tbuckley/cabot-search huggingface dataset:
Disease staging of Alzheimer’s disease using a CSF-based biomarker model
Authors: Gemma Salvadó, Kanta Horie, Nicolas R. Barthélemy, Jacob W. Vogel, Alexa Pichet Binette, Charles D. Chen, Andrew J. Aschenbrenner, Brian A. Gordon, Tammie L. S. Benzinger, David M. Holtzman, John C. Morris, Sebastian Palmqvist, Erik Stomrud, Shorena Janelidze, Rik Ossenkoppele, Suzanne E. Schindler, Randall J. Bateman, Oskar Hansson
Journal: Nature Aging (2024)

Abstract Biological staging of individuals with Alzheimer’s disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort. SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau). The CSF stages (0–5) demonstrated a correlation with increased abnormalities in other AD-related biomarkers, such as Aβ-PET and tau-PET, and aligned with longitudinal biomarker changes reflective of AD progression. Higher CSF stages at baseline were associated with an elevated hazard ratio of clinical decline. This study highlights a common molecular pathway underlying AD pathophysiology across all patients, suggesting that a single CSF collection can accurately indicate the presence of AD pathologies and characterize the stage of disease progression. The proposed staging model has implications for enhancing diagnostic and prognostic assessments in both clinical practice and the design of clinical trials.
An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors
Authors: Xuan Zhang, Baobao Song, Maximillian J. Carlino, Guangyuan Li, Kyle Ferchen, Mi Chen, Evrett N. Thompson, Bailee N. Kain, Dan Schnell, Kairavee Thakkar, Michal Kouril, Kang Jin, Stuart B. Hay, Sidharth Sen, David Bernardicius, Siyuan Ma, Sierra N. Bennett, Josh Croteau, Ornella Salvatori, Melvin H. Lye, Austin E. Gillen, Craig T. Jordan, Harinder Singh, Diane S. Krause, Nathan Salomonis, H. Leighton Grimes
Journal: Nature Immunology (2024)

Abstract Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved &gt;80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.
Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis
Authors: Sneha Mitra, Rohan Malik, Wilfred Wong, Afsana Rahman, Alexander J. Hartemink, Yuri Pritykin, Kushal K. Dey, Christina S. Leslie
Journal: Nature Genetics (2024)

Abstract We present a gene-level regulatory model, single-cell ATAC + RNA linking (SCARlink), which predicts single-cell gene expression and links enhancers to target genes using multi-ome (scRNA-seq and scATAC–seq co-assay) sequencing data. The approach uses regularized Poisson regression on tile-level accessibility data to jointly model all regulatory effects at a gene locus, avoiding the limitations of pairwise gene–peak correlations and dependence on peak calling. SCARlink outperformed existing gene scoring methods for imputing gene expression from chromatin accessibility across high-coverage multi-ome datasets while giving comparable to improved performance on low-coverage datasets. Shapley value analysis on trained models identified cell-type-specific gene enhancers that are validated by promoter capture Hi-C and are 11× to 15× and 5× to 12× enriched in fine-mapped eQTLs and fine-mapped genome-wide association study (GWAS) variants, respectively. We further show that SCARlink-predicted and observed gene expression vectors provide a robust way to compute a chromatin potential vector field to enable developmental trajectory analysis.
Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population
Authors: Yunhe Wang, Binbin Su, Junqing Xie, Clemente Garcia-Rizo, Daniel Prieto-Alhambra
Journal: Nature Human Behaviour (2024)

Abstract Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection ( n = 26,101), contemporary control with no evidence of infection ( n = 380,337) and historical control predating the pandemic ( n = 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42–1.67; P = 1.70 × 10 −24 ; difference in incidence rate: 27.36, 95% CI 21.16–34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70–2.78; P = 5.80 × 10 −10 ) than those not hospitalized (1.41, 1.30–1.53; P = 1.46 × 10 −16 ), and were reduced in fully vaccinated people (0.97, 0.80–1.19; P = 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49–1.79; P = 4.95 × 10 −26 ). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78–1.07; P = 0.278) but increased prescription risk (1.42, 1.00–2.02; P = 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders.
PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes
Authors: Ruiyang Pang, Weihao Sun, Yingyun Yang, Dahan Wen, Feng Lin, Dingding Wang, Kailong Li, Ning Zhang, Junbo Liang, Chunyang Xiong, Yuying Liu
Journal: Nature Biomedical Engineering (2024)
Cell subtype-specific effects of genetic variation in the Alzheimer’s disease brain
Authors: Masashi Fujita, Zongmei Gao, Lu Zeng, Cristin McCabe, Charles C. White, Bernard Ng, Gilad Sahar Green, Orit Rozenblatt-Rosen, Devan Phillips, Liat Amir-Zilberstein, Hyo Lee, Richard V. Pearse, Atlas Khan, Badri N. Vardarajan, Krzysztof Kiryluk, Chun Jimmie Ye, Hans-Ulrich Klein, Gao Wang, Aviv Regev, Naomi Habib, Julie A. Schneider, Yanling Wang, Tracy Young-Pearse, Sara Mostafavi, David A. Bennett, Vilas Menon, Philip L. De Jager
Journal: Nature Genetics (2024)
High‐Scale 3D‐Bioprinting Platform for the Automated Production of Vascularized Organs‐on‐a‐Chip
Authors: Anna Fritschen, Nils Lindner, Sebastian Scholpp, Philipp Richthof, Jonas Dietz, Philipp Linke, Zeno Guttenberg, Andreas Blaeser
Journal: Advanced Healthcare Materials (2024)

3D bioprinting possesses the potential to revolutionize contemporary methodologies for fabricating tissue models employed in pharmaceutical research and experimental investigations. This is enhanced by combining bioprinting with advanced organs-on-a-chip (OOCs), which includes a complex arrangement of multiple cell types representing organ-specific cells, connective tissue, and vasculature. However, both OOCs and bioprinting so far demand a high degree of manual intervention, thereby impeding efficiency and inhibiting scalability to meet technological requirements. Through the combination of drop-on-demand bioprinting with robotic handling of microfluidic chips, a print procedure is achieved that is proficient in managing three distinct tissue models on a chip within only a minute, as well as capable of consecutively processing numerous OOCs without manual intervention. This process rests upon the development of a post-printing sealable microfluidic chip, that is compatible with different types of 3D-bioprinters and easily connected to a perfusion system. The capabilities of the automized bioprint process are showcased through the creation of a multicellular and vascularized liver carcinoma model on the chip. The process achieves full vascularization and stable microvascular network formation over 14 days of culture time, with pronounced spheroidal cell growth and albumin secretion of HepG2 serving as a representative cell model.
Understanding the provenance and quality of methods is essential for responsible reuse of FAIR data
Authors: Tracey L. Weissgerber, Małgorzata Anna Gazda, Gustav Nilsonne, Gerben ter Riet, Kelly D. Cobey, Julia Prieß-Buchheit, Jorge Noro, Robert Schulz, Joeri K. Tijdink, Evgeny Bobrov, Alexandra Bannach-Brown, Delwen L. Franzen, Ugo Moschini, Florian Naudet, Ulrich Mansmann, Maia Salholz-Hillel, Anita Bandrowski, Malcolm R. Macleod
Journal: Nature Medicine (2024)
Oncolytic mineralized bacteria as potent locally administered immunotherapeutics
Authors: Chenya Wang, Liping Zhong, Jiachen Xu, Qi Zhuang, Fei Gong, Xiaojing Chen, Huiquan Tao, Cong Hu, Fuquan Huang, Nailin Yang, Junyan Li, Qi Zhao, Xinjun Sun, Yu Huo, Qian Chen, Yongxiang Zhao, Rui Peng, Zhuang Liu
Journal: Nature Biomedical Engineering (2024)
Author Correction: Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cell
Authors: Yulong Gao, Fernando Souza-Fonseca-Guimaraes, Tobias Bald, Susanna S. Ng, Arabella Young, Shin Foong Ngiow, Jai Rautela, Jasmin Straube, Nic Waddell, Stephen J. Blake, Juming Yan, Laurent Bartholin, Jason S. Lee, Eric Vivier, Kazuyoshi Takeda, Meriem Messaoudene, Laurence Zitvogel, Michele W. L. Teng, Gabrielle T. Belz, Christian R. Engwerda, Nicholas D. Huntington, Kyohei Nakamura, Michael Hölzel, Mark J. Smyth
Journal: Nature Immunology (2024)
CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib
Authors: Haosheng Li, Haoran Feng, Tao Zhang, Junwei Wu, Xiaonan Shen, Shuiyu Xu, Lianghui Xu, Shaodong Wang, Yaqi Zhang, Wenqing Jia, Xiaopin Ji, Xi Cheng, Ren Zhao
Journal: Molecular Cancer (2024)

Abstract Background Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. Methods The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids ( n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). Results Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. Conclusions CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.
Autoimmune adverse event following COVID-19 vaccination in Seoul, South Korea
Authors: Hong Jin Kim, Min-Ho Kim, Seong Jun Park, Myeong Geun Choi, Eun Mi Chun
Journal: Journal of Allergy and Clinical Immunology (2024)

There is growing evidence that the coronavirus disease 2019 (COVID-19) vaccination can affect the regulation of the immune system, leading to the development of autoimmune diseases. However, the autoimmune adverse events (AEs) after COVID-19 vaccination remain largely unclear.
CTLs heterogeneity and plasticity: implications for cancer immunotherapy
Authors: Shengkun Peng, Anqi Lin, Aimin Jiang, Cangang Zhang, Jian Zhang, Quan Cheng, Peng Luo, Yifeng Bai
Journal: Molecular Cancer (2024)

Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.
Planar amorphous silicon carbide microelectrode arrays for chronic recording in rat motor cortex
Authors: Justin R. Abbott, Eleanor N. Jeakle, Pegah Haghighi, Joshua O. Usoro, Brandon S. Sturgill, Yupeng Wu, Negar Geramifard, Rahul Radhakrishna, Sourav Patnaik, Shido Nakajima, Jordan Hess, Yusef Mehmood, Veda Devata, Gayathri Vijayakumar, Armaan Sood, Teresa Thuc Doan Thai, Komal Dogra, Ana G. Hernandez-Reynoso, Joseph J. Pancrazio, Stuart F. Cogan
Journal: Biomaterials (2024)
Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment
Authors: Tian Zhu, Steven M. Alves, Arianna Adamo, Xiaona Wen, Kevin C. Corn, Anastasia Shostak, Shereena Johnson, Nicholas D. Shaub, Shannon E. Martello, Benjamin C. Hacker, Antonio D'Amore, Rizia Bardhan, Marjan Rafat
Journal: Biomaterials (2024)

Radiation therapy (RT) is essential for triple negative breast cancer (TNBC) treatment. However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence.
Ultrasound‐Activated Piezoelectric Nanoparticles Trigger Microglia Activity Against Glioblastoma Cells
Authors: Margherita Montorsi, Carlotta Pucci, Daniele De Pasquale, Attilio Marino, Maria Cristina Ceccarelli, Martina Mazzuferi, Martina Bartolucci, Andrea Petretto, Mirko Prato, Doriana Debellis, Giorgio De Simoni, Giammarino Pugliese, Massimiliano Labardi, Gianni Ciofani
Journal: Advanced Healthcare Materials (2024)

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core a genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma-associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth. Conversely, "classically activated" M1 microglia could provide proinflammatory and antitumorigenic activity, expected to exert a beneficial effect in defeating glioblastoma. In this work, an immunotherapy approach based on proinflammatory modulation of the GAM phenotype is proposed, through a controlled and localized electrical stimulation. The developed strategy relies on the wireless ultrasonic excitation of polymeric piezoelectric nanoparticles coated with GBM cell membrane extracts, to exploit homotypic targeting in antiglioma applications. Such camouflaged nanotransducers locally generate electrical cues on GAM membranes, activating their M1 phenotype and ultimately triggering a promising anticancer activity. Collected findings open new perspectives in the modulation of immune cell activities through "smart" nanomaterials and, more specifically, provide an innovative auspicious tool in glioma immunotherapy.
Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair
Authors: Jingwen Liu, Liang Chen, Zhenyu Sun, Zaijin Tao, Volotovski Pavel, Yusheng Li, Fei Wang, Wenguo Cui, Shen Liu
Journal: Bioactive Materials (2024)

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.
3D-printed versatile biliary stents with nanoengineered surface for anti-hyperplasia and antibiofilm formation
Authors: Hyun Lee, Dong-Sung Won, Sinwoo Park, Yubeen Park, Ji Won Kim, Ginam Han, Yuhyun Na, Min-Ho Kang, Seok Beom Kim, Heemin Kang, Jun-Kyu Park, Tae-Sik Jang, Sang Jin Lee, Su A. Park, Sang Soo Lee, Jung-Hoon Park, Hyun-Do Jung
Journal: Bioactive Materials (2024)

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol-gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL
Suppressing Wnt signaling of the blood‒tumor barrier to intensify drug delivery and inhibit lipogenesis of brain metastases
Authors: Yang Tong, Pei An, Puxian Tang, Rui Mu, Yuteng Zeng, Hang Sun, Mei Zhao, Ziyan Lv, Pan Wang, Wanjun Han, Chunshan Gui, Xuechu Zhen, Liang Han
Journal: Acta Pharmaceutica Sinica B (2024)

Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties,