tbuckley/cabot-search huggingface dataset:
The prognostic value of the <scp>Dandel's</scp> index in patients undergoing tricuspid transcatheter edge‐to‐edge repair
Authors: Mohammad Kassar, Nicolas Brugger, Lukas Stolz, Muhammed Gerçek, Vera Fortmeier, Karl‐Patrik Kresoja, Jennifer von Stein, Benedikt Koell, Wolfgang Rottbauer, Bjoern Goebel, Paolo Denti, Paul Achouh, Tienush Rassaf, Manuel Barreiro‐Perez, Peter Boekstegers, Andreas Rück, Monika Zdanyte, Marianna Adamo, Flavien Vincent, Philipp Schlegel, Ralph‐Stephan von Bardeleben, Mirjam G. Wild, Stefan Toggweiler, Mathias H. Konstandin, Eric Van Belle, Marco Metra, Tobias Geisler, Rodrigo Estévez‐Loureiro, Peter Luedike, Nicole Karam, Francesco Maisano, Philipp Lauten, Mirjam Kessler, Daniel Kalbacher, Christos Iliadis, Philipp Lurz, Stephan Windecker, Jörg Hausleiter, Volker Rudolph, Fabien Praz
Journal: European Journal of Heart Failure (2024)

Aims Conventional parameters of right ventricular (RV) function are load‐dependent and therefore do not accurately reflect contractility in patients with relevant tricuspid regurgitation (TR). RV adaptability to load has been characterized using the Dandel's index in patients with heart failure, but its prognostic value in patients undergoing tricuspid transcatheter edge‐to‐edge repair (T‐TEER) has not been investigated so far. Methods and results From the EuroTR registry (2019 to 2022), patients with complete datasets and a minimum of 2‐years of follow‐up were included. RV functional parameters (i.e. tricuspid annular plane systolic excursion [TAPSE], fractional area change [FAC], TAPSE/systolic pulmonary arterial pressure [sPAP]), as well as a echocardiographic RV load adaptation index (Dandel's index) were assessed and their predictive value in terms of all‐cause mortality evaluated using logistic multivariate logistic regression. The majority of the 364 patients had secondary TR (96%) and were severely symptomatic (New York Heart Association class ≥III; 92%). At 2‐year follow‐up, 36% of patients had died. Functional RV parameters (TAPSE: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62–0.84; FAC: HR 0.73, 95% CI 0.59–0.91), coupling index (TAPSE/sPAP: HR 0.8, 95% CI 0.65–0.99) and Dandel's index (HR 0.67, 95% CI 0.53–0.85) were all associated with mortality at 2 years in univariable analyses. In a multivariate logistic regression model, the Dandel's index maintained its predictive value ( p &lt; 0.001), along with TAPSE and absence of signs of right heart failure, with an optimal threshold of 20.5 determined by the receiver‐operating characteristic analysis. This threshold also successfully predicted cardiac hospital readmission. A multivariate analysis was conducted to identify parameters linked to RV function and predicting clinical outcomes. Conclusion Assessment of the RV capacity to adjust for changes in loading conditions predicted mortality in patients with severe symptomatic TR undergoing T‐TEER. The use of a multiparametric approach including the Dandel's index to assess RV function had an incremental value for the stratification of patients into subgroups with different prognosis.
Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma
Authors: Fabian Ullrich, Paul J Bröckelmann, Amin T Turki, Abdullah M Khan, Elena-Diana Chiru, Marcus Vetter, Bastian von Tresckow, Rainer Wirth, Raul Cordoba, Valentín Ortiz-Maldonado, Tamas Fülöp, Nina Rosa Neuendorff
Journal: Journal for ImmunoTherapy of Cancer (2024)

