bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study
Authors: Kristinsson Sigurdur Y. , Tang Min , Pfeiffer Ruth M. , Björkholm Magnus , Blimark Cecilie , Mellqvist Ulf-Henrik , Wahlin Anders , Turesson Ingemar , Landgren Ola 
Published: July 2010

AbstractPatients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.
Recipient T lymphocytes modulate the severity of antibody-mediated transfusion-related acute lung injury
Authors: Fung Yoke Lin , Kim Michael , Tabuchi Arata , Aslam Rukhsana , Speck Edwin R. , Chow Leola , Kuebler Wolfgang M. , Freedman John , Semple John W. 
Published: July 2010

AbstractTransfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as one of the leading causes of transfusion-related fatalities. Nonetheless, many details of the immunopathogenesis of TRALI, particularly with respect to recipient factors are unknown. We used a murine model of antibody-mediated TRALI in an attempt to understand the role that recipient lymphocytes might play in TRALI reactions. Intravenous injection of an IgG2a antimurine major histocompatibility complex class I antibody (34-1-2s) into BALB/c mice induced moderate hypothermia and pulmonary granulocyte accumulation but no pulmonary edema nor mortality. In contrast, 34-1-2s injections into mice with severe combined immunodeficiency caused severe hypothermia, severe pulmonary edema, and approximately 40% mortality indicating a critical role for T and B lymphocytes in suppressing TRALI reactions. Adoptive transfer of purified CD8+ T lymphocytes or CD4+ T cells but not CD19+ B cells into the severe combined immunodeficiency mice alleviated the antibody-induced hypothermia, lung damage, and mortality, suggesting that T lymphocytes were responsible for the protective effect. Taken together, these results suggest that recipient T lymphocytes play a significant role in suppressing antibody-mediated TRALI reactions. They identify a potentially new recipient mechanism that controls the severity of TRALI reactions.
Comparative analysis of secreted protein evolution using expressed sequence tags from four poplar leaf rusts (Melampsora spp.)
Authors: Joly David L , Feau Nicolas , Tanguay Philippe , Hamelin Richard C 
Published: July 2010

AbstractBackgroundObligate biotrophs such as rust fungi are believed to establish long-term relationships by modulating plant defenses through a plethora of effector proteins, whose most recognizable feature is the presence of a signal peptide for secretion. Since the phenotypes of these effectors extend to host cells, their genes are expected to be under accelerated evolution stimulated by host-pathogen coevolutionary arms races. Recently, whole genome sequence data has allowed the prediction of secretomes, facilitating the identification of putative effectors.ResultsWe generated cDNA libraries from four poplar leaf rust pathogens (Melampsoraspp.) and used computational approaches to identify and annotate putative secreted proteins with the aim of uncovering new knowledge about the nature and evolution of the rust secretome. While more than half of the predicted secretome members encoded lineage-specific proteins, similarities with experimentally characterized fungal effectors were also identified. A SAGE analysis indicated a strong stage-specific regulation of transcripts encoding secreted proteins. The average sequence identity of putative secreted proteins to their closest orthologs in the wheat stem rustPuccinia graminisf. sp.triticiwas dramatically reduced compared with non-secreted ones. A comparative genomics approach based on homologous gene groups unravelled positive selection in putative members of the secretome.ConclusionWe uncovered robust evidence that different evolutionary constraints are acting on the rust secretome when compared to the rest of the genome. These results are consistent with the view that these genes are more likely to exhibit an effector activity and be involved in coevolutionary arms races with host factors.
Prevalence of Plasmodium vivax VK210 and VK247 subtype in Myanmar
Authors: Kim Tong-Soo , Kim Hyung-Hwan , Lee Sun-Sim , Na Byoung-Kuk , Lin Khin , Cho Shin-Hyeong , Kang Yoon-Joong , Kim Do-Kyung , Sohn Youngjoo , Kim Hyuck , Lee Hyeong-Woo 
Published: July 2010

Abstract

Background

Plasmodium vivax is divided into two subtypes, a dominant form, VK210 and a variant form, VK247. This division is dependent on the amino acid composition of the circumsporozoite (CS) protein. In this study, the prevalence of the VK247 variant form of P. vivax was investigated in Myanmar.

Methods
The existence of malaria parasites in blood samples was determined by microscopic examination, polymerase chain reaction (PCR) and DNA hybridization assays. To test for antibodies against P. vivax and Plasmodium falciparum in blood samples, an indirect immunofluorescence antibody test (IFAT) was performed using asexual blood antigens. An enzyme-linked immunosorbent assay with synthetic VK210 and VK247 antigens was carried out to discriminate between the P. vivax subtypes.

Results
By thick smear examination, 73 (n = 100) patients were single infected with P. vivax, one with P. falciparum and 13 with both species. By thin smear, 53 patients were single infected with P. vivax, eight with only P. falciparum and 16 with both. Most of the collected blood samples were shown to be P. vivax positive (n = 95) by PCR. All cases that were positive for P. falciparum by PCR (n = 43) were also positive for P. vivax. However, 52 cases were single infected with P. vivax. IFAT showed antibody titres from 1:32 to 1:4,096. Additionally, using specific antibodies for VK210 and VK247, ELISA showed that 12 patients had antibodies for only the VK210 subtype, 4 patients had only VK247 subtype antibodies and 21 patients had antibodies for both subtypes. Using a DNA hybridization test, 47 patients were infected with the VK210 type, one patient was infected with VK247 and 23 patients were infected with both subtypes.

Conclusions
The proportion of the VK247 subtype in Myanmar was 43.1% (n = 25) among 58 positive cases by serodiagnosis and 25.6% (n = 24) among 94 positive cases by genetic diagnosis. In both diagnostic methods, the infection status of malaria patients is highly diverse with respect to malaria species, and multiple clonal infections are prevalent in Myanmar. Therefore, the complexity of the infection should be considered carefully when diagnosing malaria in Myanmar.
Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis
Authors: Barros Karina V , Xavier Roberta AN , Abreu Gilclay G , Martinez Carlos AR , Ribeiro Marcelo L , Gambero Alessandra , Carvalho Patrícia O , Nascimento Claudia MO , Silveira Vera LF 
Published: July 2010

Abstract
It was investigated whether dietary polyunsaturated fatty acids (PUFA) could influence colonic injury, tissue DNA damage, cytokines and myeloperoxidase activity (MPO) and plasma corticosterone in DSS-induced colitis rats. Male weaning Wistar rats were fed for 47 days with an AIN-93 diet with control (C), fish (F) or a mixture of fish and soybean oil (SF). The colitis was induced from day 36 until day 42 by 3% DSS in drinking water. On day 48, blood samples were collected for corticosterone determination. The distal colon was excised for histological analysis and to quantify the cytokine (IL-4, IL-10 and INF-γ), MPO and DNA damage. The disease activity index (DAI) was recorded daily during colitis induction. The DAI, MPO, histological analyses showed decreases only in the SF group compared with the C group. IL-10 was increased and DNA damage was reduced in the groups F and SF, and an inverse correlation between these variables was found. There were no differences in corticosterone, IFN-γ and IL-4 levels. Soybean and fish oil mixture may be effective in improving colonic injury and DNA damage, and it could be an important complementary therapy in UC to reduce the use of anti-inflammatory drugs and prevent colorectal cancer.
Modulation of collagen-induced arthritis by adenovirus-mediated intra-articular expression of modified collagen type II
Authors: Tang Bo , Cullins David L , Zhou Jing , Zawaski Janice A , Park Hyelee , Brand David D , Hasty Karen A , Gaber M Waleed , Stuart John M , Kang Andrew H , Myers Linda K 
Published: July 2010

Abstract
Introduction
Rheumatoid arthritis (RA) is a systemic disease manifested by chronic inflammation in multiple articular joints, including the knees and small joints of the hands and feet. We have developed a unique modification to a clinically accepted method for delivering therapies directly to the synovium. Our therapy is based on our previous discovery of an analog peptide (A9) with amino acid substitutions made at positions 260 (I to A), 261 (A to B), and 263 (F to N) that could profoundly suppress immunity to type II collagen (CII) and arthritis in the collagen-induced arthritis model (CIA).

Methods
We engineered an adenoviral vector to contain the CB11 portion of recombinant type II collagen and used PCR to introduce point mutations at three sites within (CII124-402, 260A, 261B, 263D), (rCB11-A9) so that the resulting molecule contained the A9 sequence at the exact site of the wild-type sequence.

Results
We used this construct to target intra-articular tissues of mice and utilized the collagen-induced arthritis model to show that this treatment strategy provided a sustained, local therapy for individual arthritic joints, effective whether given to prevent arthritis or as a treatment. We also developed a novel system for in vivo bioimaging, using the firefly luciferase reporter gene to allow serial bioluminescence imaging to show that luciferase can be detected as late as 18 days post injection into the joint.

Conclusions
Our therapy is unique in that we target synovial cells to ultimately shut down T cell-mediated inflammation. Its effectiveness is based on its ability to transform potential inflammatory T cells and/or bystander T cells into therapeutic (regulatory-like) T cells which secrete interleukin (IL)-4. We believe this approach has potential to effectively suppress RA with minimal side effects.
A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes
Authors: Gornik Ivan , Vujaklija-Brajković Ana , Renar Ivana Pavlić , Gašparović Vladimir 
Published: July 2010

Abstract
Introduction
Critical illness is commonly complicated by hyperglycaemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycaemia, but not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesised that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes.

Methods
Medical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycaemia group (glucose ≥7.8 mmol/l) and normoglycaemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests.

Results
A five-year follow-up was completed for 398 patients in the normoglycaemia group, of which 14 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 193 patients finished follow-up and 33 (17.1%) developed type 2 diabetes. The relative risk for type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2).

Conclusions
Patients with hyperglycaemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated.
Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria
Authors: McCall Matthew B B , Sauerwein Robert W 
Published: July 2010

Abstract
Review underscores the ubiquitous contribution of IFN-δ to immune responses against malaria, evidence for its protective role and critical issues relating to its induction.
Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage parasites has generally been ascribed to humoral responses. A number of recent studies, however, have highlighted the existence of cellular immunity against blood-stage parasites, in particular, the prominence of IFN-γ production. Here, we have undertaken to chart the contribution of this prototypical cellular cytokine to immunity against pre-erythrocytic and blood-stage parasites. We summarize the various antiparasitic effector functions that IFN-γ serves to induce, review an array of data about its protective effects, and scrutinize evidence for any deleterious, immunopathological outcome in malaria patients. We discuss the activation and contribution of different cellular sources of IFN-γ production during malaria infection and its regulation in relation to exposure. We conclude that IFN-γ forms a central mediator of protective immune responses against pre-erythrocytic and blood-stage malaria parasites and identify a number of implications for rational malaria vaccine development.
Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari
Authors: Quevedo-Diaz Marco A , Song Chang , Xiong Yanbao , Chen Haiyan , Wahl Larry M , Radulovic Suzana , Medvedev Andrei E 
Published: July 2010

Abstract
Differential mechanisms between live and heat-killed R. akari in engaging TLR2 and TLR4 to active NF-κB, p38 MAP kinase and induce cytokine expression.
A better understanding of the pathogenesis of rickettsial disease requires elucidation of mechanisms governing host defense during infection. TLRs are primary sensors of microbial pathogens that activate innate immune cells, as well as initiate and orchestrate adaptive immune responses. However, the role of TLRs in rickettsia recognition and cell activation remains poorly understood. In this study, we examined the involvement of TLR2 and TLR4 in recognition of Rickettsia akari, a causative agent of rickettsialpox. Transfection-based complementation of TLR2/4-negative HEK293T cells with human TLR2 or TLR4 coexpressed with CD14 and MD-2 enabled IκB-α degradation, NF-κB reporter activation, and IL-8 expression in response to heat-killed (HK) R. akari. The presence of the R753Q TLR2 or D299G TLR4 polymorphisms significantly impaired the capacities of the respective TLRs to signal HK R. akari-mediated NF-κB reporter activation in HEK293T transfectants. Blocking Ab against TLR2 or TLR4 markedly inhibited TNF-α release from human monocytes stimulated with HK R. akari, and TNF-α secretion elicited by infection with live R. akari was reduced significantly only upon blocking of TLR2 and TLR4. Live and HK R. akari exerted phosphorylation of IRAK1 and p38 MAPK in 293/TLR4/MD-2 or 293/TLR2 stable cell lines, whereas only live bacteria elicited responses in TLR2/4-negative HEK293T cells. These data demonstrate that HK R. akari triggers cell activation via TLR2 or TLR4 and suggest use of additional TLRs and/or NLRs by live R. akari.
Targeted Disruption of Mapk14 (p38MAPKα) in Granulosa Cells and Cumulus Cells Causes Cell-Specific Changes in Gene Expression Profiles that Rescue COC Expansion and Maintain Fertility
Authors: Liu Zhilin , Fan Heng-Yu , Wang Yibin , Richards JoAnne S. 
Published: July 2010

