tbuckley/cabot-search huggingface dataset:
Errors in Tables in Systematic Review of Perinatal Outcomes for Women With and Without Epilepsy
Authors: Paolo Pierino Mazzone
Journal: JAMA Neurology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Clonal hematopoiesis–derived therapy-related myeloid neoplasms after autologous hematopoietic stem cell transplant for lymphoid and non-lymphoid disorders
Authors: Hussein Awada, Carmelo Gurnari, Valeria Visconte, Arda Durmaz, Teodora Kuzmanovic, Hassan Awada, Zheng Jin Tu, James R. Cook, Brian J. Bolwell, Ronald Sobecks, Matt Kalaycio, David Bosler, Jaroslaw P. Maciejewski
Journal: Leukemia (2024)

Abstract Therapy-related myeloid neoplasms (tMN) are complications of cytotoxic therapies. Risk of tMN is high in recipients of autologous hematopoietic stem cell transplantation (aHSCT). Acquisition of genomic mutations represents a key pathogenic driver but the origins, timing and dynamics, particularly in the context of preexisting or emergent clonal hematopoiesis (CH), have not been sufficiently clarified. We studied a cohort of 1507 patients undergoing aHSCT and a cohort of 263 patients who developed tMN without aHSCT to determine clinico-molecular features unique to post-aHSCT tMN. We show that tMN occurs in up to 2.3% of patients at median of 2.6 years post-AHSCT. Age ≥ 60 years, male sex, radiotherapy, high treatment burden ( ≥ 3 lines of chemotherapy), and graft cellularity increased the risk of tMN. Time to evolution and overall survival were shorter in post-aHSCT tMN vs. other tMN, and the earlier group’s mutational pattern was enriched in PPM1D and TP53 lesions. Preexisting CH increased the risk of adverse outcomes including post-aHSCT tMN. Particularly, antecedent lesions affecting PPM1D and TP53 predicted tMN evolution post-transplant. Notably, CH-derived tMN had worse outcomes than non CH-derived tMN. As such, screening for CH before aHSCT may inform individual patients’ prognostic outcomes and influence their prospective treatment plans. Presented in part as an oral abstract at the 2022 American Society of Hematology Annual Meeting, New Orleans, LA, 2022.
Unified cross-modality integration and analysis of T cell receptors and T cell transcriptomes by low-resource-aware representation learning
Authors: Yicheng Gao, Kejing Dong, Yuli Gao, Xuan Jin, Jingya Yang, Gang Yan, Qi Liu
Journal: Cell Genomics (2024)

Single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) are pivotal for investigating T cell heterogeneity. Integrating these modalities, which is expected to uncover profound insights in immunology that might otherwise go unnoticed with a single modality, faces computational challenges due to the low-resource characteristics of the multimodal data. Herein, we present UniTCR, a novel low-resource-aware multimodal representation learning framework designed for the unified cross-modality integration, enabling comprehensive T cell analysis. By designing a dual-modality contrastive learning module and a single-modality preservation module to effectively embed each modality into a common latent space, UniTCR demonstrates versatility in connecting TCR sequences with T cell transcriptomes across various tasks, including single-modality analysis, modality gap analysis, epitope-TCR binding prediction, and TCR profile cross-modality generation, in a low-resource-aware way. Extensive evaluations conducted on multiple scRNA-seq/TCR-seq paired datasets showed the superior performance of UniTCR, exhibiting the ability of exploring the complexity of immune system.
Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity
Authors: Yue Hu, Abhijit Sarkar, Kevin Song, Sara Michael, Magnus Hook, Ruoning Wang, Andras Heczey, Xiaotong Song
Journal: Cell Reports Medicine (2024)

Chimeric antigen receptor (CAR) T cell therapy is hindered in solid tumor treatment due to the immunosuppressive tumor microenvironment and suboptimal T cell persistence. Current strategies do not address nutrient competition in the microenvironment. Hence, we present a metabolic refueling approach using inosine as an alternative fuel. CAR T cells were engineered to express membrane-bound CD26 and cytoplasmic adenosine deaminase 1 (ADA1), converting adenosine to inosine. Autocrine secretion of ADA1 upon CD3/CD26 stimulation activates CAR T cells, improving migration and resistance to transforming growth factor β1 suppression. Fusion of ADA1 with anti-CD3 scFv further boosts inosine production and minimizes tumor cell feeding. In mouse models of hepatocellular carcinoma and non-small cell lung cancer, metabolically refueled CAR T cells exhibit superior tumor reduction compared to unmodified CAR T cells. Overall, our study highlights the potential of selective inosine refueling to enhance CAR T therapy efficacy against solid tumors.
Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Sean R. Corcoran, James D. Phelan, Jaewoo Choi, Galina Shevchenko, Rachel E. Fenner, Xin Yu, Sebastian Scheich, Tony Hsiao, Vivian M. Morris, Evangelia K. Papachristou, Kamal Kishore, Clive S. D'Santos, Yanlong Ji, Stefania Pittaluga, George W. Wright, Henning Urlaub, Kuan-Ting Pan, Thomas Oellerich, Jagan Muppidi, Daniel J. Hodson, Louis M. Staudt
Journal: Cancer Discovery (2024)

