BCL6 in T cells promotes type 1 diabetes by redirecting fates of insulin-autoreactive B lymphocytes.
Clark LM, McAninch JC, McNitt DH, Padgett ML, Jenkins TW, Bass LE, Nichols CM, Rathmell JC, Bonami RH.
iScience. 2026 Jun 11;29(6):115990. doi: 10.1016/j.isci.2026.115990. eCollection 2026 Jun 19.
PMID: 42305589 Free PMC article.
Abstract: Currently approved immunotherapies for type 1 diabetes (T1D) broadly target T cells and delay, but do not fully prevent, diabetes development, highlighting the need for more selective targets. Here, we show that T cell loss of the key germinal center protein, BCL6 prevents diabetes, despite the continued presence of anti-insulin B cells. This protection was associated with reduced anti-insulin B cell activation and proliferation. ΔBCL6 adoptively transferred CD4+ T cells showed reduced activation, relative to BCL6 sufficiency. Anti-insulin B cells primarily existed in extrafollicular niches and skewed toward phenotypically defined atypical and atypical memory B cell subsets in pancreas and pancreatic lymph nodes, which was reduced by T cell loss of BCL6. This work implicates CD4+ T cells in licensing extrafollicular insulin-binding B cells, a process which is restrained by T cell BCL6 deficiency. Overall, these findings support BCL6 inhibition as a promising T1D immunotherapy.
Single cell protein profiling of focal cortical dysplasia in a patient requiring multiple resections.
Elsayed NA, Naftel RP, Mobley BC, Alexander AL, Toland AM, Brockman AA, Irish JM, Ihrie RA, Ess KC.
Acta Neuropathol Commun. 2026 Mar 13;14(1):97. doi: 10.1186/s40478-026-02273-3.
PMID: 41827061 Free PMC article.
Abstract: Epilepsy affects millions worldwide with many failing to respond to standard treatments. Drug-refractory epilepsy requiring surgical intervention often presents due to developmental aberrations, such as focal cortical dysplasia (FCD). In FCD type II, somatic mutations in the mTOR pathway allow excessive activation of the mTOR kinase, causing unregulated cell growth and differentiation. Ex vivo studies of resected brain tissues offer a direct window into epileptogenic brain and disease pathophysiology. Recent studies implicate abnormal cell fate specification in FCD, but it is unclear if mutant cells are directly epileptogenic and/or whether they impact neighboring cells. Using a custom 43-antibody mass cytometry panel, we broadly assessed cell lineage and functional state across multiple sequential resections from a female child with FCD harboring a mosaic gain-of-function AKT3 mutation. Our approach used unsupervised machine learning tools to define protein-level features of dysplasia-associated cells and revealed cell populations associated with clinical outcomes. While AKT3 mutational burden did not correlate with clinical outcomes, protein profiling identified a distinct population of CUX1-high cells correlating with seizure control. Furthermore, we identified a similar cell population across multiple additional cortical malformation cases. This work demonstrates the advantage of deep single-cell protein profiling of surgically resected epilepsy tissue and provides insight on disease mechanisms that can be overlooked in traditional genetic or transcriptional studies.
Primary Graft Dysfunction after Lung Transplant in Mechanically Ventilated versus Extubated Patients.
Petrovic M, Auner S, Dörflinger AB, Tiller F, Adjei E, Eidson C, Le L, Boyce W, Schweiger T, Muraközy G, Aigner C, Jaksch P, Demarest CT, Trindade AJ, Shaver CM, Stokes JW, Wilkins A, Bacchetta M, Benazzo A, Hoetzenecker K, Schwarz S.
J Heart Lung Transplant. 2026 Jul 10:S1053-2498(26)01983-2. doi: 10.1016/j.healun.2026.07.002. Online ahead of print.
PMID: 42431560
Abstract
Background: Primary graft dysfunction grading is an important prognostic parameter following lung transplantation. Because the current ISHLT consensus classification does not differentiate between mechanically ventilated and extubated patients, we examined whether mechanical ventilation status influences the prognostic value of PGD grades for short- and long-term outcomes.
Methods: All primary bilateral lung transplants performed at the Medical University of Vienna and Vanderbilt University Medical Center (January 2017 – December 2024) were retrospectively analyzed. PGD was adjudicated per the 2016 ISHLT Consensus Statement. At each postoperative time point (T24, T48, T72), patients were stratified by PGD grade and ventilation status. ICU-free and hospital-free days were compared using Bonferroni-corrected Wilcoxon rank-sum tests. Long-term survival was assessed using Kaplan-Meier analysis and Cox models adjusted for PGD grade, center, donor and recipient age, sex, diagnosis, and ECMO bridge-to-transplant.
Results: Among 1,022 patients, 311 (30.4%) were extubated by T24, 560 (54.8%) by T48, and 651 (63.7%) by T72. Extubated patients had more ICU-free and hospital-free days across most PGD grades and time points. Kaplan-Meier analysis demonstrated significantly better survival for extubated patients among PGD 0/1 at all time points and PGD 2/3 at T24 and T48. After multivariable adjustment, mechanical ventilation was independently associated with worse survival among PGD 0/1 at T72 (HR 1.56, 95% CI: 1.12-2.16) and PGD 2/3 at T48 (HR 2.68, 95% CI: 1.20-5.98). The association within PGD2/3 at T72 did not reach statistical significance.
