tbuckley/cabot-search huggingface dataset:
Flow-controlled Expiration Reduces Lung Injury During Assisted Ventilation in Pigs with ARDS
Authors: Sashko G. Spassov, Lea Streicher, Eva Bohe, Patryk Dzierzawski, Silke Borgmann, Johannes Dinkelaker, Bernd Flamm, Johannes Spaeth, Johannes Schmidt, Stefan Schumann, Christin Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Interventional Strategies for Children with Progressive Pulmonary Hypertension Despite Optimal Therapy. An Official American Thoracic Society Clinical Practice Guideline
Authors: Don Hayes, Ann L Jennerich, Ryan D. Coleman, Eric Abston, Gregory T. Adamson, John T. Berger, Sarah P. Cohen, David S. Cooper, Pirooz Eghtesady, Francis Fynn-Thompson, R. Mark Grady, Stephanie M Hon, Charles W. Hoopes, Teresa Jewell, Hayley Lewthwaite, Michelle F. Liu, David C. McGiffin, Mary P Mullen, Athar M. Qureshi, David L.S. Morales
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Background: Pulmonary hypertension in children is progressive with wide variability in prognosis. This document provides an evidence-based clinical practice guideline for the management of children with progressive pulmonary hypertension despite optimal therapy. Methods: A multidisciplinary panel identified pertinent questions regarding the management of children with pulmonary hypertension that has progressed despite optimal therapy, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development and Evaluation approach to develop clinical recommendations. Results: After reviewing the research evidence, the panel considered the balance of desirable (benefits) and undesirable (harms and burdens) effects of the interventions in each proposed question. Valuation of our main outcomes was also considered, together with resources required, equity, acceptability, and feasibility. Recommendations were developed for or against interventional strategies specific to children with pulmonary hypertension that has progressed despite optimal therapy. Conclusions: Although there is a growing population of children with pulmonary hypertension, there is a striking lack of empirical evidence regarding management of those whose disease has progressed despite optimal pharmacotherapy. The panel formulated and provided the rationale for clinical recommendations for or against interventional strategies on the basis of this limited empirical evidence, coupled with expert opinion, to aid clinicians in the management of these complex pediatric patients. In addition, we identified important areas for future research.
Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry
Authors: David F. Moreno, Cristina Jiménez, Fernando Escalante, Elham Askari, Marta Castellanos‐Alonso, Mario Arnao, Ángela Heredia, Miguel Á. Canales, Magdalena Alcalá, Arancha Bermúdez, Ana Saus Carreres, María Casanova, Luis Palomera, Cristina Motlló, Ricarda García‐Sánchez, Pablo Ríos Rull, Ramón García‐Sanz, Carlos Fernández de Larrea
Journal: HemaSphere (2024)

Abstract Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow‐up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2‐microglobulin ≥3 mg/L, and albumin &lt;4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low‐, intermediate‐, and high‐risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of MYD88 L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5‐year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.
Causes of death among patients diagnosed with chronic lymphocytic leukemia: A population‐based study in the Netherlands, 1996–2020
Authors: Lina van der Straten, Mark‐David Levin, Manette A. W. Dinnessen, Otto Visser, Eduardus F. M. Posthuma, Jeanette K. Doorduijn, Anton W. Langerak, Arnon P. Kater, Avinash G. Dinmohamed
Journal: HemaSphere (2024)

Abstract Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population‐based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause‐specific flexible parametric survival models, we estimated cause‐specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes. Our findings reveal CLL as the predominant COD, contributing to around 40% of relative mortality, with a declining 5‐year death probability from 16.8% in 1996–2002 to 7.6% in 2010–2020. Also, deaths attributed to solid malignancies, other hematological malignancies, and other COD diminished over time, as evidenced by respective HRs (95% confidence interval) of 0.68 (0.60%–0.77%), 0.45 (0.38%–0.53%), and 0.77 (0.66%–0.90%). In summary, our comprehensive, population‐based analysis underscores a noticeable reduction in CLL‐attributed deaths and other competing causes over the studied period. Nonetheless, CLL is registered as the most prevalent cause of mortality among contemporary diagnosed patients with CLL, emphasizing the continued relevance of CLL‐centric clinical strategies and research.
Programmable Nanomodulators for Precision Therapy, Engineering Tumor Metabolism to Enhance Therapeutic Efficacy
Authors: Siwei Liu, Zhijun Liu, Huajiang Lei, Yang‐Bao Miao, Jiao Chen
Journal: Advanced Healthcare Materials (2024)

