Adaptively Weighted Top-N Recommendation for Organ Matching

Reducing the shortage of organ donations to meet the demands of patients on the waiting list has being a major challenge in organ transplantation. Because of the shortage, organ matching decision is the most critical decision to assign the limited viable organs to the most “suitable” patients. Currently, organ matching decisions are only made by matching scores calculated via scoring models, which are built by the first principles. However, these models may disagree with the actual post-transplantation matching performance (e.g., patient's post-transplant quality of life (QoL) or graft failure measurements). In this paper, we formulate the organ matching decision-making as a top-N recommendation problem and propose an Adaptively Weighted Top-N Recommendation (AWTR) method. AWTR improves performance of the current scoring models by using limited actual matching performance in historical datasets as well as the collected covariates from organ donors and patients. AWTR sacrifices the overall recommendation accuracy by emphasizing the recommendation and ranking accuracy for top-N matched patients. The proposed method is validated in a simulation study, where KAS [ 60 ] is used to simulate the organ-patient recommendation response. The results show that our proposed method outperforms seven state-of-the-art top-N recommendation benchmark methods.

miR-31, miR-155, and miR-221 expression profiles and their association with graft skin tolerance in a syngeneic vs. allogeneic murine skin transplantation model

Grafting is the gold standard for the treatment of severe skin burns. Frequently, allogeneic tissue is the only transient option for wound coverage, but their use risks damage to surrounding tissues. MicroRNAs have been associated with acute rejection of different tissues/organs. In this study, we analyzed the expression of miR-31, miR-155, and miR-221 and associate it with graft tolerance or rejection using a murine full-thickness skin transplantation model. Recipient animals for the syngeneic and allogeneic groups were BALB/c and C57BL/6 mice, respectively; donor tissues were obtained from BALB/c mice. After 7 days post-transplantation (DPT), the recipient skin and grafts in the syngeneic group maintained most of their structural characteristics and transforming growth factor (TGF)β1 and TGFβ3 expression. Allografts were rejected early (Banff grades II and IV at 3 and 7 DPT, respectively), showing damage to the skin architecture and alteration of TGFβ3 distribution. miRNAs skin expression changed in both mouse strains; miR-31 expression increased in the recipient skin of syngeneic grafts relative to that of allogeneic grafts at 3 and 7 DPT (p < 0.05 and p < 0.01, respectively); miR-221 expression increased in the same grafts at 7 DPT (p < 0.05). The only significant difference between donor tissues was observed for miR-155 expression at 7 DPT which was associated with necrotic tissue. Only miR-31 and miR-221 levels were increased in the blood of BALB/c mice that received syngeneic grafts after 7 DPT. Our data suggest that local and systemic miR-31 and miR-221 overexpression are associated with graft tolerance.

Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA). Graft pharmaceutical features pre-transplantation, and biological effects including on LCA concentrations post-transplantation, were measured. TCA-microcapsules had an oval shape and similar size compared with the control. The treatment group survived longer, showed improved glucose and interleukin-6 concentrations, and lower LCA concentrations in plasma, large intestine, faeces, liver and spleen, compared with control. Results suggest that TCA incorporation with islets encapsulated graft exerted beneficial effects, but there was no direct and significant dependency between concentrations of interleukin-6 and LCA.

Smoking Mechanics and Impact on Smoking Cessation: Two Cases of Smoking Lapse Status Post Lung Transplantation

Background Smoking behavior includes mechanisms taken on by persons to adjust for certain characteristic changes of cigarettes. However, as lung function declines due to lung-specific diseases, it is unclear how mechanical smoking behavior changes affect persons who smoke. We review two cases of patients who stopped smoking prior to and then subsequently resumed smoking after lung transplantation. Methods A retrospective review of two patients who were recipients of lung transplantation and sustained from cigarette usage prior to transplantation. Results Patient A was a 54-year-old woman who received a double lung transplant secondary to chronic obstructive pulmonary disease (COPD) in October 2017. She had stopped smoking cigarettes in July 2015 (FEV1 .56 L). Patient B was a 40-year-old man who received a double lung transplantation due to sarcoidosis in January 2015. He stopped smoking cigarettes in February 2012 (FEV1 1.15 L). Post-transplant, Patient A resumed smoking on March 2018 where her FEV1 was at 2.12 L (5 months post-transplantation), and Patient B resumed smoking in April 2017 where his FEV1 was 2.37 L (26 months post-transplantation). Conclusion We report on two patients who resumed smoking after lung transplantation. While variations of smoking mechanics have been identified as a function of nicotine yield and type of cigarette, it lung mechanics may play a role in active smoking as well. Therefore, proper screening for tobacco usage post-lung transplantation should be considered a priority in order to preserve transplanted lungs.

Elevated number of IL-21+ TFH and CD86+CD38+ B cells in blood of renal transplant recipients with AMR under conventional immuno-suppression

The objective of this study is to detect the number of different subsets of TFH and B cells in renal transplant recipients (RTR) with antibody-mediated acute rejection (AMR), acute rejection (AR), chronic rejection (CR), or transplant stable (TS). The present study was a prospective study. The numbers of ICOS +, PD-1+ and IL-21+ TFH, CD86+, CD38+, CD27+, and IgD- B cells in 21 patients with end-stage renal disease (ESRD) and post-transplant times were measured by flow cytometry. The level of serum IL-21 was detected by ELISA. The numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, CD4+CXCR5+IL-21+ TFH, CD19+CD86+, and CD19 +CD86+CD38+ B cells as well as the level of serum IL-21 in the AMR, AR, and CR groups at post-transplantation were significantly higher than those at pre-transplantation. In contrast, the number of circulating CD19+CD27+IgD B cells was significantly increased in the TS groups in respect to the other groups. Moreover, the numbers of circulating CD4+CXCR5+IL-21+ TFH cells, CD19+CD86+CD38+ B cells as well as the level of serum IL-21 were positive related to the level of serum Cr while showing negative correlated with the values of eGFR in the AMR groups at post-transplantation for 4 and 12 weeks. Circulating TFH cells may be a biomarker in RTR with AMR, which can promote the differentiation of B cells into plasma cells by activating B cells, thereby promoting disease progression.

The Proteomic Signature of Intestinal Acute Rejection in the Mouse

Intestinal acute rejection (AR) lacks a reliable non-invasive biomarker and AR surveillance is conducted through frequent endoscopic biopsies. Although citrulline and calprotectin have been suggested as AR biomarkers, these have limited clinical value. Using a mouse model of intestinal transplantation (ITx), we performed a proteome-wide analysis and investigated rejection-related proteome changes that may eventually be used as biomarkers. ITx was performed in allogenic (Balb/C to C57Bl) and syngeneic (C57Bl) combinations. Graft samples were obtained three and six days after transplantation (n = 4/time point) and quantitative proteomic analysis with iTRAQ-labeling and mass spectrometry of whole tissue homogenates was performed. Histology showed moderate AR in all allografts post-transplantation at day six. Nine hundred and thirty-eight proteins with at least three unique peptides were identified in the intestinal grafts. Eighty-six proteins varying by >20% between time points and/or groups had an alteration pattern unique to the rejecting allografts: thirty-seven proteins and enzymes (including S100-A8 and IDO-1) were significantly upregulated whereas forty-nine (among other chromogranin, ornithine aminotransferase, and arginase) were downregulated. Numerous proteins showed altered expression during intestinal AR, several of which were previously identified to be involved in acute rejection, although our results also identified previously unreported proteome changes. The metabolites and downstream metabolic pathways of some of these proteins and enzymes may become potential biomarkers for intestinal AR.

Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases

Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.