The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient’s own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases. Age profoundly affects the physiological function of the immune system. The process of biological aging is largely driven by inflammatory signaling, which is reciprocally fueled by aging-related alterations of physiology and metabolism. In the T cell compartment, aging contributes to T cell senescence and exhaustion, increased abundance of terminally differentiated cells, a corresponding attrition in naïve T cell numbers, and a decrease in the breadth of the receptor repertoire. Furthermore, inflammatory signaling drives aging-related pathologies and contributes to frailty in older individuals. Thus, there is growing evidence of biological aging modulating the efficacy and toxicity of T cell-mediated immunotherapies. Here, we review the available evidence from biological and clinical studies focusing on the relationship between T cell-mediated treatment of hematologic malignancies and age. We discuss biological features potentially impacting clinical outcomes in various scenarios, and potential strategies to improve the safety and efficacy of immune checkpoint inhibitors, T cell-engaging bispecific antibodies, and CAR-T cell therapy in older patients.
Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva
Authors: Giovanni Musso, Mella Alberto, Filippo Mariano, Maurizio Cassader, Franco De Michieli, Antonella Riva, Giovanna Petrangolini, Stefano Togni, Silvia Pinach, Roberto Gambino
Journal: Gut Microbes (2024)

We investigate the role of homeostatic mechanisms involved in acute, postprandial nutrient metabolism and nutrient-induced systemic inflammation in CKD presence and progression in Metabolic dysfunction-associated steatohepatitis (MASH). We assessed postprandial incretins (GLP-1 and GIP), intestinotropic hormone GLP-2, endotoxin LPS, Zonulin (a marker of intestinal permeability), hepatokines, adipokines and NF-kB activation in circulating MNCs during a meal tolerance test in 52 biopsy proven MASH patients randomized to curcumin Meriva or placebo and 26 matched controls. At baseline, MASH-CKD had a lower GLP-2 response and a 2-fold higher postprandial LPS and NF-kB activation in MNCs than MASH patients without CKD, but similar remaining postprandial or fasting parameters. Postprandial IAUC GLP-2 predicted the presence of CKD in MASH (OR = 0.43, 95%CI:0.32-0.80, p = 0.008) independently of liver histology and traditional risk factors. After 72 weeks, changes in IAUC GLP-2 independently predicted the presence of CKD (OR = 0.49, 95%CI:0.21-0.73, p = 0.010) and eGFR changes [β(SE) = 0.510(0.007, p = 0.006] at end-of-treatment, In MASH, an impaired GLP-2 response to meals is associated with intestinal barrier dysfunction, endotoxemia and NF-kB-mediated systemic inflammation and may promote renal dysfunction and CKD. These data provide the rationale for evaluating GLP-2 analogues in MASH-related CKD.
Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial
Authors: Neil Keshvani, Syed Rizvi, Matthew W. Segar, James W. Miller, Juan David Coellar, Kershaw V. Patel, Bethany Roehm, W.H. Wilson Tang, Ambarish Pandey
Journal: European Journal of Heart Failure (2024)
Defective <i>Atg16l1</i> in intestinal epithelial cells links to altered fecal microbiota and metabolic shifts during pregnancy in mice
Authors: Víctor A. López-Agudelo, Maren Falk-Paulsen, Richa Bharti, Ateequr Rehman, Felix Sommer, Eike Matthias Wacker, David Ellinghaus, Anne Luzius, Laura Katharina Sievers, Manuel Liebeke, Arthur Kaser, Philip Rosenstiel
Journal: Gut Microbes (2024)

Throughout gestation, the female body undergoes a series of transformations, including profound alterations in intestinal microbial communities. Changes gradually increase toward the end of pregnancy and comprise reduced α-diversity of microbial communities and an increased propensity for energy harvest. Despite the importance of the intestinal microbiota for the pathophysiology of inflammatory bowel diseases, very little is known about the relationship between these microbiota shifts and pregnancy-associated complications of the disease. Here, we explored the longitudinal dynamics of gut microbiota composition and functional potential during pregnancy and after lactation in Atg16l1∆IEC mice carrying an intestinal epithelial deletion of the Crohn's disease risk gene Atg16l1. Using 16S rRNA amplicon and shotgun metagenomic sequencing, we demonstrated divergent temporal shifts in microbial composition between Atg16l1 wildtype and Atg16l1∆IEC pregnant mice in trimester 3, which was validated in an independent experiment. Observed differences included microbial genera implicated in IBD such as Lachnospiraceae, Roseburia, Ruminococcus, and Turicibacter. Changes partially recovered after lactation. Additionally, metagenomic and metabolomic analyses suggest an increased capacity for chitin degradation, resulting in higher levels of free N-acetyl-glucosamine products in feces, alongside reduced glucose and myo-inositol levels in serum around the time of delivery. On the host side, we found that the immunological response of Atg16l1∆IEC mice is characterized by higher colonic mRNA levels of TNFα and CXCL1 in trimester 3 and a lower weight of offspring at birth. Understanding pregnancy-dependent microbiome changes in the context of IBD may constitute the first step in the identification of fecal microbial biomarkers and microbiota-directed therapies that could help improve precision care for managing pregnancies in IBD patients.
Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into <i>de novo</i> large cerebral infarction
Authors: Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim
Journal: Theranostics (2024)

It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia in mice, yet leads to various outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction.
Concurrent intratumoural Treg cell depletion and CD8+ T cell expansion via a cleavable anti-4-1BB–interleukin-15 fusion protein
Authors: Yueqi Cai, Zilong Han, Jiao Shen, Zhuangzhi Zou, Jingya Guo, Yong Liang, Shijie Li, Huiping Liao, Zhenhua Ren, Hua Peng, Yang-Xin Fu
Journal: Nature Biomedical Engineering (2024)
Vascularized tumor on a microfluidic chip to study mechanisms promoting tumor neovascularization and vascular targeted therapies
Authors: Magdalena Skubal, Benedict Mc Larney, Ngan Bao Phung, Juan Carlos Desmaras, Abdul Vehab Dozic, Alessia Volpe, Anuja Ogirala, Camila Longo Machado, Jakob Djibankov, Vladimir Ponomarev, Jan Grimm
Journal: Theranostics (2024)

The cascade of events leading to tumor formation includes induction of a tumor supporting neovasculature, as a primary hallmark of cancer. Developing vasculature is difficult to evaluate
Monitoring of cancer ferroptosis with [<sup>18</sup>F]hGTS13, a system xc- specific radiotracer
Authors: Abraham Moses, Rim Malek, Mustafa Tansel Kendirli, Pierre Cheung, Madeleine Landry, Marco Herrera-Barrera, Abbas Khojasteh, Monica Granucci, Syed A Bukhari, Jody E Hooper, Melanie Hayden-Gephart, Scott J Dixon, Lawrence D Recht, Corinne Beinat
Journal: Theranostics (2024)

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies. System xc-, an important player in cellular redox homeostasis, plays a critical role in ferroptosis by mediating the exchange of cystine for glutamate, thus regulating the availability of cysteine, a crucial precursor for glutathione synthesis, and influencing the cellular antioxidant defense system. We have recently reported the development and validation of [
Standardization and consensus in the development and application of bone organoids
Authors: Jian Wang, Xiao Chen, Ruiyang Li, Sicheng Wang, Zhen Geng, Zhongmin Shi, Yingying Jing, Ke Xu, Yan Wei, Guangchao Wang, Chongru He, Shiwu Dong, Guohui Liu, Zhiyong Hou, Zhidao Xia, Xinglong Wang, Zhou Ye, Fengjin Zhou, Long Bai, Hongbo Tan, Jiacan Su
Journal: Theranostics (2024)

Organoids, self-organized structures derived from stem cells cultured in a specific three-dimensional (3D) in vitro microenvironment, have emerged as innovative platforms that closely mimic in vivo cellular behavior, tissue architecture, and organ function. Bone organoids, a frontier in organoid research, can replicate the complex structures and functional characteristics of bone tissue. Recent advancements have led to the successful development of bone organoids, including models of callus, woven bone, cartilage, trabecular bone, and bone marrow. These organoids are widely utilized in establishing bone-related disease models, bone injury repair, and drug screening. However, significant discrepancies remain between current bone organoids and human skeletal tissues in terms of morphology and functionality, limiting their ability to accurately model human bone physiology and pathology. To address these challenges and promote standardization in the construction, evaluation, and application of bone organoids, we have convened experts and research teams with substantial expertise in the field. By integrating existing research findings, this consortium aims to establish a consensus to guide future research and application of bone organoids.
The evolving understanding of systemic mechanisms in organ-specific IgA nephropathy: a focus on gut-kidney crosstalk
Authors: Xin Wang, Xu-Jie Zhou, Xue Qiao, Mario Falchi, Jing Liu, Hong Zhang
Journal: Theranostics (2024)

