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Impaired microcirculatory function after heart transplantation is associated with increased risk for acute cellular rejection. Microvascular resistance reserve (MRR) is a novel index for assessing microcirculatory function, irrespective of epicardial coronary artery stenosis, but it has not been validated in transplanted hearts. The aim of this study was to investigate the prognostic impact of MRR in heart transplantation. The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. Coronary microcirculatory dysfunction was defined as MRR ≤3.0. Elevated microcirculatory resistance was defined as an index of microcirculatory resistance ≥15. The presence of epicardial coronary stenosis was assessed by fractional flow reserve. The primary outcome was a composite of death or biopsy-proven acute cellular rejection of grade ≥ 2R after transplantation. Among the total patients, 22.1% (34 of 154) had impaired microcirculatory function (MRR ≤3.0), and 77.9% (122 of 154) had preserved microcirculatory function (MRR >3.0). During median follow-up of 730 days (Q1-Q3: 730-730 days), patients with MRR ≤3.0 showed increased risk for a composite of death or acute cellular rejection (adjusted HR: 5.31; 95% CI: 2.65-10.64; P < 0.001), acute cellular rejection (adjusted HR: 4.83; 95% CI: 2.20-10.60; P < 0.001), and death (adjusted HR: 5.19; 95% CI: 1.24-21.62; P = 0.024). MRR was significantly associated with increased risk for death or acute cellular rejection, regardless of epicardial coronary artery stenosis (HR adjusted for fractional flow reserve: 1.89 per 1-U decrease in MRR; 95% CI: 1.46-2.46; P < 0.001) or elevated microcirculatory resistance (HR adjusted for index of microcirculatory resistance: 1.90 per 1-U decrease in MRR; 95% CI: 1.43-2.52; P < 0.001). Impaired microcirculatory function, determined by MRR early after heart transplantation, identified patients at high risk for death or acute cellular rejection, regardless of epicardial coronary artery stenosis or elevated microcirculatory resistance. (Physiologic Assessment of Microvascular Function in Heart Transplant Patients; NCT02798731) [Display omitted] [ABSTRACT FROM AUTHOR]

The role of bronchus-associated lymphoid tissue (BALT) in the regulation of immune responses to transplanted lungs remains an area of interest and controversy. Early studies in a rat pulmonary transplant model suggested BALT may accelerate rejection of grafts by inducing a local and systemic inflammatory response. Such observations were corroborated in intrapulmonary tracheal transplant models in the rat. While some human studies have described the presence of BALT in grafts that have been chronically rejected, others did not observe an association between induction of BALT and adverse outcomes. More recent investigations have found that BALT, enriched in immunoregulatory cell populations, is induced in tolerant mouse lung allografts, suggesting that such structures may be protective against rejection. Thus, the role of BALT in lung transplantation biology is complex. Insights gained from studies that focus on the role of BALT in lung transplantation may be harnessed to develop new therapies. [ABSTRACT FROM AUTHOR]

This paper aims to explore the queer experiences of black individuals through the lens of Uzodinma Iweala’s 2018 novel Speak No Evil. The narrative follows Niru, a gay Nigerian-American teenager who navigates the complexities of his identity and sexuality within the confines of his conservative family and community. By closely analysing the text, this study emphasises how the novel challenges heteronormative assumptions and examines the effects of homophobia. Individuals often face double marginalisation due to the intersection of their social identities, where multiple forms of discrimination compound their challenges. The analysis reveals how Niru’s struggles are further complicated by his status as a non-white individual in a predominantly white society. Ultimately, it provides a poignant reflection on the universal human desire for love, belonging, and the bravery required to live authentically. By placing the novel within the larger context of queer black literature, this paper argues that Speak No Evil is a significant and timely contribution to the canon, offering essential representation of the varied lived experiences of queer black people. This study highlights the importance of such narratives in cultivating empathy and enhancing a more inclusive understanding of human identity. [ABSTRACT FROM AUTHOR]

