tbuckley/cabot-search huggingface dataset:
Increased frequency of repeat expansion mutations across different populations
Authors: Kristina Ibañez, Bharati Jadhav, Matteo Zanovello, Delia Gagliardi, Christopher Clarkson, Stefano Facchini, Paras Garg, Alejandro Martin-Trujillo, Scott J Gies, Valentina Galassi Deforie, Anupriya Dalmia, Davina J Hensman Moss, Jana Vandrovcova, Clarissa Rocca, Loukas Moutsianas, Chiara Marini-Bettolo, Helen Walker, Chris Turner, Maryam Shoai, Jeffrey D Long, Pietro Fratta, Douglas R Langbehn, Sarah J Tabrizi, Mark J Caulfield, Andrea Cortese, Valentina Escott-Price, John Hardy, Henry Houlden, Andrew J Sharp, Arianna Tucci
Journal: Nature Medicine (2024)
Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial
Authors: Jing Pan, Yue Tan, Lingling Shan, Samuel Seery, Biping Deng, Zhuojun Ling, Jinlong Xu, Jiajia Duan, Zelin Wang, Kai Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Guang Hu, Taochao Tan, Ying Yuan, Zhenglong Tian, Fangrong Yan, Yajing Han, Jiecheng Zhang, Xiaoming Feng
Journal: Nature Medicine (2024)
CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms
Authors: Xin Zhou, Ying Wang, Zhangqi Dou, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti
Journal: Nature Cancer (2024)
MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33
Authors: Juan M Inclan-Rico, Camila M Napuri, Cailu Lin, Li-Yin Hung, Annabel A Ferguson, Xiaohong Liu, Qinxue Wu, Christopher F Pastore, Adriana Stephenson, Ulrich M Femoe, Fungai Musaigwa, Heather L Rossi, Bruce D Freedman, Danielle R Reed, Tomáš Macháček, Petr Horák, Ishmail Abdus-Saboor, Wenqin Luo, De'Broski R Herbert
Journal: Nature Immunology (2024)
Sacituzumab govitecan in HR+HER2− metastatic breast cancer: the randomized phase 3 EVER-132-002 trial
Authors: Binghe Xu, Shusen Wang, Min Yan, Joohyuk Sohn, Wei Li, Jinhai Tang, Xiaojia Wang, Ying Wang, Seock-Ah Im, Dongdong Jiang, Theresa Valdez, Anandaroop Dasgupta, Yiran Zhang, Yilin Yan, Kimberly M Komatsubara, Wei-Pang Chung, Fei Ma, Ming-Shen Dai
Journal: Nature Medicine (2024)
Accurate prediction of disease-risk factors from volumetric medical scans by a deep vision model pre-trained with 2D scans
Authors: Oren Avram, Berkin Durmus, Nadav Rakocz, Giulia Corradetti, Ulzee An, Muneeswar G Nittala, Prerit Terway, Akos Rudas, Zeyuan Johnson Chen, Yu Wakatsuki, Kazutaka Hirabayashi, Swetha Velaga, Liran Tiosano, Federico Corvi, Aditya Verma, Ayesha Karamat, Sophiana Lindenberg, Deniz Oncel, Louay Almidani, Victoria Hull, Sohaib Fasih-Ahmad, Houri Esmaeilkhanian, Maxime Cannesson, Charles C Wykoff, Elior Rahmani, Corey W Arnold, Bolei Zhou, Noah Zaitlen, Ilan Gronau, Sriram Sankararaman, Jeffrey N Chiang, Srinivas R Sadda, Eran Halperin
Journal: Nature Biomedical Engineering (2024)
Pneumonia Induced Rise in Glucagon Promotes Endothelial Damage and Thrombogenicity
Authors: Pegah Ramezani Rad, Vanasa Nageswaran, Lisa Peters, Leander Reinshagen, Johann Roessler, Szandor Simmons, Erik Asmus, Corey Wittig, Markus C. Brack, Geraldine Nouailles, Emiel P.C. van der Vorst, Sanne L. Maas, Kristina Sonnenschein, Barbara Verhaar, Robert Szulcek, Martin Witzenrath, Ulf Landmesser, Wolfgang M. Kuebler, Arash Haghikia
Journal: Circulation Research (2024)
Transformation of the Kidney into a Pathological Neuro-Immune-Endocrine Organ
Authors: Manako Yamaguchi, Lucas Ferreira de Almeida, Hiroki Yamaguchi, Xiuyin Liang, Jason P. Smith, Silvia Medrano, Maria Luisa S. Sequeira Lopez, R. Ariel Gomez
Journal: Circulation Research (2024)
Relationship Between Renin, Aldosterone, Aldosterone-to-Renin Ratio and Arterial Stiffness and Left Ventricular Mass Index in Young Adults
Authors: Roshan A. Ananda, StellaMay Gwini, Lawrence J. Beilin, Markus P. Schlaich, Michael Stowasser, Morag J. Young, Brendan Adler, Peter J. Fuller, Trevor A. Mori, Jun Yang
Journal: Circulation (2024)

BACKGROUND: Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease. METHODS: The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006–2009) and 27 (2016–2018) years of age. Participants with elevated high-sensitivity C-reactive protein (&gt;10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure. RESULTS: This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; P &lt;0.001) and 27 (12.0 mU/L versus 15.4 mU/L; P &lt;0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; P &lt;0.001) and 27 (21.0 versus 15.6; P &lt;0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (β=0.009 [95% CI, 0.001–0.017]; P =0.027) and between aldosterone-to-renin ratio and LVMI in females (β=0.098 [95% CI, 0.001–0.196]; P =0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age. CONCLUSIONS: Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.
Editor’s Note: Inhibition of Phosphatidylinositol 3-Kinase Destabilizes Mycn Protein and Blocks Malignant Progression in Neuroblastoma
Authors: Louis Chesler, Chris Schlieve, David D. Goldenberg, Anna Kenney, Grace Kim, Alex McMillan, Katherine K. Matthay, David Rowitch, William A. Weiss
Journal: Cancer Research (2024)
Editor’s Note: Truncated Glioma-Associated Oncogene Homolog 1 (tGLI1) Mediates Mesenchymal Glioblastoma via Transcriptional Activation of CD44
Authors: Tadas K. Rimkus, Richard L. Carpenter, Sherona Sirkisoon, Dongqin Zhu, Boris C. Pasche, Michael D. Chan, Glenn J. Lesser, Stephen B. Tatter, Kounosuke Watabe, Waldemar Debinski, Hui-Wen Lo
Journal: Cancer Research (2024)
Albumin nanoassembly bi-directionally manipulated ferroptosis in tumor and CD8+ T cells for triple-negative breast cancer therapy
Authors: Ting Yang, Zihan Liu, Zixuan Fu, Xiaojie Zhang, Yongjin Cao, Qiangwei Liang, Jiale Miao, Hao Yang, Tong Zhang, Jing Hei, Weiqing Ni, Yanhua Liu
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer (TNBC) therapy. However, the ferroptosis accompanied with down-regulation of glutathione peroxidase 4 (GPX4) lead to CD36-mediated tumor-infiltrating CD8+ T cells uptaking fatty acids, resulting in the negative action on immunotherapeutic efficacy. Herein, the albumin nanoparticles, abbreviated as LHS NPs, were designed by co-assembly of hemin, linoleic acid-cystamine, and a CD36 inhibitor sulfosuccinimide oleate, to bi-directionally manipulated ferroptosis in tumor and CD8+ T cells for TNBC therapy. LHS NPs exerted more efficient reactive oxygen species generation, glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes, which amplified the positive action on ferroptosis in tumor cells. Meanwhile, LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8+ T cells, thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death, proliferation of CD4+CD8+ T cells and natural killer cells, alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and repolarization of the M2- to M1-phenotype tumor-associated macrophages. Thus, LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lung metastasis of 4T1-tumor mice. Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8+ T cells on TNBC chemoimmunotherapy.
Remembering Hypoxia: Uncovering the Long-Term Effects of Transient Oxygen Deprivation on IFN Signaling and Progression of Breast Cancer
Authors: Stephen Connor Purdy, Heide L. Ford
Journal: Cancer Research (2024)

Hypoxia occurs in 50-60% of solid tumors and is strongly associated with an increased propensity for metastasis. Hypoxia induces tumor progression largely through inducing HIF-mediated transcription, resulting in alterations to tumor cell metabolism, as well as increases in migration and invasion. Hypoxia also results in a myriad of changes to the tumor microenvironment (TME). While many studies have examined the immediate effects of hypoxia on tumor cells and the associated TME, far fewer have focused on the long-term consequences of transient reductions in oxygen. In this issue of Cancer Research, Iriondo and colleagues examined whether short-term exposure to hypoxia leads to a “hypoxic memory” in the context of breast cancer. The authors used established cell lines and circulating tumor cell lines to demonstrate that these cells harbor a hypoxic memory that sustains downregulation of IFN signaling and antigen presentation (AP) pathways that contribute to tumor progression via alterations to tumor cells and the TME. The authors further showed that cells that have experienced hypoxia maintain the reduction in IFN signaling in vivo and are more aggressive. They determined that the hypoxic memory and reduction of IFN signaling can be reversed with a histone deacetylase inhibitor, entinostat, providing a potential means to reverse hypoxia-induced suppression of IFN signaling. As suppression of IFN signaling has the potential to influence both tumor cells and the TME, the identification of a strategy to inhibit long-term suppression of IFN signaling downstream of hypoxia could prove to be an effective means to target tumor progression. See related article by Iriondo et al., p. 3141
A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis
Authors: Haoran Xu, Ming Yue, Runhong Zhou, Pui Wang, Michael Yik-Chun Wong, Jinlin Wang, Huarong Huang, Bohao Chen, Yufei Mo, Rachel Chun-Yee Tam, Biao Zhou, Zhenglong Du, Haode Huang, Li Liu, Zhiwu Tan, Kwok-Yung Yuen, Youqiang Song, Honglin Chen, Zhiwei Chen
Journal: Cancer Research (2024)

