azeem M , Siddique Samerene , Idrees Muhammad , Tong Yigang 
Published: November 2010

Abstract

Background
H9N2 avian influenza A viruses have become panzootic in Eurasia over the last decade and have caused several human infections in Asia since 1998. To study their evolution and zoonotic potential, we conducted an in silico analysis of H9N2 viruses that have infected humans between 1997 and 2009 and identified potential novel reassortments.

Results
A total of 22 hemagglutinin (HA) and neuraminidase (NA) nucleotide and deduced amino acid sequences were retrieved from the NCBI flu database. It was identified that mature peptide sequences of HA genes isolated from humans in 2009 had glutamine at position 226 (H3) of the receptor binding site, indicating a preference to bind to the human α (2-6) sialic acid receptors, which is different from previously isolated viruses and studies where the presence of leucine at the same position contributes to preference for human receptors and presence of glutamine towards avian receptors. Similarly, strains isolated in 2009 possessed new motif R-S-N-R in spite of typical R-S-S-R at the cleavage site of HA, which isn't reported before for H9N2 cases in humans. Other changes involved loss, addition, and variations in potential glycosylation sites as well as in predicted epitopes. The results of phylogenetic analysis indicated that HA and NA gene segments of H9N2 including those from current and proposed vaccine strains belong to two different Eurasian phylogenetic lineages confirming possible genetic reassortments.

Conclusions
These findings support the continuous evolution of avian H9N2 viruses towards human as host and are in favor of effective surveillance and better characterization studies to address this issue.
Acupuncture for dry eye: a multicentre randomised controlled trial with active comparison intervention (artificial tear drop) using a mixed method approach protocol
Authors: Kim Tae-Hun , Kang Jung Won , Kim Kun Hyung , Kang Kyung-Won , Shin Mi-Suk , Jung So-Young , Kim Ae-Ran , Jung Hee-Jung , Lee Seung-Deok , Choi Jin-Bong , Choi Sun-Mi 
Published: November 2010

Abstract

Background
Previous studies of acupuncture show favourable results for both subjective and objective outcomes of dry eye. However, firm conclusions could not be drawn from these studies because the quality of the trials was too low to establish concrete evidence. Therefore, this study was designed both to avoid the flaws of the existing trials and to assess the effectiveness, cost-effectiveness and qualitative characteristics of acupuncture treatment for dry eye.

Methods/design
One hundred fifty participants with dry eye will be recruited into three independent hospitals from different areas: Korea Institute of Oriental Medicine, DongGuk University Ilsan Oriental Hospital and Dongshin University Gwangju Oriental Hospital. The number of participants required was calculated from the data of a previous, relevant study. These patients will be randomly allocated into acupuncture treatment or artificial tear groups. Either 17 acupuncture points (bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, LI11 and single GV23) will be used 3 times a week or disposable artificial tear drops (Refresh Plus®, ALLERGAN) will be provided for use at least once a day for 4 weeks. The ocular surface disease index (OSDI), tear film break-up time (TFBUT), Schirmer I test, visual analogue scale (VAS) for self-assessment of ocular discomfort, general assessment (by both acupuncture practitioners and participants) and quality of life (QOL) through the Measure Yourself Medical Outcome Profile-2 (MYMOP-2) will be assessed for approximately 3-months for each study participant. In addition, qualitative study and cost-effectiveness of acupuncture treatment will be conducted.

Trial registration
ClinicalTrials.gov (Identifier: NCT01105221).
Whole abdomen radiation therapy in ovarian cancers: a comparison between fixed beam and volumetric arc based intensity modulation
Authors: Mahantshetty Umesh , Jamema Swamidas , Engineer Reena , Deshpande Deepak , Sarin Rajiv , Fogliata Antonella , Nicolini Giorgia , Clivio Alessandro , Vanetti Eugenio , Shrivastava Shyamkishore , Cozzi Luca 
Published: November 2010

Abstract

Purpose
A study was performed to assess dosimetric characteristics of volumetric modulated arcs (RapidArc, RA) and fixed field intensity modulated therapy (IMRT) for Whole Abdomen Radiotherapy (WAR) after ovarian cancer.

