bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma
Authors: Groen Richard W. J. , Noort Willy A. , Raymakers Reinier A. , Prins Henk-Jan , Aalders Linda , Hofhuis Frans M. , Moerer Petra , van Velzen Jeroen F. , Bloem Andries C. , van Kessel Berris , Rozemuller Henk , van Binsbergen Ellen , Buijs Arjan , Yuan Huipin , de Bruijn Joost D. , de Weers Michel , Parren Paul W. H. I. , Schuringa Jan Jacob , Lokhorst Henk M. , Mutis Tuna , Martens Anton C. M. 
Published: June 2012

AbstractInteractions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.
Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study
Authors: Messinger Yoav H. , Gaynon Paul S. , Sposto Richard , van der Giessen Jeannette , Eckroth Elena , Malvar Jemily , Bostrom Bruce C. 
Published: June 2012

Abstract
Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by low remission rates and high toxicity, especially in second and subsequent relapses. Our phase 1 study, T2005-003, showed that the combination of bortezomib with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin had acceptable toxicity. We report the phase 2 expansion of this combination in patients with relapsed ALL who failed 2-3 previous regimens. Twenty-two patients with relapsed ALL were treated with bortezomib combined with this regimen; their ages ranged from 1 to 22 years, and they had either B-precursor ALL (n = 20) or T-cell ALL (n = 2). Grade 3 peripheral neuropathy developed in 2 (9%) patients. After 3 patients died from bacterial infections, treatment with vancomycin, levofloxacin, and voriconazole prophylaxis resulted in no further infectious mortality in the last 6 patients. Fourteen patients achieved complete remission (CR), and 2 achieved CR without platelet recovery, for an overall 73% response rate, meeting predefined criteria allowing for early closure. B-precursor patients faired best, with 16 of 20 (80%) CR + CR without platelet recovery, whereas the 2 patients with T-cell ALL did not respond. Thus, this combination of bortezomib with chemotherapy is active in B-precursor ALL, and prophylactic antibiotics may be useful in reducing mortality. Bortezomib merits further evaluation in combination therapy in pediatric B-precursor ALL. This study is registered at http://www.clinicaltrials.gov as NCT00440726.
Multicentre European study for the treatment of advanced emphysema with bronchial valves
Authors: Ninane Vincent , Geltner Christian , Bezzi Michela , Foccoli Pierfranco , Gottlieb Jens , Welte Tobias , Seijo Luis , Zulueta Javier J. , Munavvar Mohammed , Rosell Antoni , Lopez Marta , Jones Paul W. , Coxson Harvey O. , Springmeyer Steven C. , Gonzalez Xavier 
Published: June 2012

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis.Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n=37) or without (n=36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥4-point improvement in St George’s Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography.At 3 months, there were eight (24%) positive responders in the treated groupversusnone (0%) in the control group (p=0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean±sd-7.3±9.0%) to the non-treated lobes (6.7±14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3±16.2; control: -3.6±10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups.Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.
Barriers to an early switch from intravenous to oral antibiotic therapy in hospitalised patients with CAP
Authors: Engel Madelon F. , Postma Douwe F. , Hulscher Marlies E.J.L. , Teding van Berkhout Ferdinand , Emmelot-Vonk Marielle H. , Sankatsing Sanjay , Gaillard Carlo A.J.M. , Bruns Anke H.W. , Hoepelman Andy I.M. , Oosterheert Jan Jelrik 
Published: June 2012

Do physicians apply an early-switch strategy (from intravenous to oral antibiotics) in clinically stable patients hospitalised with community-acquired pneumonia (CAP)? If not, why not?In a multicentre prospective cohort study, adult patients admitted fori.v.CAP treatment were included. On day 3 of antibiotic treatment, clinical stability was assessed and treating resident physicians were interviewed on their switch strategies. Additionally, treating physicians were interviewed to evaluate their knowledge of and adherence to guideline advice.149 (92%) out of 162 patients were included and 97 (91%) out of 107 physicians were interviewed. A switch to oral antibiotics was possible in 68 (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out of 68. Patient factors delaying the switch were high CURB-65 (confusion of new onset, urea >7 mmol·L−1, respiratory rate of ≥30 breaths·min−1, blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg, and age ≥65 yrs) score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians' barriers to an early switch in clinically stable patients included misconceptions (26 (55%) out of 47), practical considerations (13 (28%) out of 47) and organisational factors (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians were not aware of guideline advice.The switch fromi.v.to oral antibiotics is often unnecessarily delayed in patients hospitalised with CAP due to different types of barriers.
Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement
Authors: Dara Masoud , de Colombani Pierpaolo , Petrova-Benedict Roumyana , Centis Rosella , Zellweger Jean-Pierre , Sandgren Andreas , Heldal Einar , Sotgiu Giovanni , Jansen Niesje , Bahtijarevic Rankica , Migliori Giovanni Battista 
Published: June 2012

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants.A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011.Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country.The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support).
Lung cancer risk and solid fuel smoke exposure: a systematic review and meta-analysis
Authors: Kurmi Om Prakash , Arya Pallavi Huma , Lam Kin-Bong Hubert , Sorahan Tom , Ayres Jon G. 
Published: June 2012

The aim of this systematic review was to quantify the impact of biomass fuel and coal use on lung cancer and to explore reasons for heterogeneity in the reported effect sizes.A systematic review of primary studies reporting the relationship between solid fuel use and lung cancer was carried out, based on pre-defined criteria. Studies that dealt with confounding factors were used in the meta-analysis. Fuel types, smoking, country, cancer cell type and sex were considered in sub-group analyses. Publication bias and heterogeneity were estimated.The pooled effect estimate for coal smoke as a lung carcinogen (OR 1.82, 95% CI 1.60–2.06) was greater than that from biomass smoke (OR 1.50, 95% CI 1.17–1.94). The risk of lung cancer from solid fuel use was greater in females (OR 1.81, 95% CI 1.54–2.12) compared to males (OR 1.16, 95% CI 0.79–1.69). The pooled effect estimates were 2.33 (95% CI 1.72–3.17) for adenocarcinoma, 3.58 (1.58–8.12) for squamous cell carcinoma and 1.57 (1.38–1.80) for tumours of unspecified cell type.These findings suggest that in-home burning of both coal and biomass is consistently associated with an increased risk of lung cancer.
Early detection of asthma exacerbations by using action points in self-management plans
Authors: Honkoop Persijn J. , Taylor D. Robin , Smith Andrew D. , Snoeck-Stroband Jiska B. , Sont Jacob K. 
Published: June 2012

Our aim was to validate optimal action points in written action plans for early detection of asthma exacerbations.We analysed daily symptoms and morning peak expiratory flows (PEFs) from two previous studies. Potential action points were based on analysis of symptom scores (standard deviations) percentage of personal best PEF, PEF variability in relation to a run-in period or combinations of these measures. Sensitivity and specificity for predicting exacerbations were obtained for each action point. The numbers needed to treat to prevent one exacerbation and the time interval between reaching action point criteria and the start of the exacerbation were calculated. Based on these parameters, the optimal action points for symptoms, PEF and PEF plus symptoms were determined, and their performance compared with published guidelines’ action points.The optimal action points were, for symptoms, statistical variability (standard deviations) and, for PEF, <70% of personal best. The combination of PEF plus symptoms performed best, with improved specificity and earlier detection. The main benefits associated with using these action points was to reduce false positive rates for detecting exacerbations.Early detection of asthma exacerbations can be improved using a composite action point comprising symptoms and PEF measurements over 1 week.
Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis
Authors: Günther Andreas , Korfei Martina , Mahavadi Poornima , von der Beck Daniel , Ruppert Clemens , Markart Philipp 
Published: June 2012

