Citations

Abstract Introduction: Attending to survivorship including distress in the contexts of social drivers (SDH) is critical but lacking. In response, this novel research on Black CaP survivors (CaPS) aims to measure SDH distresses and assess utility of a digital intervention to inform survivorship studies, practice and outcomes. Method: Informed by the Science of Survivorship, and our pilot study with multisectoral stakeholders, we assessed SDH and acceptability/utility of a digital Survivorship Care (SC) Toolkit. SCToolkit is a digitized whole-person care with guidance from multisectoral stakeholders e.g., clinicians and survivors. SCToolkit includes: ASCO informed treatment summary template for diagnostics, treatments, side effects, care team, genetics, and comorbidities, and patient active guide on survivorship concerns, provider communication, health advisories, survivorship care booklet, SDH FINDHELP resource, and survivorship videos. SCToolkit was delivered via survivors’ personal REDCap file, and can be uploaded to their EMR patient portal for easy-to-use survivorship roadmap accessible on smartphones, laptops, and computers. Motivational Interviewing was provided via Zoom to facilitate digital efficacy and SCToolkit use. Descriptive analyses were conducted using SAS. Citation Format: Kimlin Ashing, Floyd Willis, Christopher Williams, John McCall, Gaole Song, Douglas Adu-Fokuo, Erika Galdamez, Fornati Bedell, Cassandra N. Moore, EWAN COBRAN, Che Ngufor, Kathleen J. Yost, Timethia J. Bonner, Getachew Dagne, Arnold Merriweather, Ernest T. Kaninjing, Rotimi Oladapo, Roxana S. Dronca, Folakemi T. Odedina. Examining contextual distress and utility of a digital survivorship care toolkit [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 880.

A bstract Alzheimer’s disease (AD) presents with substantial clinical and anatomical heterogeneity, including both typical amnestic and atypical variants such as posterior cortical atrophy and logopenic primary progressive aphasia. Although neurofibrillary tangle (NFT) burden is a defining pathological feature of AD, its regional distribution varies across clinical phenotypes, suggesting that selective neuronal vulnerability may shape disease presentation. However, the cellular and molecular determinants underlying this vulnerability remain incompletely understood. Here, we profiled single-nucleus transcriptomes across multiple brain regions, including hippocampal (CA1) and neocortical (superior temporal gyrus and occipital cortex) regions, from individuals with typical and atypical AD and healthy controls. Integrative analysis identified major cell classes and resolved diverse excitatory and inhibitory neuronal subpopulations that were reproducibly observed across regions and individuals. Using quasi-binomial regression models to assess compositional changes, we quantified subtype-specific vulnerability associated with AD pathology. We identified a distinct excitatory neuronal subpopulation characterized by NRGN and BEX1 expression, which showed reproducible depletion across multiple regions, with the strongest evidence in amnestic AD and in neocortical regions in lvPPA. This vulnerable population showed concordance with previously reported AD-associated excitatory neuron signatures, supporting a conserved transcriptional program of susceptibility. Genes enriched in this population were associated with chemical synaptic transmission and regulation of synaptic plasticity and formed interconnected networks in protein-protein interaction analyses. These findings suggest that intrinsic properties related to synaptic function may predispose specific neuronal populations to degeneration in AD. Together, our results define a conserved, transcriptionally distinct excitatory neuron subpopulation that is selectively vulnerable across AD phenotypes and brain regions. This work provides a framework for linking regional pathology to cell-type-specific susceptibility and highlights synaptic regulatory pathways as potential contributors to neuronal degeneration in Alzheimer’s disease.

Introduction Increasing publication of fraudulent clinical trials poses a serious threat to evidence-based medicine. In the VITALITY Study I, we demonstrated that contamination by retracted trials significantly distorts evidence synthesis. The upcoming VITALITY Study II will take a step further and investigate how such problematic evidence undermines the credibility of guideline recommendations. Methods and analyses The VITALITY Study II will adopt a retrospective cohort design and will be structured as three work packages (WPs). To start with, a cohort of clinical practice guidelines (CPGs) that were contaminated by retracted trials and/or meta-analyses that included retracted trials will be established based on forward citation searching (WP1). Then, recommendations from these CPGs that used evidence from retracted trials and/or meta-analyses that synthesised these retracted trials will be re-evaluated after removing such problematic evidence, in terms of both the direction and strength of effect sizes (WP2). Finally, the subsequent impact on patient outcomes attributable to distorted recommendations will be estimated on a hypothetical population, measured by the number of expected benefit loss and the number of expected harm increment per 100 000 patients (WP3). Ethics and dissemination Formal ethical approval is not necessary for this study as it does not involve human or animal participants, nor does it involve the collection of primary data. We will disseminate the findings through publication in peer-reviewed journals and, whenever possible, presentations at academic conferences.