We aimed to compare the anti-angiotensin II type I receptor (AT1R) antibody levels considering the development of anti-HLA antibodies after transplantation, pathologically confirmed humoral or vascular rejection reactions and late complications.Forty-nine hypertensive patients who had presented to the Division of Nephrology, Transplantation Outpatient Clinic of Memorial Health Group Hospitals Transplant Units and Istanbul Medical Faculty for live kidney transplantation and underwent transplantation between 2015 and 2019, were included in our study. Among our patients (29 males/20 females), 76 % had primary hypertension, and 24 % had secondary hypertension. In this study, serum AT1R antibody levels before and after transplantation were measured using the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. The anti-HLA antibody was detected with the Luminex method using the single antigen bead (SAB) assay.The AT1R antibody was found positive in 7 (18.9 %) of 37 patients who had primary hypertension and in 4 (33.3 %) of 12 patients who had secondary hypertension (p=0.426). The examination of the frequencies of development of post-transplant anti-HLA antibodies showed that the frequency of AT1R antibody positivity was found higher in the group with positive anti-HLA antibodies compared to the levels in the group with negative anti-HLA antibodies (p=0.002). The comparison of the pre-transplant and post-transplant values showed that the AT1R antibody level was statistically significantly decreased after transplantation [7.3/6.6 (3.2–21.1) vs. 6.2/4.7 (1.5–24.5), p=0.001].The findings of our study suggest that the evaluation of the AT1R antibody levels among non-HLA antibodies may be important for predicting the immunological risk before transplantation. [ABSTRACT FROM AUTHOR]

Understanding donor-reactive T-cell behavior post-transplantation is challenging owing to the rarity and diversity of these cells. Here, we aimed to evaluate the relevance of an assay for rapidly detecting alloreactive T cells in a mouse transplantation model. After 18 h of one-way mixed lymphocyte reaction (MLR) culture with pre-activated donor-derived stimulators, CD4+ and CD8+ donor-reactive T cells were identified by CD154 and CD137 expression, respectively. Using full MHC mismatched mouse skin transplant models, we observed an increased donor-reactive T-cell proportion by direct presentation with elevated interferon gamma and granzyme B production 7 days post-transplantation, before graft rejection. Immunosuppression with CTLA-4 IgG and anti-CD154 antibody varied depending on donor-recipient strain combinations. On day 7, donor-reactive CD8+ T-cell proportions were lower in the tolerance model (BALB/c to C3H/HeJ) than in the rejection model (BALB/c to C57BL/6); conventional proliferation readout after 4 days of MLR could not distinguish these responses. Overall, although the conventional readout for evaluating T-cell proliferation following an MLR quantifies the precursor frequency of alloreactive T cells, the assay reported herein assesses T-cell activation markers after a short-term MLR to characterize immediate immune status. These findings offer a promising tool to elucidate immune responses post-transplantation. [ABSTRACT FROM AUTHOR]

Background: The role of regulatory CD8pos T cells (CD8pos Tregs) and cytotoxic CD8pos responder T cells (CD8pos Tresps) in maintaining stable graft function in kidney transplant recipients (KTR) remains largely unclear. The pathogenesis of graft deterioration in case of rejection involves the exhaustive differentiation of both CD8pos T cell subsets, but the causal mechanisms have not yet been identified. Methods: In this study, we separately investigated the differentiation of CD8posTregs/Tresps in 134 stable KTR with no evidence of renal graft rejection, in 41 KTR diagnosed with biopsy-confirmed rejection at enrolment and in 5 patients who were unremarkable at enrolment, but developed rejection within three years of enrolment. We were investigating whether changed differentiation of CCR7posCD45RAposCD31pos recent thymic emigrant (RTE) cells via CD45RAnegCD31pos memory (CD31pos memory) cells (pathway 1), via direct proliferation (pathway 2), or via CCR7posCD45RA+CD31neg resting mature naïve (MN) cells (pathway 3) into CD45RAnegCD31neg memory (CD31neg memory) cells affects the CD8pos Treg/Tresp ratio or identifies a CD8pos Treg/Tresp subset that predicts or confirms renal allograft rejection. Results: We found that RTE Treg differentiation via pathway 1 was age-independently increased in KTR, who developed graft rejection during the follow-up period, leading to abundant MN Treg and central memory Treg (CM Treg) production and favoring a strongly increased CD8pos Treg/Tresp ratio. In KTR with biopsy-confirmed rejection at the time of enrolment, an increased differentiation of RTE Tregs into CCR7negCD45RAposCD31neg terminally differentiated effector memory (CD31neg TEMRA Tregs) and CD31pos memory Tregs was observed. CD31neg memory Treg production was maintained by alternative differentiation of resting MN Tregs, resulting in increased effector memory Treg (EM Treg) production, while the CD8pos Treg/Treg ratio was unaffected. An altered differentiation of CD8pos Tresps was not observed, shifting the Treg/Tresp ratio in favor of Tregs. Conclusions: Our results show that exhaustive CD8pos Treg differentiation into CM Tregs may lead to future rejection, with a shift towards EM Treg production and an accumulation of CD31neg TEMRA Tregs in KTR with current rejection. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is a life-saving treatment for end-stage kidney disease, but allograft rejection remains a critical challenge, requiring accurate and timely diagnosis. The study aims to evaluate the integration of Fourier Transform Infrared (FTIR) spectroscopy and machine learning algorithms as a minimally invasive method to detect kidney allograft rejection and differentiate between T Cell-Mediated Rejection (TCMR) and Antibody-Mediated Rejection (AMR). Additionally, the goal is to discriminate these rejection types aiming to develop a reliable decision-making support tool. Methods: This retrospective study included 41 kidney transplant recipients and analyzed 81 serum samples matched to corresponding allograft biopsies. FTIR spectroscopy was applied to pre-biopsy serum samples, and Naïve Bayes classification models were developed to distinguish rejection from non-rejection and classify rejection types. Data preprocessing involved, e.g., atmospheric compensation, second derivative, and feature selection using Fast Correlation-Based Filter for spectral regions 600–1900 cm−1 and 2800–3400 cm−1. Model performance was assessed via area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, and accuracy. Results: The Naïve Bayes model achieved an AUC-ROC of 0.945 in classifying rejection versus non-rejection and AUC-ROC of 0.989 in distinguishing TCMR from AMR. Feature selection significantly improved model performance, identifying key spectral wavenumbers associated with rejection mechanisms. This approach demonstrated high sensitivity and specificity for both classification tasks. Conclusions: The integration of FTIR spectroscopy with machine learning may provide a promising, minimally invasive method for early detection and precise classification of kidney allograft rejection. Further validation in larger, more diverse populations is needed to confirm these findings' reliability. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the diagnostic accuracy of combining donor-derived cell-free DNA (dd-cfDNA) fraction and absolute quantification in detecting kidney allograft rejection. Methods: A prospective study was conducted from December 2019 to April 2021 at the First Affiliated Hospital of Sun Yat-sen University. Kidney transplant recipients who underwent biopsy, including cases of T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and borderline rejection, were included. dd-cfDNA fraction and absolute concentrations were measured, and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) analysis. The double-positive and double-negative methods were applied to assess performance. Results: A total of 50 kidney transplant recipients were included. The dd-cfDNA fraction cutoff of 1.08% achieved 93.33% sensitivity and 91.43% specificity (AUC = 0.95), with an NPV of 96.97% and a PPV of 82.35%. The absolute dd-cfDNA threshold of 32 cp/mL yielded 80.00% sensitivity and 71.43% specificity (AUC = 0.78), with an NPV of 89.29% and a PPV of 54.55%. The double-positive method provided superior accuracy, with a PPV of 91.67% and an NPV of 89.47%, demonstrating 73.33% sensitivity and 97.14% specificity. The double-negative method achieved 100% NPV and 100% sensitivity. Conclusions: Combining dd-cfDNA fraction and absolute quantification improves diagnostic accuracy for kidney transplant rejection, especially ABMR. The double-positive and double-negative approaches show high predictive value, offering potential clinical value for monitoring kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Mucosal or endobronchial biopsies (EBB) are typically used in the diagnosis of directly visualized bronchial lesions, infection, and sarcoidosis, but their utility in the evaluation of lung transplant recipients is controversial. EBB represents an attractive alternative to transbronchial biopsy (TBB): EBB provides straightforward sampling of airway pathology with decreased complication rates due to minimal and visualizable bleeding and the elimination of pneumothorax risk. In lung transplant recipients, EBB may be obtained when TBB is too high-risk, including in the setting of acute lung allograft dysfunction (ALAD) requiring mechanical ventilation or in advanced chronic lung allograft dysfunction (CLAD). Most centers do not include EBB in post-transplant surveillance or for-cause bronchoscopy protocols, possibly due to a lack of a common histologic interpretation system. Previous work has demonstrated that lymphocytic inflammation in lung transplant EBB is associated with acute cellular rejection and future risk for CLAD, but these have not translated into subsequent studies on clinical utility or into clinical practice. Recent multicenter studies suggest that gene expression-based diagnostics leveraging EBB may outperform histologic grading and provide important prognostic utility in predicting graft loss. Herein, we will review what is known about the lung transplant mucosa including recent diagnostic advances and propose how EBB analyses could be incorporated into research studies and clinical workflows. We propose that mucosal sampling could provide safe, consistent, and informative data to improve patient outcomes after lung transplant. [ABSTRACT FROM AUTHOR]

AbstractMinority stress theory posits a direct link for LGBTQ+ individuals between societal treatment (distal factors) and health concerns (Brooks, 1981; Meyer, 2003). Bi+individuals (individuals who are attracted to more than one gender) have disproportionately high rates of these concerns (Polihronakis et al., 2021). This study uses a reflexive thematic analysis to understand the biphobic experiences of bi+ men in hopes of knowing how best to tailor interventions aimed at reducing adverse health outcomes. Covert and overt experiences such as microaggressions, rejection, discrimination, harassment, and trauma were identified as common themes. Internalized biphobia was found to be a major commonality, typically following a biphobic event. Several participants also identified a religious basis for their experiences of biphobia. Participants identified these experiences as having a significant impact on their wellbeing. Each of the participants shared stories that provide insight into bi+ men’s experiences with biphobia. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4+ T cells (CD4+Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4+Tm, and the EdU method was used to detect the effect of Stattic on CD4+Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4+Tm (CD4+CD44+CD62L+) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4+Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4+Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4+Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4+Tm- mediated acute rejection. [ABSTRACT FROM AUTHOR]