Idiopathic pulmonary fibrosis (IPF) is a life-threatening condition, with a median survival of <3 yrs. The pathophysiology is not fully understood, but chronic injury of alveolar epithelial type II cells (AECII) is considered key.In IPF, disturbed folding and processing of surfactant proteins and impaired DNA repair may represent underlying reasons for maladaptive endoplasmic reticulum stress responses, increased reactive oxygen species production and/or DNA damage. Excessive AECII apoptosis occurs, leading to permanently perturbed epithelial homeostasis. The role of secondary hits also becomes evident. These may aggravate the disease and result in increased epithelial turnover, exhausting the regenerative capacity of progenitors and disturbing epithelial–mesenchymal interactions. Fibroblast proliferation, transdifferentiation and matrix deposition may be mediated through various mechanisms including epithelial–mesenchymal transition, fibrocyte invasion or expansion of a local fibroblast population.Treatment modalities aiming to attenuate epithelial injury are currently in early pre-clinical development and may reach the clinical arena in only a few years. Meanwhile, novel drugs acting on highly activated fibroblasts such as pirfenidone, an anti-fibrotic drug authorised for IPF in the European Union, or BIBF 1120, a novel triple-kinase inhibitor (blocking vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor) currently under clinical investigation, seem to attenuate the progression of IPF.
Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes
Authors: Cottin Vincent 
Published: June 2012

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic disease, with no effective treatment and a median survival time of 2–5 yrs. The search for effective treatment has involved numerous clinical trials of investigational agents without significant success until 2011, when European approval was given for the first treatment for IPF, pirfenidone. Four key clinical trials supported the efficacy and tolerability of pirfenidone.In recently published results from two phase III randomised, double-blind, placebo-controlled, multinational trials evaluating pirfenidone (studies 004 and 006), patients with mild-to-moderate IPF were screened for eligibility using the following functional criteria: forced vital capacity (FVC) ≥50% predicted; diffusing capacity of the lung for carbon monoxide ≥35%; and 6-min walk test (6MWT) distance ≥150 m.Only study 004 met the primary end-point of change in per cent predicted FVC at week 72 (p<0.001). Pooled analysis of primary end-point data from both studies also showed that pirfenidone significantly reduced the decline in per cent predicted FVC compared to placebo (p<0.005). Evidence of beneficial effects of pirfenidone treatment was also observed with regard to several secondary end-points, including progression-free survival time, categorical FVC change, and mean change from baseline to week 72 in 6MWT distance.Pirfenidone was generally well tolerated, with the most common side-effects being gastrointestinal discomfort and photosensitivity. The pooled study results, coupled with recent data regarding the prognostic significance of changes in FVC and 6MWT, provide further evidence of a clinically meaningful treatment benefit with pirfenidone in patients with IPF.
Primary prevention: exposure reduction, skin exposure and respiratory protection
Authors: Heederik Dick , Henneberger Paul K. , Redlich Carrie A. 
Published: June 2012

Interventions for the primary prevention of occupational asthma have been reported in the medical literature, understanding the effectiveness of these efforts could help future interventions.The aim of our study was to evaluate the existing knowledge regarding the impact of controlling work exposure on the prevention of occupational asthma. We conducted systematic literature searches through April 2010 to examine if control of workplace exposures is effective for primary prevention of sensitisation and occupational asthma.The literature search for primary prevention of occupational asthma yielded 29 studies. Assessment of the available information led to the following conclusions and recommendations concerning primary prevention of occupational asthma. Exposure elimination is the strongest and preferred primary preventive approach to reduce the burden of occupational asthma. If elimination is not possible, exposure reduction is the second best option for primary prevention of occupational asthma.The evidence for the effectiveness of respirators in preventing occupational asthma is limited, and other options higher in the list of controls for occupational exposures, notably eliminating or minimising exposures at the source or in the environment, should be used preferentially. There is strong evidence to recommend not using powdered allergen-rich natural rubber latex gloves. There is weak evidence that suggests workers should minimise skin exposure to asthma-inducing agents.
Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine candidate and its protective efficacy against fowl typhoid in chickens
Authors: Chaudhari Atul A , Jawale Chetan V , Kim Sam Woong , Lee John Hwa 
Published: June 2012