Abstract Polatuzumab vedotin (Pola-V) is an antibody–drug conjugate directed to the CD79B subunit of the B-cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in diffuse large B-cell lymphoma (DLBCL). To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B. Our results reveal the striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity. Genetic, pharmacological, and enzymatic approaches that remove sialic acid from N-linked glycans enhanced lymphoma killing by Pola-V. Pola-V toxicity was also modulated by KLHL6, an E3 ubiquitin ligase that is recurrently inactivated in germinal center derived lymphomas. We reveal how KLHL6 targets CD79B for degradation in normal and malignant germinal center B cells, thereby determining expression of the surface BCR complex. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic. Significance: These findings unravel the molecular basis of response heterogeneity to Pola-V and identify approaches that might be deployed therapeutically to enhance the efficacy of CD79B-specific tumor killing. In addition, they reveal a novel post-translational mechanism used by normal and malignant germinal center B cells to regulate expression of the BCR. See related commentary by Leveille, p. 1577 See related article by Meriranta et al.
Correction: Germinal center–dependent and –independent memory B cells produced throughout the immune response
Authors: Charlotte Viant, Tobias Wirthmiller, Mohamed A. ElTanbouly, Spencer T. Chen, Ervin E. Kara, Melissa Cipolla, Victor Ramos, Thiago Y. Oliveira, Leonidas Stamatatos, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2024)
Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance
Authors: Jianfeng Cui, Xiaochen Liu, Qinghong Shang, Shuna Sun, Shouzhen Chen, Jianping Dong, Yaofeng Zhu, Lei Liu, Yangyang Xia, Yong Wang, Lu Xiang, Bowen Fan, Jiafeng Zhan, Yadi Zhou, Pengxiang Chen, Renchang Zhao, Xiaofei Liu, Nianzeng Xing, Dalei Wu, Benkang Shi, Yongxin Zou
Journal: Molecular Cancer (2024)

Abstract Background CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. Methods The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. Results OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. Conclusions We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.
The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression
Authors: A Medina-Herrera, I Vazquez, I Cuenca, J M Rosa-Rosa, B Ariceta, C Jimenez, M Fernandez-Mercado, M J Larrayoz, N C Gutierrez, M Fernandez-Guijarro, V Gonzalez-Calle, P Rodriguez-Otero, A Oriol, L Rosiñol, A Alegre, F Escalante, J De La Rubia, A I Teruel, F De Arriba, M T Hernandez, J Lopez-Jimenez, E M Ocio, N Puig, B Paiva, J J Lahuerta, J Bladé, J F San Miguel, M V Mateos, J Martinez-Lopez, M J Calasanz, R Garcia-Sanz
Journal: Blood Cancer Journal (2024)

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.
imply: improving cell-type deconvolution accuracy using personalized reference profiles
Authors: Guanqun Meng, Yue Pan, Wen Tang, Lijun Zhang, Ying Cui, Fredrick R. Schumacher, Ming Wang, Rui Wang, Sijia He, Jeffrey Krischer, Qian Li, Hao Feng
Journal: Genome Medicine (2024)

Abstract Using computational tools, bulk transcriptomics can be deconvoluted to estimate the abundance of constituent cell types. However, existing deconvolution methods are conditioned on the assumption that the whole study population is served by a single reference panel, ignoring person-to-person heterogeneity. Here, we present imply , a novel algorithm to deconvolute cell type proportions using personalized reference panels. Simulation studies demonstrate reduced bias compared with existing methods. Real data analyses on longitudinal consortia show disparities in cell type proportions are associated with several disease phenotypes in Type 1 diabetes and Parkinson’s disease. imply is available through the R/Bioconductor package ISLET at https://bioconductor.org/packages/ISLET/ .
Biomimetic Peripheral Nerve Stimulation Promotes the Rat Hindlimb Motion Modulation in Stepping: An Experimental Analysis
Authors: Pengcheng Xi, Qingyu Yao, Yafei Liu, Jiping He, Rongyu Tang, Yiran Lang
Journal: Cyborg and Bionic Systems (2024)

Peripheral nerve stimulation is an effective neuromodulation method in patients with lower extremity movement disorders caused by stroke, spinal cord injury, or other diseases. However, most current studies on rehabilitation using sciatic nerve stimulation focus solely on ankle motor regulation through stimulation of common peroneal and tibial nerves. Using the electrical nerve stimulation method, we here achieved muscle control via different sciatic nerve branches to facilitate the regulation of lower limb movements during stepping and standing. A map of relationships between muscles and nerve segments was established to artificially activate specific nerve fibers with the biomimetic stimulation waveform. Then, characteristic curves depicting the relationship between neural electrical stimulation intensity and joint control were established. Finally, by testing the selected stimulation parameters in anesthetized rats, we confirmed that single-cathode extraneural electrical stimulation could activate combined movements to promote lower limb movements. Thus, this method is effective and reliable for use in treatment for improving and rehabilitating lower limb motor dysfunction.
Augmented Recognition of Distracted Driving State Based on Electrophysiological Analysis of Brain Network
Authors: Geqi Qi, Rui Liu, Wei Guan, Ailing Huang
Journal: Cyborg and Bionic Systems (2024)

