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Abascal, F., Juan, D., Jungreis, I., Martinez, L., Rigau, M., Rodriguez, J. M., et al. (2018). Loose ends: almost one in five human genes still have unresolved coding status. Nucleic Acids Res., .
Abstract: Seventeen years after the sequencing of the human genome, the human proteome is still under revision. One in eight of the 22 210 coding genes listed by the Ensembl/GENCODE, RefSeq and UniProtKB reference databases are annotated differently across the three sets. We have carried out an in-depth investigation on the 2764 genes classified as coding by one or more sets of manual curators and not coding by others. Data from large-scale genetic variation analyses suggests that most are not under protein-like purifying selection and so are unlikely to code for functional proteins. A further 1470 genes annotated as coding in all three reference sets have characteristics that are typical of non-coding genes or pseudogenes. These potential non-coding genes also appear to be undergoing neutral evolution and have considerably less supporting transcript and protein evidence than other coding genes. We believe that the three reference databases currently overestimate the number of human coding genes by at least 2000, complicating and adding noise to large-scale biomedical experiments. Determining which potential non-coding genes do not code for proteins is a difficult but vitally important task since the human reference proteome is a fundamental pillar of most basic research and supports almost all large-scale biomedical projects.
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Abrams, C. M., Hijano, D. R., & Bagga, B. (2018). Abdominal Pain in the Setting of Atypical Hemolytic Uremic Syndrome Caused by Streptococcus pneumoniae Pneumonia. Glob Pediatr Health, 5, 2333794x18762866.
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Abuelo, J. G. (2018). Treatment of Severe Hyperkalemia: Confronting 4 Fallacies. Kidney Int Rep, 3(1), 47–55.
Abstract: Severe hyperkalemia is a medical emergency that can cause lethal arrhythmias. Successful management requires monitoring of the electrocardiogram and serum potassium concentrations, the prompt institution of therapies that work both synergistically and sequentially, and timely repeat dosing as necessary. It is of concern then that, based on questions about effectiveness and safety, many physicians no longer use 3 key modalities in the treatment of severe hyperkalemia: sodium bicarbonate, sodium polystyrene sulfonate (Kayexalate [Concordia Pharmaceuticals Inc., Oakville, ON, Canada], SPS [CMP Pharma, Farmville, NC]), and hemodialysis with low potassium dialysate. After reviewing older reports and newer information, I believe that these exclusions are ill advised. In this article, I briefly discuss the treatment of severe hyperkalemia and detail why these modalities are safe and effective and merit inclusion in the treatment of severe hyperkalemia.
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Achilli, A., Olivieri, A., Semino, O., & Torroni, A. (2018). Ancient human genomes-keys to understanding our past. Science, 360(6392), 964–965.
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Adams, D. R., & Eng, C. M. (2018). Next-Generation Sequencing to Diagnose Suspected Genetic Disorders. N Engl J Med, 379(14), 1353–1362.
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Adrian, T., Hornum, M., Eriksson, F., Hansen, J. M., Pilely, K., Garred, P., et al. (2018). Mannose-binding lectin genotypes and outcome in end-stage renal disease: a prospective cohort study. Nephrol Dial Transplant, 33(11), 1991–1997.
Abstract: Background: Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft. Methods: A total of 98 patients with ESRD accepted for living-donor renal transplantation or on the waiting list for transplantation were included and prospectively followed for an average of 9 years (range 7.5-9.9). Medical records were evaluated regarding transplantation status, diabetes mellitus, vascular parameters and infections for all the patients. Cox regression models and logistic regression analysis were used for statistical analyses. The cohort was divided into two groups according to the MBL2 genotype (normal A/A versus variant A/O or O/O). Results: We found no evidence for an association between the MBL2 genotype and all-cause mortality, cardiovascular events or bacterial infections (pneumonia, urinary tract infection, fistula infection or other infections). Conclusion: In this cohort, the MBL2 genotype did not seem to be associated with any long-term clinical effects in ESRD patients on dialysis or with a functioning graft.
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Aevermann, B. D., Novotny, M., Bakken, T., Miller, J. A., Diehl, A. D., Osumi-Sutherland, D., et al. (2018). Cell type discovery using single-cell transcriptomics: implications for ontological representation. Hum Mol Genet, 27(R1), R40–R47.
Abstract: Cells are fundamental function units of multicellular organisms, with different cell types playing distinct physiological roles in the body. The recent advent of single-cell transcriptional profiling using RNA sequencing is producing ‘big data’, enabling the identification of novel human cell types at an unprecedented rate. In this review, we summarize recent work characterizing cell types in the human central nervous and immune systems using single-cell and single-nuclei RNA sequencing, and discuss the implications that these discoveries are having on the representation of cell types in the reference Cell Ontology (CL). We propose a method, based on random forest machine learning, for identifying sets of necessary and sufficient marker genes, which can be used to assemble consistent and reproducible cell type definitions for incorporation into the CL. The representation of defined cell type classes and their relationships in the CL using this strategy will make the cell type classes being identified by high-throughput/high-content technologies findable, accessible, interoperable and reusable (FAIR), allowing the CL to serve as a reference knowledgebase of information about the role that distinct cellular phenotypes play in human health and disease.
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Afshinnia, F., Rajendiran, T. M., Soni, T., Byun, J., Wernisch, S., Sas, K. M., et al. (2018). Impairedβ-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKD. J Am Soc Nephrol, 29(1), 295–306.
Abstract: Studies of lipids in CKD, including ESRD, have been limited to measures of conventional lipid profiles. We aimed to systematically identify 17 different lipid classes and associate the abundance thereof with alterations in acylcarnitines, a metric ofβ-oxidation, across stages of CKD. From the Clinical Phenotyping Resource and Biobank Core (CPROBE) cohort of 1235 adults, we selected a panel of 214 participants: 36 with stage 1 or 2 CKD, 99 with stage 3 CKD, 61 with stage 4 CKD, and 18 with stage 5 CKD. Among participants, 110 were men (51.4%), 64 were black (29.9%), and 150 were white (70.1%), and the mean (SD) age was 60 (16) years old. We measured plasma lipids and acylcarnitines using liquid chromatography-mass spectrometry. Overall, we identified 330 different lipids across 17 different classes. Compared with earlier stages, stage 5 CKD associated with a higher abundance of saturated C16-C20 free fatty acids (FFAs) and long polyunsaturated complex lipids. Long-chain-to-intermediate-chain acylcarnitine ratio, a marker of efficiency ofβ-oxidation, exhibited a graded decrease from stage 2 to 5 CKD (P<0.001). Additionally, multiple linear regression revealed that the long-chain-to-intermediate-chain acylcarnitine ratio inversely associated with polyunsaturated long complex lipid subclasses and the C16-C20 FFAs but directly associated with short complex lipids with fewer double bonds. We conclude that increased abundance of saturated C16-C20 FFAs coupled with impairedβ-oxidation of FFAs and inverse partitioning into complex lipids may be mechanisms underpinning lipid metabolism changes that typify advancing CKD.
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Agarwal, R., & Sinha, A. D. (2018). Big data in nephrology-a time to rethink. Nephrol Dial Transplant, 33(1), 1–3.
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Akcakaya, P., Bobbin, M. L., Guo, J. A., Malagon-Lopez, J., Clement, K., Garcia, S. P., et al. (2018). In vivo CRISPR editing with no detectable genome-wide off-target mutations. Nature, .
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