bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ‘endless struggle’: a qualitative study of general practitioners’ and practice nurses’ experiences of managing multimorbidity in socio-economically deprived areas of Scotland
Authors: O'Brien Rosaleen , Wyke Sally , Guthrie Bruce , Watt Graham , Mercer Stewart 
Published: October 2010

Objectives: To understand general practitioners’ (GPs) and practice nurses’ (PNs) experiences of managing multimorbidity in deprived areas and elicit views on what might help. Methods: Qualitative interviews with 19 GPs and PNs in four practices with a high percentage of patients living in the top 15% most deprived areas of Scotland. Data were analysed using constant comparison. Results: Professionals’ discussions of how they managed multimorbidity captured: (1) definitions of multimorbidity that included multiple social, psychological, and health problems associated with deprivation; (2) descriptions of the ‘endless struggle’ of patients trying to manage illnesses in the midst of chaotic lives with limited personal, social, and material resources; (3) accounts of the ongoing struggle of professionals trying to manage, with personal consequences for some; and (4) ideas on what might help, including ‘whole person’ approaches. Discussion: Professionals’ discussions of the difficulties that they face personally and attempt to help those most in need reflect both the continuing existence of the ‘inverse care law’ and the need for whole system changes to enhance the effectiveness of primary care for patients with multimorbidity in deprived areas.
Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells
Authors: Mahdipour Elahe , Charnock Jayne C. , Mace Kimberly A. 
Published: October 2010

Abstract
Injury induces the recruitment of bone marrow-derived cells (BMDCs) that contribute to the repair and regeneration process. The behavior of BMDCs in injured tissue has a profound effect on repair, but the regulation of BMDC behavior is poorly understood. Aberrant recruitment/retention of these cells in wounds of diabetic patients and animal models is associated with chronic inflammation and impaired healing. BMD Gr-1+CD11b+ cells function as immune suppressor cells and contribute significantly to tumor-induced neovascularization. Here we report that Gr-1+CD11b+ cells also contribute to injury-induced neovascularization, but show altered recruitment/retention kinetics in the diabetic environment. Moreover, diabetic-derived Gr-1+CD11b+ cells fail to stimulate neovascularization in vivo and have aberrant proliferative, chemotaxis, adhesion, and differentiation potential. Previously we demonstrated that gene transfer of HOXA3 to wounds of diabetic mice is taken up by and expressed by recruited BMDCs. This is associated with a suppressed inflammatory response, enhanced neovascularization, and accelerated wound healing. Here we show that sustained expression of Hoxa3 in diabetic-derived BMD Gr-1+CD11b+ cells reverses their diabetic phenotype. These findings demonstrate that manipulation of adult stem/progenitor cells ex vivo could be used as a potential therapy in patients with impaired wound healing.
Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe)
Authors: Wassel Christina L. , Lange Leslie A. , Keating Brendan J. , Taylor Kira C. , Johnson Andrew D. , Palmer Cameron , Ho Lindsey A. , Smith Nicholas L. , Lange Ethan M. , Li Yun , Yang Qiong , Delaney Joseph A. , Tang Weihong , Tofler Geoffrey , Redline Susan , Taylor Herman A. , Wilson James G. , Tracy Russell P. , Jacobs David R. , Folsom Aaron R. , Green David , O'Donnell Christopher J. , Reiner Alexander P. 
Published: October 2010

