Proteomics for Clinical Assessment of Kidney Disease

Kidney disease is one of the fastest growing causes of death worldwide, disclosing an unmet clinical need for early diagnosis and optimized risk stratification that allows high risk patient selection for clinical trials and for more intensive nephroprotective interventions in the clinic. The current issue of PROTEOMICS—Clinical Applications contains four manuscripts that explore different aspects of clinical proteomics implementation in the context of acute kidney injury, chronic kidney disease and, more specifically, diabetic kidney disease, and kidney transplantation from a diagnostic and risk stratification point of view. Overall, the evidence discussed suggests that chronic kidney disease is an example where clinical proteomics has become a valuable tool ready for clinical implementation, expected to have a major impact in patient management.The author was supported by FIS PI16/02057, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, and Comunidad de Madrid B2017/BMD- 3686 CIFRA2-CM

A review of the criteria for non-invasive diagnosis of cardiac transthyretin amyloidosis

Introduction: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal infiltrative cardiomyopathy (ATTR-CM) characterized by congestive cardiac failure, often with preserved left ventricular ejection fraction, and significant risk of conduction disease. Diagnosis is often delayed or missed due to poor specificity of echocardiography and the historical requirement for a histological diagnosis, frequently an endomyocardial biopsy. Areas covered: Following a detailed literature review focusing on peer reviewed articles (Pubmed, Cochrane Library, Google Scholar), from 1995 to 2020, alongside international diagnostic guidelines and expert opinion in the field, this article will explore the current non-invasive diagnostic criteria for ATTR-CM including the role of transthoracic echocardiography, cardiac MRI, bone scintigraphy, and assessment for exclusion of a clonal dyscrasia. Expert opinion: ATTR-CM is an emerging and increasingly diagnosed cause of heart failure, particularly in the elderly. Promising novel therapies make accurate and swift diagnosis of the disease vital. With the increasing use of cardiac MRI to investigate cardiomyopathy and repurposing of technetium-labeledbone scintigraphy, clinicians are now often able to diagnose ATTR-CM without recourse to an endomyocardial biopsy

Pauci Immune crescentic glomerulonephritis in a patient with T-cell lymphoma and argyria

Background Silver is a transition metal, toxic when ingested in significant amounts, causing argyria (skin deposition) and argyrosis (eye deposition). It is excreted mainly via the gastrointestinal tract with only small amounts eliminated by the kidneys, and rarely have cases of nephrotoxicity due to silver been reported. Here we present the case of a woman who used colloidal silver as an alternative remedy for a T cell lymphoma, who subsequently developed argyria and a pauci-immune crescentic glomerulonephritis with evidence of extensive glomerular basement membrane silver deposition. Case Presentation A 47 year old woman of Indo-Asian descent with a T-cell lymphoma who refused conventional chemotherapy for 18 months but self-medicated with a remedy containing colloidal silver, was admitted with acute dialysis-dependent kidney injury. A kidney biopsy demonstrated a pauci-immune crescentic glomerulonephritis with deposition of silver particles in the mesangium and along the glomerular basement membranes. The patient was treated with intravenous methylprednisolone and intravenous cyclophosphamide and recovered independent renal function. Conclusion Chronological evolution of the the pauci-immune glomerulonephritis suggests that a cellular immune-mediated process was induced, potentially mediated by lymphomatous T cells directed at the glomerular basement membrane, following silver deposition. Immunosuppressive therapy improved the situation and allowed cessation of haemodialysis, supporting the hypothesis of an immune-mediated process

Fuzzy modeling and parameters optimization for the enhancement of biodiesel production from waste frying oil over montmorillonite clay K-30

Transesterification is a promising technology for the biodiesel production to provide an alternative fuel that considers the environmental concerns. From the economic and environmental protection points of view, utilization of waste frying oil for the production of biodiesel addresses very beneficial impacts. Production of higher yield of biodiesel is a challenging process in order to commercialize it with a lower cost. The current study focuses on the influence of different parameters such as reaction temperature (°C), reaction period (min), oil to methanol ratio and amount of catalyst (wt%) on the production of biodiesel. The main objective of this work is to develop a model via fuzzy logic approach in order to maximize the biodiesel produced from waste frying oil using montmorillonite Clay K-30 as a catalyst. The optimization for the operating parameters has been performed via particle swarm optimization (PSO) approach. During the optimization process, the decision variables were represented by four different operating parameters: temperature (40–140 °C), reaction period (60–300 min), oil/methanol ratio (1:6–1:18) and amount of catalyst (1–5 wt%). The model has been validated with the experimental data and compared with the optimal results reported based on other optimization techniques. Results showed the increment of biodiesel production by 15% using the proposed strategy compared to the earlier study. The obtained biodiesel production yield reached 93.70% with the optimal parameters for a temperature at 69.66 °C, a reaction period of 300 min, oil/methanol ratio of 1:9 and an amount of catalyst of 5 wt%