In this study, we propose an electrophysiological analysis-based brain network method for the augmented recognition of different types of distractions during driving. Driver distractions, such as cognitive processing and visual disruptions during driving, lead to distinct alterations in the electroencephalogram (EEG) signals and the extracted brain networks. We designed and conducted a simulated experiment comprising 4 distracted driving subtasks. Three connectivity indices, including both linear and nonlinear synchronization measures, were chosen to construct the brain network. By computing connectivity strengths and topological features, we explored the potential relationship between brain network configurations and states of driver distraction. Statistical analysis of network features indicates substantial differences between normal and distracted states, suggesting a reconfiguration of the brain network under distracted conditions. Different brain network features and their combinations are fed into varied machine learning classifiers to recognize the distracted driving states. The results indicate that XGBoost demonstrates superior adaptability, outperforming other classifiers across all selected network features. For individual networks, features constructed using synchronization likelihood (SL) achieved the highest accuracy in distinguishing between cognitive and visual distraction. The optimal feature set from 3 network combinations achieves an accuracy of 95.1% for binary classification and 88.3% for ternary classification of normal, cognitively distracted, and visually distracted driving states. The proposed method could accomplish the augmented recognition of distracted driving states and may serve as a valuable tool for further optimizing driver assistance systems with distraction control strategies, as well as a reference for future research on the brain–computer interface in autonomous driving.
Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes
Authors: Nechama Wieder, Elston N. D’Souza, Alexandra C. Martin-Geary, Frederik H. Lassen, Jonathan Talbot-Martin, Maria Fernandes, Sonia P. Chothani, Owen J. L. Rackham, Sebastian Schafer, Julie L. Aspden, Daniel G. MacArthur, Robert W. Davies, Nicola Whiffin
Journal: Genome biology (2024)

Abstract Background Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity. Results We investigate 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated. Conclusions Our results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them.
ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels
Authors: Yang Lin, Chang-Hyun Gil, Kimihiko Banno, Masataka Yokoyama, Matthew Wingo, Ellen Go, Nutan Prasain, Ying Liu, Takashi Hato, Hisamichi Naito, Taku Wakabayashi, Musia Sominskaia, Meng Gao, Kevin Chen, Fuqiang Geng, Jesus Maria Gomez Salinero, Sisi Chen, W. Christopher Shelley, Momoko Yoshimoto, Sergio Li Calzi, Michael P. Murphy, Kyoji Horie, Maria B. Grant, Ryan Schreiner, David Redmond, David P. Basile, Shahin Rafii, Mervin C. Yoder
Journal: Circulation (2024)

Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative potential and vessel-forming capacity compared with mature ECs. Nevertheless, a marker to identify vascular clonal repopulating ECs (CRECs) in murine and human individuals is lacking, and, hence, the mechanism for the proliferative, self-renewal, and vessel-forming potential of CRECs is elusive.
Disruption of metazoan gene regulatory networks in cancer alters the balance of co-expression between genes of unicellular and multicellular origins
Authors: Anna S. Trigos, Felicia Bongiovanni, Yangyi Zhang, Maia Zethoven, Richard Tothill, Richard Pearson, Anthony T. Papenfuss, David L. Goode
Journal: Genome biology (2024)

Abstract Background Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose that an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer. Results We combine gene co-expression analysis to infer changes to GRNs in cancer with protein sequence conservation data to distinguish genes with UC and MC origins. Co-expression networks created using RNA sequencing data from 31 tumor types and normal tissue samples are divided into modules enriched for UC genes, MC genes, or mixed UC-MC modules. The greatest differences between tumor and normal tissue co-expression networks occur within mixed UC-MC modules. MC and UC genes not commonly co-expressed in normal tissues form distinct co-expression modules seen only in tumors. The degree of rewiring of genes within mixed UC-MC modules increases with tumor grade and stage. Mixed UC-MC modules are enriched for somatic mutations in cancer genes, particularly amplifications, suggesting an important driver of the rewiring observed in tumors is copy number changes. Conclusions Our study shows the greatest changes to gene co-expression patterns during tumor progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.
Neutrophil‐driven and interleukin‐36γ‐associated ocular surface inflammation in chronic Stevens–Johnson syndrome
Authors: Madhuri Amulya Koduri, Tejaswini Pingali, Deeksha Prasad, Vijay Singh, Swati Singh, Swapna S. Shanbhag, Sayan Basu, Vivek Singh
Journal: Allergy (2024)

This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).