Abstract Memory T cells play a key role in immune protection against cancer. Vaccine-induced tissue-resident memory T (TRM) cells in the lung have been shown to protect against lung metastasis. Identifying the source of lung TRM cells can help to improve strategies, preventing tumor metastasis. Here, we found that a prime-boost vaccination approach using intramuscular DNA vaccine priming, followed by intranasal live-attenuated influenza-vectored vaccine (LAIV) boosting induced higher frequencies of lung CD8+ TRM cells compared with other vaccination regimens. Vaccine-induced lung CD8+ TRM cells, but not circulating memory T cells, conferred significant protection against metastatic melanoma and mesothelioma. Central memory T (TCM) cells induced by the DNA vaccination were major precursors of lung TRM cells established after the intranasal LAIV boost. Single-cell RNA sequencing analysis indicated that transcriptional reprogramming of TCM cells for differentiation into TRM cells in the lungs started as early as day 2 post the LAIV boost. Intranasal LAIV altered the mucosal microenvironment to recruit TCM cells via CXCR3-dependent chemotaxis and induced CD8+ TRM-associated transcriptional programs. These results identified TCM cells as the source of vaccine-induced CD8+ TRM cells that protect against lung metastasis. Significance: Prime-boost vaccination shapes the mucosal microenvironment and reprograms central memory T cells to generate lung resident memory T cells that protect against lung metastasis, providing insights for the optimization of vaccine strategies.
Neural Circuitry and Therapeutic Targeting of Depressive Symptoms in Schizophrenia Spectrum Disorders
Authors: Julia Gallucci, Ju-Chi Yu, Lindsay D. Oliver, Hajer Nakua, Peter Zhukovsky, Erin W. Dickie, Zafiris J. Daskalakis, George Foussias, Daniel M. Blumberger, Colin Hawco, Aristotle N. Voineskos
Journal: American Journal of Psychiatry (2024)

Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs).
The Next Frontier for Colorectal Cancer Screening: Blood-Based Tests
Authors: Christian Rolfo, Alessandro Russo
Journal: Cancer Research (2024)

Colorectal cancer is associated with substantial morbidity and mortality worldwide. Detection of early colorectal cancer is possible through approved screening tests but overall adherence is quite low. Implementation of effective noninvasive options could increase screening uptake and prevent a significant number of deaths. Noninvasive early cancer detection can potentially be achieved using a liquid biopsy. In this issue of Cancer Research, Cao and colleagues report on a novel multidimensional fragmentomics assay, named FRAGTECT, for colorectal cancer detection in circulating cell-free DNA with promising results. See related article by Cao et al., p. 3286
Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies
Authors: Yunuo Yang, Jiaxuan Wu, Wenjun Zhou, Guang Ji, Yanqi Dang
Journal: MedComm (2024)

Abstract Metabolism‐related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies.
Macrophage Corpses for Immunoregulation and Targeted Drug Delivery in Treatment of Collagen-induced Arthritis Mice
Authors: Yuhuan Li, Jiayin Lv, Shuchen Liu, Zhuoran Wang, Yu Gao, Zheyuan Fan, Lei Huang, Jing Cui, Boya Zhang, Xinchen Liu, Zhuo Zhang, Te Liu, Daowei Li, Modi Yang
Journal: Biomaterials (2024)
Nicotinamide mononucleotide supplementation rescues mitochondrial and energy metabolism functions and ameliorates inflammatory states in the ovaries of aging mice
Authors: Jinghui Liang, Feiling Huang, Xueyu Hao, Peng Zhang, Rong Chen
Journal: MedComm (2024)