Abstract
Several common genomic loci, involving various immunity- and metabolism-related genes, have been associated with plasma fibrinogen in European Americans (EAs). The genetic determinants of fibrinogen in African Americans (AAs) are poorly characterized. Using a vascular gene-centric array in 23 634 EA and 6657 AA participants from 6 studies comprising the Candidate Gene Association Resource project, we examined the association of 47 539 common and lower frequency variants with fibrinogen concentration. We identified a rare Pro265Leu variant in FGB (rs6054) associated with lower fibrinogen. Common fibrinogen gene single nucleotide polymorphisms (FGB rs1800787 and FGG rs2066861) significantly associated with fibrinogen in EAs were prevalent in AAs and showed consistent associations. Several fibrinogen locus single nucleotide polymorphism associated with lower fibrinogen were exclusive to AAs; these include a newly reported association with FGA rs10050257. For IL6R, IL1RN, and NLRP3 inflammatory gene loci, associations with fibrinogen were concordant between EAs and AAs, but not at other loci (CPS1, PCCB, and SCL22A5-IRF1). The association of FGG rs2066861 with fibrinogen differed according to assay type used to measure fibrinogen. Further characterization of common and lower-frequency genetic variants that contribute to interpopulation differences in fibrinogen phenotype may help refine our understanding of the contribution of hemostasis and inflammation to atherothrombotic risk.
American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer
Authors: Rizzo J. Douglas , Brouwers Melissa , Hurley Patricia , Seidenfeld Jerome , Arcasoy Murat O. , Spivak Jerry L. , Bennett Charles L. , Bohlius Julia , Evanchuk Darren , Goode Matthew J. , Jakubowski Ann A. , Regan David H. , Somerfield Mark R. 
Published: October 2010

Abstract
Purpose: To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Methods: An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. Results: The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. Recommendations: For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration–approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.
Genomic analysis and relatedness of P2-like phages of the Burkholderia cepacia complex
Authors: Lynch Karlene H , Stothard Paul , Dennis Jonathan J 
Published: October 2010

Abstract

Background
The Burkholderia cepacia complex (BCC) is comprised of at least seventeen Gram-negative species that cause infections in cystic fibrosis patients. Because BCC bacteria are broadly antibiotic resistant, phage therapy is currently being investigated as a possible alternative treatment for these infections. The purpose of our study was to sequence and characterize three novel BCC-specific phages: KS5 (vB_BceM-KS5 or vB_BmuZ-ATCC 17616), KS14 (vB_BceM-KS14) and KL3 (vB_BamM-KL3 or vB_BceZ-CEP511).

Results
KS5, KS14 and KL3 are myoviruses with the A1 morphotype. The genomes of these phages are between 32317 and 40555 base pairs in length and are predicted to encode between 44 and 52 proteins. These phages have over 50% of their proteins in common with enterobacteria phage P2 and so can be classified as members of the Peduovirinae subfamily and the "P2-like viruses" genus. The BCC phage proteins similar to those encoded by P2 are predominantly structural components involved in virion morphogenesis. As prophages, KS5 and KL3 integrate into an AMP nucleosidase gene and a threonine tRNA gene, respectively. Unlike other P2-like viruses, the KS14 prophage is maintained as a plasmid. The P2 E+E' translational frameshift site is conserved among these three phages and so they are predicted to use frameshifting for expression of two of their tail proteins. The lysBC genes of KS14 and KL3 are similar to those of P2, but in KS5 the organization of these genes suggests that they may have been acquired via horizontal transfer from a phage similar to λ. KS5 contains two sequence elements that are unique among these three phages: an ISBmu 2-like insertion sequence and a reverse transcriptase gene. KL3 encodes an EcoRII-C endonuclease/methylase pair and Vsr endonuclease that are predicted to function during the lytic cycle to cleave non-self DNA, protect the phage genome and repair methylation-induced mutations.

Conclusions
KS5, KS14 and KL3 are the first BCC-specific phages to be identified as P2-like. As KS14 has previously been shown to be active against Burkholderia cenocepacia in vivo, genomic characterization of these phages is a crucial first step in the development of these and similar phages for clinical use against the BCC.
A transcriptomic analysis of gene expression in the venom gland of the snake Bothrops alternatus (urutu)
Authors: Cardoso Kiara C , Da Silva Márcio J , Costa Gustavo GL , Torres Tatiana T , Del Bem Luiz Eduardo V , Vidal Ramon O , Menossi Marcelo , Hyslop Stephen 
Published: October 2010

Abstract

Background
The genus Bothrops is widespread throughout Central and South America and is the principal cause of snakebite in these regions. Transcriptomic and proteomic studies have examined the venom composition of several species in this genus, but many others remain to be studied. In this work, we used a transcriptomic approach to examine the venom gland genes of Bothrops alternatus, a clinically important species found in southeastern and southern Brazil, Uruguay, northern Argentina and eastern Paraguay.

