bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for HIV among tuberculosis patients: a cross-sectional study in Sindh, Pakistan
Authors: Hasnain Jamshed , Memon Ghulam Nabi , Memon Ashraf , Channa Abid Ali , Creswell Jacob , Shah Sharaf Ali 
Published: October 2012

ObjectiveTo describe feasibility and results of systematic screening of tuberculosis (TB) patients for HIV.DesignCross-sectional study.SettingSix selected sentinel sites (public DOTS clinics) in the province of Sindh, Pakistan.ParticipantsAll TB patients aged 16–60 years registered for treatment from April 2008 to March 2012.MeasurementDemographic information of registered TB patients, screening for HIV through rapid testing and confirmation by referral lab of Sindh AIDS Control Program, according to national guidelines.ResultsOf a total of 18 461 registered TB patients, 12 882 fulfilled the inclusion criteria and were given education and counselling. Of those counselled 12 552 (97.4%) were screened for HIV using a rapid test. Men made up 48% of the sample and 76.5% of patients had pulmonary TB. Of the total patients tested, 42 (0.34%) were HIV-positive after confirmatory testing at the Sindh AIDS Control Program Laboratory. Prevalence of HIV among male patients was 0.67% whereas prevalence among female patients was 0.03% (p value <0.001). Prevalence of HIV among pulmonary TB patients was 0.29% and among extrapulmonary TB patients was 0.48% (p value=0.09).ConclusionIn public DOTS clinics in Pakistan it is feasible to test TB patients for HIV. Prevalence of HIV is three times higher among TB patients as compared with the general population in Pakistan. Although the results are not representative of Pakistan or Sindh province they cover a large catchment area and closely match WHO estimate for the country. Routinely screening all TB patients for HIV infection, especially targeting men and ensuring antiretroviral therapy, can significantly improve TB/HIV collaborative activities in Pakistan and identify many cases of HIV, improve health outcomes and save lives.
Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression
Authors: Chen Paul Chih-Hsueh , Yu Hui-Jung , Chang Yen-Hwa , Pan Chin-Chen 
Published: October 2012

BackgroundSeveral studies have employed immunohistochemistry to detect Her2/neuoverexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder cancer (NMIBC) using fluorescence in situ hybridisation (FISH).AimTo evaluate Her2 amplification in NMIBC (Ta/T1), to correlate the findings with recurrence and progression, and compare the Her2 status between primary and progressive tumours.MethodsFISH and immunohistochemistry for Her2/neuwere performed on tissue arrays consisting of 36 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 190 low grade urothelial carcinomas (LG-UCs) and 178 high grade urothelial carcinomas (HG-UCs). 32 cases with specimens of both primary and progressive tumours (from Ta/T1 to T2–4) were included for comparative analyses.Results16 HG-UCs (9.0%) showed Her2 gene amplification while none of the PUNLMPs and LG-UCs showed this aberration. There was 100% concordance in the status of Her2 amplification between primary and progressive lesions. Immunohistochemistry and FISH results were in closest agreement when overexpression was defined as 50% of tumour cells showing immunoreactivity. The cumulative incidences of recurrence and progression in Her2-amplified HG-UC were significantly higher than in those without amplification.ConclusionsA subset of high-grade NMIBCs contain Her2 amplification and are associated with markedly aggressive behaviour. Her2 diagnostics are valuable for distinguishing patients who require diligent surveillance and would potentially benefit from anti-Her2 therapies.
CD24: a potential new marker in differentiating malignant mesothelioma from pulmonary adenocarcinoma
Authors: Pinato David J , Nya Paul , Sharma Rohini , Mauri Francesco A 
Published: October 2012

BackgroundThe differential diagnosis between malignant mesothelioma (MM) and metastatic lung adenocarcinoma (MLA) often relies on immunohistochemical studies, with no individual immunomarker holding satisfactory discrimination ability.MethodsWe investigated the diagnostic accuracy of CD24 immunoreactivity on 134 patients including 69 cases of MM and 65 MLA.ResultsThe expression of CD24 favoured MLA, with 57/65 cases showing positive cytoplasmic staining compared with 9/69 MM (p<0.001), whose immunopositivity pattern was prevalently membranous (7/9 cases).ConclusionsCD24 positivity can accurately discriminate MM from MLA. Prospective studies are warranted to clarify whether CD24 could integrate with other immunomarkers to facilitate the diagnosis of mesothelial malignancies.
Better retrieval of lymph nodes in colorectal resection specimens by pathologists’ assistants
Authors: Kuijpers C C H J , van Slooten H J , Schreurs W H , Moormann G R H M , Abtahi M A , Slappendel A , Cliteur V , van Diest P J , Jiwa N M 
Published: October 2012

