| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 11. |
- Al Alawi, AM, et al.
(author)
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Lactation Ketoacidosis: A case series
- 2019
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In: Sultan Qaboos University medical journal. - : Sultan Qaboos University Medical Journal. - 2075-0528 .- 2075-051X. ; 19:4, s. e359-e363
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Journal article (other academic/artistic)abstract
- Lactation ketoacidosis is an extremely rare type of high anion gap metabolic acidosis. We report two lactating women who were diagnosed with lactation ketoacidosis. The first patient presented to the Emergency Department at Royal Darwin Hospital, Darwin, Australia, in 2018 with lethargy, nausea and abdominal pain after she commenced a new diet regimen based on three meals of protein per day and free of glucose, gluten and dairy products. The second patient presented to the Emergency Department at Sultan Qaboos University Hospital, Muscat, Oman, in 2018 with headache, severe malaise, epigastric pain and worsening of gastroesophageal symptoms. Blood investigation results showed that both patients had high anion gap metabolic acidosis, ketosis and hypoglycaemia. The patients responded well to intravenous dextrose and resumption of a balanced diet. Both patients were able to continue breastfeeding and remained well on follow-up.Keywords: Breastfeeding; Starvation; Hypoglycemia; Ketosis; Acid-Base Imbalance; Metabolic Diseases; Ketone Bodies; Fasting; Case Series; Australia; Oman.
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| 12. |
- Al Alawi, AM, et al.
(author)
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Lactation Ketoacidosis: A Systematic Review of Case Reports
- 2020
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In: Medicina (Kaunas, Lithuania). - : MDPI AG. - 1648-9144. ; 56:6
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Journal article (peer-reviewed)abstract
- Background and Objective: Lactation ketoacidosis is a rare cause of high anion gap metabolic acidosis affecting breastfeeding mothers. We aim to review and analyze all cases of lactation ketoacidosis reported. Materials and Methods: A systematic search of PubMed/MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL), identifying relevant case reports published from 1 January 1970 to 31 December 2019. We extracted the following data: the first author, country, year of publication, age of the mother, age of the child, weight/body mass index (BMI) of the mother, precipitating factors, presenting symptoms, biochemical results, treatment, breastfeeding, and time from presentation to the resolution of ketoacidosis. Results: Sixteen case reports and 1 case series reporting 18 cases of lactation ketoacidosis were found. Presenting symptoms were nausea (72%, 13/18), vomiting (67%, 12/18), malaise (56%, 10/18), abdominal pain (44%, 8/18), dyspnea (33%, 6/18), headache (22%, 4/18), and palpitation (11%, 2/18). Dieting and physical exercise to lose weight were reported in 76% (14/18). The treatments included IV dextrose, sodium bicarbonate, insulin, rehydration, monitoring and replacement of electrolytes, and resumption of a balanced diet. The prognoses were good, with no mortalities. Conclusions: lactation ketoacidosis should be suspected in unwell breastfeeding women with high anion gap metabolic acidosis, after excluding other causes.
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- Al Alawi, AM, et al.
(author)
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Magnesium and Human Health: Perspectives and Research Directions
- 2018
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In: International journal of endocrinology. - : Hindawi Limited. - 1687-8337 .- 1687-8345. ; 2018, s. 9041694-
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Journal article (peer-reviewed)abstract
- Magnesium is the fourth most abundant cation in the body. It has several functions in the human body including its role as a cofactor for more than 300 enzymatic reactions. Several studies have shown that hypomagnesemia is a common electrolyte derangement in clinical setting especially in patients admitted to intensive care unit where it has been found to be associated with increase mortality and hospital stay. Hypomagnesemia can be caused by a wide range of inherited and acquired diseases. It can also be a side effect of several medications. Many studies have reported that reduced levels of magnesium are associated with a wide range of chronic diseases. Magnesium can play important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases. This review is aimed at comprehensively collating the current available published evidence and clinical correlates of magnesium disorders.
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| 18. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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