Homotopy Theoretic Models of Type Theory

We introduce the notion of a logical model category which is a Quillen model category satisfying some additional conditions. Those conditions provide enough expressive power that one can soundly interpret dependent products and sums in it. On the other hand, those conditions are easy to check and provide a wide class of models some of which are listed in the paper.Comment: Corrected version of the published articl

Breast cancer image classification using pattern-based Hyper Conceptual Sampling method

The increase in biomedical data has given rise to the need for developing data sampling techniques. With the emergence of big data and the rise of popularity of data science, sampling or reduction techniques have been assistive to significantly hasten the data analytics process. Intuitively, without sampling techniques, it would be difficult to efficiently extract useful patterns from a large dataset. However, by using sampling techniques, data analysis can effectively be performed on huge datasets, to produce a relatively small portion of data, which extracts the most representative objects from the original dataset. However, to reach effective conclusions and predictions, the samples should preserve the data behavior. In this paper, we propose a unique data sampling technique which exploits the notion of formal concept analysis. Machine learning experiments are performed on the resulting sample to evaluate quality, and the performance of our method is compared with another sampling technique proposed in the literature. The results demonstrate the effectiveness and competitiveness of the proposed approach in terms of sample size and quality, as determined by accuracy and the F1-measure. 2018This contribution was made possible by NPRP-07-794-1-145 grant from the Qatar National Research Fund (a member of Qatar foundation). The statements made herein are solely the responsibility of the authors.Scopu

Renal Transplant Outcomes in Amyloidosis

Background: Outcomes after renal transplantation have traditionally been poor in systemic amyloid A (AA) amyloidosis and systemic light chain (AL) amyloidosis, with high mortality and frequent recurrent disease. We sought to compare outcomes with matched transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy (DN), and identify factors predictive of outcomes. Methods: We performed a retrospective cohort study of 51 systemic AL and 48 systemic AA amyloidosis patients undergoing renal transplantation. Matched groups were generated by propensity score matching. Patient and death-censored allograft survival were compared via Kaplan–Meier survival analyses, and assessment of clinicopathological features predicting outcomes via Cox proportional hazard analyses. Results: One-, 5- and 10-year death-censored unadjusted graft survival was, respectively, 94, 91 and 78% for AA amyloidosis, and 98, 93 and 93% for AL amyloidosis; median patient survival was 13.1 and 7.9 years, respectively. Patient survival in AL and AA amyloidosis was comparable to DN, but poorer than ADPKD [hazard ratio (HR) = 3.12 and 3.09, respectively; P 12 mm (HR = 26.58; P = 0.03), while survival was predicted by haematologic response (very good partial or complete response; HR = 0.07; P = 0.018). In AA amyloidosis, recurrent amyloid was associated with elevated serum amyloid A concentration but not with outcomes. Conclusions: Renal transplantation outcomes for selected patients with AA and AL amyloidosis are comparable to those with DN. In AL amyloidosis, IVSd thickness and achievement of deep haematologic response pre-transplant profoundly impact patient survival

Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis

Aims: Congo red staining of an endomyocardial biopsy is the diagnostic gold-standard in suspected cardiac amyloidosis (CA), but the procedure is associated with the risk, albeit small, of serious complications, and delay in diagnosis due to the requirement for technical expertise. In contrast, abdominal fat pad fine needle aspiration (FPFNA) is a simple, safe and well-established procedure in systemic amyloidosis, but its diagnostic sensitivity in patients with suspected CA remains unclear. Methods and results: We assessed the diagnostic sensitivity of FPFNA in 600 consecutive patients diagnosed with CA [216 AL amyloidosis, 113 hereditary transthyretin (ATTRm), and 271 wild-type transthyretin (ATTRwt) amyloidosis] at our Centre. Amyloid was detected on Congo red staining of FPFNAs in 181/216 (84%) patients with cardiac AL amyloidosis, including 100, 97, and 78% of those with a large, moderate, and small whole-body amyloid burden, respectively, as assessed by serum amyloid P (SAP) component scintigraphy (P < 0.001); the deposits were successfully typed as AL by immunohistochemistry in 102/216 (47%) cases. Amyloid was detected in FPFNAs of 51/113 (45%) patients with ATTRm CA, and only 42/271 (15%) cases with ATTRwt CA. Conclusions: FPFNA has reasonable diagnostic sensitivity in cardiac AL amyloidosis, particularly in patients with a large whole-body amyloid burden. Although the diagnostic sensitivity of FPFNA is substantially lower in transthyretin CA, particularly ATTRwt, it may nevertheless sometimes obviate the need for endomyocardial biopsy