Epilepsy-related mortality, including Sudden Unexpected Death in Epilepsy and suicide, is a crucial topic within the interdisciplinary scope of caring for people with epilepsy (PWE). This review highlights best practices that emphasize proactive education for patients, caregivers, and communities, as well as evidence-based strategies and interventions for seizure management aimed at reducing mortality risk. It further underscores the essential contribution of the multidisciplinary care team in managing epilepsy-related mortality, highlighting considerations such as comorbid behavioral health conditions, challenges with treatment adherence, the use of the ketogenic diet, and the impact of social determinants of health and health disparities on historically marginalized populations. The authors provide actionable insights to address these challenges and barriers and enhance the outcomes and quality of life for PWE and their loved ones.

Background: Primary spine/pelvic tumors are aggressive, and en bloc resection is often essential. While stereotactic navigation is increasingly used for instrumentation in spine surgery, its specific role in tumor resection remains incompletely defined. Purpose: We sought to describe (1) reported rates of achieving negative margins, (2) local recurrence, (3) complications attributed to navigation, and (4) comparative outcomes from studies involving nonnavigated controls. Methods: We conducted a systematic review according to preferred reporting items for systematic reviews and meta-analysis guidelines. Databases were queried for studies investigating the use of stereotactic navigation in primary spine/pelvic tumor surgery. Outcomes including surgical margin status, local recurrence, and complications were extracted and qualitatively synthesized using a best-evidence approach. Results: Twenty-one studies with 240 patients were included. The mean patient age was 46 years with follow-up of 33.4 months. Tumors were most often located in the sacrum/pelvis (81.3%), followed by the thoracic (8.3%), cervical (5.8%), and lumbar spine (4.6%). Chordoma (31.7%) and chondrosarcoma (27.1%) were the most frequently reported types. Negative surgical margins were achieved in 88.3% of cases. Local recurrence was reported in 16% of patients, with the highest observed in chondrosarcoma (32.4%). Complications occurred in 30.3% of patients; however, only 1% (2 cases) were attributed to navigation use. Two comparative studies examining navigated versus nonnavigated cohorts suggested improved bony margins and lower recurrence risk with navigation. Conclusion: Early studies suggest that stereotactic navigation may be a feasible and safe adjunct for the resection of primary spine/pelvic tumors, particularly in achieving adequate bony margins. However, the current evidence is limited to small retrospective studies with heterogeneity in methodology, tumor type, and follow-up. Level of Evidence: Level IV: Systematic review of level-III and level-IV studies.

Elucidating the structure and function of enteropeptidase (EP) is essential for advancing our understanding of its biological significance, particularly in regulating trypsinogen activation. Using cryo-EM and enzymatic activity, we uncovered the significance of the CUB2 domain in mediating the cleavage of macromolecular substrates. We identified crucial binding loops and key residues for EP’s proteolytic function. The mutation E574A enhanced the proteolytic activity of EP, whereas the mutation N619A diminished its cleavage efficiency, highlighting the importance of surface-charged interactions in modulating EP’s activity. A proteolytic cycle was proposed to deepen our understanding of the trypsinogen activation by EP. This work offers valuable insights into the molecular mechanisms underlying EP’s interaction with its substrate, and opens up avenues for therapeutically modulating EP-mediated proteolysis.

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.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), with acute interstitial nephritis (ICI-AIN) being the most common irAE. While the exact mechanism remains unclear, upregulation of IFN-γ and TNF-α pathways has been implicated. This study used a humanized chimeric PD-1/PD-L1 mouse model to assess renal effects of ICIs, alone or combined with proinflammatory cytokines, and to test if selective TNF-α blockade could prevent ICI-AIN. Mice were randomly divided into 4 experimental groups: Control, ICI-Only, ICI-Cytokines (ICI-Cyt), and ICI-Block (ICI-TNF-α blockade). Renal function and cytokine profiles were assessed, while kidney tissue was analyzed using microscopy and single-cell RNA-seq. Histology revealed increased renal infiltration of CD4 + /CD8 + T cells in ICI-treated groups and decreased TNF-α expression following TNF-α blockade. Additionally, kidney tissue ELISA demonstrated reduced IFN-γ levels following TNF-α blockade. Plasma IL-6, MCP-1, and TNF-α were lower in ICI-Block mice. Single-cell RNA-seq revealed shifts in immune cell populations and genes of interest including Bcl2a1 , Icos , Il18r1 , Ccr2 , and Jaml . This humanized model replicates ICI-AIN key features, revealing a synergistic role of ICIs and proinflammatory cytokines. TNF-α blockade demonstrated protective effects, supporting its potential role in mitigating the risk of ICI-AIN.