| 141. |
- McCarthy, Bridget J, et al.
(författare)
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Risk factors for oligodendroglial tumors : A pooled international study
- 2011
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Ingår i: Neuro-Oncology. - Charlottesville, VA : Carden Jennings Pub.. - 1522-8517 .- 1523-5866. ; 13:2, s. 242-250
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Tidskriftsartikel (refereegranskat)abstract
- Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
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| 142. |
- Meiby, Elinor, et al.
(författare)
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Fragment Screening by Weak Affinity Chromatography : Comparison with Established Techniques for Screening against HSP90
- 2013
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 85:14, s. 6756-6766
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Tidskriftsartikel (refereegranskat)abstract
- The increasing use of fragment-based lead discovery (FBLD) in industry as well as in academia creates a high demand for sensitive and reliable methods to detect the binding of fragments to act as starting points in drug discovery programs. Nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), and X-ray crystallography are well-established methods for fragment finding, and thermal shift and fluorescence polarization (FP) assays are used to a lesser extent. Weak affinity chromatography (WAC) was recently introduced as a new technology for fragment screening. The study presented here compares screening of 111 fragments against the ATPase domain of HSP90 by all of these methods, with isothermal titration calorimetry (ITC) used to confirm the most potent hits. The study demonstrates that WAC is comparable to the established methods of ligand-based NMR and SPR as a hit-id method, with hit correlations of 88% and 83%, respectively. The stability of HSP90 WAC columns was also evaluated and found to give 90% reproducibility even after 207 days of storage. A good correlation was obtained between the various technologies, validating WAC as an effective technology for fragment screening.
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| 143. |
- Melin, Beatrice S., et al.
(författare)
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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| 144. |
- Meretoja, Atte, et al.
(författare)
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Stroke doctors : Who are we? A World Stroke Organization survey
- 2017
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 12:8, s. 858-868
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Tidskriftsartikel (refereegranskat)abstract
- Background Specialist training provides skilled workforce for service delivery. Stroke medicine has evolved rapidly in the past years. No prior information exists on background or training of stroke doctors globally. Aims To describe the specialties that represent stroke doctors, their training requirements, and the scientific organizations ensuring continuous medical education. Methods The World Stroke Organization conducted an expert survey between June and November 2014 using e-mailed questionnaires. All Organization for Economic Co-operation and Development countries with >1 million population and other countries with >50 million population were included ( n = 49, total 5.6 billion inhabitants, 85% of global strokes). Two stroke experts from each selected country were surveyed, discrepancies resolved, and further information on identified stroke-specific curricula sought. Results We received responses from 48 (98%) countries. Of ischemic stroke patients, 64% were reportedly treated by neurologists, ranging from 5% in Ireland to 95% in the Netherlands. Per thousand annual strokes there were average six neurologists, ranging from 0.3 in Ethiopia to 33 in Israel. Of intracerebral hemorrhage patients, 29% were reportedly treated by neurosurgeons, ranging from 5% in Sweden to 79% in Japan, with three neurosurgeons per thousand strokes, ranging from 0.1 in Ethiopia to 24 in South Korea. Most countries had a stroke society (86%) while only 10 (21%) had a degree or subspecialty for stroke medicine. Conclusions Stroke doctor numbers, background specialties, and opportunities to specialize in stroke vary across the globe. Most countries have a scientific society to pursue advancement of stroke medicine, but few have stroke curricula.
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| 145. |
- Merrihew, Gennifer E., et al.
(författare)
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Use of shotgun proteomics for the identification, confirmation, and correction of C. elegans gene annotations
- 2008
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 18:10, s. 1660-1669
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Tidskriftsartikel (refereegranskat)abstract
- We describe a general mass spectrometry-based approach for gene annotation of any organism and demonstrate its effectiveness using the nematode Caenorhabditis elegans. We detected 6779 C. elegans proteins (67,047 peptides), including 384 that, although annotated in WormBase WS150, lacked cDNA or other prior experimental support. We also identified 429 new coding sequences that were unannotated in WS150. Nearly half (192/429) of the new coding sequences were confirmed with RT-PCR data. Thirty-three (approximately 8%) of the new coding sequences had been predicted to be pseudogenes, 151 (approximately 35%) reveal apparent errors in gene models, and 245 (57%) appear to be novel genes. In addition, we verified 6010 exon-exon splice junctions within existing WormBase gene models. Our work confirms that mass spectrometry is a powerful experimental tool for annotating sequenced genomes. In addition, the collection of identified peptides should facilitate future proteomics experiments targeted at specific proteins of interest.
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| 146. |
- Minja, Daniel T. R., et al.
(författare)
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Plasmodium falciparum Mutant Haplotype Infection during Pregnancy Associated with Reduced Birthweight, Tanzania
- 2013
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 19:9, s. 1446-1454
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Tidskriftsartikel (refereegranskat)abstract
- Intermittent preventive treatment during pregnancy with sulfadoxine pyrimethamine (IPTp-SP) is a key strategy in the control of pregnancy-associated malaria. However, this strategy is compromised by widespread drug resistance from single-nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. During September 2008 October 2010, we monitored a cohort of 924 pregnant women in an area of Tanzania with declining malaria transmission. P falciparum parasites were genotyped, and the effect of infecting haplotypes on birthweight was assessed. Of the genotyped parasites, 9.3%, 46.3%, and 44.4% had quadruple or less, quintuple, and sextuple mutated haplotypes, respectively. Mutant haplotypes were unrelated to SP doses. Compared with infections with the less-mutated haplotypes, infections with the sextuple haplotype mutation were associated with lower (359 g) birth-weights. Continued use of the suboptimal IPTp-SP regimen should be reevaluated, and alternative strategies (e.g., intermittent screening and treatment or intermittent treatment with safe and effective alternative drugs) should be evaluated.
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| 147. |
- Minja, Daniel T. R., et al.
(författare)
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Reliability of rapid diagnostic tests in diagnosing pregnancy associated malaria in North Eastern Tanzania
- 2012
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875 .- 1475-2875. ; 11, s. 211-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. Methods: A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen (TM)) or HRP-2 only (Paracheck Pf (R) and ParaHIT (R) f), microscopy and nested Plasmodium species diagnostic PCR. Results: From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 - 1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Conclusions: Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool.
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| 148. |
- Moell, Andrea, et al.
(författare)
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Cell Separation in Vibrio cholerae Is Mediated by a Single Amidase Whose Action Is Modulated by Two Nonredundant Activators
- 2014
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Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 196:22, s. 3937-3948
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis and hydrolysis of septal peptidoglycan (PG) are critical processes at the conclusion of cell division that enable separation of daughter cells. Cleavage of septal PG is mediated by PG amidases, hydrolytic enzymes that release peptide side chains from the glycan strand. Most gammaproteobacteria, including Escherichia coli, encode several functionally redundant periplasmic amidases. However, members of the Vibrio genus, including the enteric pathogen Vibrio cholerae, encode only a single PG amidase, AmiB. Here, we show that V. cholerae AmiB is crucial for cell division and growth. Genetic and biochemical analyses indicated that AmiB is regulated by two activators, EnvC and NlpD, at least one of which is required for AmiB's localization to the cell division site. Localization of the activators (and thus of AmiB) is dependent upon the cell division protein FtsN. These factors mediate septal PG cleavage in E. coli as well; however, their precise roles vary between the two organisms in a number of ways. Notably, even though V. cholerae EnvC and NlpD appear to be functionally redundant under most growth conditions tested, NlpD is specifically required for intestinal colonization in the infant mouse model of cholera and for V. cholerae resistance against bile salts, perhaps due to environmental regulation of AmiB or its activators. Collectively, our findings reveal that although the cellular components that enable cleavage of septal PG appear to be generally conserved between E. coli and V. cholerae, they can be combined into diverse functional regulatory networks.
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| 149. |
- Mohseni, Shahin, 1978-, et al.
(författare)
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Common bile duct stones management : A network meta-analysis
- 2022
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Ingår i: Journal of Trauma and Acute Care Surgery. - : Lippincott Williams & Wilkins. - 2163-0755 .- 2163-0763. ; 93:5, s. E155-E165
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Timely management is critical for treating symptomatic common bile duct (CBD) stones; however, a single optimal management strategy has yet to be defined in the acute care setting. Consequently, this systematic review and network meta-analysis, comparing one-stage (CBD exploration or intraoperative endoscopic retrograde cholangiopancreatography [ERCP] with simultaneous cholecystectomy) and two-stage (precholecystectomy or postcholecystectomy ERCP) procedures, was undertaken with the main outcomes of interest being postprocedural complications and hospital length of stay (LOS).METHODS: PubMed, SCOPUS, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were methodically queried for articles from 2010 to 2021. The search terms were a combination of medical subject headings terms and the subsequent terms: gallstone; common bile duct (stone); choledocholithiasis; cholecystitis; endoscopic retrograde cholangiography/ERCP; common bile duct exploration; intraoperative, preoperative, perioperative, and postoperative endoscopic retrograde cholangiography: stone extraction; and one-stage and two-stage procedure. Studies that compared two procedures or more were included, whereas studies not recording complications (bile leak, hemorrhage, pancreatitis, perforation, intra-abdominal infections, and other infections) or LOS were excluded. A network meta-analysis was conducted to compare the four different approaches for managing CBD stones.RESULTS: A total of 16 studies (8,644 participants) addressing the LOS and 41 studies (19,756 participants) addressing postprocedural complications were included in the analysis. The one-stage approaches were associated with a decrease in LOS compared with the two-stage approaches. Common bile duct exploration demonstrated a lower overall risk of complications compared with preoperative ERCP, but there were no differences in the overall risk orcomplications in the remaining comparisons. However, differences in specific postprocedural complications were detected between the four different approaches managing CBD stones.CONCLUSION: This network meta-analysis suggests that both laparoscopic CBD exploration and intraoperative ERCP have equally good outcomes and provide a preferable single-anesthesia patient pathway with a shorter overall length of hospital stay compared with the two-stage approaches.
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| 150. |
- Nyström, Daniel, et al.
(författare)
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Biomimetic Surface Modification of Honeycomb Films via a "Grafting From" Approach
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:15, s. 12748-12754
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Tidskriftsartikel (refereegranskat)abstract
- Hydrophobic isoporous membranes were fabricated using the "breath figure" method from polystyrene stars synthesized via ATRP. The living polymer chain ends at the surface of the films were then used, without further modification, in a "grafting-from" approach to grow surface-linked polyglycidyl methacrylate chains under conditions that maintained the regular honeycomb structure. This versatile functional surface was then used as a platform to build a small library of surfaces using a variety of simple chemistries: (i) the acid hydrolysis of the epoxide to form bis-alcohol groups and (ii) utilizing the "click-like" epoxide-amine reaction to functionalize the surface with a model biomolecule-(biotinamido)pentylamine. The successful modifications were confirmed by a combination of spectroscopic and biological means. Changes in the growth characteristics of nonmotile Psychrobacter sp. strain, SW5, on the honeycomb films, provided further evidence confirming changes in the hydrophobicity of the surface upon grafting.
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