Results
A cDNA library of 5,350 expressed sequence tags (ESTs) was produced and assembled into 838 contigs and 4512 singletons. BLAST searches of relevant databases showed 30% hits and 70% no-hits, with toxin-related transcripts accounting for 23% and 78% of the total transcripts and hits, respectively. Gene ontology analysis identified non-toxin genes related to general metabolism, transcription and translation, processing and sorting, (polypeptide) degradation, structural functions and cell regulation. The major groups of toxin transcripts identified were metalloproteinases (81%), bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%), phospholipases A2 (5.6%), serine proteinases (1.9%) and C-type lectins (1.5%). Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. Phospholipases A2 were essentially acidic; no basic PLA2 were detected. Minor toxin transcripts were related to L-amino acid oxidase, cysteine-rich secretory proteins, dipeptidylpeptidase IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and double-specificity phosphatase Dusp6, showed high sequence identity to similar proteins from other snakes. In addition to the above features, single-nucleotide polymorphisms, microsatellites, transposable elements and inverted repeats that could contribute to toxin diversity were observed.

Conclusions

Bothrops alternatus venom gland contains the major toxin classes described for other Bothrops venoms based on trancriptomic and proteomic studies. The predominance of type PIII metalloproteinases agrees with the well-known hemorrhagic activity of this venom, whereas the lower content of serine proteases and C-type lectins could contribute to less marked coagulopathy following envenoming by this species. The lack of basic PLA2 agrees with the lower myotoxicity of this venom compared to other Bothrops species with these toxins. Together, these results contribute to our understanding of the physiopathology of envenoming by this species.
Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer
Authors: Lim Do Hyoung , Park Se Hoon , Park Keon Woo , Kang Jung Hun , Oh Sung Yong , Hwang In Gyu , Kwon Jung Mi , Lee Sang-Cheol , Lee Hui-Young , Kim Hyeong Su , Lim Ho Yeong , Kang Won Ki 
Published: October 2010

Abstract

Backgrounds
Cisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers.

Methods
In 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS).

Results
The median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin level

Conclusion
All of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.
Physician's manual reporting underestimates mortality: evidence from a population-based HIV/AIDS treatment program
Authors: Au-Yeung Christopher G , Anema Aranka , Chan Keith , Yip Benita , Montaner Julio SG , Hogg Robert S 
Published: October 2010

AbstractBackgroundIn clinical and cohort research, mortality estimates are often derived from manual reports generated by physicians or electronic reports from vital event registries. We examined the rate of underreporting of deaths by manual methods as compared with electronic reports from a vital event registry.MethodsThe retrospective analyses included deaths among participants registered in an observational cohort who initiated highly-active antiretroviral therapy (HAART) between August 1, 1996 and June 30, 2006. Deaths were routinely reported manually by physicians and through annual electronic record linkages with a population-based vital event registry. Multivariate logistic regression was carried out to assess independent predictors of death reporting by manual methods.ResultsOf the 3,116 individuals included in the analyses, 622 (20.0%) died during follow-up. Manual reporting by physicians only identified 377 (60.6%), while electronic linkages captured 598 (96.1%) of all deaths. Multivariate analysis indicated that deaths among individuals with lower CD4 cell count, higher HIV plasma viral load, a history of injection drug use, and under the care of an HIV-experienced physicians were more likely to be reported manually. Furthermore, non-accidental deaths were more likely to be reported manually, and manual reporting of deaths increased over time.ConclusionsRelying only on manual reports to ascertain deaths significantly underestimates the total number of deaths in the population. This can generate important biases when evaluating the impact of therapeutic interventions in the populational setting.
Patterns of physical activity in different domains and implications for intervention in a multi-ethnic Asian population: a cross-sectional study
Authors: Khaing Nang Ei Ei , Khoo Eric YH , Salim Agus , Tai E Shyong , Lee Jeannette , Van Dam Rob M 
Published: October 2010

Abstract

Background
The benefits of regular physical activity for quality of life and disease prevention have been well documented. Identification of low activity groups would facilitate interventional programs. Many studies have focussed on leisure time activity, which may not capture the spectrum of physical activity relevant to disease prevention. Furthermore, few studies have been conducted in urban Asian settings.

Methods
We evaluated physical activity in different domains (leisure time, occupational, household and transportation) and its sociodemographic determinants in 4750 adult Chinese, Malay, and Asian Indian Singaporeans. Physical activity was assessed using locally validated questionnaires.

Results
Occupational and household activity contributed substantially more to total physical activity than leisure time or transportation activity. However, when only activity of at least moderate intensity was considered leisure time activity contributed most to total physical activity. Higher socio-economic status was associated with more leisure time activity, but less total physical activity due to reduced activity in the other domains. Chinese ethnicity was also associated with less total physical activity as a result of less activity in non-leisure time domains.

Conclusions
In assessing levels of physical activity and recommending changes, it is important to consider physical activity in different domains. Focus on leisure-time physical activity alone could identify the wrong groups for intervention and miss opportunities for increasing physical activity in populations.
Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption
Authors: Sørensen Mette G , Karsdal Morten A , Dziegiel Morten H , Boutin Jean A , Nosjean Olivier , Henriksen Kim 
Published: October 2010

AbstractBackgroundBone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts.MethodsHuman osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours). The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue.ResultsOf the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently.ConclusionsIn conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.
α-TEA-induced death receptor dependent apoptosis involves activation of acid sphingomyelinase and elevated ceramide-enriched cell surface membranes
Authors: Li Jing , Yu Weiping , Tiwary Richa , Park Sook-Kyung , Xiong Ailian , Sanders Bob G , Kline Kimberly 
Published: October 2010

Abstract

Background
Alpha-tocopherol ether-linked acetic acid (α-TEA), an analog of vitamin E (RRR-alpha-tocopherol), is a potent and selective apoptosis-inducing agent for human cancer cells in vivo and in vitro. α-TEA induces apoptosis via activation of extrinsic death receptors Fas (CD95) and DR5, JNK/p73/Noxa pathways, and suppression of anti-apoptotic mediators Akt, ERK, c-FLIP and survivin in breast, ovarian and prostate cancer cells.

Results
In this study, we demonstrate that α-TEA induces the accumulation of cell surface membrane ceramide, leading to co-localization with Fas, DR5, and FADD, followed by activation of caspases-8 and -9 and apoptosis in human MDA-MB-231 breast cancer cells. α-TEA treatment leads to increased acid sphingomyelinase (ASMase) activity by 30 min, peaking at 4 hrs, which is correlated with ASMase translocation from cytosol to the cell surface membrane. Functional knockdown of ASMase with either the chemical inhibitor, desipramine, or siRNA markedly reduces α-TEA-induced cell surface membrane accumulation of ceramide and its co-localization with Fas, DR5, and FADD, cleavage of caspases-8 and -9 and apoptosis, suggesting an early and critical role for ASMase in α-TEA-induced apoptosis. Consistent with cell culture data, immunohistochemical analyses of tumor tissues taken from α-TEA treated nude mice bearing MDA-MB-231 xenografts show increased levels of cell surface membrane ceramide in comparison to tumor tissues from control animals.

Conclusion
Taken together, these studies demonstrate that ASMase activation and membrane ceramide accumulation are early events contributing to α-TEA-induced apoptosis in vitro and perhaps in vivo.
Colonization, mouse-style
Authors: Gabriel Sofia I , Jóhannesdóttir Fríða , Jones Eleanor P , Searle Jeremy B 
Published: October 2010

Abstract
Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice.
See research article: http://www.biomedcentral.com/1471-2148/10/325