BackgroundErrors in surgical pathology are partly due to the increasing workload of pathologists. To reduce this workload, ‘pathologists’ assistants’ (PAs) have been trained to take over some of the pathologists’ recurrent tasks. One of these tasks is the precise examination of ≥10 lymph nodes (LNs), which is of paramount importance to reduce the risk of understaging of colorectal cancer patients.AimsTo evaluate the role of PAs in harvesting LNs in colorectal resection specimens and, by doing so, in improving patient safety.MethodsLN harvest was retrospectively reviewed in 557 pathology reports on colorectal resection specimens collected in two Dutch hospitals from 2008 until 2011.ResultsPAs sampled ≥10 LNs in significantly more cases than pathologists did (83.2% vs 60.9% in hospital A and 79.2% vs 67.6% in hospital B) and recovered on average significantly more LNs than pathologists did (18.5 vs 12.2 in hospital A and 16.6 vs 13.2 in hospital B). PAs harvested a significantly higher percentage of LNs <5 mm than pathologists did (64.2% vs 53.7%). The percentages of colon cancer patients eligible for adjuvant chemotherapy due to inadequate LN sampling alone were significantly higher for cases dissected by pathologists than for those dissected by PAs (17.3% vs 1.1% in hospital A and 13.1% vs 3.4% in hospital B)ConclusionsPAs contribute to patient safety since they recover more and, in particular, smaller LNs from colorectal resection specimens than pathologists do. Moreover, they help to reduce costs and morbidity by reducing the number of patients eligible for adjuvant chemotherapy due to inadequate LN sampling alone.
Do state breastfeeding laws in the USA promote breast feeding?
Authors: Hawkins Summer Sherburne , Stern Ariel Dora , Gillman Matthew W 
Published: October 2012

ObjectivesDespite the passage of state laws promoting breast feeding, a formal evaluation has not yet been conducted to test whether and/or what type of laws may increase breast feeding. The enactment of breastfeeding laws in different states in the USA creates a natural experiment. We examined the impact of state breastfeeding laws on breastfeeding initiation and duration as well as on disparities in these infant feeding practices.MethodsUsing data from the Pregnancy Risk Assessment Monitoring System, we conducted differences-in-differences models to examine breastfeeding status before and after the institution of laws between 2000 and 2008 among 326 263 mothers from 32 states in the USA. For each mother, we coded the presence of two types of state breastfeeding laws. Mothers reported whether they ever breast fed or pumped breast milk (breastfeeding initiation) and, if so, how long they continued. We defined breastfeeding duration as continuing to breast feed for ≥4 weeks.ResultsBreastfeeding initiation was 1.7 percentage points higher in states with new laws to provide break time and private space for breastfeeding employees (p=0.01), particularly among Hispanic mothers (adjusted coefficient 0.058). While there was no overall effect of laws permitting mothers to breast feed in any location, among Black mothers we observed increases in breastfeeding initiation (adjusted coefficient 0.056). Effects on breastfeeding duration were in the same direction, but slightly weaker.ConclusionsState laws that support breast feeding appear to increase breastfeeding rates. Most of these gains were observed among Hispanic and Black women and women of lower educational attainment suggesting that such state laws may help reduce disparities in breast feeding.
Pain assessment in neonates and infants in the post-operative period following cardiac surgery
Authors: Cury Mariana R J , Martinez Francisco E , Carlotti Ana P C P 
Published: October 2012

Abstract

Purpose
We aimed to test the convergent validity of the COMFORT scale and the Cardiac Analgesic Assessment Scale (CAAS) and to evaluate changes in physiological parameters over time in response to a painful procedure in neonates and infants following cardiac surgery.

Methods
From October 2006 to May 2008, 16 children were prospectively evaluated over 1–3 days after cardiac surgery while they remained on mechanical ventilation and received infusions of sedatives and analgesics. Pain was assessed by the COMFORT scale and CAAS before and during endotracheal tube suctioning. Heart rate, systemic systolic blood pressure, pulmonary artery pressure, oxygen saturation and pupil size were recorded at the same times.

