bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of epigallocatechin gallate supplementation in schizophrenia and bipolar disorder: an 8-week, randomized, double-blind, placebo-controlled study
Authors: Loftis Jennifer M. , Wilhelm Clare J. , Huckans Marilyn 
Published: October 2012

Objectives: Strategies that focus on the reduction of oxidative stress and inflammation may have therapeutic benefit for the treatment of schizophrenia. This clinical trial sought to determine, in a double-blind study, whether epigallocatechin gallate (EGCG), a green tea extract, is a useful adjunct to maintenance antipsychotic medication. Methods: Adults with schizophrenia, schizoaffective disorder or bipolar disorder who were maintained on antipsychotic and other psychotropic medications were randomized to supplemental EGCG or placebo. Study participants completed clinical assessments and blood draws to evaluate supplemental treatment effects on psychiatric symptoms and plasma inflammatory markers. Results: A total of 34 participants (17 EGCG, 17 placebo) were randomized and 25 participants (14 EGCG, 11 placebo) completed the study. Both treatment groups showed significant reductions in psychotic, depressive and anxiety symptoms from baseline to end of treatment. However, EGCG did not significantly affect psychiatric symptoms or inflammatory markers, as compared with placebo. Adverse effects were mild and comparable between groups. Conclusion: There was no signal for a therapeutic effect of the green tea extract EGCG on psychiatric symptoms in this placebo-controlled pilot study.
Lenalidomide-mediated enhanced translation of C/EBPα-p30 protein up-regulates expression of the antileukemic microRNA-181a in acute myeloid leukemia
Authors: Hickey Christopher J. , Schwind Sebastian , Radomska Hanna S. , Dorrance Adrienne M. , Santhanam Ramasamy , Mishra Anjali , Wu Yue-Zhong , Alachkar Houda , Maharry Kati , Nicolet Deedra , Mrózek Krzysztof , Walker Alison , Eiring Anna M. , Whitman Susan P. , Becker Heiko , Perrotti Danilo , Wu Lai-Chu , Zhao Xi , Fehniger Todd A. , Vij Ravi , Byrd John C. , Blum William , Lee L. James , Caligiuri Michael A. , Bloomfield Clara D. , Garzon Ramiro , Marcucci Guido 
Published: October 2012

AbstractRecently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBPα transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBPα-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and up-regulates the microRNA expression. Furthermore, we show that lenalidomide, a drug approved for myelodysplastic syndromes and multiple myeloma, enhances translation of the C/EBPα-p30 isoform, resulting in higher miR-181a levels. In xenograft mouse models, ectopic miR-181a expression inhibits tumor growth. Similarly, lenalidomide exhibits antitumorigenic activity paralleled by increased miR-181a expression. This regulatory pathway may explain an increased sensitivity to apoptosis-inducing chemotherapy in subsets of AML patients. Altogether, our data provide a potential explanation for the improved clinical outcomes observed in CEBPA-mutated CN-AML patients, and suggest that lenalidomide treatment enhancing the C/EBPα-p30 protein levels and in turn miR-181a may sensitize AML blasts to chemotherapy.
Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma
Authors: Richter Joshua , Neparidze Natalia , Zhang Lin , Nair Shiny , Monesmith Tamara , Sundaram Ranjini , Miesowicz Fred , Dhodapkar Kavita M. , Dhodapkar Madhav V. 
Published: October 2012

AbstractNatural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of α-galactosylceramide–loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase in serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans (trial registered at clinicaltrials.gov: NCT00698776).
Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the Nagasaki Transplant Group experience
Authors: Itonaga Hidehiro , Tsushima Hideki , Taguchi Jun , Fukushima Takuya , Taniguchi Hiroaki , Sato Shinya , Ando Koji , Sawayama Yasushi , Matsuo Emi , Yamasaki Reishi , Onimaru Yasuyuki , Imanishi Daisuke , Imaizumi Yoshitaka , Yoshida Shinichiro , Hata Tomoko , Moriuchi Yukiyoshi , Uike Naokuni , Miyazaki Yasushi 
Published: October 2012

