tbuckley/cabot-search huggingface dataset:
Adaptive immunity of materials: Implications for tissue healing and regeneration
Authors: Jung-Hwan Lee, Seong-Jin Shin, Jun Hee Lee, Jonathan C Knowles, Hae-Hyoung Lee, Hae-Won Kim
Journal: Bioactive Materials (2024)

Recent cumulative findings signify the adaptive immunity of materials as a key agenda in tissue healing that can improve regenerative events and outcomes. Modulating immune responses, mainly the recruitment and functions of T and B cells and their further interplay with innate immune cells (e.g., dendritic cells, macrophages) can be orchestrated by materials. For instance, decellularized matrices have been shown to promote muscle healing by inducing T helper 2 (Th2) cell immunity, while synthetic biopolymers exhibit differential effects on B cell responses and fibrosis compared decellularized matrices. We discuss the recent findings on how implantable materials instruct the adaptive immune events and the subsequent tissue healing process. In particular, we dissect the materials' physicochemical properties (shape, size, topology, degradation, rigidity, and matrix dynamic mechanics) to demonstrate the relations of these parameters with the adaptive immune responses
The challenge of structural violence
Authors: Nicholas S Hopkinson
Journal: BMJ (2024)

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Epigenetic Biomarkers for Understanding Adverse Experiences and Health
Authors: Anne K. Bozack, Sarah M. Merrill, Andres Cardenas
Journal: JAMA Network Open (2024)

Christian K. Dye, PhD; Daniel M. Alschuler, MS; Haotian Wu, PhD; Cristiane Duarte, PhD; Catherine Monk, PhD; Daniel W. Belsky, PhD; Seonjoo Lee, PhD; Kieran O'Donnell, PhD; Andrea A. Baccarelli, MD, PhD; Pamela Scorza, PhD
Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns
Authors: Christian K. Dye, Daniel M. Alschuler, Haotian Wu, Cristiane Duarte, Catherine Monk, Daniel W. Belsky, Seonjoo Lee, Kieran O’Donnell, Andrea A. Baccarelli, Pamela Scorza
Journal: JAMA Network Open (2024)

Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations.
Perinatal Psychotherapy Use and Costs Before and After Federally Mandated Health Insurance Coverage
Authors: Kara Zivin, Xiaosong Zhang, Anca Tilea, Stephanie V. Hall, Lindsay K. Admon, Ashlee J. Vance, Vanessa K. Dalton
Journal: JAMA Network Open (2024)

Insurance coverage affects health care access for many delivering women diagnosed with perinatal mood and anxiety disorders (PMADs). The Mental Health Parity and Addiction Equity Act (MHPAEA; passed in 2008) and the Patient Protection and Affordable Care Act (ACA; passed in 2010) aimed to improve health care access.
DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma
Authors: Jiayi Zhang, Zihui Ni, Yu Zhang, Yan Guo, Rundong Zhai, Mengqi Wang, Zizhen Gong, Mengyao Wang, Fanrui Zeng, Ziyue Gu, Qianming Chen, Laikui Liu, Zhiyong Wang, Weiwen Zhu
Journal: Cancer Research (2024)

Tumor invasion and metastasis are the underlying causes of high mortality rate due to oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for an in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ-associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA sequencing analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation to accumulate in the nucleus where it enhanced cytochrome c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In samples from patients with OSCC, expression of DAZAP1 positively correlated with COX16 and a high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis. Significance: The RNA-binding protein DAZAP1 undergoes phase separation to enhance COX16 expression and mediate metabolic reprogramming that enables tumor metastasis, highlighting DAZAP1 as a potential metabolic target for cancer therapy.
Unraveling the impact of therapeutic drug monitoring via machine learning for patients with sepsis
Authors: H. Ceren Ates, Abdallah Alshanawani, Stefan Hagel, Menino O. Cotta, Jason A. Roberts, Can Dincer, Cihan Ates
Journal: Cell Reports Medicine (2024)

Clinical studies investigating the benefits of beta-lactam therapeutic drug monitoring (TDM) among critically ill patients are hindered by small patient groups, variability between studies, patient heterogeneity, and inadequate use of TDM. Accordingly, definitive conclusions regarding the efficacy of TDM remain elusive. To address these challenges, we propose an innovative approach that leverages data-driven methods to unveil the concealed connections between therapy effectiveness and patient data, collected through a randomized controlled trial (DRKS00011159; 10th October 2016). Our findings reveal that machine learning algorithms can successfully identify informative features that distinguish between healthy and sick states. These hold promise as potential markers for disease classification and severity stratification, as well as offering a continuous and data-driven "multidimensional" Sequential Organ Failure Assessment (SOFA) score. The positive impact of TDM on patient recovery rates is demonstrated by unraveling the intricate connections between therapy effectiveness and clinically relevant data via machine learning.
Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer’s disease
Authors: Yona Levites, Eric B. Dammer, Yong Ran, Wangchen Tsering, Duc Duong, Measho Abreha, Joshna Gadhavi, Kiara Lolo, Jorge Trejo-Lopez, Jennifer Phillips, Andrea Iturbe, Aya Erquizi, Brenda D. Moore, Danny Ryu, Aditya Natu, Kristy Dillon, Jose Torrellas, Corey Moran, Thomas Ladd, Farhana Afroz, Tariful Islam, Jaishree Jagirdar, Cory C. Funk, Max Robinson, Srikant Rangaraju, David R. Borchelt, Nilüfer Ertekin-Taner, Jeffrey W. Kelly, Frank L. Heppner, Erik C.B. Johnson, Karen McFarland, Allan I. Levey, Stefan Prokop, Nicholas T. Seyfried, Todd E. Golde
Journal: Cell Reports Medicine (2024)

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid β (Aβ)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aβ amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aβ in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.
Clinical and molecular risk factors in extracranial malignant rhabdoid tumors – Towards an integrated model of high-risk tumors
Authors: Victoria E. Fincke, Mona Steinbügl, Hye-Jung E. Chun, Karolina Nemes, Marlena Mucha, Maurice Loßner, Felix Dorn, Katharina Gastberger, Sebastian Bühner, Martin Sill, Thomas Kröncke, Reiner Siebert, Patrick Melchior, Rhoikos Furtwängler, Matthias Schlesner, Christian Vokuhl, Christoph Röcken, Pascal D. Johann, Michael C. Frühwald
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Extracranial malignant rhabdoid tumors (eMRT) are a challenging entity. Despite the use of multimodal treatment approaches, therapy failure occurs in 55% to 67% of these. Molecular markers for identification of patients at increased risk for relapse or refractory (R/R) disease are not available. Clinical characteristics may only insufficiently predict the individual course of disease. Experimental Design: Using the EU-RHAB database, we analyzed a cohort of 121 patients with eMRT clinically. For 81 patients, molecular and clinical data were available, which were further complemented with publicly available DNA molecular data from 92 eMRTs. We aimed to delineate molecular risk factors by dissecting the DNA methylome of these tumors. Moreover, we establish clinical characteristics and treatment details of R/R disease in a subcohort of 80 patients. Results: Using consensus hierarchical clustering, we identified three distinct subgroups, one of which (eMRT standard risk) was associated with significantly improved survival, irrespective of germline status and/or localization. At the transcriptome level, this subgroup was characterized by an overexpression of genes involved in muscle development. A relevant proportion of patients developed distant relapses or progressions; the median time to the event was 4 months, underlining the need for early identification and risk stratification of R/R disease. The overall survival was significantly decreased in patients with progressive disease when compared with relapse cases, and reaching complete remission during salvage therapy provided a survival benefit. Conclusions: Our analysis of eMRT in this comprehensive cohort provides novel insights into the patterns of relapse and integrates molecular and clinical risk factors to guide clinical decision-making.
CD137 (4-1BB) and T-Lymphocyte Exhaustion
Authors: Paula Molero-Glez, Arantza Azpilikueta, Laura Mosteo, Javier Glez-Vaz, Belen Palencia, Ignacio Melero
Journal: Clinical Cancer Research (2024)

CD137 (4-1BB) costimulation results in the potent activation of antitumor T lymphocytes and elicits antitumor efficacy that is synergistic with anti-PD(L)1 checkpoint inhibitors, especially when using bispecific constructs. Emerging experimental evidence indicates that 4-1BB ligation prevents and may revert T-cell exhaustion. See related article by Jeon et al., p. 4155.
Recent developments in immunotherapy for gastrointestinal tract cancers
Authors: Xiaoyi Chong, Yelizhati Madeti, Jieyuan Cai, Wenfei Li, Lin Cong, Jialin Lu, Liyang Mo, Huizhen Liu, Siyi He, Chao Yu, Zhiruo Zhou, Boya Wang, Yanshuo Cao, Zhenghang Wang, Lin Shen, Yakun Wang, Xiaotian Zhang
Journal: Journal of Hematology & Oncology (2024)

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.
The early life exposome and autism risk: a role for the maternal microbiome?
Authors: Claudia M. Di Gesù, Shelly A. Buffington
Journal: Gut Microbes (2024)

Autism spectrum disorders (ASD) are highly heritable, heterogeneous neurodevelopmental disorders characterized by clinical presentation of atypical social, communicative, and repetitive behaviors. Over the past 25 years, hundreds of ASD risk genes have been identified. Many converge on key molecular pathways, from translational control to those regulating synaptic structure and function. Despite these advances, therapeutic approaches remain elusive. Emerging data unearthing the relationship between genetics, microbes, and immunity in ASD suggest an integrative physiology approach could be paramount to delivering therapeutic breakthroughs. Indeed, the advent of large-scale multi-OMIC data acquisition, analysis, and interpretation is yielding an increasingly mechanistic understanding of ASD and underlying risk factors, revealing how genetic susceptibility interacts with microbial genetics, metabolism, epigenetic (re)programming, and immunity to influence neurodevelopment and behavioral outcomes. It is now possible to foresee exciting advancements in the treatment of some forms of ASD that could markedly improve quality of life and productivity for autistic individuals. Here, we highlight recent work revealing how gene X maternal exposome interactions influence risk for ASD, with emphasis on the intrauterine environment and fetal neurodevelopment, host–microbe interactions, and the evolving therapeutic landscape for ASD.
KHSRP Stabilizes m6A-Modified Transcripts to Activate FAK Signaling and Promote Pancreatic Ductal Adenocarcinoma Progression
Authors: Zilan Xu, Yifan Zhou, Shaoqiu Liu, Hongzhe Zhao, Ziming Chen, Rui Li, Mei Li, Xudong Huang, Shuang Deng, Lingxing Zeng, Sihan Zhao, Shaoping Zhang, Xiaowei He, Ji Liu, Chunling Xue, Ruihong Bai, Lisha Zhuang, Quanbo Zhou, Rufu Chen, Dongxin Lin, Jian Zheng, Jialiang Zhang
Journal: Cancer Research (2024)

Abstract N 6-Methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV, and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer. Significance: KHSRP is a m6A-binding protein that stabilizes expression of FAK pathway mRNAs and that can be targeted to suppress FAK signaling and curb pancreatic ductal adenocarcinoma progression.
Landscape of glycolytic metabolites and their regulating proteins in myocardium from human heart failure with preserved ejection fraction
Authors: Navid Koleini, Mariam Meddeb, Liang Zhao, Mohammad Keykhaei, Seoyoung Kwon, Farnaz Farshidfar, Virginia S. Hahn, Erika L. Pearce, Kavita Sharma, David A. Kass
Journal: European Journal of Heart Failure (2024)
Broad-spectrum antibiotics disrupt homeostatic efferocytosis
Authors: Pedro H. V. Saavedra, Alissa J. Trzeciak, Allie Lipshutz, Andrew W. Daman, Anya J. O’Neal, Zong-Lin Liu, Zhaoquan Wang, Jesús E. Romero-Pichardo, Waleska Saitz Rojas, Giulia Zago, Marcel R. M. van den Brink, Steven Z. Josefowicz, Christopher D. Lucas, Christopher J. Anderson, Alexander Y. Rudensky, Justin S. A. Perry
Journal: Nature Metabolism (2024)
Single-nucleus chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry
Authors: Poornima Bhat-Nakshatri, Hongyu Gao, Aditi S. Khatpe, Adedeji K. Adebayo, Patrick C. McGuire, Cihat Erdogan, Duojiao Chen, Guanglong Jiang, Felicia New, Rana German, Lydia Emmert, George Sandusky, Anna Maria Storniolo, Yunlong Liu, Harikrishna Nakshatri
Journal: Nature Medicine (2024)
Heart failure with improved versus persistently reduced left ventricular ejection fraction: A comparison of the BIOSTAT‐CHF (European) study with the ASIAN‐HF registry
Authors: Thong Huy Cao, Wan Ting Tay, Donald J.L. Jones, John G.F. Cleland, Jasper Tromp, Johanna Elisabeth Emmens, Tiew‐Hwa Katherine Teng, Chanchal Chandramouli, Oliver Charles Slingsby, Stefan D. Anker, Kenneth Dickstein, Gerasimos Filippatos, Chim C. Lang, Marco Metra, Piotr Ponikowski, Nilesh J. Samani, Dirk J. Van Veldhuisen, Faiez Zannad, Inder S. Anand, Carolyn S.P. Lam, Adriaan A. Voors, Leong L. Ng
Journal: European Journal of Heart Failure (2024)

We investigated the prevalence, clinical characteristics, and prognosis of patients with heart failure (HF) with improved ejection fraction (HFimpEF).
Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial
Authors: Peter J. Illingworth, Christos Venetis, David K. Gardner, Scott M. Nelson, Jørgen Berntsen, Mark G. Larman, Franca Agresta, Saran Ahitan, Aisling Ahlström, Fleur Cattrall, Simon Cooke, Kristy Demmers, Anette Gabrielsen, Johnny Hindkjær, Rebecca L. Kelley, Charlotte Knight, Lisa Lee, Robert Lahoud, Manveen Mangat, Hannah Park, Anthony Price, Geoffrey Trew, Bettina Troest, Anna Vincent, Susanne Wennerström, Lyndsey Zujovic, Thorir Hardarson
Journal: Nature Medicine (2024)

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference -1.7%; 95% confidence interval -7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 .
Creating large-scale genetic diversity in Arabidopsis via base editing-mediated deep artificial evolution
Authors: Xiang Wang, Wenbo Pan, Chao Sun, Hong Yang, Zhentao Cheng, Fei Yan, Guojing Ma, Yun Shang, Rui Zhang, Caixia Gao, Lijing Liu, Huawei Zhang
Journal: Genome biology (2024)

Base editing is a powerful tool for artificial evolution to create allelic diversity and improve agronomic traits. However, the great evolutionary potential for every sgRNA target has been overlooked. And there is currently no high-throughput method for generating and characterizing as many changes in a single target as possible based on large mutant pools to permit rapid gene directed evolution in plants.
Long COVID science, research and policy
Authors: Ziyad Al-Aly, Hannah Davis, Lisa McCorkell, Letícia Soares, Sarah Wulf-Hanson, Akiko Iwasaki, Eric J. Topol
Journal: Nature Medicine (2024)

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system and can be severely disabling. The cumulative global incidence of long COVID is around 400 million individuals, which is estimated to have an annual economic impact of approximately $1 trillion-equivalent to about 1% of the global economy. Several mechanistic pathways are implicated in long COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement dysregulation, endothelial inflammation and microbiome dysbiosis. Long COVID can have devastating impacts on individual lives and, due to its complexity and prevalence, it also has major ramifications for health systems and economies, even threatening progress toward achieving the Sustainable Development Goals. Addressing the challenge of long COVID requires an ambitious and coordinated-but so far absent-global research and policy response strategy. In this interdisciplinary review, we provide a synthesis of the state of scientific evidence on long COVID, assess the impacts of long COVID on human health, health systems, the economy and global health metrics, and provide a forward-looking research and policy roadmap.
Real-life intrinsic capacity screening data from the ICOPE-Care program
Authors: Philipe de Souto Barreto, Emmanuel Gonzalez-Bautista, Heike A. Bischoff-Ferrari, Vitor Pelegrim de Oliveira, Renato Gorga Bandeira de Mello, Sandrine Andrieu, Caroline Berbon, Neda Tavassoli, John R. Beard, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas
Journal: Nature Aging (2024)
Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder
Authors: Alban Ziegler, Joanne Carroll, Jennifer M. Bain, Tristan T. Sands, Robert J. Fee, David Uher, Cara H. Kanner, Jacqueline Montes, Sarah Glass, Julie Douville, Laurence Mignon, Joseph G. Gleeson, Stanley T. Crooke, Wendy K. Chung
Journal: Nature Medicine (2024)