Conclusions: Mechanical ventilation status carries prognostic information not captured by the current PGD grade. Within PGD0/1 at 72 hours, the largest subgroup in the cohort, mechanical ventilation was independently associated with worse long-term survival, a finding that replicated at both centers. Future PGD classification revisions should include ventilatory status to improve prognostic accuracy.
Standard Model Imaging in the Brain and Spinal Cord of MS Patients: Initial Assessment and Comparison to Diffusion Tensor Imaging.
Witt A, Cronin AE, Busher B, Stuart I, Sweeney G, O’Grady KP, Smith SA, By S, Schilling K.
NMR Biomed. 2026 Aug;39(8):e70354. doi: 10.1002/nbm.70354.
PMID: 42420209 Free PMC article.
Abstract: Multiple sclerosis (MS) pathology manifests across the central nervous system (CNS), yet magnetic resonance imaging (MRI) studies frequently assess the brain and spinal cord (SC) in isolation. It remains unclear whether microstructural injury in normal-appearing white matter (NAWM) and lesions manifests identically across these distinct anatomical environments or if advanced biophysical models offer diagnostic advantages over standard diffusion techniques. We performed a comprehensive 3T MRI protocol with same-session brain and cervical SC imaging on 34 persons with relapsing-remitting MS (pwRRMS) and 36 healthy controls (HCs). We focused on diffusion frameworks (diffusion tensor imaging [DTI], standard model imaging with free water [SMIfw]) to quantify and compare microstructural integrity between the brain and cervical SC for the first time. Specifically, we assessed the feasibility of SMI for clinical implementation in terms of sensitivity (contrast between lesions and NAWM in pwRRMS) and reliability (HC reproducibility). Our findings indicate that both simple (DTI) and advanced (SMI) models are sensitive to MS-related microstructural changes, but the utility varied by region: notably, SMI-derived neurite density fraction (f) emerged as a robust marker of MS pathology in both the brain and SC, while DTI metrics like fractional anisotropy (FA) and radial diffusivity (RD) showed comparable sensitivity exclusively in the brain. Though axonal loss appears to be a global feature detectable even in early-stage disease, the inflammatory or edematous environment of lesions differs fundamentally between the brain and SC. Taken together, these findings demonstrate the utility of SMI for comprehensive CNS assessment and support its potential for future usage in clinical trials and improved disease monitoring.
Literature Reviews After AI.
Bogdanov S, da Silva Hucke AT, Landman BA.
J Med Imaging (Bellingham). 2026 May;13(3):030101. doi: 10.1117/1.JMI.13.3.030101. Epub 2026 Jun 26.
PMID: 42368355
Abstract: This editorial revisits the enduring role of literature reviews in scientific training and communication, emphasizing that their value lies in expert synthesis rather than simple aggregation of sources. In an era of AI-assisted discovery and summarization, the authors argue that peer-reviewed reviews must provide deeper perspective on how fields evolve and how evidence interconnects. They outline updated expectations for review and perspective articles, stressing that human judgment remains essential for interpreting and validating the scientific record.
Do Cellular Allografts Improve Spinal Fusion Enough to Justify Their Cost and Potential Risk? A Systematic Review of Efficacy, Safety, and Cost.
Okonkwo DD, Jain H, Sarikonda A, Younus I, Abtahi AM, Stephens BF, Wilson BR, Zuckerman SL.
Neurosurg Pract. 2026 Jul 9;7(4):e000266. doi: 10.1227/neuprac.0000000000000266. eCollection 2026 Aug.
PMID: 42421892 Free PMC article. Review.
Abstract
Background and objectives: Cellular bone allografts, developed to provide osteogenic properties similar to autologous bone graft without donor site morbidity, are increasingly used in spinal fusion surgery; however, their clinical efficacy, safety, and cost-effectiveness relative to cell-free alternatives remain incompletely defined. Therefore, we sought to systematically review the clinical evidence on cellular bone allografts in spinal fusion, specifically evaluating fusion rates, complications, and cost.
Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of PubMed/Embase databases was conducted for English-language studies published between 2010 and 2025, evaluating cellular bone allografts in human spinal fusion. Studies reporting fusion outcomes in cervical and/or lumbar spine were included. Data were extracted on study design, cohort size, imaging modality used for fusion assessment, fusion rates, complications, and costs. Cervical and lumbar fusion outcomes were analyzed separately. Graft products were also evaluated individually. Publicly reported disease transmission events were also reviewed.