Abstract
MAPK14 (p38MAPKα) is critical for FSH and prostaglandin E (PGE)2 signaling cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in culture, indicating that this kinase might impact follicular development and COC expansion in vivo. Because Mapk14 knockout mice are embryonic lethal, we generated GC specific Mapk14 knockout mice (Mapk14gc−/−) by mating Mapk14fl/fl and Cyp19-Cre mice. Unexpectedly, the Mapk14gc−/− female mice were fertile. Analyses of gene expression patterns showed that amphiregulin (Areg) and epiregulin (Ereg), two key regulators of ovulation and COC expansion, were up-regulated in the GCs but down-regulated in cumulus cells of the mutant mice in vivo. COCs from the mutant mice expanded and expressed matrix-related genes, if cultured with AREG, but not when cultured with forskolin or PGE2, the latter being a key factor regulating MAPK14 activity in cumulus cells. Conversely, when GCs from the Mapk14gc−/− mice were cultured with forskolin, they produced more Areg and Ereg mRNA than did wild-type GCs. These results indicate that disruption of Mapk14 selectively alters the expression of Areg and other genes in each cell type. Greater AREG and EREG produced by the GCs appears to by-pass and compensate for the critical need for MAPK14 signaling and induction of Areg/Ereg (and hence matrix genes) by PGE2 in cumulus cells of the mutant mice. In conclusion, although MAPK14 is not overtly essential for preovulatory follicle development or events associated with ovulation and luteinization in vivo, it does impact gene expression profiles.
Review of the flowability measuring techniques for powder metallurgy industry
Authors: Kulkarni P A , Berry R J , Bradley M S A 
Published: July 2010

The flowability of bulk solids can be treated as one of the fundamental properties that determine their behaviour through industrial processes. Developing a standard meaningful test for measuring flowability has always been a challenge and numerous methods exist, based on the correlation of a number of physical properties such as gravity flowrate, internal strength, bulk density change, etc., which are thought to represent the ability of a powder to flow in some sort of a conceptual situation. Different industries have employed and standardized different techniques for flowability measurement, and the results these obtain may not correlate. The article details an investigation into the ability of various flowability measuring methods to detect small changes in the powder flow properties. Four flowability measuring methods, Hall flow, Hausner ratio, compressibility, and shear cell (manual and automated), were used to measure the flowability of four physically and chemically similar iron blends. Industry standard methods and the shear cell were not able to rank the blends with confidence. Influence of container wall friction is also investigated in the presented work.
Private sector treatment centres are treating less complex patients than the NHS
Authors: Mason Anne , Street Andrew , Verzulli Rossella 
Published: July 2010

Summary Objectives In England, patients can choose to have their NHS elective care delivered by private (or ‘independent sector’) providers or by the NHS. Providers are paid a fixed tariff for each type of procedure. Our objectives were to compare NHS providers with private treatment centres in terms of (a) the quality of data coding and (b) patient complexity. Design We compared elective patients aged 18 years and over treated in the NHS and private sectors using the Hospital Episode Statistics (HES) data for 2007–2008. The absence of diagnostic information was used as a measure of data quality. We analysed differences in complexity for each of the 30 Healthcare Resource Groups (HRGs) that together account for 78% of coded private treatment centre activity. Statistical significance was assessed at the 1% level. Setting Hospitals and treatment centres. Main outcome measures Patient complexity was assessed by four characteristics: age; number of diagnoses; number of procedures; and income deprivation of residential area. Results NHS providers treated almost 7 million adult elective patients in 2007–2008. Fewer than 100,000 patients were treated by private providers (1.3% of elective activity). Less than 1% of NHS patients lacked diagnostic information compared to 36% of patients treated by private providers. For the top 30 HRGs, NHS patients had significantly (p<0.01) higher levels of co-morbidity, underwent more procedures and were more likely to come from deprived areas compared with patients treated by private providers. Although patients treated in private settings tended to be younger, the difference was not statistically significant. Conclusions Some private companies provide poor quality data. In general, the NHS is treating more complex patients than private providers. If complexity drives costs, then a fair reimbursement system would require higher payments for NHS providers.
Laparoscopic splenectomy: a personal series of 140 consecutive cases
Authors: Pattenden Clare J , Mann Christopher D , Metcalfe Matthew S , Dyer Martin , Lloyd David M 
Published: July 2010

Laparoscopic splenectomy has emerged as a safe and effective treatment for a variety of haematological conditions. The objective was to review the results from a large personal series from the perspective of outcomes according to operative time, conversion to open operation, complications and mortality. The application of laparoscopic splenectomy to cases of splenomegaly without hand assistance is examined. A retrospective review of 140 patients undergoing laparoscopic splenectomy at a single university hospital by one surgeon during 1994-2006. Case notes were reviewed and data collected on operative time, conversion to open procedure, morbidity and mortality. Particular reference was made towards the results of cases of splenomegaly. In total 140 laparoscopic splenectomies were performed with a complication rate of 15% and no mortality. The median operative time was 100 min and conversion to open procedure was necessary in 2.1%. Conversion for cases of splenomegaly was only 5.7%. The median hospital stay was 3 days. Laparoscopic splenectomy is a safe procedure with acceptable morbidity. A laparoscopic approach for splenomegaly is feasible.