Abstract
In order to develop a novel, safe and immunogenic fowl typhoid (FT) vaccine candidate, a Salmonella Gallinarum ghost with controlled expression of the bacteriophage PhiX174 lysis gene E was constructed using pMMP99 plasmid in this study. The formation of the Salmonella Gallinarum ghost with tunnel formation and loss of cytoplasmic contents was observed by scanning electron microscopy and transmission electron microscopy. No viable cells were detectable 24 h after the induction of gene E expression by an increase in temperature from 37 °C to 42 °C. The safety and protective efficacy of the Salmonella Gallinarum ghost vaccine was tested in chickens that were divided into four groups: group A (non-immunized control), group B (orally immunized), group C (subcutaneously immunized) and group D (intramuscularly immunized). The birds were immunized at day 7 of age. None of the immunized animals showed any adverse reactions such as abnormal behavior, mortality, or signs of FT such as anorexia, depression, or diarrhea. These birds were subsequently challenged with a virulent Salmonella Gallinarum strain at 3 weeks post-immunization (wpi). Significant protection against the virulent challenge was observed in all immunized groups based on mortality and post-mortem lesions compared to the non-immunized control group. In addition, immunization with the Salmonella Gallinarum ghosts induced significantly high systemic IgG response in all immunized groups. Among the groups, orally-vaccinated group B showed significantly higher levels of secreted IgA. A potent antigen-specific lymphocyte activation response along with significantly increased percentages of CD4+ and CD8+ T lymphocytes found in all immunized groups clearly indicate the induction of cellular immune responses. Overall, these findings suggest that the newly constructed Salmonella Gallinarum ghost appears to be a safe, highly immunogenic, and efficient non-living bacterial vaccine candidate that protects against FT.
Interaction of the European genotype porcine reproductive and respiratory syndrome virus (PRRSV) with sialoadhesin (CD169/Siglec-1) inhibits alveolar macrophage phagocytosis
Authors: De Baere Miet I , Van Gorp Hanne , Delputte Peter L , Nauwynck Hans J 
Published: June 2012

AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus that shows a restricted in vivo tropism for subsets of porcine macrophages, with alveolar macrophages being major target cells. The virus is associated with respiratory problems in pigs of all ages and is commonly isolated on farms with porcine respiratory disease complex (PRDC). Due to virus-induced macrophage death early in infection, PRRSV hampers the innate defence against pathogens in the lungs. In addition, the virus might also directly affect the antimicrobial functions of macrophages. This study examined whether interaction of European genotype PRRSV with primary alveolar macrophages (PAM) affects their phagocytic capacity. Inoculation of macrophages with both subtype I PRRSV (LV) and subtype III PRRSV (Lena) showed that the virus inhibits PAM phagocytosis. Similar results were obtained using inactivated PRRSV (LV), showing that initial interaction of the virion with the cell is sufficient to reduce phagocytosis, and that no productive infection is required. When macrophages were incubated with sialoadhesin- (Sn) or CD163-specific antibodies, two entry mediators of the virus, only Sn-specific antibodies downregulated the phagocytic capacity of PAM, indicating that interaction with Sn, but not CD163, mediates the inhibitory effect of PRRSV on phagocytosis. In conclusion, this study shows that European genotype PRRSV inhibits PAM phagocytosis in vitro, through the interaction with its internalization receptor Sn. If similar events occur in vivo, this interaction may be important in the development of PRDC, as often seen in the field.
Expression of Nucleophosmin/NPM1 correlates with migration and invasiveness of colon cancer cells
Authors: Liu Yan , Zhang Fei , Zhang Xiao-fang , Qi Li-sha , Yang Lei , Guo Hua , Zhang Ning 
Published: June 2012

AbstractBackgroundWe aimed to examine the expression level of Nucleophosmin (NPM1) protein in colon cancer tissues and to investigate the potential role of NPM1 in the regulation of cell migration and invasiveness.MethodsImmunohistochemical assay was performed to examine the expression pattern of NPM1 in 31 groups of colonic carcinoma samples, including colon tumors, adjacent normal tissues, and matched metastatic lymph nodes from the same patients. Small interfering RNA technique and exogenous expression of wild type NPM1 methods were used to further verify the function of NPM1.ResultsHigh-expression of NPM1 correlates with lymph node metastasis (P = 0.0003) and poor survival rate of human colon cancer patients (P = 0.017). SiRNA-mediated reduction of NPM1 was also shown to inhibit the migration and invasiveness of metastatic colon cancer HCT116 cell line. In addition, the exogenous expression of NPM1 in HT29 cells, a NPM1 low expression and low invasive colon cancer cell line, enhanced cell migration and invasiveness along with increased cell proliferation.ConclusionsThe current study uncovered the critical role of NPM1 in the regulation of colon cancer cells migration and invasion, and NPM1 may serve as a potential marker for the prognosis of colon cancer patients.