Noninvasive pharmacological strategies like nicotinamide mononucleotide (NMN) supplementation can effectively address age-related ovarian infertility by maintaining or enhancing oocyte quality and quantity. This study revealed that ovarian nicotinamide adenine dinucleotide levels decline with age, but NMN administration significantly restores these levels, preventing ovarian atrophy and enhancing the quality and quantity of ovulated oocytes. Improvements in serum hormone secretion and antioxidant factors, along with decreased expression of proinflammatory factors, were observed. Additionally, a significant increase in the number of ovarian follicles in aging individuals was noted. Scanning electron microscopy data indicated that NMN significantly alters the density and morphology of lipid droplets and mitochondria in granulosa cells, suggesting potential targets and mechanisms. Transcriptomic analysis and validation experiments collectively suggested that the beneficial effects of NMN on aging ovaries are mediated through enhanced mitochondrial function, improved energy metabolism, and reduced inflammation levels. Our results suggest that NMN supplementation could improve the health status of aging ovaries and enhance ovarian reserve, offering new insights into addressing fertility challenges in older women through assisted reproductive technology.
3D‐Printed‐Cryogel‐Impregnated Functionalized Scaffold Augments Bone Regeneration in Critical Tibia Fracture in Goat
Authors: Aman Nikhil, Mudasir B. Gugjoo, Ankita Das, Syed M. Ahmad, Ashok Kumar
Journal: Advanced Healthcare Materials (2024)

Abstract Critical‐size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano‐hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin‐nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein‐2 (BMP‐2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D‐printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical‐size defect (25 × 10 × 5 mm) in goat tibia. After 4 months, the scaffold is well‐integrated with adjacent native bone, with osteoinduction observed in the cryogel‐filled region and osteoconduction over the printed scaffold. X‐ray radiography and micro‐CT analysis showed bone in‐growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78).
When is prostate cancer really cancer?
Authors: Matthew R Cooperberg, Avery E Braun, Alejandro Berlin, Adam S Kibel, Scott E Eggener, Gladell P Paner, Yuri E Nikiforov, Laura J Esserman, Theo van der Kwast, Jeff Simko, Alastair D Lamb, Laurence Klotz, Declan G Murphy, Caroline M Moore, Ruth Etzioni, Andrew Vickers, Derya Tilki, Mohamed Jalloh, Quoc Trinh, Kosj Yamoah, Howard Wolinsky, Leszek Izdebski, C J Stimpson, Charles J Ryan, Timothy J Wilt, Hashim U Ahmed, Felix Y Feng
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Prostate cancer (PC) is a major cause of cancer-related deaths worldwide, with far more diagnoses than deaths annually. Recent discussions have challenged whether Grade Group 1 (GG1) PC should be labeled “cancer” due to its indolent nature. To address this question, an international symposium convened stakeholders from various fields. We summarize key discussion points: autopsy studies reveal GG1 is so common in aging males as to be perhaps a normal aspect of aging. Pure GG1 has no capacity to metastasize. Modern diagnostic pathways focus on detecting higher-grade disease, explicitly omitting biopsy if GG 2 or higher is not suspected, so GG1 has effectively become an “incidentaloma.” Recent spatial transcriptomics of prostate sections identifies a continuum of genomic changes—including alterations characteristic of malignancy in histologically normal regions, so the designation of cancer based entirely on conventional pathology findings increasingly seems arbitrary at least to an extent. Pathologists discussed heterogeneity and diagnostic challenges, suggesting “acinar neoplasm” as one possible alternative label. GG1 should not be considered “normal,” and absolutely requires ongoing active surveillance; whether patients would adhere to surveillance absent a cancer diagnosis is unknown. Patient perspectives highlighted the adverse effects of overtreatment and the burden of a cancer diagnosis. The anticipated impact on screening and treatment varies across health-care systems, but many believe public health would on balance greatly improve if GG1—along with lesions in other organs with no capacity to cause symptoms or threaten life—were labeled something other than “cancer.” Ultimately, our goal is to reduce PC mortality while minimizing harms associated with both overdiagnosis and overtreatment.
Long‐term follow‐up of the <scp>TRED</scp>‐<scp>HF</scp> trial: Implications for therapy in patients with dilated cardiomyopathy and heart failure remission
Authors: Leanne Cheng, Daniel Hammersley, Aaraby Ragavan, Saad Javed, Srinjay Mukhopadhyay, John Gregson, Jennie Han, Zohya Khalique, Amrit Lota, Antonis Pantazis, A. John Baksi, Gerald Carr‐White, Antonio de Marvao, James Ware, Upasana Tayal, Dudley J. Pennell, John G.F. Cleland, Sanjay K. Prasad, Brian P. Halliday
Journal: European Journal of Heart Failure (2024)