tbuckley/cabot-search huggingface dataset:
Supporting self-management of low back pain with an internet intervention with and without telephone support in primary care (SupportBack 2): a randomised controlled trial of clinical and cost-effectiveness
Authors: Adam W A Geraghty, Taeko Becque, Lisa C Roberts, Jonathan C Hill, Nadine E Foster, Lucy Yardley, Beth Stuart, David A Turner, Elaine Hay, Gareth Griffiths, Frances Webley, Lorraine Durcan, Alannah Morgan, Stephanie Hughes, Sarah Bathers, Stephanie Butler-Walley, Simon Wathall, Gemma Mansell, Malcolm White, Firoza Davies, Paul Little
Journal: The Lancet Rheumatology (2024)

Low back pain is prevalent and a leading cause of disability. We aimed to determine the clinical and cost-effectiveness of an accessible, scalable internet intervention for supporting behavioural self-management (SupportBack).
The role of dementia in the association between APOE4 and all-cause mortality: pooled analyses of two population-based cohort studies
Authors: Mélina Régy, Aline Dugravot, Séverine Sabia, Catherine Helmer, Christophe Tzourio, Bernard Hanseeuw, Archana Singh-Manoux, Julien Dumurgier
Journal: The Lancet Healthy Longevity (2024)
Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis
Authors: Blossom C M Stephan, Louie Cochrane, Aysegul Humeyra Kafadar, Jacob Brain, Elissa Burton, Bronwyn Myers, Carol Brayne, Aliya Naheed, Kaarin J Anstey, Ammar W Ashor, Mario Siervo
Journal: The Lancet Healthy Longevity (2024)

More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors.
Sex as a predictor of clinical phenotype and determinant of immune response in IgG4-related disease: a retrospective study of patients fulfilling the American College of Rheumatology–European League Against Rheumatism classification criteria
Authors: Isha Jha, Grace A McMahon, Cory A Perugino, Guy Katz, Zachary S Wallace, Ana Fernandes, Bohang Jiang, Yuqing Zhang, Aubree E McMahon, Thomas V Guy, Hang Liu, Yasmin G Hernandez-Barco, Shiv Pillai, John H Stone
Journal: The Lancet Rheumatology (2024)
Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease patient-derived tissue
Authors: Benjamin Jevans, Fay Cooper, Yuliia Fatieieva, Antigoni Gogolou, Yi-Ning Kang, Restuadi Restuadi, Dale Moulding, Pieter Vanden Berghe, Igor Adameyko, Nikhil Thapar, Peter W Andrews, Paolo De Coppi, Anestis Tsakiridis, Conor J McCann
Journal: Gut (2024)

Objective Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from the failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs). Design ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single-cell RNA sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors’ capacity to integrate and affect functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility. Results We found that our protocol consistently gives rise to high yields of a cell population exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons/glia within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed significantly increased basal contractile activity and increased responses to electrical stimulation compared with control tissue. Conclusion Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and increase functional responses in human HSCR patient colonic tissue.
Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration
Authors: Jiayi Yuan, Bingbing Sun, Weixing Ma, Chao Cai, Zhenzhen Huang, Peiyi Zhou, Lei Yi, Lubin Liu, Shixuan Chen
Journal: Bioactive Materials (2024)

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.
Interactions between LAMP3+ dendritic cells and T-cell subpopulations promote immune evasion in papillary thyroid carcinoma
Authors: Zhiyuan Wang, Xiaoyu Ji, Ye Zhang, Fan Yang, Hongyue Su, Hao Zhang, Zhendong Li, Wenqian Zhang, Wei Sun
Journal: Journal for ImmunoTherapy of Cancer (2024)

The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets. This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples. A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3+) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3+ DCs promote CD8+ T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3+ DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion. Our findings expound valuable insights into the role of the interaction between LAMP3+ DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.
Self-assembled carbon monoxide nanogenerators managing sepsis through scavenging multiple inflammatory mediators
Authors: Yang Wu, Xia Chen, Zhaolin Zeng, Bei Chen, Zhenxing Wang, Zhiyong Song, Hui Xie
Journal: Bioactive Materials (2024)

