Kind Of Rejection Research Articles

Tacrolimus Intrapatient Variability on Graft Outcomes inAdherent Renal Transplantation Patients: A Cross-SectionalStudy.

Tacrolimus is the mainstem of immunosuppressive therapy in kidney transplant patients. It has high intrapatient variability (Tac-IPV), which has been reported to affect graft function by predisposing patients to rejection or nephrotoxicity. We conducted this study with the aim of assessing the influence of Tac-IPV on 2-year graft function, biopsy-proven rejection, and infections in compliant renal recipients. In this single-center retrospective analytic cross-sectional study, 250 patients who underwent transplantation from March 21, 2018, to March 20, 2020 and had at least three outpatient tacrolimus trough levels on the same daily dose 6 to 12 months after transplantation were recruited. Tac-IPV was defined as a coefficient variation of > 15%. Graft function, biopsy-proven rejection, cytomegalovirus (CMV) and BK virus viremia, and calcineurin inhibitor (CNI) toxicity were evaluated. Of 202 transplant recipients, 128 were included with a mean age of 45.48 ± 13.14 years. The median Tac-IPV was 13.28% with 43.75% of patients with Tac-IPV > 15%. There were no significant differences in graft function, rejection, CNI toxicity, and CMV viremia among the groups during the 24-month study (P > .05). However, BK viremia was significantly higher among patients with Tac-IPV > 15% (13 vs. 2.9%, P = .042). The risk of antibody mediated rejection alone (22.7 vs. 2.9%) or any kind of rejection (22.7 vs. 11.8%) was significantly higher in patients with higher Tac-IPV, and in those who had mean trough levels below 7 ng/mL (P = .015, .032; respectively). Tac-IPV is low in adherent patients (with the median of 13.28%) and maintaining tacrolimus trough level above 7 ng/mL can overcome the adverse graft outcome of Tac-IPV in compliant kidney transplant recipients. DOI: 10.52547/ijkd.7815.

ExKidneyBERT: a language model for kidney transplant pathology reports and the crucial role of extended vocabularies.

Pathology reports contain key information about the patient's diagnosis as well as important gross and microscopic findings. These information-rich clinical reports offer an invaluable resource for clinical studies, but data extraction and analysis from such unstructured texts is often manual and tedious. While neural information retrieval systems (typically implemented as deep learning methods for natural language processing) are automatic and flexible, they typically require a large domain-specific text corpus for training, making them infeasible for many medical subdomains. Thus, an automated data extraction method for pathology reports that does not require a large training corpus would be of significant value and utility. To develop a language model-based neural information retrieval system that can be trained on small datasets and validate it by training it on renal transplant-pathology reports to extract relevant information for two predefined questions: (1) "What kind of rejection does the patient show?"; (2) "What is the grade of interstitial fibrosis and tubular atrophy (IFTA)?" Kidney BERT was developed by pre-training Clinical BERT on 3.4K renal transplant pathology reports and 1.5M words. Then, exKidneyBERT was developed by extending Clinical BERT's tokenizer with six technical keywords and repeating the pre-training procedure. This extended the model's vocabulary. All three models were fine-tuned with information retrieval heads. The model with extended vocabulary, exKidneyBERT, outperformed Clinical BERT and Kidney BERT in both questions. For rejection, exKidneyBERT achieved an 83.3% overlap ratio for antibody-mediated rejection (ABMR) and 79.2% for T-cell mediated rejection (TCMR). For IFTA, exKidneyBERT had a 95.8% exact match rate. ExKidneyBERT is a high-performing model for extracting information from renal pathology reports. Additional pre-training of BERT language models on specialized small domains does not necessarily improve performance. Extending the BERT tokenizer's vocabulary library is essential for specialized domains to improve performance, especially when pre-training on small corpora.

Evolved computers with culture. Commentary: From computers to cultivation: reconceptualizing evolutionary psychology

Evolved computers with culture. Commentary: From computers to cultivation: reconceptualizing evolutionary psychology

Rebuffs and rebuttals I: how rejected is rejected?

Rebuffs and rebuttals I: how rejected is rejected?