Results
During endotracheal suctioning on the first day, there was a significant increase in COMFORT and CAAS scores, systemic systolic blood pressure tended to decrease, pulmonary artery pressure significantly increased and there was a significant reduction in oxygen saturation. Heart rate and pupil size did not change significantly during the painful procedure throughout the study. COMFORT scores significantly correlated with CAAS scores on all days. Nevertheless, agreement for the detection of pain between both scales was weak (κ&lt;0.5). The COMFORT scale detected more patients with pain.

Conclusions
There was poor agreement between the COMFORT scale and CAAS for detection of pain in neonates and infants who had undergone cardiac surgery. A reduction in systemic systolic blood pressure and a rise in pulmonary artery pressure were observed during painful stimulation on the first post-operative day. For this population, a pain scale scoring physiological parameters according to their variation to higher and lower values should be developed.
A COMPARATIVE STUDY FOR TWO-DAMAGE MODELLING MODELS USING COMPOSITE MATERIAL
Authors: CHEBBI EL. , JARRAYA A. , DAMMAK F. 
Published: October 2012

Purpose- This paper describes finite element fatigue damage modeling. Design/Methodology/Approach- Fatigue life prediction and damage progressive evaluation are analytically studied. We present a numerical implementation of the studied models into the home made finite element code MPEF. Numerical simulations are performed on composite and metallic material. We carried out a parametric study to investigate the influence of model's parameters on the damage accumulation and their sensitivity on its kinetics. Simulations are conducted for two different loading levels to characterize cumulative damage and to study loading sequence effect. A comparative study is performed to characterize the efficiency of the two models to describe the damage evolution for the two different materials. Findings- Numerical examples are presented to illustrate its performance. Originality/value- This paper intends to present a comparative study of the damage evolution for metallic and composite material under uniaxial loading. The effect of the loading sequence will be investigated.
Targeting CD4+ T-Helper Cells Improves the Induction of Antitumor Responses in Dendritic Cell–Based Vaccination
Authors: Aarntzen Erik H.J.G. , De Vries I. Jolanda M. , Lesterhuis W. Joost , Schuurhuis Danita , Jacobs Joannes F.M. , Bol Kalijn , Schreibelt Gerty , Mus Roel , De Wilt Johannes H.W. , Haanen John B.A.G. , Schadendorf Dirk , Croockewit Alexandra , Blokx Willeke A.M. , Van Rossum Michelle M. , Kwok William W. , Adema Gosse J. , Punt Cornelis J.A. , Figdor Carl G. 
Published: October 2012

Abstract
To evaluate the relevance of directing antigen-specific CD4+ T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)–restricted epitopes alone or both MHC class I and II (MHC-I/II)–restricted epitopes. We enrolled 33 stage III and IV HLA-A*02:01–positive patients with melanoma in this study, of whom 29 were evaluable for immunologic response. Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II–restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status. In 4 of 15 patients vaccinated with MHC-I/II–loaded DCs and 1 of 14 patients vaccinated with MHC-I–loaded DCs, we detected TAA-specific CD8+ T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8+ T cells. If TAA-specific CD4+ T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8+ T-cell responses. In 3 of 13 patients tested, we detected TAA-specific CD4+CD25+FoxP3− T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells. Vaccination with MHC-I/II–loaded DCs resulted in improved clinical outcome compared with matched control patients treated with dacarbazine (DTIC), median overall survival of 15.0 versus 8.3 months (P = 0.089), and median progression-free survival of 5.0 versus 2.8 months (P = 0.0089). In conclusion, coactivating TAA-specific CD4+ T-helper cells with DCs pulsed with both MHC class I and II–restricted epitopes augments TAA-specific CD8+ T-cell responses, contributing to improved clinical responses. Cancer Res; 73(1); 19–29. ©2012 AACR.
Loss of PPP2R2A Inhibits Homologous Recombination DNA Repair and Predicts Tumor Sensitivity to PARP Inhibition
Authors: Kalev Peter , Simicek Michal , Vazquez Iria , Munck Sebastian , Chen Liping , Soin Thomas , Danda Natasha , Chen Wen , Sablina Anna 
Published: October 2012