For patients with end-stage heart disease and borderline hemodynamics, high human leukocyte antigen allosensitization presents a barrier to heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant on a single patient without liver disease. We describe this patient's course to date as well as 4 subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization. [ABSTRACT FROM AUTHOR]

This autoethnography focuses on the entanglements of how various forms of "rejection" and/or "exclusion" hit the embodied knowing of the immigrant "I" and their multiple ways of being and doing. In examining a multiplicity of selves, the author expresses their inner experiences as an outsider across various times and places. Through a poetic space, certain life events, emerging from the language's performativity, permit us to read life-writing texts not as a record but as the liminal space where a sense of self is realized or, in some instances, de-realized. The author questions whether it is even possible for the rejected individuals to articulate their realities in academy. This work encapsulates the theme of searching for a place, both physically and metaphorically. This article calls for the ethical necessity of writing personal experiences as felt knowledge, rectifying the prevailing discourse about an/other's being and knowing. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that 1-year graft and recipient survival rates are above 90% in most transplant centers, improving long-term graft survival remains an important challenge. Immunosuppressant nonadherence has been recognized as one of the important risk factors for long-term graft failure. Understanding the modifiable correlates and risk factors for medication non-adherence is essential to develop interventions to improve adherence and thus long-term transplantation outcomes. Methods: This study conducted a questionnaire survey on 431 renal transplant recipients who were followed up in the outpatient clinic between January 2022 and January 2023, and 409 valid questionnaires were returned. The BAASIS questionnaire was used to assess the prevalence of nonadherence to immunosuppressive therapy (implementation phase) in Chinese renal transplant recipients and to explore the multilevel correlates of immunosuppressive nonadherence. The BAASIS questionnaire was used to categorize renal transplant recipients into adherent (n = 239) and non-adherent (n = 170) groups, and a prospective cohort study with a 1-year follow-up was conducted to explore the impact of immunosuppressant non-adherence on clinical outcomes. Results: The prevalence of nonadherence to immunosuppressant therapy in renal transplant recipients in this study was as high as 41.6%. The number of years post-transplant (OR: 1.240, 95% CI: 1.136–1.353, p < 0.001) and the frequency of twice-daily dosing (OR: 5.145, 95% CI: 2.690–9.840, p < 0.001) were positively correlated with immunosuppressive nonadherence. There was a significant difference in TAC IPV (Intra-individual Variability) between the adherent and nonadherent groups (22.7 ± 8.7 vs. 25.4 ± 11.6, p = 0.010). Renal function remained stable during the follow-up period in the recipients in the adherence group and tended to decrease in the recipients in the non-adherence group (F = 4.932, p = 0.001). The rates of graft loss (7.1% vs. 1.7%, p = 0.006) and rejection (12.4% vs. 4.2%, p = 0.002) were higher in the nonadherent group than in the adherent group. Conclusion: Longer time post-transplant and higher frequency of immunosuppressive dosing were positively associated with nonadherence to immunosuppressives medication. Immunosuppressant nonadherence was associated with adverse graft outcomes. [ABSTRACT FROM AUTHOR]

The majority of submitted manuscripts, across all article-journal types, may be rejected for one or more reasons... While the reasons for rejection vary between desk, post-peer-review, and post-editorial-review rejections, many of the issues raised could be easily avoided by devoting enough time to planning and conceptualizing the work under consideration. Indeed, Aristotle (384--322 BC) in the Rhetoric (the art of persuasion), which was a theory of - civic discourse - stated: "The mistake lies in the beginning; as the proverb says, 'Well begun is half done;' so an error at the beginning, though quite small, bears the same ratio to the errors in the other parts." This quote seems especially appropriate in this case. This paper examines the various reasons for which an article may not be accepted or considered for publication and then the paper moves into providing an explanation of the different reasons by which an article may not be considered for publication based on the reviewer's belief, faith, professional discrepancies or methodological outcomes. Well organised and sufficient preparation is the key to success. The authors hope that people across academia and other professional experts can use this discussion when leading trainingbuilding research workshops to create awareness and assist researchers in planning and writing research papers that have better probabilities of acceptance, yet are easy to assimilate for the average reader and truly advance knowledge. [ABSTRACT FROM AUTHOR]