Tumor metabolism is crucial in the continuous advancement and complex growth of cancer. The emerging field of nanotechnology has made significant strides in enhancing the understanding of the complex metabolic intricacies inherent to tumors, offering potential avenues for their strategic manipulation to achieve therapeutic goals. This comprehensive review delves into the interplay between tumor metabolism and various facets of cancer, encompassing its origins, progression, and the formidable challenges posed by metastasis. Simultaneously, it underscores the classification of programmable nanomodulators and their transformative impact on enhancing cancer treatment, particularly when integrated with modalities such as chemotherapy, radiotherapy, and immunotherapy. This review also encapsulates the mechanisms by which nanomodulators modulate tumor metabolism, including the delivery of metabolic inhibitors, regulation of oxidative stress, pH value modulation, nanoenzyme catalysis, nutrient deprivation, and RNA interference technology, among others. Additionally, the review delves into the prospects and challenges of nanomodulators in clinical applications. Finally, the innovative concept of using nanomodulators to reprogram metabolic pathways is introduced, aiming to transform cancer cells back into normal cells. This review underscores the profound impact that tailored nanomodulators can have on tumor metabolic, charting a path toward pioneering precision therapies for cancer.
Bilayer Scaffolds Synergize Immunomodulation and Rejuvenation via Layer‐Specific Release of CK2.1 and the “Exercise Hormone” Lac‐Phe for Enhanced Osteochondral Regeneration
Authors: Po‐Lin Liu, Shu‐Hang He, Zhi‐Han Shen, Xu‐Ran Li, Qing‐Song Deng, Zhan‐Ying Wei, Chang‐Ru Zhang, Xiao‐Qiu Dou, Tong‐He Zhu, Helen Dawes, Jian Lu, Shang‐Chun Guo, Shi‐Cong Tao
Journal: Advanced Healthcare Materials (2024)

Repairing osteochondral defects necessitates the intricate reestablishment of the microenvironment. The cartilage layer consists of a porous gelatin methacryloyl hydrogel (PGelMA) covalently crosslinked with the chondroinductive peptide CK2.1 via a "linker" acrylate-PEG-N-hydroxysuccinimide (AC-PEG-NHS). This layer is optimized for remodeling the senescent microenvironment in the cartilage region, thereby establishing a regenerative microenvironment that supports chondrogenesis. For the bone layer, silk fibroin methacryloyl (SilMA) is coated onto a three dimensional (3D)-printed 45S5 bioactive glass scaffold (BG scaffold). The "exercise hormone" N-lactoyl-phenylalanine (Lac-Phe) is loaded onto the SilMA, endowing it with diversified functions to regulate the osteogenic microenvironment. Systematic analysis in vitro reveals that PGelMA-CK2.1 shifts the microenvironment from a pro-inflammatory into an anti-inflammatory condition, and alleviates cellular senescence, thus modifying the cartilage microenvironment to improve the recruitment, proliferation and chondral differentiation of bone marrow mesenchymal stem cells (BMSCs). The scaffold bone layer enhances microvascular endothelial cell proliferation, migration, and angiogenic activities, which, couple with increased BMSC recruitment and regulatory mechanisms directing BMSC differentiation, favor a shift in the "osteogenesis-adipogenesis" balance toward enhanced osteogenesis. In vivo, it is found that this biphasic biomimetic scaffold favors simultaneous dual tissue regeneration. This approach facilitates the development of bioactive regenerative scaffolds and holds great potential for clinical application.
Combination therapy of favipiravir and nitazoxanide to treat respiratory viral infections in severe T-cell deficient children: a single center experience.
Authors: Tiphaine Arlabosse, Alexandra Y Kreins, Philip Ancliff, Rossa Brugha, Iek Leng Cheng, Robert Chiesa, Bairavi Indrakumar, Winnie Ip, Amy I Jacobs, Giovanna Lucchini, Stephen D Marks, Elizabeth Rivers, Helen Spencer, Austen Worth, Seilesh Kadambari, Judith Breuer
Journal: Journal of Infection (2024)
Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143–GSK3β in human nasal epithelial cells
Authors: Meiqian Xu, Mei Ren, Xinyin Zhang, Wenxu Peng, Hao Li, Wenjing Liao, Jianlei Xie, Xiaowen Zhang
Journal: Journal of Allergy and Clinical Immunology (2024)
Self-healing Ppy-Hydrogel Promotes Diabetic Skin Wound Healing through Enhanced Sterilization and Macrophage Orchestration Triggered by NIR
Authors: Zhuangzhuang Chu, Xingdan Liu, Tong Zhao, Dongya Jiang, Jing Zhao, Xiaohua Dong, Kelvin W K Yeung, Xuanyong Liu, Yun Liao, Liping Ouyang
Journal: Biomaterials (2024)
Multifaceted role of <i>TRIM28</i> in health and disease
Authors: Mazaher Maghsoudloo, Khatere Mokhtari, Behdokht Jamali, Amir Gholamzad, Maliheh Entezari, Mehrdad Hashemi, Junjiang Fu
Journal: MedComm (2024)

