bluuebunny/crossref_metadata_2025_split huggingface dataset:
Summarizing historical information on controls in clinical trials
Authors: Neuenschwander Beat , Capkun-Niggli Gorana , Branson Michael , Spiegelhalter David J 
Published: February 2010

Background Historical information is always relevant when designing clinical trials, but it might also be incorporated in the analysis. It seems appropriate to exploit past information on comparable control groups. Purpose Phase IV and proof-of-concept trials are used to discuss aspects of summarizing historical control data as prior information in a new trial. The importance of a fair assessment of the similarity of control parameters is emphasized. Methods The methodology is meta-analytic-predictive. Heterogeneity of control parameters is expressed via the between-trial variation, which is the key parameter determining the prior effective sample size and its upper bound (prior maximum sample size). Results For a Phase IV trial (930 control patients in 11 historical trials) between-trial heterogeneity was fairly small, resulting in a prior effective sample size of approximately 90 patients. For a proof-of-concept trial (363 patients in four historical trials) heterogeneity was moderate to substantial, resulting in a prior effective sample size of approximately 20. For another proof-of-concept trial (14 patients in one historical trial), assuming substantial heterogeneity implied a prior effective sample size of 7. The prior effective sample size can only be large if the amount of historical data is large and between-trial heterogeneity is small. The prior effective sample size is bounded by the prior maximum sample size (ratio of within- to between-trial variance), irrespective of the amount of historical data. Limitations The meta-analytic-predictive approach assumes exchangeability of control parameters across trials. Due to the difficulty to quantify between-trial variability, sensitivity of conclusions regarding assumptions and type of inference should be assessed. Conclusions The use of historical control information is a valuable option and may lead to more efficient clinical trials. The proposed approach is attractive for nonconfirmatory trials, but under certain circumstances extensions to the confirmatory setting could be envisaged as well. Clinical Trials 2010; 7: 5—18. http://ctj.sagepub.com
Methodological issues in the use of composite endpoints in clinical trials: examples from the HIV field
Authors: Wittkop Linda , Smith Colette , Fox Zoe , Sabin Caroline , Richert Laura , Aboulker Jean-Pierre , Phillips Andrew , Chêne Genevieve , Babiker Abdel , Thiébaut Rodolphe ,   NEAT-WP4
Published: February 2010

Background In many fields, the choice of a primary endpoint for a trial is not always the ultimate clinical endpoint of interest, but rather some surrogate endpoint believed to be relevant for predicting the effect of the intervention on the clinical endpoint. The classic example of such a field is clinical HIV treatment research, where a variety of primary endpoints are used to evaluate the efficacy of new antiretroviral drugs or new combinations of existing drugs. The choice of endpoint reflects either the goal of therapy as recommended by treatment guidelines (e.g. rapid virological suppression) or the licensing requirements of official drug approval organizations (e.g. time to loss of virological response [TLOVR]). Purpose To review the diversity of endpoints used in recent clinical trials in HIV infection and highlight the methodological issues. Methods We identified articles relating to antiretroviral therapy by searching PubMed and through hand searches of relevant conference abstracts. We restricted the search to randomized controlled trials conducted in HIV-infected adults published/presented from January 2005 until March 2008. Results We identified 28 trials in antiretroviral-naive patients (i.e. patients who were starting antiretroviral therapy for the first time at the time of randomization) and 23 trials in antiretroviral-experienced patients. Most trials were performed for purposes of drug licensing, but others were focused on strategies of using approved drugs. Most trials (40 of 51) used a composite primary endpoint (TLOVR in 13). Of note, 22 of these 40 studies reported that they had used a purely virological efficacy endpoint, but the primary endpoint was actually a composite one due to the way in which missing data and treatment switches were considered as failures. Limitations Examples are restricted to HIV clinical trials. Conclusions Whilst most current HIV clinical trials use composite primary endpoints, there are substantial differences in the components that make up these endpoints. In HIV and other fields where precise definitions are variable, guidelines for standardization of definition and reporting would greatly improve the ability to compare trial results. Clinical Trials 2010; 7: 19—35. http:// ctj.sagepub.com
Lineage-specific combinatorial action of enhancers regulates mouse erythroid Gata1 expression
Authors: Drissen Roy , Guyot Boris , Zhang Lin , Atzberger Ann , Sloane-Stanley Jackie , Wood Bill , Porcher Catherine , Vyas Paresh 
Published: February 2010