Methods and Materials
Plans for IMRT and RA were optimised for 5 patients prescribing 25 Gy to the whole abdomen (PTV_WAR) and 45 Gy to the pelvis and pelvic nodes (PTV_Pelvis) with Simultaneous Integrated Boost (SIB) technique. Plans were investigated for 6 MV (RA6, IMRT6) and 15 MV (RA15, IMRT15) photons. Objectives were: for both PTVs V90% > 95%, for PTV_Pelvis: Dmax < 105%; for organs at risk, maximal sparing was required. The MU and delivery time measured treatment efficiency. Pre-treatment Quality assurance was scored with Gamma Agreement Index (GAI) with 3% and 3 mm thresholds.

Results
IMRT and RapidArc resulted comparable for target coverage. For PTV_WAR, V90% was 99.8 ± 0.2% and 93.4 ± 7.3% for IMRT6 and IMRT15, and 98.4 ± 1.7 and 98.6 ± 0.9% for RA6 and RA15. Target coverage resulted improved for PTV_Pelvis. Dose homogeneity resulted slightly improved by RA (Uniformity was defined as U5-95% = D5%-D95%/Dmean). U5-95% for PTV_WAR was 0.34 ± 0.05 and 0.32 ± 0.06 (IMRT6 and IMRT15), 0.30 ± 0.03 and 0.26 ± 0.04 (RA6 and RA15); for PTV_Pelvis, it resulted equal to 0.1 for all techniques. For organs at risk, small differences were observed between the techniques. MU resulted 3130 ± 221 (IMRT6), 2841 ± 318 (IMRT15), 538 ± 29 (RA6), 635 ± 139 (RA15); the average measured treatment time was 18.0 ± 0.8 and 17.4 ± 2.2 minutes (IMRT6 and IMRT15) and 4.8 ± 0.2 (RA6 and RA15). GAIIMRT6 = 97.3 ± 2.6%, GAIIMRT15 = 94.4 ± 2.1%, GAIRA6 = 98.7 ± 1.0% and GAIRA15 = 95.7 ± 3.7%.

Conclusion
RapidArc showed to be a solution to WAR treatments offering good dosimetric features with significant logistic improvements compared to IMRT.
Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21
Authors: El-Khatib Mona , Geara Fady , Haddadin Makhluf J , Gali-Muhtasib Hala 
Published: November 2010

Abstract

Introduction
We have shown that the radio sensitizer DCQ enhances sensitivity of HCT116 human colon cancer cells to hypoxia. However, it is not known whether the p53 or p21 genes influence cellular response to DCQ. In this study, we used HCT116 that are either wildtype for p53 and p21, null for p53 or null for p21 to understand the role of these genes in DCQ toxicity.

Methods
HCT116 cells were exposed to DCQ and incubated under normoxia or hypoxia and the viability, colony forming ability, DNA damage and apoptotic responses of these cells was determined, in addition to the modulation of HIF-1α and of p53, p21, caspase-2, and of the ataxia telangiectasia mutated (ATM) target PIDD-C.

Results
DCQ decreased colony forming ability and viability of all HCT116 cells to a greater extent under hypoxia than normoxia and the p21-/-cell line was most sensitive. Cells had different HIF-1α responses to hypoxia and/or drug treatment. In p53+/+, DCQ significantly inhibited the hypoxia-induced increases in HIF-1α protein, in contrast to the absence of a significant HIF-1α increase or modulation by DCQ in p21-/- cells. In p53-/- cells, 10 μM DCQ significantly reduced HIF-1α expression, especially under hypoxia, despite the constitutive expression of this protein in control cells. Higher DCQ doses induced PreG1-phase increase and apoptosis, however, lower doses caused mitotic catastrophe. In p53+/+ cells, apoptosis correlated with the increased expression of the pro-apoptotic caspase-2 and inhibition of the pro-survival protein PIDD-C. Exposure of p53+/+ cells to DCQ induced single strand breaks and triggered the activation of the nuclear kinase ATM by phosphorylation at Ser-1981 in all cell cycle phases. On the other hand, no drug toxicity to normal FHs74 Int human intestinal cell line was observed.

Conclusions
Collectively, our findings indicate that DCQ reduces the colony survival of HCT116 and induces apoptosis even in cells that are null for p53 or p21, which makes it a molecule of clinical significance, since many resistant colon tumors harbor mutations in p53.
Optimizing pentose utilization in yeast: the need for novel tools and approaches
Authors: Young Eric , Lee Sun-Mi , Alper Hal 
Published: November 2010

AbstractHexose and pentose cofermentation is regarded as one of the chief obstacles impeding economical conversion of lignocellulosic biomass to biofuels. Over time, successful application of traditional metabolic engineering strategy has produced yeast strains capable of utilizing the pentose sugars (especially xylose and arabinose) as sole carbon sources, yet major difficulties still remain for engineering simultaneous, exogenous sugar metabolism. Beyond catabolic pathways, the focus must shift towards non-traditional aspects of cellular engineering such as host molecular transport capability, catabolite sensing and stress response mechanisms. This review highlights the need for an approach termed 'panmetabolic engineering', a new paradigm for integrating new carbon sources into host metabolic pathways. This approach will concurrently optimize the interdependent processes of transport and metabolism using novel combinatorial techniques and global cellular engineering. As a result, panmetabolic engineering is a whole pathway approach emphasizing better pathways, reduced glucose-induced repression and increased product tolerance. In this paper, recent publications are reviewed in light of this approach and their potential to expand metabolic engineering tools. Collectively, traditional approaches and panmetabolic engineering enable the reprogramming of extant biological complexity and incorporation of exogenous carbon catabolism.
Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes
Authors: Slovak Marilyn L , Smith David D , Bedell Victoria , Hsu Ya-Hsuan , O'Donnell Margaret , Forman Stephen J , Gaal Karl , McDaniel Lisa , Schultz Roger , Ballif Blake C , Shaffer Lisa G 
Published: November 2010

Abstract

Background
Recent genome-wide microarray-based research investigations have revealed a high frequency of submicroscopic copy number alterations (CNAs) in the myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic hybridization (aCGH) has the potential to detect new clinically relevant genomic markers in a diagnostic laboratory.

Results
We performed an exploratory study on 30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid leukemia (AML) (% bone marrow blasts ≤ 30%, range 0-30%, median, 8%) by aCGH, using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample data were compared to corresponding cytogenetics, fluorescence in situ hybridization (FISH), and clinical-pathological findings. Previously unidentified imbalances, in particular those considered submicroscopic aberrations (< 10 Mb), were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new CNAs in 14/30 (47%) patients, including 28 submicroscopic or hidden aberrations verified by FISH studies. Cryptic 344-kb RUNX1 deletions were found in three patients at time of AML transformation. Other hidden CNAs involved 3q26.2/EVI1, 5q22/APC, 5q32/TCERG1,12p13.1/EMP1, 12q21.3/KITLG, and 17q11.2/NF1. Gains of CCND2/12p13.32 were detected in two patients. aCGH failed to detect a balanced translocation (n = 1) and low-level clonality (n = 4) in five karyotypically aberrant samples, revealing clinically important assay limitations.

