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| 2. |
- Amgad, M, et al.
(författare)
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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
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| 3. |
- El-Sayed, Ashraf S. A., et al.
(författare)
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Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants : Genome Mining and Metabolic Manipulation
- 2020
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:13
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Forskningsöversikt (refereegranskat)abstract
- Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids "Taxol" is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree,Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark ofT. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi fromTaxusspp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceaeand Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.
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| 4. |
- El-Sayed, Ashraf S. A., et al.
(författare)
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Purification and biochemical characterization of taxadiene synthase from bacillus koreensis and stenotrophomonas maltophilia
- 2021
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Ingår i: Scientia pharmaceutica. - : MDPI. - 0036-8709 .- 2218-0532. ; 89:4
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Tidskriftsartikel (refereegranskat)abstract
- Taxadiene synthase (TDS) is the rate-limiting enzyme of Taxol biosynthesis that cyclizes the geranylgeranyl pyrophosphate into taxadiene. Attenuating Taxol productivity by fungi is the main challenge impeding its industrial application; it is possible that silencing the expression of TDS is the most noticeable genomic feature associated with Taxol-biosynthetic abolishing in fungi. As such, the characterization of TDS with unique biochemical properties and autonomous expression that is independent of transcriptional factors from the host is the main challenge. Thus, the objective of this study was to kinetically characterize TDS from endophytic bacteria isolated from different plants harboring Taxol-producing endophytic fungi. Among the recovered 23 isolates, Bacillus koreensis and Stenotrophomonas maltophilia achieved the highest TDS activity. Upon using the Plackett–Burman design, the TDS productivity achieved by B. koreensis (18.1 µmol/mg/min) and S. maltophilia (14.6 µmol/mg/min) increased by ~2.2-fold over the control. The enzyme was purified by gel-filtration and ion-exchange chromatography with ~15 overall folds and with molecular subunit structure 65 and 80 kDa from B. koreensis and S. maltophilia, respectively. The chemical identity of taxadiene was authenticated from the GC-MS analyses, which provided the same mass fragmentation pattern of authentic taxadiene. The tds gene was screened by PCR with nested primers of the conservative active site domains, and the amplicons were sequenced, displaying a higher similarity with tds from T. baccata and T. brevifolia. The highest TDS activity by both bacterial isolates was recorded at 37–40 °C. The Apo-TDSs retained ~50% of its initial holoenzyme activities, ensuring their metalloproteinic identity. The activity of purified TDS was completely restored upon the addition of Mg2+, confirming the identity of Mg2+ as a cofactor. The TDS activity was dramatically reduced upon the addition of DTNB and MBTH, ensuring the implementation of cysteine-reactive thiols and ammonia groups on their active site domains. This is the first report exploring the autonomous robust expression TDS from B. koreensis and S. maltophilia with a higher affinity to cyclize GGPP into taxadiene, which could be a novel platform for taxadiene production as intermediary metabolites of Taxol biosynthesis.
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- Salman, Muhammad, et al.
(författare)
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Evaluation of Conspiracy Beliefs, Vaccine Hesitancy, and Willingness to Pay towards COVID-19 Vaccines in Six Countries from Asian and African Regions : A Large Multinational Analysis
- 2022
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination protects people from serious illness and associated complications. Conspiracy theories and misinformation on vaccines have been rampant during the COVID-19 pandemic and are considered significant drivers of vaccine hesitancy. Since vaccine hesitancy can undermine efforts to immunize the population against COVID-19 and interferes with the vaccination rate, this study aimed to ascertain the COVID-19-vaccine-related conspiracy beliefs, vaccine hesitancy, views regarding vaccine mandates, and willingness to pay for vaccines among the general population. A web-based, cross-sectional survey was conducted (April-August 2021) among the adult population in six countries (Pakistan, Saudi Arabia, India, Malaysia, Sudan, and Egypt). Participants were recruited using an exponential, non-discriminate snowball sampling method. A validated self-completed electronic questionnaire was used for the data collection. All the participants responded to questions on various domains of the study instrument, including conspiracy beliefs, vaccine hesitancy, and willingness to pay. The responses were scored according to predefined criteria and stratified into various groups. All data were entered and analyzed using SPSS version 22. A total of 2481 responses were included in the study (Pakistan 24.1%, Saudi Arabia 19.5%, India 11.6%, Malaysia 8.1%, Sudan 19.3%, and Egypt 17.3%). There was a preponderance of participants <= 40 years old (18-25 years: 55.8%, 26-40 years: 28.5%) and females (57.1%). The average score of the COVID-19 vaccine conspiracy belief scale (C19V-CBS) was 2.30 +/- 2.12 (median 2; range 0-7). Our analysis showed that 30% of the respondents were found to achieve the ideal score of zero, indicating no conspiracy belief. The mean score of the COVID-19 vaccine hesitancy scale (C19V-HS) was 25.93 +/- 8.11 (range: 10-50). The majority (45.7%) had C19V-HA scores of 21-30 and nearly 28% achieved a score greater than 30, indicating a higher degree of hesitancy. There was a significant positive correlation between conspiracy beliefs and vaccine hesitancy (Spearman's rho = 0.547, p < 0.001). Half of the study population were against the vaccine mandate. Respondents in favor of governmental enforcement of COVID-19 vaccines had significantly (p < 0.001) lower scores on the C19V-CBS and C19V-HS scale. Nearly 52% reported that they would only take vaccine if it were free, and only 24% were willing to pay for COVID-19 vaccines. A high prevalence of conspiracy beliefs and vaccine hesitancy was observed in the targeted countries. Our findings highlight the dire need for aggressive measures to counter the conspiracy beliefs and factors underlying this vaccine hesitancy.
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