tbuckley/cabot-search huggingface dataset:
Challenges and Strategies for Endothelializing Decellularized Small‐Diameter Tissue‐Engineered Vessel Grafts
Authors: Heng Ding, Xiaojie Hou, Zhen Gao, Yingqiang Guo, Bin Liao, Juyi Wan
Journal: Advanced Healthcare Materials (2024)

Abstract Vascular diseases are the leading cause of ischemic necrosis in tissues and organs, necessitating using vascular grafts to restore blood supply. Currently, small vessels for coronary artery bypass grafts are unavailable in clinical settings. Decellularized small‐diameter tissue‐engineered vessel grafts (SD‐TEVGs) hold significant potential. However, they face challenges, as simple implantation of decellularized SD‐TEVGs in animals leads to thrombosis and calcification due to incomplete endothelialization. Consequently, research and development focus has shifted toward enhancing the endothelialization process of decellularized SD‐TEVGs. This paper reviews preclinical studies involving decellularized SD‐TEVGs, highlighting different strategies and their advantages and disadvantages for achieving rapid endothelialization of these vascular grafts. Methods are analyzed to improve the process while addressing potential shortcomings. This paper aims to contribute to the future commercial viability of decellularized SD‐TEVGs.
Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss
Authors: Hui-Yang Lei, Gui-Lin Pi, Ting He, Rui Xiong, Jing-Ru Lv, Jia-Le Liu, Dong-Qin Wu, Meng-Zhu Li, Kun Shi, Shi-Hong Li, Na-Na Yu, Yang Gao, Hui-Ling Yu, Lin-Yu Wei, Xin Wang, Qiu-Zhi Zhou, Pei-Lin Zou, Jia-Yang Zhou, Ying-Zhou Liu, Nai-Ting Shen, Jie Yang, Dan Ke, Qun Wang, Gong-Ping Liu, Xi-Fei Yang, Jian-Zhi Wang, Ying Yang
Journal: Military Medical Research (2024)

Abstract Background Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary. Methods We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice. Results The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory. Conclusion This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.
STAT3 protects hematopoietic stem cells by preventing activation of a deleterious autocrine type-I interferon response
Authors: Bhakti Patel, Yifan Zhou, Rachel L. Babcock, Feiyang Ma, M. Anna Zal, Dhiraj Kumar, Yusra B. Medik, Laura M. Kahn, Josué E. Pineda, Elizabeth M. Park, Sarah M. Schneider, Ximing Tang, Maria Gabriela Raso, Collene R. Jeter, Tomasz Zal, Karen Clise-Dwyer, Khandan Keyomarsi, Filippo G. Giancotti, Simona Colla, Stephanie S. Watowich
Journal: Leukemia (2024)

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin−ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, and interferon (IFN) pathways in Stat3-deficient HSPCs. Stat3-deficient LSKs accumulated γH2AX and showed increased expression of DNA sensors and type-I IFN (IFN-I), while treatment with A151-ODN inhibited expression of IFN-I and IFN-responsive genes. Further, the blockade of IFN-I receptor signaling suppressed aberrant cell cycling, STAT1 activation, and nuclear p53 accumulation. Collectively, our results show that STAT3 inhibits a deleterious autocrine IFN response in HSCs to maintain long-term HSC function. These data signify the importance of ensuring therapeutic STAT3 inhibitors are targeted specifically to diseased cells to avoid off-target loss of healthy HSPCs.
Precision Culture Scaling to Establish High‐Throughput Vasculogenesis Models
Authors: Nicholas R. Dennison, Maximilian Fusenig, Lisa Grönnert, Manfred F. Maitz, Maria Alejandra Ramirez Martinez, Manja Wobus, Uwe Freudenberg, Martin Bornhäuser, Jens Friedrichs, Peter D. Westenskow, Carsten Werner
Journal: Advanced Healthcare Materials (2024)

Hydrogel-based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high-throughput screening workflows remains challenging. In this study, a new precision culture scaling (PCS-X) methodology combines statistical techniques (design of experiment and multiple linear regression) with automated, parallelized experiments and analyses to customize hydrogel-based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells. Variations of cell density, growth factor supplementation, and media composition are systematically explored to induce vasculogenesis in endothelial mono- and cocultures with mesenchymal stromal cells or retinal microvascular pericytes in 384-well plate formats. The developed cultures are shown to respond to vasculogenesis inhibitors in a compound- and dose-dependent manner, demonstrating the scope and power of PCS-X in creating parallelized tissue and disease models for drug discovery and individualized therapies.
Use of cancer-directed therapy at the end of life among adolescents and young adults
Authors: Jennifer W Mack, Colin Cernik, Lanfang Xu, Cecile A Laurent, Lauren Fisher, Nancy Cannizzaro, Julie Munneke, Robert M Cooper, Joshua R Lakin, Corey M Schwartz, Mallory Casperson, Andrea Altschuler, Lori Wiener, Lawrence H Kushi, Chun R Chao, Hajime Uno
Journal: JNCI Journal of the National Cancer Institute (2024)

Adolescents and young adults frequently receive chemotherapy near death. We know less about the use of targeted agents and immunotherapy or trends over time.
Updates on mouse models of Alzheimer’s disease
Authors: Michael Z Zhong, Thomas Peng, Mariana Lemos Duarte, Minghui Wang, Dongming Cai
Journal: Molecular Neurodegeneration (2024)

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disease in the United States (US). Animal models, specifically mouse models have been developed to better elucidate disease mechanisms and test therapeutic strategies for AD. A large portion of effort in the field was focused on developing transgenic (Tg) mouse models through over-expression of genetic mutations associated with familial AD (FAD) patients. Newer generations of mouse models through knock-in (KI)/knock-out (KO) or CRISPR gene editing technologies, have been developed for both familial and sporadic AD risk genes with the hope to more accurately model proteinopathies without over-expression of human AD genes in mouse brains. In this review, we summarized the phenotypes of a few commonly used as well as newly developed mouse models in translational research laboratories including the presence or absence of key pathological features of AD such as amyloid and tau pathology, synaptic and neuronal degeneration as well as cognitive and behavior deficits. In addition, advantages and limitations of these AD mouse models have been elaborated along with discussions of any sex-specific features. More importantly, the omics data from available AD mouse models have been analyzed to categorize molecular signatures of each model reminiscent of human AD brain changes, with the hope to guide future selection of most suitable models for specific research questions to be addressed in the AD field.
Liquid–liquid phase separation of H3K27me3 reader BP1 regulates transcriptional repression
Authors: Guangfei Tang, Haoxue Xia, Yufei Huang, Yuanwen Guo, Yun Chen, Zhonghua Ma, Wende Liu
Journal: Genome biology (2024)

Abstract Background Bromo-adjacent homology-plant homeodomain domain containing protein 1 (BP1) is a reader of histone post-translational modifications in fungi. BP1 recognizes trimethylation of lysine 27 in histone H3 (H3K27me3), an epigenetic hallmark of gene silencing. However, whether and how BP1 participates in transcriptional repression remains poorly understood. Results We report that BP1 forms phase-separated liquid condensates to modulate its biological function in Fusarium graminearum . Deletion assays reveal that intrinsically disordered region 2 (IDR2) of BP1 mediates its liquid–liquid phase separation. The phase separation of BP1 is indispensable for its interaction with suppressor of Zeste 12, a component of polycomb repressive complex 2. Furthermore, IDR2 deletion abolishes BP1-H3K27me3 binding and alleviates the transcriptional repression of secondary metabolism-related genes, especially deoxynivalenol mycotoxin biosynthesis genes. Conclusions BP1 maintains transcriptional repression by forming liquid–liquid phase-separated condensates, expanding our understanding of the relationship between post-translational modifications and liquid–liquid phase separation.
Modeling multiple sclerosis using mobile and wearable sensor data
Authors: Shkurta Gashi, Pietro Oldrati, Max Moebus, Marc Hilty, Liliana Barrios, Firat Ozdemir, Veronika Kana, Andreas Lutterotti, Gunnar Rätsch, Christian Holz
Journal: npj Digital Medicine (2024)

Abstract Multiple sclerosis (MS) is a neurological disease of the central nervous system that is the leading cause of non-traumatic disability in young adults. Clinical laboratory tests and neuroimaging studies are the standard methods to diagnose and monitor MS. However, due to infrequent clinic visits, it is fundamental to identify remote and frequent approaches for monitoring MS, which enable timely diagnosis, early access to treatment, and slowing down disease progression. In this work, we investigate the most reliable , clinically useful , and available features derived from mobile and wearable devices as well as their ability to distinguish people with MS (PwMS) from healthy controls, recognize MS disability and fatigue levels. To this end, we formalize clinical knowledge and derive behavioral markers to characterize MS. We evaluate our approach on a dataset we collected from 55 PwMS and 24 healthy controls for a total of 489 days conducted in free-living conditions. The dataset contains wearable sensor data – e.g., heart rate – collected using an arm-worn device, smartphone data – e.g., phone locks – collected through a mobile application, patient health records – e.g., MS type – obtained from the hospital, and self-reports – e.g., fatigue level – collected using validated questionnaires administered via the mobile application. Our results demonstrate the feasibility of using features derived from mobile and wearable sensors to monitor MS. Our findings open up opportunities for continuous monitoring of MS in free-living conditions and can be used to evaluate and guide the effectiveness of treatments, manage the disease, and identify participants for clinical trials.
Mutation order in acute myeloid leukemia identifies uncommon patterns of evolution and illuminates phenotypic heterogeneity
Authors: Matthew Schwede, Katharina Jahn, Jack Kuipers, Linde A Miles, Robert L Bowman, Troy Robinson, Ken Furudate, Hidetaka Uryu, Tomoyuki Tanaka, Yuya Sasaki, Asiri Ediriwickrema, Brooks Benard, Andrew J Gentles, Ross Levine, Niko Beerenwinkel, Koichi Takahashi, Ravindra Majeti
Journal: Leukemia (2024)
Increased 68Ga-FAPI Uptake in Capillary Hemangiomas in an Adult Patient
Authors: Jia Deng, Dongmei Zhang, Jian Yang, Dengsai Peng, Yue Chen
Journal: Clinical Nuclear Medicine (2024)

A 67-year-old woman was enrolled in our 68 Ga-FAPI PET/CT tumor clinical trial due to her lung adenocarcinoma. The PET/CT scan additionally revealed increased uptake of FAPI in the tongue. Combined with the patient's medical history and the contrast-enhanced CT of the maxillofacial region, it was suspected to be a hemangioma. Subsequently, the patient underwent surgery and was diagnosed with capillary hemangioma of the left side of her tongue.
Prodromal symptoms of hereditary angioedema (<scp>HAE</scp>) attacks: A patient survey in <scp>UK</scp> and Spain
Authors: Patrick F. K. Yong, Mar Guilarte
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Disparities in pediatric anaphylaxis triggers and management across Asia
Authors: Agnes Sze Yin Leung, Elizabeth Huiwen Tham, Punchama Pacharn, Yuhan Xing, Hoang Kim Tu Trinh, Sooyoung Lee, Kangmo Ahn, Pantipa Chatchatee, Sakura Sato, Motohiro Ebisawa, Bee Wah Lee, Gary Wing Kin Wong
Journal: Allergy (2024)

Abstract Background The epidemiology and management of anaphylaxis are not well‐reported in Asia. Methods A regional pediatric anaphylaxis registry was established by the Asia‐Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia‐Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. Results Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school‐age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7–17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. Conclusions The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two‐thirds of cases received adrenaline treatment, pre‐hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia‐Pacific.
Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications
Authors: Siyu Wang, Hua Wang, Chenbei Li, Binfeng Liu, Shasha He, Chao Tu
Journal: MedComm (2024)

Abstract Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in‐depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.
Reply to the correspondence on “Basophil activation test as predictor of severity and threshold of allergic reactions to egg”
Authors: Alexandra F. Santos, Grammatiki Antoneria, Zainab Jama, Jana Ilangovan, Vikki Houghton
Journal: Allergy (2024)

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Application Value of 68Ga-FAPI PET/CT in the Evaluation of Myelofibrotic Diseases
Authors: Ya Liu, Xue Li, Li Jing, Chunmei Guo, Zibei Wan, Feiyu Zhang, Pengqiang Wu, Zhanwen Huang
Journal: Clinical Nuclear Medicine (2024)

Purpose Fibroblast activation protein is highly expressed in neoplastic lesions and various fibrotic tissues, making it an attractive target for disease evaluation. 68 Ga-labeled fibroblast activation protein inhibitor (FAPI), a new tumor interstitial imaging agent, holds promise for evaluating myelofibrosis. Therefore, this study aimed to use 68 Ga-FAPI PET/CT for the noninvasive visualization and quantification of the extent of myelofibrosis. Patients and Methods This was a prospective clinical study involving 22 patients with myelofibrosis who underwent 68 Ga-FAPI PET/CT. The uptake of 68 Ga-FAPI was measured in their respective bone marrow and spleen, and the obtained imaging findings were compared with laboratory, cytogenetic, and histopathological data. Results 68 Ga-FAPI uptake in the bone marrow was significantly and positively correlated with the myelofibrosis grade ( r &gt; 0.8, P &lt; 0.001). 68 Ga-FAPI PET/CT showed visually negative results in patients with grades 0–1 myelofibrosis and positive in those with grades 2–3, but the level of involvement varied. 68 Ga-FAPI PET/CT provides a noninvasive means of visualizing the extent of systemic bone marrow involvement and differentiation between the early and advanced stages of fibrosis. Conclusions 68 Ga-FAPI PET/CT shows promise as a method for visualizing and quantifying myelofibrosis, providing suitable sites for bone marrow biopsy. The extent of 68 Ga-FAPI uptake by bone marrow increases with the progression of myelofibrosis, thus it is a simple and noninvasive measurement that can be used to evaluate the progression of myelofibrosis. Nevertheless, although 68 Ga-FAPI PET/CT has demonstrated a potential value in prognostic assessment, further confirmation is needed.
The European Innovation Network as a hub for medicines innovation in Europe
Authors: Eleonora Agricola, Caroline Auriche-Benichou, Helena Baiao, Oriane Blanquie, Teodora Bodea, Tomáš Boráň, John-Joseph Borg, Valentina Cordo’, Maria Di Marzo, Lars Dmowski Rugholm, Falk Ehmann, Rúna Hauksdóttir Hvannberg, Ralf Herold, Alar Irs, Simona Jurkovič Mlakar, Robert Klaus, Juha Kolehmainen, Christophe Lahorte, Wiebke Löbker, Anna Mäkinen Salmi, Yoana Nuevo Ordoñez, Laurence O’Dwyer, Anna Maria Gerdina Pasmooij, Ingvil Saeterdal, Bronislava Spakova, Viktoriia Starokozhko, Bettina Ziegele, Katarzyna Zywiec
Journal: Nature Reviews Drug Discovery (2024)
Prediction of metabolites associated with somatic mutations in cancers by using genome-scale metabolic models and mutation data
Authors: GaRyoung Lee, Sang Mi Lee, Sungyoung Lee, Chang Wook Jeong, Hyojin Song, Sang Yup Lee, Hongseok Yun, Youngil Koh, Hyun Uk Kim
Journal: Genome biology (2024)

Abstract Background Oncometabolites, often generated as a result of a gene mutation, show pro-oncogenic function when abnormally accumulated in cancer cells. Identification of such mutation-associated metabolites will facilitate developing treatment strategies for cancers, but is challenging due to the large number of metabolites in a cell and the presence of multiple genes associated with cancer development. Results Here we report the development of a computational workflow that predicts metabolite-gene-pathway sets. Metabolite-gene-pathway sets present metabolites and metabolic pathways significantly associated with specific somatic mutations in cancers. The computational workflow uses both cancer patient-specific genome-scale metabolic models (GEMs) and mutation data to generate metabolite-gene-pathway sets. A GEM is a computational model that predicts reaction fluxes at a genome scale and can be constructed in a cell-specific manner by using omics data. The computational workflow is first validated by comparing the resulting metabolite-gene pairs with multi-omics data (i.e., mutation data, RNA-seq data, and metabolome data) from acute myeloid leukemia and renal cell carcinoma samples collected in this study. The computational workflow is further validated by evaluating the metabolite-gene-pathway sets predicted for 18 cancer types, by using RNA-seq data publicly available, in comparison with the reported studies. Therapeutic potential of the resulting metabolite-gene-pathway sets is also discussed. Conclusions Validation of the metabolite-gene-pathway set-predicting computational workflow indicates that a decent number of metabolites and metabolic pathways appear to be significantly associated with specific somatic mutations. The computational workflow and the resulting metabolite-gene-pathway sets will help identify novel oncometabolites and also suggest cancer treatment strategies.