Conclusions
The detection of previously known and unknown genomic alterations suggests that aCGH has considerable promise for identification of both recurring microscopic and submicroscopic genomic imbalances that contribute to myeloid disease pathogenesis and progression. These findings suggest that development of higher-resolution microarray platforms could improve karyotyping in clinical practice.
New diagnostics for tuberculosis: fulfilling patient needs first
Authors: Lemaire Jean‐François , Casenghi Martina 
Published: November 2010

BackgroundAn effective tuberculosis (TB) control programme requires early diagnosis and immediate initiation of treatment. Any delays in diagnosing TB not only impair a patient's prognosis, but also increase the risks of transmitting the disease within the community. Unfortunately, the most recent TB diagnostic tools still depend on high‐infrastructure laboratories, making them poorly adapted for use in resource‐limited settings. Additionally, existing tests show poor performance in diagnosing TB in children, people living with HIV/AIDS, and extrapulmonary forms of the disease. As a consequence, TB patients are still to date left with either fair access to poor diagnostics or poor access to fair diagnostics.DiscussionThis article discusses recent efforts to identify the minimal test specifications for a new TB point‐of‐care diagnostic test through an approach based on medical and patient needs. As a first step, survey interviews with field practitioners were designed in order to identify the top‐priority medical needs in resource‐limited settings concerning new TB diagnostics. Subsequently, an expert meeting convening field practitioners, laboratory experts, diagnostic test developers and researchers was held with the objective of defining the minimal test specifications for a new TB point‐of‐care test that would meet the identified medical needs. Finally, gaps in, as well as potential solutions for, enabling the development of adequate, patient needs‐driven, low‐cost new TB diagnostic tests specifically designed for vulnerable populations are discussed.SummaryAny new TB point‐of‐care diagnostic test should be designed to meet minimal specifications satisfying the most urgent medical needs in resource‐poor settings. The major gaps for developing a new TB point‐of‐care test include identification of new biomarkers, simplification of technological platforms, development of adequate and accessible specimen banks, and identification and definition of reference standards for diagnosis of childhood TB. Innovative research and development funding ensuring de‐linkage of research and development costs from the price of the new product, such as a prize fund mechanism, could help focus these efforts towards the delivery of a much‐needed point‐of‐care diagnostic test for TB.
Sexual behaviour does not reflect HIV‐1 prevalence differences: a comparison study of Zimbabwe and Tanzania
Authors: Mapingure Munyaradzi P , Msuya Sia , Kurewa Nyaradzai E , Munjoma Marshal W , Sam Noel , Chirenje Mike Z , Rusakaniko Simbarashe , Saugstad Letten F , de Vlas Sake J , Stray‐Pedersen Babill 
Published: November 2010

BackgroundSubstantial heterogeneity in HIV prevalence has been observed within sub‐Saharan Africa. It is not clear which factors can explain these differences. Our aim was to identify risk factors that could explain the large differences in HIV‐1 prevalence among pregnant women in Harare, Zimbabwe, and Moshi, Tanzania.MethodsCross‐sectional data from a two‐centre study that enrolled pregnant women in Harare (N = 691) and Moshi (N = 2654) was used. Consenting women were interviewed about their socio‐demographic background and sexual behaviour, and tested for presence of sexually transmitted infections and reproductive tract infections. Prevalence distribution of risk factors for HIV acquisition and spread were compared between the two areas.ResultsThe prevalence of HIV‐1 among pregnant women was 26% in Zimbabwe and 7% in Tanzania. The HIV prevalence in both countries rises constantly with age up to the 25‐30 year age group. After that, it continues to rise among Zimbabwean women, while it drops for Tanzanian women. Risky sexual behaviour was more prominent among Tanzanians than Zimbabweans. Mobility and such infections as HSV‐2, trichomoniasis and bacterial vaginosis were more prevalent among Zimbabweans than Tanzanians. Reported male partner circumcision rates between the two countries were widely different, but the effect of male circumcision on HIV prevalence was not apparent within the populations.ConclusionsThe higher HIV‐1 prevalence among pregnant women in Zimbabwe compared with Tanzania cannot be explained by differences in risky sexual behaviour: all risk factors tested for in our study were higher for Tanzania than Zimbabwe. Non‐sexual transmission of HIV might have played an important role in variation of HIV prevalence. Male circumcision rates and mobility could contribute to the rate and extent of spread of HIV in the two countries.
Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study
Authors: Karlsson Sari , Heikkinen Milja , Pettilä Ville , Alila Seija , Väisänen Sari , Pulkki Kari , Kolho Elina , Ruokonen Esko ,   the Finnsepsis Study Group
Published: November 2010

Abstract
Introduction
This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care.

Methods
PCT was analyzed from blood samples of all patients at baseline, and 155 patients 72 hours later.

Results
The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later. Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with community-acquired infections were higher than with nosocomial infections (P = 0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe sepsis with positive blood cultures was associated with higher PCT levels than with negative cultures (P = < 0.001). Patients with septic shock had higher PCT concentrations than patients without (P = 0.02). PCT concentrations did not differ between hospital survivors and nonsurvivors (P = 0.64 and P = 0.99, respectively), but mortality was lower in patients whose PCT concentration decreased > 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs. 29.8%, P = 0.007).

Conclusions
PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.
Population-Based Risks of CNS Tumors in Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study
Authors: Taylor Aliki J. , Little Mark P. , Winter David L. , Sugden Elaine , Ellison David W. , Stiller Charles A. , Stovall Marilyn , Frobisher Clare , Lancashire Emma R. , Reulen Raoul C. , Hawkins Michael M. 
Published: November 2010

Purpose CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain. Methods The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken. Results There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and ≥ 40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed. Conclusion The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.
Routine Preventive Care and Cancer Surveillance in Long-Term Survivors of Colorectal Cancer: Results From National Surgical Adjuvant Breast and Bowel Project Protocol LTS-01
Authors: Kunitake Hiroko , Zheng Ping , Yothers Greg , Land Stephanie R. , Fehrenbacher Louis , Giguere Jeffrey K. , Wickerham Lawrence , Ganz Patricia A. , Ko Clifford Y. 
Published: November 2010

Purpose National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol LTS-01 examines routine preventive care and cancer surveillance in long-term colorectal cancer (CRC) survivors previously treated in NSABP adjuvant trials. Patients and Methods Long-term CRC survivors (≥ 5 years) from five completed NSABP trials (Protocols C-05, C-06, C-07, R-02, and R-03) at 60 study sites were recruited and surveyed using preventive health care items from the National Health Interview Survey (NHIS). A 3:1 comparison cohort case-matched by age, sex, race, and education was created from the 2005 NHIS. Contingency tables and multivariate models were used to compare cohorts and determine predictors of preventive care and cancer surveillance. Results A total of 708 patients in protocol LTS-01 (681 patients with colon cancer, 27 patients with rectal cancer) completed the interview: 57.1% male, mean age 66.2 years (standard deviation = 10.6), median survival 8 years. Patients in the LTS-01 protocol were more likely to have a usual source of health care (97.7% v 93.8%, P < .0001), have received a flu shot in the past 12 months (67.5% v 44.3%, P < .0001), and have undergone cancer screening by Pap smear (67.3% v 54.8%, P < .0001), mammogram (80.4% v 70.7%, P < .0001), and prostate-specific antigen test (84.5% v 74.5%, P < .0001) than patients in the NHIS cohort. For CRC surveillance, 96.5% of patients in protocol LTS-01 had a colonoscopy, 88.2% had a carcinoembryonic antigen test, and 66.4% had a computed tomography scan in the previous 5 years. Health insurance was the best predictor of cancer screening for all three methods (odds ratio = 2.6 to 4.5). No factor was uniformly associated with CRC surveillance. Conclusion This select population of long-term CRC survivors who participated in clinical trials achieved better routine preventive care and cancer screening than the general population and high rates of cancer surveillance.