Results: Of 643 studies identified, 22 met the inclusion criteria (cervical: 9, lumbar: 12, combined cervical/lumbar: 1). No randomized controlled trials were identified. Reported fusion rates were high and ranged from 90.0% to 98.5% in the cervical spine and 82.0% to 100.0% in the lumbar; however, cohort sizes varied widely, and fusion assessment methods were heterogeneous, with many studies relying on a single imaging modality. No study demonstrated a statistically significant improvement in fusion rates compared with cell-free allografts or other graft controls. Reported graft-related complications were rare in clinical studies although 2 widely reported tuberculosis outbreaks linked to contaminated cellular allografts underscore persistent safety concerns. Limited cost data indicate that cellular allografts are substantially more expensive than cell-free alternatives but less costly than recombinant human bone morphogenetic protein-2.
Conclusion: Although cellular bone allografts demonstrate high reported fusion rates, current evidence does not establish clinical superiority over cell-free allografts. Methodological heterogeneity, limited cohort sizes, safety considerations, and higher costs highlight the need for larger, rigorously designed comparative studies to define their true clinical value.
Evaluating the effects of aging on distribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.
Ligocki AP, Sorets AG, Abdulrahman AM, Francini N, Park JC, Lee JH, Ford WT, Lyons SM, Fritsch EL, Lamantia ZE, Christov PP, Tehrani EE, Duvall CL, Lippmann ES.
Mol Ther. 2026 Jun 15:S1525-0016(26)00505-8. doi: 10.1016/j.ymthe.2026.06.028. Online ahead of print.
PMID: 42298821 Free article.
Mosaic loss of Y chromosome associates with lung function, emphysema, and epigenetic aging.
Saw WY, Kim K, Huang Y, Yun JH, Ma X, Bacon J, Pershad Y, Levy D, O’Connor GT, Boerwinkle E, Barr RG, Rich SS, Rotter JI, Carson AP, Raffield LM, Gharib SA, Bartz TM, Psaty BM, Sofer T, North KE, Kaplan RC, Oelsner EC, Manichaikul A, Bick AG, Scheet P, Reiner AP; NHLBI Trans-Omics for Precision Medicine Consortium; Jakubek YA, Auer PL, Cho MH, DeMeo DL.
Am J Respir Crit Care Med. 2026 Jul 1;212(7):1483-1494. doi: 10.1093/ajrccm/aamag120.
PMID: 42085243 Free PMC article.
Real-time cardiac power output index predicts imminent need for extracorporeal membrane oxygenation after heart transplantation.
Ahmad A, Rali AS, Wang CC, Petrovic M, Williams AM, Trahanas J, Bommareddi S, Absi T, Quintana E, McGann K, Devries S, Lowman J, Siddiqi H, Brinkley M, Tsai S, Menachem JN, Pedrotty D, Sacks S, Zalawadiya S, Ukita R, Bacchetta M, Schlendorf K, Shah AS, Lindenfeld J, Lima B.
JHLT Open. 2026 May 20;13:100597. doi: 10.1016/j.jhlto.2026.100597. eCollection 2026 Aug.
PMID: 42305105 Free PMC article.
Old may still be gold: 45- to 55-year-old donors yield safe early outcomes in adult heart transplantation.
Bommareddi S, Wang CC, Ahmad A, Trahanas J, Lima B, McGann KC, Petrovic M, Devries S, Lowman J, Absi T, Quintana E, Schlendorf K, Bacchetta M, Shah AS, Williams AM.
JTCVS Open. 2026 Apr 9;31:101802. doi: 10.1016/j.xjon.2026.101802. eCollection 2026 Jun.
PMID: 42381940 Free PMC article.
Evaluating the Efficacy and Safety of Venous Flow-Through Flaps in Hand Reconstructive Surgery: A Systematic Review.
Gutama B, Lumani V, Abbott EN, De Oliveira N, Nordahl E, Torres-Guzman RA, Cornely RM, Savitz B, Alter N, Reddy AP, Masiha SA, Bhandari PL, Thayer W, Elmaraghi S, Lineaweaver WC.
Ann Plast Surg. 2026 Jun 29. doi: 10.1097/SAP.0000000000004768. Online ahead of print.
PMID: 42372219
Vascular Anomalies: A Comprehensive Review of Etiology, Complications, and Management Strategies.
Johnson J, Prabha M, Hadnot Z, Reddy AP, Gergoudis FR, Giannas E, Galdyn I.
Ann Plast Surg. 2026 Jun 29. doi: 10.1097/SAP.0000000000004791. Online ahead of print.
PMID: 42372193
Multi-ancestry gene expression models amplify transcriptome-wide association study discovery and validation.
Bledsoe X, Watkins N, Bowen-Moore T, Shaw M, Shah RV, Gamazon ER.
Nat Commun. 2026 Jul 4. doi: 10.1038/s41467-026-75193-4. Online ahead of print.
PMID: 42401576 Free article.
Programmed cell death ligand 1 (PD-L1) inhibition in tumor naïve mice is bone-sparing throughout the lifespan.
Searcy MB, Joseph GJ, Kane JF, Challa L, Tanaka H, Uppuganti S, Smith JA, Rosenthal EL, Harrison DG, Nyman JS, Weivoda MM, Johnson RW.
J Bone Miner Res. 2026 Jul 9:zjag104. doi: 10.1093/jbmr/zjag104. Online ahead of print.
PMID: 42424413