Sepsis, a life-threatening syndrome of organ damage resulting from dysregulated inflammatory response, is distinguished by overexpression of inflammatory cytokines, excessive generation of reactive oxygen/nitrogen species (RONS), heightened activation of pyroptosis, and suppression of autophagy. However, current clinical symptomatic supportive treatment has failed to reduce the high mortality. Herein, we developed self-assembled multifunctional carbon monoxide nanogenerators (Nano CO), as sepsis drug candidates, which can release CO in response to ROS, resulting in clearing bacteria and activating the heme oxygenase-1/CO system. This activation strengthened endogenous protection and scavenged multiple inflammatory mediators to alleviate the cytokine storm, including scavenging RONS and cfDNA, inhibiting macrophage activation, blocking pyroptosis and activating autophagy. Animal experiments show that Nano CO has a good therapeutic effect on mice with LPS-induced sepsis, which is manifested in hypothermia recovery, organ damage repair, and a 50% decrease in mortality rates. Taken together, these results illustrated the efficacy of multifunctional Nano CO to target clearance of multiple mediators in sepsis treatment and act against other refractory inflammation-related diseases.
Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu’s arteritis
Authors: Chenglong Fang, Lihong Du, Shang Gao, Yuexin Chen, Zuoguan Chen, Zhiyuan Wu, Lili Li, Jing Li, Xiaofeng Zeng, Mengtao Li, Yongjun Li, Xinping Tian
Journal: Annals of the Rheumatic Diseases (2024)

Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK.
Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain
Authors: Christoph Baerwald, Edgar Stemmler, Sixten Gnüchtel, Katharina Jeromin, Björn Fritz, Michael Bernateck, Daniela Adolf, Peter C Taylor, Ralf Baron
Journal: Annals of the Rheumatic Diseases (2024)

To determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity.
NIR‐II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy
Authors: Jinxuan Li, Mengting Gao, Yuhang Wang, Wenxuan Wang, Shichao Meng, Xin Zhang, Chongqing Zhang, Pengmin Liu, Xiaodong Zhang, Ziliang Zheng, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H
Deletion of the mRNA endonuclease Regnase-1 promotes NK cell anti-tumor activity via OCT2-dependent transcription of Ifng
Authors: Xin Sun, Yasuharu Nagahama, Shailendra Kumar Singh, Yuuki Kozakai, Hiroshi Nabeshima, Kiyoharu Fukushima, Hiroki Tanaka, Daisuke Motooka, Eriko Fukui, Eric Vivier, Diego Diez, Shizuo Akira
Journal: Immunity (2024)

Limited infiltration and activity of natural killer (NK) and T cells within the tumor microenvironment (TME) correlate with poor immunotherapy responses. Here, we examined the role of the endonuclease Regnase-1 on NK cell anti-tumor activity. NK cell-specific deletion of Regnase-1 (Reg1ΔNK) augmented cytolytic activity and interferon-gamma (IFN-γ) production in vitro and increased intra-tumoral accumulation of Reg1ΔNK-NK cells in vivo, reducing tumor growth dependent on IFN-γ. Transcriptional changes in Reg1ΔNK-NK cells included elevated IFN-γ expression, cytolytic effectors, and the chemokine receptor CXCR6. IFN-γ induced expression of the CXCR6 ligand CXCL16 on myeloid cells, promoting further recruitment of Reg1ΔNK-NK cells. Mechanistically, Regnase-1 deletion increased its targets, the transcriptional regulators OCT2 and IκBζ, following interleukin (IL)-12 and IL-18 stimulation, and the resulting OCT2-IκBζ-NF-κB complex induced Ifng transcription. Silencing Regnase-1 in human NK cells increased the expression of IFNG and POU2F2. Our findings highlight NK cell dysfunction in the TME and propose that targeting Regnase-1 could augment active NK cell persistence for cancer immunotherapy.
Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems
Authors: Toomas Mets, Tatsuaki Kurata, Karin Ernits, Marcus J.O. Johansson, Sophie Z. Craig, Gabriel Medina Evora, Jessica A. Buttress, Roni Odai, Kyo Coppieters‘t Wallant, Jose A. Nakamoto, Lena Shyrokova, Artyom A. Egorov, Christopher Ross Doering, Tetiana Brodiazhenko, Michael T. Laub, Tanel Tenson, Henrik Strahl, Chloe Martens, Alexander Harms, Abel Garcia-Pino, Gemma C. Atkinson, Vasili Hauryliuk
Journal: Cell Host & Microbe (2024)

Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC. HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Chaperone HigC recognizes gpV and ChAD via analogous aromatic molecular patterns, with gpV outcompeting ChAD to trigger toxicity. For CmdTAC, the CmdT ADP-ribosyltransferase toxin modifies mRNA to halt protein synthesis and limit phage propagation. Finally, we establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with a HigC chaperone phage sensor. Collectively, these findings reveal the potential of TAC systems in broad-spectrum antiphage defense.
Letter to editor:“Association of follow-up neutrophil-to-lymphocyte ratio and systemic inflammation response index with stroke-associated pneumonia and functional outcomes in cerebral hemorrhage patients: a case controlled study”
Authors: Yanfei Yang, Yang Wen, Jun Li
Journal: International Journal of Surgery (2024)

aDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China bDepartment of Neurosurgery Department, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China † These authors have contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: First Affiliated Hospital of Dalian Medical University CHINA. E-mail address: [email protected] (J. Li). This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0/
Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells
Authors: Patrick Fernandes Rodrigues, Tihana Trsan, Grozdan Cvijetic, Darya Khantakova, Santosh K. Panda, Zhaoyuan Liu, Florent Ginhoux, Marina Cella, Marco Colonna
Journal: Immunity (2024)

Conventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8
Mast cells control lung type 2 inflammation via prostaglandin E2-driven soluble ST2
Authors: Kinan Alhallak, Jun Nagai, Kendall Zaleski, Sofia Marshall, Tamara Salloum, Tahereh Derakhshan, Hiroaki Hayashi, Chunli Feng, Radomir Kratchmarov, Juying Lai, Virinchi Kuchibhotla, Airi Nishida, Barbara Balestrieri, Tanya Laidlaw, Daniel F. Dwyer, Joshua A. Boyce
Journal: Immunity (2024)
From the Beginning to the End: Effects of Proteinuria along the Renal Tubule
Authors: Louisa M.S. Gerhardt
Journal: Journal of the American Society of Nephrology (2024)

Fifth Department of Medicine, Faculty of Medicine Mannheim of the University of Heidelberg, University Medical Center Mannheim, Mannheim, Germany Correspondence: Dr. Louisa M.S. Gerhardt, email: [email protected] See related article, "Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria," on pages XXX–XXX.
An inducible genetic tool to track and manipulate specific microglial states reveals their plasticity and roles in remyelination
Authors: Kia M. Barclay, Nora Abduljawad, Zuolin Cheng, Min Woo Kim, Lu Zhou, Jin Yang, Justin Rustenhoven, Jose A. Mazzitelli, Leon C.D. Smyth, Dvita Kapadia, Simone Brioschi, Wandy Beatty, JinChao Hou, Naresha Saligrama, Marco Colonna, Guoqiang Yu, Jonathan Kipnis, Qingyun Li
Journal: Immunity (2024)

Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative-region-associated microglia (PAMs) in developing white matter and disease-associated microglia (DAMs) prevalent in various neurodegenerative conditions. PAMs and DAMs share a similar core gene signature. However, the extent of the dynamism and plasticity of these microglial states, as well as their functional significance, remains elusive, partly due to the lack of specific tools. Here, we generated an inducible Cre driver line, Clec7a-CreER
Results of the TARGET-TP Randomized Clinical Trial—Reply
Authors: Marliese Alexander, Rory Wolfe, Kate Burbury
Journal: JAMA Oncology (2024)

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Obstacles to Biosimilar Acceptance and Uptake in Oncology
Authors: Daniel K. Mroczek, Katherina Hauner, George J. Greene, Karen Kaiser, John Devin Peipert, Mary Golf, Sheetal Kircher, Sara Shaunfield, Madison Lylerohr, David Cella
Journal: JAMA Oncology (2024)

Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars.