| 1. |
- Chapman, Lesley M, et al.
(författare)
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A crowdsourced set of curated structural variants for the human genome
- 2020
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- A high quality benchmark for small variants encompassing 88 to 90% of the reference genome has been developed for seven Genome in a Bottle (GIAB) reference samples. However a reliable benchmark for large indels and structural variants (SVs) is more challenging. In this study, we manually curated 1235 SVs, which can ultimately be used to evaluate SV callers or train machine learning models. We developed a crowdsourcing app - SVCurator - to help GIAB curators manually review large indels and SVs within the human genome, and report their genotype and size accuracy. SVCurator displays images from short, long, and linked read sequencing data from the GIAB Ashkenazi Jewish Trio son [NIST RM 8391/HG002]. We asked curators to assign labels describing SV type (deletion or insertion), size accuracy, and genotype for 1235 putative insertions and deletions sampled from different size bins between 20 and 892,149 bp. 'Expert' curators were 93% concordant with each other, and 37 of the 61 curators had at least 78% concordance with a set of 'expert' curators. The curators were least concordant for complex SVs and SVs that had inaccurate breakpoints or size predictions. After filtering events with low concordance among curators, we produced high confidence labels for 935 events. The SVCurator crowdsourced labels were 94.5% concordant with the heuristic-based draft benchmark SV callset from GIAB. We found that curators can successfully evaluate putative SVs when given evidence from multiple sequencing technologies.
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| 2. |
- El-Garawani, Islam, et al.
(författare)
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The Ameliorative Role of Acacia senegal Gum against the Oxidative Stress and Genotoxicity Induced by the Radiographic Contrast Medium (Ioxitalamate) in Albino Rats
- 2021
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Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Arabic gum (Acacia senegal, AG) is proven effective antioxidant and cytoprotective agent. The present study was designed to test this notion by investigating the possible role of AG against the radiographic contrast medium (Ioxitalamate, Telebrix-35®, TBX)-induced oxidative stress and genotoxicity. Albino rats were divided into four groups and supplied with either; distilled water, daily 10% (w/v) AG, an intravenous dose of TBX (1600 mg I/kg b.wt) and co-administration of TBX and AG. Rats were sacrificed and blood samples were collected to assess the genotoxicity employing the peripheral blood leucocytes fluorescent double staining; namely the acridine orange/ethidium bromide (AO/EB) staining and alkaline comet assay. Further, chromosomal analyses were done in bone marrow cells. Serum urea and creatinine levels, in addition to malondialdehyde (MDA), nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in kidney tissues were measured. Liquid chromatography-mass spectrophotometry (LC-MS-MS) was performed to identify the chemical composition of AG extract. Kidney functions, single/double-stranded DNA damage, chromosomal aberrations, mitotic index, MDA and NO levels were significantly (p < 0.001) increased in TBX-treated group compared to the control and AG-treated one. Meanwhile, CAT and GSH activities were significantly diminished and the AG supplementation significantly (p < 0.001) ameliorated these effects compared with the control and AG-treated groups. Five compounds have been identified using GNPS networking including 7,3′,4′-Trihydroxyisoflavone, Noscapine, Tetrahydropapaveroline, Costunolide, Hesperidin. In conclusion, results of the present study suggest that AG exerted a protective role against TBX-induced oxidative stress and genotoxicity which may be attributed to the active metabolites in the gum.
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| 3. |
- El-Seedi, Hesham R., et al.
(författare)
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Plant extracts and compounds for combating schistosomiasis
- 2023
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Ingår i: Phytochemistry Reviews. - : Springer Science and Business Media LLC. - 1568-7767 .- 1572-980X. ; 22:6, s. 1691-1806
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Tidskriftsartikel (refereegranskat)abstract
- Schistosomiasis is a vector-borne water-based disease caused by Schistosoma blood flukes. It mostly affects people in low-income regions, 90% of reported cases being in developing countries. Schistosoma has a complex lifecycle, alternately infecting mammalian hosts and snails. The snails hosting the parasite are the most viable targets. Selective preparations for reducing the parasite pool in snails and infected water are required as current molluscicides are also nontoxic to other organisms, including fish, and thus affect food supplies in infected areas. Plants (e.g. Annona crassiflora Mart., A. muricata L., and A. montana Macfad.) are attractive potential sources as alternative molluscicides and novel entity to treat the disease owned to their diverse biologically potent compounds including; saponins, alkaloids, terpenoids, and tannins. Additionally, they can be locally cultivated, providing income for farmers and reducing treatment costs. Here, we review plants, plant extracts and isolated compounds that have shown activities against the host snails or Schistosoma in various parts of its life cycle. Plants have a lot of potential and will continue to contribute feasible, effective medicines and/or pesticides; more research is warranted to fully explore their future applications.
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| 4. |
- El-Seedi, Hesham R., et al.
(författare)
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Plant extracts and compounds for combating schistosomiasis
- 2023
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Ingår i: Phytochemistry Reviews. - : Springer. - 1568-7767 .- 1572-980X. ; 22:6, s. 1691-1806
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Tidskriftsartikel (refereegranskat)abstract
- Schistosomiasis is a vector-borne water-based disease caused by Schistosoma blood flukes. It mostly affects people in low-income regions, 90% of reported cases being in developing countries. Schistosoma has a complex lifecycle, alternately infecting mammalian hosts and snails. The snails hosting the parasite are the most viable targets. Selective preparations for reducing the parasite pool in snails and infected water are required as current molluscicides are also nontoxic to other organisms, including fish, and thus affect food supplies in infected areas. Plants (e.g. Annona crassiflora Mart., A. muricata L., and A. montana Macfad.) are attractive potential sources as alternative molluscicides and novel entity to treat the disease owned to their diverse biologically potent compounds including; saponins, alkaloids, terpenoids, and tannins. Additionally, they can be locally cultivated, providing income for farmers and reducing treatment costs. Here, we review plants, plant extracts and isolated compounds that have shown activities against the host snails or Schistosoma in various parts of its life cycle. Plants have a lot of potential and will continue to contribute feasible, effective medicines and/or pesticides; more research is warranted to fully explore their future applications.
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| 5. |
- Lane, Jennifer C E, et al.
(författare)
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Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study.
- 2021
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:7, s. 3222-3234
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Tidskriftsartikel (refereegranskat)abstract
- Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA.We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2<40%.A total of 918144 and 290383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis.HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation.Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.
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| 6. |
- Lindberg, Sara, et al.
(författare)
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Expanded HILUS Trial: A Pooled Analysis of Risk Factors for Toxicity From Stereotactic Body Radiation Therapy of Central and Ultracentral Lung Tumors
- 2023
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Ingår i: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS. - 0360-3016 .- 1879-355X. ; 117:5, s. 1222-1231
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stereotactic body radiation therapy for tumors near the central airways implies high-grade toxic effects, as concluded from the HILUS trial. However, the small sample size and relatively few events limited the statistical power of the study. We therefore pooled data from the prospective HILUS trial with retrospective data from patients in the Nordic countries treated outside the prospective study to evaluate toxicity and risk factors for high-grade toxic effects. Methods and Materials: All patients were treated with 56 Gy in 8 fractions. Tumors within 2 cm of the trachea, the mainstem bronchi, the intermediate bronchus, or the lobar bronchi were included. The primary endpoint was toxicity, and the secondary endpoints were local control and overall survival. Clinical and dosimetric risk factors were analyzed for treatment-related fatal toxicity in univariable and multivariable Cox regression analyses.Results: Of 230 patients evaluated, grade 5 toxicity developed in 30 patients (13%), of whom 20 patients had fatal bronchopul-monary bleeding. The multivariable analysis revealed tumor compression of the tracheobronchial tree and maximum dose to the mainstem or intermediate bronchus as significant risk factors for grade 5 bleeding and grade 5 toxicity. The 3-year local control and overall survival rates were 84% (95% CI, 80%-90%) and 40% (95% CI, 34%-47%), respectively.Conclusions: Tumor compression of the tracheobronchial tree and high maximum dose to the mainstem or intermediate bronchus increase the risk of fatal toxicity after stereotactic body radiation therapy in 8 fractions for central lung tumors. Simi-lar dose constraints should be applied to the intermediate bronchus as to the mainstem bronchi.
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| 7. |
- Makadia, Rupa, et al.
(författare)
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Evaluating the impact of alternative phenotype definitions on incidence rates across a global data network.
- 2023
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Ingår i: JAMIA open. - 2574-2531. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome.We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates.Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52.The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition.Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.
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| 8. |
- Roberts, Fiona, et al.
(författare)
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Rehabilitation Before and After Autologous Haematopoietic Stem Cell Transplantation (AHSCT) for Patients With Multiple Sclerosis (MS) : Consensus Guidelines and Recommendations for Best Clinical Practice on Behalf of the Autoimmune Diseases Working Party, Nurses Group, and Patient Advocacy Committee of the European Society for Blood and Marrow Transplantation (EBMT)
- 2020
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used to treat people with multiple sclerosis (MS). Supported by an evolving evidence base, AHSCT can suppress active inflammation in the central nervous system and induce long-term changes in immune cell populations, thereby stabilizing, and, in some cases, reversing disability in carefully selected MS patients. However, AHSCT is an intensive chemotherapy-based procedure associated with intrinsic risks, including profound cytopenia, infection, and organ toxicity, accompanied by an on-going degree of immuno-compromise and general deconditioning, which can be associated with a transient increase in functional impairment in the early stages after transplantation. Although international guidelines and recommendations have been published for clinical and technical aspects of AHSCT in MS, there has been no detailed appraisal of the rehabilitation needed following treatment nor any specific guidelines as to how this is best delivered by hospital and community-based therapists and wider multidisciplinary teams in order to maximize functional recovery and quality of life. These expert consensus guidelines aim to address this unmet need by summarizing the evidence-base for AHSCT in MS and providing recommendations for current rehabilitation practice along with identifying areas for future research and development.
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| 9. |
- Voss, Erica A, et al.
(författare)
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Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.
- 2023
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Ingår i: EClinicalMedicine. - 2589-5370. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.None.
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