AbstractPrecise spatiotemporal control of Gata1 expression is required in both early hematopoietic progenitors to determine erythroid/megakaryocyte versus granulocyte/monocyte lineage output and in the subsequent differentiation of erythroid cells and megakaryocytes. An enhancer element upstream of the mouse Gata1 IE (1st exon erythroid) promoter, mHS−3.5, can direct both erythroid and megakaryocytic expression. However, loss of this element ablates only megakaryocytes, implying that an additional element has erythroid specificity. Here, we identify a double DNaseI hypersensitive site, mHS−25/6, as having erythroid but not megakaryocytic activity in primary cells. It binds an activating transcription factor complex in erythroid cells where it also makes physical contact with the Gata1 promoter. Deletion of mHS−25/6 or mHS−3.5 in embryonic stem cells has only a modest effect on in vitro erythroid differentiation, whereas loss of both elements ablates both primitive and definitive erythropoiesis with an almost complete loss of Gata1 expression. Surprisingly, Gata2 expression was also concomitantly low, suggesting a more complex interaction between these 2 factors than currently envisaged. Thus, whereas mHS−3.5 alone is sufficient for megakaryocytic development, mHS−3.5 and mHS−25/6 collectively regulate erythroid Gata1 expression, demonstrating lineage-specific differences in Gata1 cis-element use important for development of these 2 cell types.
CLEC-2 activates Syk through dimerization
Authors: Hughes Craig E. , Pollitt Alice Y. , Mori Jun , Eble Johannes A. , Tomlinson Michael G. , Hartwig John H. , O'Callaghan Christopher A. , Fütterer Klaus , Watson Steve P. 
Published: February 2010

AbstractThe C-type lectin receptor CLEC-2 activates platelets through Src and Syk tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including phospholipase-C γ2. Signaling is initiated through phosphorylation of a single conserved tyrosine located in a YxxL sequence in the CLEC-2 cytosolic tail. The signaling pathway used by CLEC-2 shares many similarities with that used by receptors that have 1 or more copies of an immunoreceptor tyrosine-based activation motif, defined by the sequence Yxx(L/I)x6-12Yxx(L/I), in their cytosolic tails or associated receptor chains. Phosphorylation of the conserved immunoreceptor tyrosine-based activation motif tyrosines promotes Syk binding and activation through binding of the Syk tandem SH2 domains. In this report, we present evidence using peptide pull-down studies, surface plasmon resonance, quantitative Western blotting, tryptophan fluorescence measurements, and competition experiments that Syk activation by CLEC-2 is mediated by the cross-linking through the tandem SH2 domains with a stoichiometry of 2:1. In support of this model, cross-linking and electron microscopy demonstrate that CLEC-2 is present as a dimer in resting platelets and converted to larger complexes on activation. This is a unique mode of activation of Syk by a single YxxL-containing receptor.
Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function
Authors: Chitteti Brahmananda R. , Cheng Ying-Hua , Poteat Bradley , Rodriguez-Rodriguez Sonia , Goebel W. Scott , Carlesso Nadia , Kacena Melissa A. , Srour Edward F. 
Published: February 2010

AbstractHematopoietic stem (HSC) and progenitor (HPC) cell fate is governed by intrinsic and extrinsic parameters. We examined the impact of hematopoietic niche elements on HSC and HPC function by analyzing the combined effect of osteoblasts (OBs) and stromal cells (SCs) on Lineage−Sca-1+CD117+ (LSK) cells. CFU expansion and marrow repopulating potential of cultured Lineage−Sca-1+CD117+ cells were significantly higher in OB compared with SC cultures, thus corroborating the importance of OBs in the competence of the hematopoietic niche. OB-mediated enhancement of HSC and HPC function was reduced in cocultures of OBs and SCs, suggesting that SCs suppressed the OB-mediated hematopoiesis-enhancing activity. Although the suppressive effect of SC was mediated by adipocytes, probably through up-regulation of neuropilin-1, the OB-mediated enhanced hematopoiesis function was elaborated through Notch signaling. Expression of Notch 2, Jagged 1 and 2, Delta 1 and 4, Hes 1 and 5, and Deltex was increased in OB cultures and suppressed in SC and OB/SC cultures. Phenotypic fractionation of OBs did not segregate the hematopoiesis-enhancing activity but demonstrated that this function is common to OBs from different anatomic sites. These data illustrate that OBs promote in vitro maintenance of hematopoietic functions, including repopulating potential by up-regulating Notch-mediated signaling between HSCs and OBs.
STAT3 is constitutively phosphorylated on serine 727 residues, binds DNA, and activates transcription in CLL cells
Authors: Hazan-Halevy Inbal , Harris David , Liu Zhiming , Liu Jie , Li Ping , Chen Xiaomin , Shanker Sreejesh , Ferrajoli Alessandra , Keating Michael J. , Estrov Zeev 
Published: February 2010