Abstract
Reversible phosphorylation plays a critical role in DNA repair. Here, we report the results of a loss-of-function screen that identifies the PP2A heterotrimeric serine/threonine phosphatases PPP2R2A, PPP2R2D, PPP2R5A, and PPP2R3C in double-strand break (DSB) repair. In particular, we found that PPP2R2A-containing complexes directly dephosphorylated ATM at S367, S1893, and S1981 to regulate its retention at DSB sites. Increased ATM phosphorylation triggered by PPP2R2A attenuation dramatically upregulated the activity of the downstream effector kinase CHK2, resulting in G1 to S-phase cell-cycle arrest and downregulation of BRCA1 and RAD51. In tumor cells, blocking PPP2R2A thereby impaired the high-fidelity homologous recombination repair pathway and sensitized cells to small-molecule inhibitors of PARP. We found that PPP2R2A was commonly downregulated in non–small cell lung carcinomas, suggesting that PPP2R2A status may serve as a marker to predict therapeutic efficacy to PARP inhibition. In summary, our results deepen understanding of the role of PP2A family phosphatases in DNA repair and suggest PPP2R2A as a marker for PARP inhibitor responses in clinic. Cancer Res; 72(24); 6414–24. ©2012 AACR.
Kinase Pathway Dependence in Primary Human Leukemias Determined by Rapid Inhibitor Screening
Authors: Tyner Jeffrey W. , Yang Wayne F. , Bankhead Armand , Fan Guang , Fletcher Luke B. , Bryant Jade , Glover Jason M. , Chang Bill H. , Spurgeon Stephen E. , Fleming William H. , Kovacsovics Tibor , Gotlib Jason R. , Oh Stephen T. , Deininger Michael W. , Zwaan Christian Michel , Den Boer Monique L. , van den Heuvel-Eibrink Marry M. , O'Hare Thomas , Druker Brian J. , Loriaux Marc M. 
Published: October 2012

Abstract
Kinases are dysregulated in most cancers, but the frequency of specific kinase mutations is low, indicating a complex etiology in kinase dysregulation. Here, we report a strategy to rapidly identify functionally important kinase targets, irrespective of the etiology of kinase pathway dysregulation, ultimately enabling a correlation of patient genetic profiles to clinically effective kinase inhibitors. Our methodology assessed the sensitivity of primary leukemia patient samples to a panel of 66 small-molecule kinase inhibitors over 3 days. Screening of 151 leukemia patient samples revealed a wide diversity of drug sensitivities, with 70% of the clinical specimens exhibiting hypersensitivity to one or more drugs. From this data set, we developed an algorithm to predict kinase pathway dependence based on analysis of inhibitor sensitivity patterns. Applying this algorithm correctly identified pathway dependence in proof-of-principle specimens with known oncogenes, including a rare FLT3 mutation outside regions covered by standard molecular diagnostic tests. Interrogation of all 151 patient specimens with this algorithm identified a diversity of kinase targets and signaling pathways that could aid prioritization of deep sequencing data sets, permitting a cumulative analysis to understand kinase pathway dependence within leukemia subsets. In a proof-of-principle case, we showed that in vitro drug sensitivity could predict both a clinical response and the development of drug resistance. Taken together, our results suggested that drug target scores derived from a comprehensive kinase inhibitor panel could predict pathway dependence in cancer cells while simultaneously identifying potential therapeutic options. Cancer Res; 73(1); 285–96. ©2012 AACR.
Development of Gene Expression–Based Score to Predict Sensitivity of Multiple Myeloma Cells to DNA Methylation Inhibitors
Authors: Moreaux Jérôme , Rème Thierry , Leonard Wim , Veyrune Jean-Luc , Requirand Guilhem , Goldschmidt Hartmut , Hose Dirk , Klein Bernard 
Published: October 2012

AbstractMultiple myeloma is a plasma cell cancer with poor survival, characterized by the clonal expansion of multiple myeloma cells (MMC), primarily in the bone marrow. Novel compounds are currently tested in this disease, but partial or minor patients' responses are observed for most compounds used as a single agent. The design of predictors for drug efficacy could be most useful to better understand basic mechanisms targeted by these drugs and design clinical trials. In the current study, we report the building of a DNA methylation score (DM score) predicting the efficacy of decitabine, an inhibitor of DNA methyltransferase (DNMT), targeting methylation-regulated gene expression. DM score was built by identifying 47 genes regulated by decitabine in human myeloma cell lines and the expression of which in primary MMCs of previously untreated patients is predictive for overall survival. A high DM score predicts patients' poor survival, and, of major interest, high sensitivity of primary MMCs or human myeloma cell lines to decitabine in vitro. Thus, DM score could be useful to design novel treatments with DMNT inhibitor in multiple myeloma and has highlighted 47 genes, the gene products of which could be important for multiple myeloma disease development. Mol Cancer Ther; 11(12); 2685–92. ©2012 AACR.
The Novel miR-7515 Decreases the Proliferation and Migration of Human Lung Cancer Cells by Targeting c-Met
Authors: Lee Ji Min , Yoo Jung Ki , Yoo Hanna , Jung Ho Yong , Lee Dong Ryul , Jeong Hye Cheol , Oh Seoung Hun , Chung Hyung Min , Kim Jin Kyeoung 
Published: October 2012