The interplay between multiple organs, known as inter-organ crosstalk, represents a complex and essential research domain in understanding the mechanisms and therapies for kidney diseases. The kidneys not only interact pathologically with many other organs but also communicate with other systems through various signaling pathways. It is of paramount importance to comprehend these mechanisms for the development of more efficient therapeutic strategies. Despite extensive research in IgA nephropathy (IgAN), the most common kidney disease, the elaboration mechanism of IgAN remains challenging. Numerous studies suggest that alterations in the intestinal microbiome and its metabolites are pivotal in the progression of IgAN, opening new avenues for understanding its mechanisms. Interestingly, certain presumed probiotics, such as
A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice
Authors: Chunyang Li, Cheng Miao, Yao Ge, Jiaxing Wu, Panpan Gao, Songlin Yin, Pei Zhang, Hongbin Yang, Bo Tian, Wenqiang Chen, Xiao Qian Chen
Journal: Theranostics (2024)

: The periaqueductal gray (PAG) is a central hub for the regulation of aggression, whereas the circuitry and molecular mechanisms underlying this regulation remain uncharacterized. In this study, we investigate the role of a distinct cell type,
iRGD-TRP-PK1-modified red blood cell membrane vesicles as a new chemotherapeutic drug delivery and targeting system in head and neck cancer
Authors: Suwen Bai, Zunyun Wang, Yuxin Zhang, Yunyun Yang, Yuan Wei, Yumei Luo, Minghua Wang, Bing Shen, Wei He, Zhenye Yang, Hui Hui, Juan Du
Journal: Theranostics (2024)

Chemotherapy is essential for treating tumors, including head and neck cancer (HNC). However, the toxic side effects of chemotherapeutic drugs limit their widespread use. Therefore, a targeted delivery system that can transport the drug to the pathological site while minimizing damage to healthy tissues is urgently needed.
Naphthalene-based fluorescent probes for glutathione and their applications in living cells and patients with sepsis: Erratum
Authors: Jun Li, Younghee Kwon, Kyung Soo Chung, Chang Su Lim, Dayoung Lee, Yongkang Yue, Jisoo Yoon, Gyoungmi Kim, Sang-Jip Nam, Youn Wook Chung, Hwan Myung Kim, Caixia Yin, Ji-Hwan Ryu, Juyoung Yoon
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.22252.].
Rc3h1 negatively regulates osteoclastogenesis by limiting energy metabolism
Authors: Liuyuan Chen, Yuangang Su, Chaofeng Wang, Qian Huang, Weiwei Chen, Na Hai, Jikang Wang, Haoyu Lian, Jinmin Zhao, Jiake Xu, Qian Liu
Journal: Theranostics (2024)

Osteoclasts are giant bone-resorbing cells that need vigorous mitochondrial respiration to support their activation. Rc3h1, an RNA-binding protein, precisely governs the homeostasis of mRNA. However, the precise role of Rc3h1 in regulating iron metabolism and mitochondrial respiration in osteoclasts is not yet understood.
Advances in adhesive hydrogels applied for ophthalmology: An overview focused on the treatment
Authors: Ke Yan, Qinghe Zhang, Qiuping Liu, Yi Han, Zuguo Liu
Journal: Theranostics (2024)

Adhesive hydrogels, composed of hydrophilic polymers arranged in a three-dimensional network, have emerged as a pivotal innovation in ophthalmology due to their ability to securely adhere to ocular tissues while providing sustained therapeutic effects. The eye, with its delicate structure and specific needs, presents unique challenges for drug delivery and tissue regeneration. This review explores the transformative potential of adhesive hydrogels in addressing these challenges across a range of ocular conditions, including corneal injuries, cataracts, glaucoma, vitreoretinal disorders, and ocular trauma. By detailing the mechanisms of polymerization and adhesion, this paper highlights how these materials can be customized for specific ophthalmic applications, offering insights into their current use and future possibilities. The emphasis is placed on the clinical significance and future directions of adhesive hydrogels in advancing ophthalmic therapy, potentially revolutionizing the treatment of complex eye diseases.
Targeted demethylation of cathepsin D via epigenome editing rescues pathology in Alzheimer's disease mouse model
Authors: Moonsu Park, Hongji Ryu, Suyeon Heo, Boyoung Kim, Junhang Park, Key-Hwan Lim, Sang-Bae Han, Hanseul Park
Journal: Theranostics (2024)

Cathepsin D (Ctsd) has emerged as a promising therapeutic target for Alzheimer's disease (AD) due to its role in degrading intracellular amyloid beta (Aβ). Enhancing Ctsd activity could reduce Aβ42 accumulation and restore the Aβ42/40 ratio, offering a potential AD treatment strategy.
Leveraging plant-derived nanovesicles for advanced nucleic acid-based gene therapy
Authors: Meihong Chai, Bowen Gao, Shihua Wang, Liping Zhang, Xing Pei, Baosen Yue, Xueyan Zhen, Mingzhen Zhang
Journal: Theranostics (2024)

Gene therapy has evolved into a pivotal approach for treating genetic disorders, extending beyond traditional methods of directly repairing or replacing defective genes. Recent advancements in nucleic acid-based therapies-including mRNA, miRNA, siRNA, and DNA treatments have expanded the scope of gene therapy to include strategies that modulate protein expression and deliver functional genetic material without altering the genetic sequence itself. This review focuses on the innovative use of plant-derived nanovesicles (PDNVs) as a promising delivery system for these nucleic acids. PDNVs not only enhance the stability and bioavailability of therapeutic nucleic acids but also improve their specificity and efficacy in targeted gene therapy applications. They have shown potential in the treatment of various diseases, including cancer and inflammatory conditions. By examining the unique properties of PDNVs and their role in overcoming the limitations of conventional delivery methods, this review highlights the transformative potential of PDNV-based nucleic acid therapies in advancing the field of gene therapy.
Optical molecular imaging in oral- and oropharyngeal squamous cell carcinoma using a novel uPAR-targeting near-infrared imaging agent FG001 (ICG-glu-glu-AE105): An explorative phase II clinical trial
Authors: Amanda Oester Andersen, Anders Christensen, Karina Straede, Mads Lawaetz, Christoffer Holst Hahn, Nicklas Rubek, Irene Wessel, Giedrius Lelkaitis, Katalin Kiss, Natasja Paaske, Anne Poulsen, Christian von Buchwald, Andreas Kjaer
Journal: Theranostics (2024)

: In oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC), frequent inadequate surgical margins highlight the importance of precise intraoperative identification and delineation of cancerous tissue for improving patient outcomes.
B cells and tertiary lymphoid structures in tumors: immunity cycle, clinical impact, and therapeutic applications
Authors: Xing Wu, Qibo Huang, Xiaoping Chen, Binhao Zhang, Junnan Liang, Bixiang Zhang
Journal: Theranostics (2024)

Tumorigenesis involves a multifaceted and heterogeneous interplay characterized by perturbations in individual immune surveillance. Tumor-infiltrating lymphocytes, as orchestrators of adaptive immune responses, constitute the principal component of tumor immunity. Over the past decade, the functions of tumor-specific T cells have been extensively elucidated, whereas current understanding and research regarding intratumoral B cells remain inadequate and underexplored. The delineation of B cell subsets is contingent upon distinct surface proteins and the specific transcription factors that define these subsets have yet to be fully described. Consequently, there is a pressing need for extensive and comprehensive exploration into tumor-infiltrating B cells and their cancer biology. Notably, B cells and other cellular entities assemble within the tumor milieu to establish tertiary lymphoid structures that facilitate localized immune activation and furnish novel insights for tumor research. It is of great significance to develop therapeutic strategies based on B cells, antibodies, and tertiary lymphoid structures. In this review, we address the role of B cells and tertiary lymphoid structures in tumor microenvironment, with the highlight on their spatiotemporal effect, prognostic value and therapeutic applications in tumor immunity.