TAP1–/– mice present oligoclonal BV‐BJ expansions following the rejection of grafts bearing self antigens

Our previous work showed that transporter associated with antigen processing 1 (TAP1)-/- (H-2b) mice rejected grafts from H-2b mice which display a normal density of class I major histocompatibility complex (MHC) molecules at the cell surface. Our results indicated that H-2b molecules themselves may be a target in this kind of rejection and that CD4+ T cells play a major role in this autoreactive process. Our data also suggested that TAP1-/- mice, in addition to the well-recognized phenotype of class I and CD8+ T-cell deficiency, present a functional alteration in their autoreactive CD4+ T-cell repertoires. In this model of inflammatory autoreactivity to modified self, we have analysed T-cell receptor (TCR) V-beta-J-beta (BV-BJ) usage by complementarity determining region 3 (CDR3) length spectratyping in splenocytes from naïve TAP1-/- mice and transplanted TAP1-/- mice that rejected B6 heart grafts or responded to synthetic self H-2Kb peptides. Importantly, oligoclonal T-cell expansions shared by different animals were detected in the peripheral T-cell repertoire of transplanted TAP1-/- mice. Such public expansions were also induced in vitro by H-2Kb peptides, suggesting that dominant class I peptides can induce preferential expansions of restricted T-cell populations during rejection. Some of these public T-cell expansions were also detected in transplanted mice even before in vitro stimulation with peptides, indicating that post-transplantation expansion of these populations had occurred in vivo. The functional activity of these T-cell populations awaits elucidation, as do the underlying mechanisms involved in the inflammatory autoreactive process, in TAP1-/- mice.

Non-adaptive cellular immune responses as studied in euthymic and athymic nude rats

The athymic nude (rnu) rat lacks a functional thymus and normal alloreactive T cells. These animals, therefore, have been widely used as tools for studying thymus-independent immune responses. The absence of functional T cells would, to most investigators, indicate that these rats have a defective cellular immune defence. However, although rnu rats accept organ allografts infinitely, they are nevertheless capable of rejecting allografts consisting of lymphocytes or bone marrow cells with increased vigour, and this via antibody-independent mechanisms. These rejection phenomena have operationally been termed allogeneic lymphocyte cytotoxicity (ALC) and allogeneic bone marrow cell cytotoxicity (ABC). Unlike organ allograft immunity this kind of rejection requires no presensitization of the recipient and is surprisingly rapid: it commences within a few hours of i.v. injection of the allogeneic cells and is usually complete by 24 h. Moreover, products coded for by genes within, or closely linked to the major histocompatibility complex (MHC), are clearly involved in the interaction between effector and target cells, as grafted cells from MHC-congenic rat strains are vigorously rejected. In contrast to the defective T cell immune responses in athymic nude rats, the natural killer (NK) cell function is not impaired, and it has been suggested that the spontaneous rejection of MHC-incompatible lymphohematopoietic cells is in fact mediated by NK cells. If the MHC antigens themselves serve as targets in this kind of allorejection, this hypothesis is in apparent contrast with the prevailing view that recognition by NK cells is not guided by, or directed against, MHC-antigens on the target cell surface. Aging athymic nude mice and rats generate cells that rearrange and express T cell receptor (TCR) genes, and this has raised the possibility that T cells or T-like cells in athymic nude animals are responsible for ALC and ABC. This possibility urged the device of an in vitro test system for identification and further characterization of the effector cells in these rejection phenomena. Under appropriate conditions, cells from the rnu rat spleen or liver with natural killer function, i.e. the ability to lyse certain kinds of tumor cells in vitro, are also spontaneously cytotoxic for allogeneic small lymphocytes and bone marrow cells in vitro. Furthermore, these cells can be grown in vitro in the presence of interleukin 2 (IL-2) to generate populations of lymphokine-activated killer (LAK) cells, and these cells have the same spectrum of alloreactivity in ALC and ABC as the native NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Rejection and the use of chemical agents

The Avoidance of Rejection Scales (of self, by others and of others) were specifically developed to assist the psychometric documentation of choice of an avoidance versus confrontation strategy to the issue of rejection. Three kinds of rejection were examined concurrently with respect to the use of 7 chemical agents related to health and social behavior: tobacco, alcoholic beverages, tranquilizers, medication, stimulants, soft drugs (such as marijuana), and hard drugs (such as heroin). Results of analysis based on a sample of 300 individuals revealed that Low scorers (confronters) reported less use of chemical agents in 15 of the 18 cases wherein a posteriori comparisons among High, Medium and Low Scorer Groups indicated statistically significant differences. Some indication of curvilinearity was indicated in 5 of the statistically significant comparisons. In addition, the strongest linearity between the Rejection Scales and the use of Chemical Agents appeared in the following descending order: Of Others, Of Self and By Others. These results suggest a value to awareness strategies, though not in all cases.