Abstract
MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression in human diseases, including lung cancer. miRNAs have oncogenic and nononcogenic functions in lung cancer. In this study, we report the identification of a novel miRNA, miR-7515, from lung cancer cells. The novel miR-7515 was characterized using various predictive programs and experimental methods. miR-7515 was able to forming a stem-loop structure and its sequence was conserved in mammals. The expression level of miR-7515 in lung cancer cells and tissues was profiled using TaqMan miRNA assays. miR-7515 was downregulated in lung cancer compared with normal human lung cells and tissues. The target of miR-7515 was determined using a dual luciferase reporter assay. Expression of the target gene was determined by quantitative RT-PCR and Western blot analysis after transfection with miR-7515. miR-7515 directly suppressed human mesenchymal–epithelial transition factor (c-Met) by binding to the 3′ untranslated region (UTR). Overexpression of miR-7515 significantly decreased cell-cycle–related proteins downstream of c-Met through c-Met inhibition. Cell proliferation and migration were examined using the XTT proliferation assay and the Transwell migration assay. miR-7515 led to decreased cell proliferation, migration and invasion in a lung cancer cell line. These results suggest that miR-7515 plays an important role in the proliferation and migration of lung cancer cells through c-Met regulation. Mol Cancer Res; 11(1); 43–53. ©2012 AACR.
Characterizing the Molecular Spatial and Temporal Field of Injury in Early-Stage Smoker Non–Small Cell Lung Cancer Patients after Definitive Surgery by Expression Profiling
Authors: Kadara Humam , Shen Li , Fujimoto Junya , Saintigny Pierre , Chow Chi-Wan , Lang Wenhua , Chu Zuoming , Garcia Melinda , Kabbout Mohamed , Fan You-Hong , Behrens Carmen , Liu Diane A. , Mao Li , Lee J. Jack , Gold Kathryn A. , Wang Jing , Coombes Kevin R. , Kim Edward S. , Hong Waun Ki , Wistuba Ignacio I. 
Published: October 2012

Abstract
Gene expression alterations in response to cigarette smoke have been characterized in normal-appearing bronchial epithelium of healthy smokers, and it has been suggested that adjacent histologically normal tissue displays tumor-associated molecular abnormalities. We sought to delineate the spatial and temporal molecular lung field of injury in smoker patients with early-stage non–small cell lung cancer (NSCLC; n = 19) who were accrued into a surveillance clinical trial for annual follow-up and bronchoscopies within 1 year after definitive surgery. Bronchial brushings and biopsies were obtained from six different sites in the lung at the time of inclusion in the study and at 12, 24, and 36 months after the first time point. Affymetrix Human Gene 1.0 ST arrays were used for whole-transcript expression profiling of airways (n = 391). Microarray analysis identified gene features (n = 1,165) that were nonuniform by site and differentially expressed between airways adjacent to tumors relative to more distant samples as well as those (n = 1,395) that were significantly altered with time up to 3 years. In addition, gene interaction networks mediated by phosphoinositide 3-kinase (PI3K) and extracellular signal–regulated kinase (ERK)1/2 were modulated in adjacent compared with contralateral airways and the latter network with time. Furthermore, phosphorylated AKT and ERK1/2 immunohistochemical expression were significantly increased with time (nuclear pAKT, P = 0.03; cytoplasmic pAKT, P &lt; 0.0001; pERK1/2, P = 0.02) and elevated in adjacent compared with more distant airways (nuclear pAKT, P = 0.04; pERK1/2, P = 0.03). This study highlights spatial and temporal cancer–associated expression alterations in the molecular field of injury of patients with early-stage NSCLCs after definitive surgery that warrant further validation in independent studies. Cancer Prev Res; 6(1); 8–17. ©2012 AACR.