AbstractChronic lymphocytic leukemia (CLL) is the most common leukemia in the Western hemisphere, but its pathogenesis is still poorly understood. Constitutive tyrosine phosphorylation (p) of signal transducer and activator of transcription (STAT) 3 occurs in several solid tumors and hematologic malignancies. In CLL, however, STAT3 is constitutively phosphorylated on serine 727, not tyrosine 705, residues. Because the biologic significance of serine pSTAT3 in CLL is not known, we studied peripheral blood cells of 106 patients with CLL and found that, although tyrosine pSTAT3 was inducible, serine pSTAT3 was constitutive in all patients studied, regardless of blood count, disease stage, or treatment status. In addition, we demonstrated that constitutive serine pSTAT3 translocates to the nucleus by the karyopherin-β nucleocytoplasmic system and binds DNA. Dephosphorylation of inducible tyrosine pSTAT3 did not affect STAT3-DNA binding, suggesting that constitutive serine pSTAT3 binds DNA. Furthermore, infection of CLL cells with lentiviral STAT3-small hairpin RNA reduced the expression of several STAT3-regulated survival and proliferation genes and induced apoptosis, suggesting that constitutive serine pSTAT3 initiates transcription in CLL cells. Taken together, our data suggest that constitutive phosphorylation of STAT3 on serine 727 residues is a hallmark of CLL and that STAT3 be considered a therapeutic target in this disease.
In vivo role of leukocyte ADAM17 in the inflammatory and host responses during E. coli-mediated peritonitis
Authors: Long Chunmei , Wang Yue , Herrera Amy H , Horiuchi Keisuke , Walcheck Bruce 
Published: February 2010

Abstract
A novel in vivo role for ADAM17 in modulating inflammation and host resistance against a Gram-negative bacterial infection.
Inflammation is the body's initial response to infection, which is harmful when excessive, as exemplified in sepsis inflammatory syndromes. Ectodomain shedding by the membrane metalloprotease ADAM17 is an emerging regulator of inflammation, as it directs the activity of various inflammatory modulators. At this time, however, little is known about the in vivo function of ADAM17. Here, we show that ADAM17-deficient leukocytes afforded mice a survival benefit following Escherichia coli-mediated peritoneal sepsis, which was associated with a reduction in systemic proinflammatory cytokine levels and bacterial burden. A more rapid yet transitory neutrophil infiltration into the peritoneal cavity of conditional ADAM17 knockout mice was observed when compared with control mice, suggesting a mechanism for their enhanced clearance of bacteria. Preventing the shedding of L-selectin augments neutrophil recruitment, and we show that L-selectin shedding by peritoneal neutrophils in conditional ADAM17 knockout mice was impaired. Moreover, their peritoneal TNF-α levels were markedly lower than control mice following E. coli challenge. These events indicate key molecular processes involved in the altered time course of neutrophil recruitment in conditional ADAM17 knockout mice. Overall, our study provides novel in vivo evidence of the instrumental role of ADAM17 in modulating inflammation and host resistance during Gram-negative bacterial infection.
Synthesis and Structure of Group 10 Metal Complexes with New Tripodal Tetradentate Ligand Bearing One Phosphine and Three Thioether Moieties
Authors: Takeda Nobuhiro , Tanaka Yusuke , Sakakibara Fumiaki , Unno Masafumi 
Published: February 2010