Abstract
Adult T-cell leukemia/lymphoma (ATL) relapse is a serious therapeutic challenge after allogeneic hematopoietic stem cell transplantation (allo-SCT). In the present study, we retrospectively analyzed 35 patients who experienced progression of or relapsed persistent ATL after a first allo-SCT at 3 institutions in Nagasaki prefecture (Japan) between 1997 and 2010. Twenty-nine patients were treated by the withdrawal of immune suppressants as the initial intervention, which resulted in complete remission (CR) in 2 patients. As the second intervention, 9 patients went on to receive a combination of donor lymphocyte infusion and cytoreductive therapy and CR was achieved in 4 patients. Of 6 patients who had already had their immune suppressants discontinued before the relapse, 3 patients with local recurrence received local cytoreductive therapy as the initial treatment, which resulted in CR for more than 19 months. Donor lymphocyte infusion–induced remissions of ATL were durable, with 3 cases of long-term remission of more than 3 years and, interestingly, the emergence or progression of chronic GVHD was observed in all of these cases. For all 35 patients, overall survival after relapse was 19.3% at 3 years. The results of the present study suggest that induction of a graft-versus-ATL effect may be crucial to obtaining durable remission for ATL patients with relapse or progression after allo-SCT.
Effects of inpatient pulmonary rehabilitation in patients with interstitial lung disease
Authors: Huppmann Patrick , Sczepanski Bernd , Boensch Martina , Winterkamp Sandra , Schönheit-Kenn Ursula , Neurohr Claus , Behr Juergen , Kenn Klaus 
Published: October 2012

Pulmonary rehabilitation is recommended for patients with chronic lung diseases including idiopathic pulmonary fibrosis according to international guidelines. However, data for patients with interstitial lung disease (ILD) are limited. We examined the effect of an inpatient pulmonary rehabilitation on functional status and quality of life in ILD patients.We evaluated 402 consecutive ILD patients who were admitted to a specialised pulmonary rehabilitation centre (1999–2010). All patients performed a standardised pulmonary rehabilitation programme including pulmonary function tests, blood-gas analysis, 6-min walk test (6MWT), dyspnoea rating and health-related quality of life questionnaire (the 36-item short-form health survey; SF-36) on admission and discharge.Mean duration of pulmonary rehabilitation was 30±1 days. 6MWT distance improved by 46±3 m (308±6 mversus354±6 m; p<0.001). Dyspnoea rating did not change. Lung function testing showed marginal improvement of vital capacity (+1±0%; p = 0.002). The SF-36 questionnaire demonstrated an increase in all eight sub-scores as well as in the physical and mental health summary scores (physical 6±1 points, p<0.001; mental health 10±1 points, p<0.001). Moreover, patients with signs of pulmonary hypertension also benefited from pulmonary rehabilitation.In a large cohort of patients with ILD, pulmonary rehabilitation had a positive impact on functional status and quality of life. Considering the limited treatment options in this patient population pulmonary rehabilitation appears to be a valuable adjunct therapy.
Endotoxin levels in homes and classrooms of Dutch school children and respiratory health
Authors: Jacobs José H. , Krop Esmeralda J.M. , de Wind Siegfried , Spithoven Jack , Heederik Dick J.J. 
Published: October 2012

Several studies describe indoor pollutant exposure in homes and to a lesser extent in schools. Population studies that include both environments are sparse. This study aims to assess endotoxin levels in primary schools and homes of children. Endotoxin was also studied in relation to asthma and sensitisation.10 schools with (index) and without (reference) dampness were selected, based on reports and inspections. Cases and controls were selected from 169 homes based on the presence or absence of asthma-like symptoms of children. Classroom and bedroom airborne settled dust was sampled using electrostatic dust fall collectors.Average endotoxin levels in schools ranged from 2178 to 6914 endotoxin units (EU)·m−2per week compared with 462–1285 EU·m−2per week in homes. After mutual adjustment for home and school endotoxin, school endotoxin was positively associated with nonatopic asthma (OR 1.11, 95% CI 0.97–1.27), while no associations with endotoxin were found at home.The high endotoxin levels in schools compared with homes indicate that exposure at school can contribute considerably to environmental endotoxin exposure of children and teachers. Our results also suggest that endotoxin in schools may be associated with nonatopic asthmatic symptoms in pupils, although the results require reproduction because of the modest sample size.
Influence of perfusate temperature on nasal potential difference
Authors: Bronsveld Inez , Vermeulen François , Sands Dorotha , Leal Teresinha , Leonard Anissa , Melotti Paola , Yaakov Yasmin , de Nooijer Roel , De Boeck Kris , Sermet Isabelle , Wilschanski Michael , Middleton Peter G. 
Published: October 2012

Nasal potential difference (NPD) quantifies abnormal ion transport in cystic fibrosis. It has gained acceptance as an outcome measure for the investigation of new therapies.To quantify the effect of solution temperature on NPD, we first examined the effect of switching from room temperature (20–25°C) to warmed (32–37°C) solutions andvice versaduring each perfusion step. Secondly, standard protocols were repeated at both temperatures in the same subjects.Changing solution temperature did not alter NPD during perfusion with Ringer’s solution (<1 mV) (p>0.1). During perfusion with zero chloride solution, changing from room temperature to warmed solutions tended to decrease absolute NPD (i.e.it became less negative) by 0.9 mV (p>0.1); changing from warmed to room temperature increased NPD by 2.1 mV (p<0.05). During isoprenaline perfusion, changing from room temperature to warmed solutions increased NPD by 1.5 mV (p<0.01) and from warmed to room temperature decreased NPD by 1.4 mV (p<0.05).For full protocols at room temperature or warmed in the same subjects, mean values were similar (n = 24). During warmed perfusion, group results for total chloride response had a larger standard deviation. As this increased variability will probably decrease the power of trials, this study suggests that solutions at room temperature should be recommended for the measurement of NPD.
Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country
Authors: Jenkins Helen E. , Plesca Valeriu , Ciobanu Anisoara , Crudu Valeriu , Galusca Irina , Soltan Viorel , Serbulenco Aliona , Zignol Matteo , Dadu Andrei , Dara Masoud , Cohen Ted 
Published: October 2012

Multidrug-resistant tuberculosis (MDR-TB) is a major concern in countries of the former Soviet Union. The reported risk of resistance among tuberculosis (TB) cases in the Republic of Moldova is among the highest in the world. We aimed to produce high-resolution spatial maps of MDR-TB risk and burden in this setting.We analysed national TB surveillance data collected between 2007 and 2010 in Moldova. High drug susceptibility testing coverage and detailed location data permitted identification of subregional areas of higher MDR-TB risk. We investigated whether the distribution of cases with MDR-TB risk factors could explain this observed spatial variation in MDR-TB.3447 MDR-TB cases were notified during this period; 24% of new and 62% of previously treated patients had MDR-TB. Nationally, the estimated annual MDR-TB incidence was 54 cases per 100 000 persons and >1000 cases per 100 000 persons within penitentiaries. We identified substantial geographical variation in MDR-TB burden and hotspots of MDR-TB. Locations with a higher percentage of previously incarcerated TB cases were at greater risk of being MDR-TB hotspots.Spatial analyses revealed striking geographical heterogeneity of MDR-TB. Methods to identify locations of high MDR-TB risk and burden should allow for better resource allocation and more appropriate targeting of studies to understand local mechanisms driving resistance.
Lung clearance index in adult cystic fibrosis patients: the role of convection-dependent lung units
Authors: Verbanck Sylvia , Paiva Manuel , Paeps Erika , Schuermans Daniel , Malfroot Anne , Vincken Walter , Vanderhelst Eef 
Published: October 2012

We investigated the extent of convective ventilation heterogeneity contributing to the observed lung clearance index values in adult cystic fibrosis patients, as the result of two simulated scenarios, either 1) a fixed part of the lungs becoming increasingly less compliant, or 2) an increasingly greater part of the lung being less compliant.In 25 cystic fibrosis patients and 25 matched controls, we computed the lung clearance index and also quantified curvilinearity of the washout concentration curve, where curvilinearity is equal to 0 (linear in semilog plot) reflects homogeneous ventilation and curvilinearity equal to 1 corresponds to the presence of an infinitesimally slowly emptying lung unit.In the cystic fibrosis group (forced expiratory volume in 1 s 27–100% predicted), lung clearance index and curvilinearity average±sdvalues were 10.3±2.3 and 0.57±0.13, respectively, and were significantly different from control values (6.2±0.4 and 0.18±0.07; both p<0.001); lung clearance index and curvilinearity were also correlated (R = 0.67; p<0.001). The average curvilinearity value in the cystic fibrosis group was found to be compatible with a cumulative volume of underventilated lung of 40–50%, depending on the simulation scenario considered.The degree of washout curvilinearity observed here indicates that a major determinant of the abnormal lung clearance index values observed in adult cystic fibrosis patients is ventilation heterogeneity generated between convection-dependent lung units, while the remainder of lung clearance index abnormality with respect to normal controls potentially represents the small airways within these lung zones.
Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes
Authors: Falzon Dennis , Gandhi Neel , Migliori Giovanni B. , Sotgiu Giovanni , Cox Helen S. , Holtz Timothy H. , Hollm-Delgado Maria-Graciela , Keshavjee Salmaan , DeRiemer Kathryn , Centis Rosella , D'Ambrosio Lia , Lange Christoph G. , Bauer Melissa , Menzies Dick 
Published: October 2012

A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome.Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95% CI 57–72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95% CI 45–66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95% CI 36–60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95% CI 27–53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95% CI 1.4–16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95% CI 1.4–26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6–9.0 months duration and the total duration of treatment 20.1–25.0 months.In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success.All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.
The successful experimental induction of necrotic enteritis in chickens by Clostridium perfringens: a critical review
Authors: Shojadoost Bahram , Vince Andrew R , Prescott John F 
Published: October 2012

Abstract
Necrotic enteritis (NE) is one of the most important enteric diseases in poultry and is a high cost to the industry worldwide. It is caused by avian-specific, Necrotic Enteritis Beta toxin (NetB)-producing, strains of Clostridium perfringens that also possess in common other virulence-associated genes. In Europe the disease incidence has increased since the ban on in-feed “growth promoting” antibiotics. Because of this, many recent studies of NE have focused on finding different ways to control the disease, and on understanding its pathogenesis. Frustratingly, reproduction of the disease has proven impossible for some researchers. This review describes and discusses factors known to be important in reproducing the disease experimentally, as well as other considerations in reproducing the disease. The critical bacterial factor is the use of virulent, netB-positive, strains; virulence can be enhanced by using tpeL- positive strains and by the use of young rather than old broth cultures to increase toxin expression. Intestinal damaging factors, notably the use of concurrent or preceding coccidial infection, or administration of coccidial vaccines, combined with netB-positive C. perfringens administration, can also be used to induce NE. Nutritional factors, particularly feeding high percentage of cereals containing non-starch polysaccharides (NSP) (wheat, rye, and barley) enhance disease by increasing digesta viscosity, mucus production and bacterial growth. Animal proteins, especially fish meal, enhance C. perfringens proliferation and toxin production. Other factors are discussed that may affect outcome but for which evidence of their importance is lacking. The review compares the different challenge approaches; depending on the aim of particular studies, the different critical factors can be adjusted to affect the severity of the lesions induced. A standardized scoring system is proposed for international adoption based on gross rather than histopathological lesions; if universally adopted this will allow better comparison between studies done by different researchers. Also a scoring system is provided to assist decisions on humane euthanasia of sick birds.
Euchromatin islands in large heterochromatin domains are enriched for CTCF binding and differentially DNA-methylated regions
Authors: Wen Bo , Wu Hao , Loh Yuin-Han , Briem Eirikur , Daley George Q , Feinberg Andrew P 
Published: October 2012

Abstract

Background
The organization of higher order chromatin is an emerging epigenetic mechanism for understanding development and disease. We and others have previously observed dynamic changes during differentiation and oncogenesis in large heterochromatin domains such as Large Organized Chromatin K (lysine) modifications (LOCKs), of histone H3 lysine-9 dimethylation (H3K9me2) or other repressive histone posttranslational modifications. The microstructure of these regions has not previously been explored.

Results
We analyzed the genome-wide distribution of H3K9me2 in two human pluripotent stem cell lines and three differentiated cells lines. We identified > 2,500 small regions with very low H3K9me2 signals in the body of LOCKs, which were termed as euchromatin islands (EIs). EIs are 6.5-fold enriched for DNase I Hypersensitive Sites and 8-fold enriched for the binding of CTCF, the major organizer of higher-order chromatin. Furthermore, EIs are 2–6 fold enriched for differentially DNA-methylated regions associated with tissue types (T-DMRs), reprogramming (R-DMRs) and cancer (C-DMRs). Gene ontology (GO) analysis suggests that EI-associated genes are functionally related to organ system development, cell adhesion and cell differentiation.

Conclusions
We identify the existence of EIs as a finer layer of epigenomic architecture within large heterochromatin domains. Their enrichment for CTCF sites and DNAse hypersensitive sites, as well as association with DMRs, suggest that EIs play an important role in normal epigenomic architecture and its disruption in disease.