Citations

ABSTRACT Post-transplant lymphoproliferative disease (PTLD) remains a challenging and high-impact complication of kidney transplantation, requiring thoughtful prevention, timely recognition, and multidisciplinary management. Key strategies include careful selection of immunosuppressive regimens, particularly avoiding belatacept in Epstein–Barr virus (EBV)-seronegative recipients and exercising caution with lymphodepleting induction in EBV-mismatched pairs, along with targeted EBV surveillance in high-risk patients. Once PTLD is suspected or confirmed, accurate staging and a stepwise treatment approach beginning with reduction of immunosuppression and escalating to rituximab, chemotherapy, or advanced cellular therapies are essential, with EBV-CTLs and chimeric antigen receptor T-cell therapy offering promising options in refractory disease. Close monitoring for infectious complications, cytopenias, and rejection is critical throughout treatment. Importantly, a prior history of PTLD should not preclude future transplantation in appropriately selected patients with sustained remission. Continued research is needed to refine surveillance strategies, clarify optimal treatment sequencing, and improve long-term outcomes for kidney transplant recipients at risk for or affected by PTLD.

Objective Pre‐mortem diagnosis of parkinsonism is often challenging due to atypical presentations, overlapping syndromes, and co‐pathologies. This study aimed to develop a machine learning‐based algorithm predicting neuropathology in parkinsonism using chronological clinical presentations, which has previously been underexplored. Methods Clinical information was automatically abstracted from medical records of the Mayo Clinic Brain Bank using fine‐tuned Generative Pre‐trained Transformer 4 models. Patients who developed parkinsonism within 3 years of disease onset were included. Six machine learning models were trained with age, sex, family history, and 197 clinical presentations paired with onset information to predict neuropathologic diagnoses, including co‐pathologies. Results Among 7,825 donors, 949 met inclusion criteria, representing 9 neuropathologic categories: Lewy body disease (LBD; n = 128), LBD with Alzheimer's disease (AD; n = 136), progressive supranuclear palsy (PSP; n = 303), PSP with AD (n = 56), PSP with LBD (n = 27), multiple system atrophy (MSA; n = 120), corticobasal degeneration (CBD; n = 99), AD (n = 43), and frontotemporal lobar degeneration (FTLD; n = 37). The CatBoost algorithm achieved an area under the receiver operating characteristic curve of 0.83 across the 9 diagnostic categories at 3 years after onset. Important predictors included age at onset, restricted eye movement, and tremor. The model remained robust to incomplete data, requiring only 23 of 200 parameters for reliable predictions with an area under the curve of 0.80. The algorithm was implemented into a user‐friendly program providing diagnostic probabilities with visualizations of parameter contributions. Interpretation This neuropathology‐confirmed diagnostic algorithm provides a cost‐effective and interpretable screening tool for parkinsonism, bridging biomarker testing and molecular‐targeted therapies. ANN NEUROL 2026;99:1405–1414

Purpose of review Living donor transplantation is the optimal treatment for end-stage renal disease and end-stage liver disease. For the recipient, the benefits of living donation include improved duration of graft survival compared to deceased donation and avoidance of lengthy waiting time and risks of dialysis. For transplant centers, a robust living donor program results in consistent transplant case volumes, daytime cases and a decreased reliance on potentially unfavorable allocation policy changes. Transplant programs require a playbook of actionable initiatives based on consensus best practices and peer-reviewed data to optimize opportunities to increase living donor evaluation and surgery within current legal and policy frameworks. Relevant findings Strategies to increase center living donor volume include utilization of culturally competent transplant education and outreach, development of living donor champion programs, wider utilization of financial assistance programs available to living donors, increased enrollment in paired donor exchange services and adaptation of modern evidence-based selection and evaluation criteria. Summary Understanding the current landscape of living donor transplantation and exploring areas of innovation is imperative to a center's ability to continue to serve the full spectrum of patients with end stage organ disease to the best of our collective ability.