Abstract
A new tripodal tetradentate ligand bearing one phosphine and three thioether moieties, [2-(i-PrS)C6H4]3P (1b), was synthesized by the reaction of [2-(i-PrS)C6H4]Li with PCl3 in good yield. Ligand 1b reacted with NiCl2·6H2O in the presence of NaBF4 to afford a five-coordinate complex, [NiCl(1b)]BF4 (2), with slightly distorted trigonal-bipyramidal geometry. Reaction of 1b with [PdCl2(PhCN)2] gave a five-coordinate complex, [PdCl(1b)]Cl (3a). Anion-exchange reaction of palladium(II) complex 3a with NaBF4 afforded [PdCl(1b)]BF4 (3b) with distorted trigonal-bipyramidal structure. Reaction of 1b with [PtCl2(cod)] resulted in the formation of a four-coordinate square-planar complex, [PtCl2(1b)] (4). The structures of 2, 3b, and 4 in crystalline state were determined by X-ray structural analysis and are described in detail. The structures of 2–4 in solution were also discussed.
Preparation and Reactivity of Vitamin B12–TiO2 Hybrid Catalyst Immobilized on a Glass Plate
Authors: Shimakoshi Hisashi , Abiru Makoto , Kuroiwa Keita , Kimizuka Nobuo , Watanabe Midori , Hisaeda Yoshio 
Published: February 2010

Abstract
The vitamin B12–TiO2 hybrid catalyst was effectively immobilized on a glass plate, and the immobilized catalyst shows an efficient reactivity for various molecular transformations, such as the 1,2-migration of a phenyl group and dechlorination of perchloroethylene during irradiation by UV light.
Chronic Pulmonary Toxicity Study of Indium‐Tin Oxide and Indium Oxide Following Intratracheal Instillations into the Lungs of Hamsters
Authors: Tanaka Akiyo , Hirata Miyuki , Homma Toshiaki , Kiyohara Yutaka 
Published: February 2010

Chronic Pulmonary Toxicity Study of Indium‐Tin Oxide and Indium Oxide Following Intratracheal Instillations into the Lungs of Hamsters: Akiyo Tanaka, et al. Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu UniversityObjectivesThe aim of this study was to clarify the chronic toxicological effects of indium‐tin oxide (ITO) and indium oxide (In2O3) on laboratory animals.MethodsMale Syrian golden hamsters were intratracheally administered 3 mg/kg or 6 mg/kg of ITO particles, or 2.7 mg/kg or 5.4 mg/kg of In2O3 particles, containing 2.2 mg/kg or 4.5 mg/kg of indium, twice a week, for 8 wk. Control hamsters were given vehicle of distilled water only. The hamsters were euthanized serially up to 78 wk after the final instillation and the toxicological effects were determined.ResultsBody weight gain was significantly suppressed in the ITO 6 mg/kg‐treated hamsters compared with the control group, but not in the ITO 3 mg/kg‐treated or In2O3‐treated hamsters. Relative lung weights among all the indium‐treated groups were significantly increased compared to that in the control group throughout the observation period. The serum indium concentration among all the indium‐treated groups gradually increased up to the end of the observation period. Histopathologically, foci of slight to severe pulmonary inflammatory response with diffuse alveolar or bronchiolar cell hyperplasia, expansion of the alveolar spaces and interstitial fibrotic proliferation were present in all the indium‐treated hamsters and the severity of these lesions worsened with the passage of time. Lung benign adenomas were only manifest in 3 out of 15 of the ITO 6 mg/kg‐treated hamsters.ConclusionsThe present results clearly demonstrate that ITO and In 2O3 particles caused chronic pulmonary toxicity when repeated intratracheal instillations were given to hamsters.
Interactive Effects of Job Stress and Body Mass Index on Over‐eating
Authors: Takaki Jiro , Minoura Akira , Irimajiri Hirohiko , Hayama Asako , Hibino Yuri , Kanbara Sakiko , Sakano Noriko , Ogino Keiki 
Published: February 2010

