Effects of multisensory simultaneity judgment training on the comprehension and cortical processing of speech in noise: a randomized controlled trial.
Kunnath AJ, Bertisch HS, Kim AS, Gifford RH, Wallace MT.
Sci Rep. 2025 Apr 15;15(1):12956. doi: 10.1038/s41598-025-96121-4.
PMID: 40234646 Free PMC article. Clinical Trial.
Understanding speech in noise can be facilitated by integrating auditory and visual speech cues. Audiovisual temporal acuity, which can be indexed by the temporal binding window (TBW), is critical for this process and can be enhanced through simultaneity judgment training. We hypothesized that multisensory training would narrow the TBW and improve speech understanding in noise. Participants were randomized to receive either training and testing (n = 15) or testing-only (n = 15) over three days. Trained participants demonstrated significant narrowing in their mean TBW size (403ms to 345ms; p = 0.030), whereas control participants did not (409ms to 474ms; p = 0.061). Although there were no group-level changes in word recognition scores, trained participants with larger TBW decreases exhibited larger improvements in auditory word recognition in noise (R2 = 0.291; p = 0.038). Individual differences in responses to training were found to be related to differences in cortical speech processing using functional near-infrared spectroscopy. Low audiovisual-evoked activity in the left middle temporal gyrus (R2 = 0.87; p = 0.006), left angular and superior temporal gyrus (R2 = 0.85; p = 0.006), and visual cortices (R2 = 0.74; p = 0.041) was associated with larger improvements in auditory word recognition after training. Multisensory training transfers benefits to speech comprehension in noise, and this effect may be mediated by upregulating activity in multisensory cortical networks for individuals with low baseline activity
Keywords: Audiovisual training; Multisensory integration; Perceptual plasticity; Simultaneity judgment; Speech in noise; fNIRS.
Interallelic gene conversion of leukemia-associated single nucleotide variants.
Silver AJ, Brown DJ, Olmstead SD, Watke JM, Gorska AE, Tanner L, Ramsey HE, Savona MR.
Gene. 2025 Jul 20;958:149493. doi: 10.1016/j.gene.2025.149493. Epub 2025 Apr 11.
PMID: 40222687 Free article.
CRISPR-Cas9 is a useful tool for inserting precise genetic alterations through homology-directed repair (HDR), although current methods largely rely on provision of an exogenous repair template. Here, we tested the possibility of interchanging heterozygous single nucleotide variants (SNVs) using mutation-specific guide RNA, and the cell’s own wild-type allele rather than an exogenous template. Using high-fidelity Cas9 to perform allele-specific CRISPR across multiple human leukemia cell lines as well as in primary hematopoietic cells from patients with leukemia, we find high levels of reversion to wild-type in the absence of exogenous template. Moreover, we demonstrate that bulk treatment to revert a truncating mutation in ASXL1 using CRISPR-mediated interallelic gene conversion (IGC) is sufficient to prolong survival in a human cell line-derived xenograft model (median survival 33 days vs 27.5 days; p = 0.0040). These results indicate that IGC is a useful laboratory tool which can be applied to numerous types of leukemia and can meaningfully alter cellular phenotypes at scale. Because our method targets single-base mutations, rather than larger variants targeted by IGC in prior studies, it greatly expands the pool of genetic lesions which could potentially be targeted by IGC. This technique may reduce cost and complexity for experiments modeling phenotypic consequences of SNVs. The principles of SNV-specific IGC demonstrated in this proof-of-concept study could be applied to investigate the phenotypic effects of targeted clonal reduction of leukemogenic SNV mutations.
Keywords: CRISPR/Cas9; Clonal hematopoiesis; Gene editing; Interallelic gene conversion; Leukemia.
Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis.
Fankhauser RG, Johnson DB, Moslehi JJ, Balko JM.
Nat Cardiovasc Res. 2025 May;4(5):526-538. doi: 10.1038/s44161-025-00640-2. Epub 2025 May 7.
PMID: 40335724 Review.
In this Review, we present a comprehensive analysis of preclinical models used to study immune checkpoint inhibitor-associated myocarditis (hereafter ICI-myocarditis), a potentially lethal immune-related adverse event. We begin by providing an overview of immune checkpoint inhibitors, highlighting how their efficacy in cancer treatment is counterbalanced by their predisposition to cause immune-related adverse events. Next, we draw from human data to identify disease features that an effective mouse model should ideally mimic. After that, we present a critical evaluation of a wide variety of existing mouse models including genetic, pharmacological and humanized models. We summarize insights gathered about the underlying mechanisms of ICI-myocarditis and the role of mouse models in these discoveries. We conclude with a perspective on the future of preclinical models, highlighting potential model improvements and research directions that could strengthen our understanding of ICI-myocarditis, ultimately improving patient outcomes.
Potassium-Dependent Coupling of Retinal Astrocyte Light Response to Müller Glia.
Holden JM, Boal AM, Wareham LK, Calkins DJ.
Glia. 2025 Apr 22. doi: 10.1002/glia.70022. Online ahead of print.
PMID: 40264285
Oxidation of low-density lipoprotein by hemoglobin causes pulmonary microvascular endothelial barrier dysfunction through lectin-like oxidized LDL receptor 1.
Meegan JE, Riedmann KJ, Gonski S, Douglas JS, Bogart AM, Ware LB, Bastarache JA.
Am J Physiol Lung Cell Mol Physiol. 2025 May 1;328(5):L748-L755. doi: 10.1152/ajplung.00026.2025. Epub 2025 Apr 18.
PMID: 40249953 Free article.
Impaired CAMK4 Activity Limits Atherosclerosis and Reprograms Myelopoiesis.
Gonzalez AL, Youwakim CM, Leake BF, Fuller KK, Rahman SMJ, Dungan MM, Gu K, Bonin JL, Cavnar AB, Michell DL, Davison LM, Cutchins C, Chu YE, Yuan S, Yurdagul A Jr, Traylor JG, Orr AW, Kohutek ZA, Linton MF, MacNamara KC, Ferrell PB, Vickers KC, Madhur MS, Brown JD, Doran AC.
Arterioscler Thromb Vasc Biol. 2025 May 8. doi: 10.1161/ATVBAHA.125.322530. Online ahead of print.
PMID: 40336480
Unsupervised discovery of clinical disease signatures using probabilistic independence.
Lasko TA, Stead WW, Still JM, Li TZ, Kammer M, Barbero-Mota M, Strobl EV, Landman BA, Maldonado F.
J Biomed Inform. 2025 Apr 23;166:104837. doi: 10.1016/j.jbi.2025.104837. Online ahead of print.
PMID: 40280380 Free article.
Normothermic regional perfusion in donation after circulatory death compared with brain dead donors: Single-center cardiac allograft outcomes.
Williams AM, Ahmad A, Bommareddi S, Lima B, Nguyen D, Quintana E, Wang CC, Petrovic M, Siddiqi HK, Amancherla K, Rali AS, DeVries SA, Keck CD, Scholl SR, Lepore AJ, Warhoover M, Schlendorf KH, Shah AS, Pasrija C, Trahanas JM.
J Thorac Cardiovasc Surg. 2025 Apr 2:S0022-5223(25)00183-7. doi: 10.1016/j.jtcvs.2025.02.023. Online ahead of print.
PMID: 40319403
The effect of warm ischemic intervals on primary graft dysfunction in normothermic regional perfusion for donation after circulatory death heart transplant.
Wang CC, Petrovic M, Ahmad A, Navid W, Eidson C, Walker D, Harris T, Trahanas J, Bommareddi S, Nguyen DQ, Absi T, Williams AM, Quintana E, DeVries S, Siddiqi H, Schlendorf KH, Bacchetta M, Shah AS, Lima B.
J Thorac Cardiovasc Surg. 2025 Apr 18:S0022-5223(25)00290-9. doi: 10.1016/j.jtcvs.2025.03.037. Online ahead of print.
PMID: 40319402 Free article.
PGI2 restricts trained ILC2 responses in allergic inflammation.
Zhou W, Zhang J, Norlander AE, Cook DP, Toki S, Abney M, Rusznak M, Thomas C, Warren C, Richmond BW, Gibson-Corley K, Milne GL, Newcomb DC, Peebles RS Jr.
J Immunol. 2025 May 7:vkaf088. doi: 10.1093/jimmun/vkaf088. Online ahead of print.
PMID: 40334085
High-Frequency Utilization of the Outpatient Messaging System in a Specialized Outpatient Catatonia Clinic for Individuals with Autism Spectrum Disorder.
Smith JR, Sengstack DG, McCoy AB, Lim S, Marler S, Williams ZJ, Hossain N, Luccarelli J.
J Child Adolesc Psychopharmacol. 2025 Apr 30. doi: 10.1089/cap.2025.0034. Online ahead of print.
PMID: 40302606