Abstract The role of DNA topoisomerase II beta (TOP2B) in cardiomyocyte differentiation is poorly understood. To address this, Human induced pluripotent stem cells (hiPSC) were differentiated into cardiomyocytes (CM) that are wildtype or contain a genomic deletion of Topoisomerase 2B (BKO). Both WT and BKO hiPSC could be induced to differentiate into sheets of beating cardiomyocytes. BKO hiPSC take slightly longer to differentiate into sheets of beating CM than WT iPSC. RNA was prepared from both undifferentiated and differentiated WT and BKO hiPSC. RNA seq was used to examine gene expression changes when the WT and BKO hiPSC were differentiated into CM. Gene expression changes following differentiation of BKO cells were largely similar to those in WT cells. In addition, the differentiated WT CM were treated with dexrazoxane (ICRF-187), a TOP2 catalytic inhibitor that targets both TOP2A and TOP2B, or topobexin, a new TOP2B selective catalytic inhibitor. Topobexin inhibition partially phenocopied a TOP2B deletion and thus providing an alternative to TOP2B gene knockout in many cell lines. In future, hiPSC derived CM with and without TOP2B and inhibition by topobexin ex vivo CM could be used to study anthracycline-induced cardiotoxicity and to screen for cardioprotectants. Highlights Used CRISPR-Cas9 to delete TOP2B from hiPSC Produced beating cardiomyocytes from both WT and TOP2B null hiPSC Transcriptome analysis of WT and TOP2B null hiPSC and derived cardiomyocytes RNA seq showed he specific TOP2B inhibitor topobexin largely phenocopies TOP2B gene inactivation in iPSC derived cardiomyocytes. Topobexin inhibition could be used as an alternative to a TOP2B gene knockout in many different cell types, speeding up the analysis of the function of TOP2B.

ABSTRACT Background Adolescent and young adult (AYA) kidney transplant recipients (KTR) are susceptible to risk‐taking behaviors that peak during transfer from pediatric to adult healthcare, resulting in poorer outcomes. Professional guidelines support healthcare transition (HCT) practices to mitigate this risk; however, HCT perspectives and practices among providers, especially adult providers caring for KTR in the US, have not been widely studied. Methods An online survey of American Society of Transplantation (AST) members was conducted targeting both adult providers (AP) and pediatric providers (PP). Results The survey was completed by 135 respondents (predominantly US), including 61 PP and 74 AP. US respondents who disclosed their center ID represented 30% of all programs. Providers agreed that HCT was important (PP 97%, AP 94%) and a shared responsibility (PP 91% and AP 84%). Respondents to our survey frequently worked within transition programs (PP 70% vs. AP 48%), but the majority did not have a formal HCT policy to guide them (PP 43%, AP 21%). Multidisciplinary transition clinics were rare (PP 27%, AP 23%). Only 64% of PP included targeted HCT education either as part of a routine visit or a HCT session. Perceived barriers to providing HCT interventions were similar in both groups, including a lack of provider resources, outcomes tracking, provider communication, and patient/caregiver feedback. Conclusion Providers recognize the importance of HCT and the joint responsibility of PP and AP but have difficulty following best practices. A multipronged approach will be necessary to address barriers. Our survey reminds us of the gap that persists in providing AYAs with a seamless transfer from pediatric to adult care.

ABSTRACT Background Infection enteritis is associated with the development of irritable bowel syndrome (IBS) and functional dyspepsia. Aim This study aimed to examine the long‐term risk of IBS and functional dyspepsia, and associated health care utilisation following infection enteritis. Methods We conducted a retrospective cohort study using TriNetX U.S. Network. Adults with infection enteritis were identified and matched to controls, balancing demographics and comorbidities. Primary outcomes were the risk of incident IBS and functional dyspepsia diagnoses at 1, 5, and 10 years. Secondary outcomes were rates of IBS‐ and functional dyspepsia‐related medications, endoscopy, abdominal imaging, and hospitalizations. Pathogen‐specific and multivariate analyses were performed to assess variations in IBS risk. Results After matching, 202,244 patients were identified in each study cohort. At 1 year of follow‐up, the infection enteritis cohort had higher rates of IBS (RR = 2.35; 95% CI: 2.14–2.59), functional dyspepsia (RR = 2.02; 95% CI: 1.84–2.22), use of IBS‐related medications (RR = 1.29; 95% CI: 1.26–1.31), functional dyspepsia‐related medications (RR = 1.56; 95% CI: 1.55–1.59), abdominal imaging (RR = 2.42; 95% CI: 2.29–2.54), and Oesophagogastroduodenoscopy/colonoscopy (RR = 1.57; 95% CI: 1.50–1.65). These risks remained significantly higher in the IE cohort at 5 and 10 years. Salmonella/Shigella (RR = 6.48), and Giardia lamblia (RR = 5.05) had the highest risk of developing incident IBS. Conclusion Infection enteritis was associated with increased risk of IBS and functional dyspepsia, rates of related medication use, and greater healthcare utilisation.

Summary Human parvovirus B19 (B19V) exhibits a strict tropism for erythroid progenitor cells, which is governed by the VP1 unique region (VP1u). This region mediates cell-specific uptake by interacting with an unknown cellular receptor, termed VP1uR. Proximity labeling in permissive erythroid cells identified transferrin receptor 1 (TfR1/CD71) as the predominant membrane protein associated with VP1u. VP1u constructs colocalized with TfR1 at the cell surface of erythroid cells. Incubation with anti-TfR1 antibody OKT9 abolished binding and uptake of recombinant VP1u. While OKT9 efficiently inhibited B19V uptake and infection, it did not block virus binding to host cells. Direct binding assays confirmed interaction of VP1u to human TfR1. Using cryoEM we solved the 2.4 Å structure of the TfR1-VP1u complex, mapping the binding site and identifying the specific interactions. These findings establish TfR1 as the previously unknown receptor, VP1uR, required for B19V uptake.

Abstract GPNMB (Glycoprotein non-metastatic melanoma protein B) is a canonical transcriptional target of MiT/TFE proteins (TFEB/TFE3/MITF), expressed at low levels in normal tissues but upregulated in numerous MiT/TFE-driven tumors such as translocation RCC, alveolar soft part sarcoma and MITF-driven melanoma, where it is associated with poor prognosis. CDX-011 (CR011-MMAE) is an anti-GPNMB ADC, with demonstrated efficacy in pre-clinical models of TFE3-fusion RCC. To further characterize GPNMB functionality and value as a cell-surface therapeutic target in tRCC, we engineered cell lines with genomic deletion of GPNMB via CRSIPR-Cas9 editing. Deletion of GPNMB in PRCC-TFE3 cell lines [UOK120/UOK124] significantly decreased clonogenic growth in 2D, spheroid size and viability and tumor xenograft growth in NSG mice and was associated with a decrease in phosphorylation of mTORC1 substrates [p-P70S6K, p-4EBP1]. We then examined expression of CD44, the primary receptor for GPNMB, and a tumor-associated antigen associated with poor prognosis in many cancers. Expression of CD44 and its ligand SPP1/OPN, was significantly increased in bulk RNA-Seq data from multiple transgenic models of SFPQ-TFE3, PRCC-TFE3 and ASPSCR1-TFE3, in human tRCC cases compared to normal kidney, and in SFPQ-TFE3/ PRCC-TFE3 transgenic kidney tumors and an ASPSCR-TFE3 PDX model, by immunoblotting and IHC, with increased membrane localization. shRNA-mediated depletion of CD44 profoundly and specifically decreased clonogenicity of multiple TFE3-fusion lines, with no effect seen in ccRCC lines. In conclusion, GPNMB regulates the growth of tRCC cells, potentially via an autocrine mechanism involving its receptor CD44, and targeting GPNMB-CD44 signaling may be of therapeutic benefit in tRCC. Citation Format: Kaushal Asrani, Juhyung Woo, Kewen Feng, Thiago Vidotto, Adrianna Amaral, Vikrant Palande, Jayaprakash Mandal, Eddie Imada, Christopher Thoburn, Sangeeta Ray, Huili Li, Yasser Ged, Nirmish Singla, John A. Copland, Laura Schmidt, W. Marston Linehan, Pedram Argani, Tamara Lotan. GPNMB:CD44 signaling drives tumor progression in translocation renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Kidney Cancer Research: From Molecular Insights to Therapeutic Breakthroughs; 2026 Mar 13-16; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_2):Abstract nr B014.

Individuals with inflammatory bowel disease (IBD) experience overlooked deficits in objectively measured cognitive functioning; however, there is limited knowledge about self-reported cognitive symptoms in this group. Sleep characteristics, such as insomnia, poor sleep quality, or fragmented sleep, may be key modifiable factors that are associated with cognitive symptoms among individuals with IBD. This study aimed to describe cognitive symptoms and examine the relationship between these symptoms and sleep characteristics among adults with IBD. We conducted a descriptive, cross-sectional study using the Pittsburgh Sleep Quality Index, wrist actigraphy, the Insomnia Severity Index, and the FACT-Cog Perceived Cognitive Impairments subscale. Bivariate statistics were used to evaluate relationships between variables. The sample included 83 participants (mean age 40.44 years [standard deviation 10.7], 71% female). Over 77% ( n = 60) had poor self-reported sleep quality, and 69.5% ( n = 57) had clinically meaningful insomnia. The most frequently reported cognitive symptoms (experienced two or more times a week) were trouble concentrating (51.3%), forgetting names (43.8%), forgetting intended tasks (38.9%), and slow thinking (37.6%). Insomnia severity was moderately correlated with three out of the four most common cognitive symptoms (trouble concentrating: r s = .51, p < .01; forgetting intended tasks: r s = .38, p < .01; slow thinking: r s = .46, p < .01). Future research is needed to examine relationships between objective cognitive measures and sleep characteristics and to test the effects of insomnia treatment on daytime cognitive symptoms in this complex patient population.