Interactive Effects of Job Stress and Body Mass Index on Over‐eating: Jiro Takaki, et al. Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjectivesRecent prospective evidence drawn from the Whitehall II cohort reported by Kivimäki et al. implies that stressful situations are related to decreased body weight in thin men and increased body weight in obese men, whereas no corresponding interactive effects are observed in women. The mechanism underlying this phenomenon remains unknown, and the purpose of this study was to confirm our hypothesis that the relevant mechanism is behavioral (e.g., over‐eating).MethodsThe subjects of this survey were 607 Japanese workers (response rate: 60.5%) in four organizations. The questionnaire solicited demographic information and included the Bulimia scale of the Eating Disorder Inventory‐EZ to measure tendencies toward overeating as well as the Japanese version of the Effort‐Reward Imbalance Questionnaire (ERIQ). Body mass index (BMI) was calculated on the basis of data obtained during medical check‐ups. We tested for linear and interactive effects with hierarchical regression analyses.ResultsBMI was significantly (p<0.05) associated with over‐eating both univariately and after adjusting for age in both sexes. Significant (p<0.05) interactions showed that ERIQ effort scores and effort‐reward ratios were more positively associated with over‐eating in men with higher BMIs, and ERIQ reward and financial remuneration scores were more negatively associated with over‐eating in men with higher BMIs. No corresponding interactive effects were observed among women.ConclusionsThe results demonstrate that stressful situations are more associated with over‐eating in men with higher BMIs. This might explain, in part, the mechanism underpinning the interactive effects proposed by Kivimäki et al.
Basic Occupational Health Services in Baoan, China
Authors: Chen Yongwen , Chen Jinxi , Sun Yuwei , Liu Yimin , Wu Likang , Wang Ya , Yu Shujiang 
Published: February 2010

Basic Occupational Health Services in Baoan, China: Yongwen Chen, et al. Center for Disease Control and Prevention of Baoan, P.R. ChinaObjectivesThe aim of the study was to develop a model of basic occupational health services (BOHS) in Baoan, which could provide occupational health services (OHS) universally for workers and control occupational hazards.MethodsSteps involved in the BOHS strategy included construction of the BOHS system, capacity building, health training and education, surveillance of workplaces and the health of workers, risk assessment, control and evaluation processes.ResultsThis model provided BOHS to employees universally, especially migrant workers in small‐ and medium‐sized enterprises (SMEs) who had been underserved. It expanded the coverage of OHS and improved their content. The knowledge and recognition rate of occupational diseases, the coverage rates of working places and workers rose significantly after three years development. Furthermore, BOHS were cost‐effective and accepted by both employers and employees.ConclusionsOur experience suggests that a BOHS strategy might be a feasible and effective way of protecting the health of workers confronted with occupational hazards.
Cellulose sulphuric acid as a biodegradable and reusable catalyst for the Knoevenagel condensation
Authors: Shelke Kiran , Sapkal Suryakant , Niralwad Kirti , Shingate Bapurao , Shingare Murlidhar 
Published: February 2010

Abstract
A green, mild and efficient method for Knoevenagel condensation of 3-formylchromone/2-chlroquinoline-3-carbaldehyde with active methylene compounds such as Meldrum’s acid/ethyl cyanoacetate using biosupported cellulose sulphuric acid (CSA) in the solid-state by grinding under solvent-free condition has been developed. This method provides several advantages including environmental friendliness, shor t reaction times, high yields and a simple work-up procedure. Moreover, the CSA was successfully reused for four cycles without significant loss of activity.
Rapid synthesis and biological evaluation of 1,4-dihydropyridine derivatives containing a benzothiazolyl moiety
Authors: Mithlesh  , Pareek Pawan , Kant Ravi , Shukla Sanjeev , Ojha Krishan 
Published: February 2010

Abstract
A series of N-(6-methylbenzothiazolyl)-2,3,5,6-tetrasubstituted-4-(aryl)-1,4-dihydropyridines were synthesized by reaction of 2-amino-6-methylbenzothiazole, aromatic aldehyde and active methylene compound in methanol by conventional, as well as, microwave irradiation (solvent free and solid support) methods. The microwave irradiation technique gives better yield and shorter reaction time. Among solid supported microwave irradiation better yields are obtained in acidic alumina as compared to silica, neutral alumina, and basic alumina. All compounds were tested for antibacterial and antifungal activities and results have been compared with standard drugs. Entomological activities were also tested. The results showed that a change in the substitution pattern in 1,4-dihydropyridine derivatives may cause a marked effect on their antimicrobial activity.
Role of temperature in the numerical analysis of CaO under high pressure
Authors: Bhardwaj Purvee , Singh Sadhna 
Published: February 2010

Abstract
In this paper we focus on the elastic and thermodynamic properties of the B1 phase of CaO by using the modified TBP model, including the role of temperature. We have successfully obtained the phase transition pressure and volume change at different temperatures. In addition elastic constants and bulk modulus of B1 phase of CaO at different temperatures are discussed. Our results are comparable with the previous ones at high temperatures and pressures. The thermodynamical properties of the B1 phase of CaO are also predicted.