Abstract The TRIM (tripartite motif) family, with TRIM28 as a key member, plays a vital role in regulating health and disease. TRIM28 contains various functional domains essential for transcriptional regulation, primarily through its interaction with KRAB‐ZNF proteins, which influence chromatin remodeling and gene expression. Despite extensive research, the precise mechanisms by which TRIM28 impacts health and disease remain elusive. This review delves into TRIM28 ’s multifaceted roles in maintaining health, contributing to a variety of diseases, and influencing cancer progression. In cancers, TRIM28 exhibits a dual nature, functioning as both a tumor promoter and suppressor depending on the cellular context and cancer type. The review also explores its critical involvement in processes such as DNA repair, cell cycle regulation, epithelial‐to‐mesenchymal transition, and the maintenance of stem cell properties. By uncovering TRIM28 ’s complex roles across different cancers and other diseases, this review underscores its potential as a therapeutic target. The significance of TRIM28 as a versatile regulator opens the door to innovative therapeutic strategies, particularly in cancer treatment and the management of other diseases. Ongoing research into TRIM28 may yield key insights into disease progression and novel treatment options.
Metabolomics‐driven approaches for identifying therapeutic targets in drug discovery
Authors: Shanshan Pan, Luan Yin, Jie Liu, Jie Tong, Zichuan Wang, Jiahui Zhao, Xuesong Liu, Yong Chen, Jing Miao, Yuan Zhou, Su Zeng, Tengfei Xu
Journal: MedComm (2024)

Abstract Identification of therapeutic targets can directly elucidate the mechanism and effect of drug therapy, which is a central step in drug development. The disconnect between protein targets and phenotypes under complex mechanisms hampers comprehensive target understanding. Metabolomics, as a systems biology tool that captures phenotypic changes induced by exogenous compounds, has emerged as a valuable approach for target identification. A comprehensive overview was provided in this review to illustrate the principles and advantages of metabolomics, delving into the application of metabolomics in target identification. This review outlines various metabolomics‐based methods, such as dose–response metabolomics, stable isotope‐resolved metabolomics, and multiomics, which identify key enzymes and metabolic pathways affected by exogenous substances through dose‐dependent metabolite–drug interactions. Emerging techniques, including single‐cell metabolomics, artificial intelligence, and mass spectrometry imaging, are also explored for their potential to enhance target discovery. The review emphasizes metabolomics' critical role in advancing our understanding of disease mechanisms and accelerating targeted drug development, while acknowledging current challenges in the field.
LINC01764 promotes colorectal cancer cells proliferation, metastasis, and 5‐fluorouracil resistance by regulating glucose and glutamine metabolism via promoting c‐MYC translation
Authors: Ran Duan, Yujia Zhai, Qiushuang Wang, Liqin Zhao, Yixuan Wang, Nuoya Yu, Jieyun Zhang, Weijian Guo
Journal: MedComm (2024)

Abstract Few biomarkers are available for predicting chemotherapeutic response and prognosis in colorectal cancer (CRC). Long‐noncoding RNAs (lncRNAs) are essential for CRC development and growth. Therefore, studying lncRNAs may reveal potential predictors of chemotherapy response and prognosis in CRC. LINC01764 was analyzed using datasets from Fudan University Shanghai Cancer Center's advanced CRC patients’ RNA‐seq and The Cancer Genome Atlas datasets. Gene set enrichment analysis was employed to detect related pathways. Cotransfection experiments, RNA pulldown assays, RNA‐binding protein immunoprecipitation, protein synthesis activity, and dual‐luciferase reporter assays were performed to determine interactions among LINC01764, hnRNPK, and c‐MYC. High LINC01764 expression correlates with metastasis, a poor response to FOLFOX/XELOX chemotherapy, and a poor prognosis in CRC. LINC01764 enhance glycolysis and glutamine metabolism to promote CRC cells proliferation, metastasis, and 5‐fluorouracil (5‐FU) resistance. LINC01764 specifically binds to hnRNPK, facilitating its interaction with c‐MYC mRNA and promoting internal ribosome entry site (IRES)‐dependent translation of c‐MYC, thereby exerting oncogenic effects. LINC01764 induced 5‐FU chemoresistance by upregulating the c‐MYC, glucose, and glutamine metabolism pathways, which downregulated UPP1 , crucial for activating 5‐FU. Conclusively, LINC01764 promotes CRC progression and 5‐FU resistance through hnRNPK‐mediated‐c‐MYC IRES‐dependent translational regulation, which suggests its potential as a predictor of CRC chemotherapy response and prognosis.
Reliability and validity of instruments containing reported sleep measures among children from birth to &lt;5 years of age: A systematic review
Authors: Olga Antsygina, Scott Rollo, Nora McRae, Jean-Philippe Chaput, Mark S Tremblay
Journal: Sleep Medicine Reviews (2024)

Valid and reliable sleep measures during the early years are crucial for practitioners and researchers seeking accurate evaluation methods. The authors in this review systematically examined the psychometric properties of instruments containing reported sleep measures in children from birth to <5 years of age. The search was conducted using several electronic databases, including MEDLINE, EMBASE, PsycINFO, Web of Science, CINAHL, SPORTDiscus, Scopus and HaPI, with the most recent update on August 30, 2022. The quality of the included studies was assessed using the COSMIN methodology. A total of 79 studies were analyzed. However, none of these measures had undergone a comprehensive evaluation of all psychometric properties. Unfortunately, suitable reported sleep measures for children aged 0-4.99 years could not be identified through this review. Further research is needed to develop and validate psychometrically robust sleep assessment tools for this specific age group.
Biosynthetic potential of the gut microbiome in longevous populations
Authors: Sheng Liu, Zhao Zhang, Xudong Wang, Yan Ma, Hengfang Ruan, Xing Wu, Baoxia Li, Xiangyu Mou, Tao Chen, Zhengqi Lu, Wenjing Zhao
Journal: Gut Microbes (2024)

Gut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.
A three-layer perspective on miRNA regulation in β cell inflammation
Authors: Stefano Auddino, Elena Aiello, Giuseppina Emanuela Grieco, Francesco Dotta, Guido Sebastiani
Journal: Trends in Endocrinology and Metabolism (2024)

MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression post-transcriptionally and influence numerous biological processes. Aberrant miRNA expression is linked to diseases such as diabetes mellitus; indeed, miRNAs regulate pancreatic islet inflammation in both type 1 (T1D) and type 2 diabetes (T2D). Traditionally, miRNA research has focused on canonical sequences and offers a two-layer view - from expression to function. However, advances in RNA sequencing have revealed miRNA variants, called isomiRs, that arise from alternative processing or modifications of canonical sequences. This introduces a three-layer view - from expression, through sequence modifications, to function. We discuss the potential link between cellular stresses and isomiR biogenesis, and how this association could improve our knowledge of islet inflammation and dysfunction.
ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis
Authors: Lixue Cao, Haojie Peng, Yanzhen Chen, Baijin Xia, Tao Zeng, Jialing Guo, Fei Yu, Haiyan Ye, Hui Zhang, Xinxin Chen
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The failure of conventional therapies and the propensity for recurrence and metastasis make triple-negative breast cancer (TNBC) a formidable challenge with grim prognoses and diminished survival rates. Immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapy, presents innovative and potentially more effective strategies for addressing TNBC. Within this context, the inducible costimulator (ICOS), a member of the CTLA4/CD28 family, plays a crucial role in regulating immune responses and T-cell differentiation by binding to its ligand ICOSL. However, the impact of the ICOS/ICOSL axis on cancer varies. Methods In this study, immunohistochemistry was conducted to examine the expression level of ICOSL in TNBC tumor tissues. We developed ICOS-enhanced B7H3-CAR-T cells (ICOS-B7H3-CAR) using the third-generation CAR-T cell technology, which featured magnified ICOS expression and targeted the B7H3 antigen. Xenograft and metastasis models of TNBC were conducted to examine the cytotoxicity and durability of CAR-T cells in tumors. Overexpression and CRISPR/Cas9-mediated knockout (KO) techniques were employed to regulate the expression of ICOSL on TNBC cell lines. Results Notably, we observed elevated ICOSL expression in TNBC tumor tissues, which correlated with poor survival prognosis in patients with TNBC. Compared with conventional B7H3-CAR-T cells, ICOS-B7H3-CAR-T cells significantly inhibited the tumor growth of TNBC cells both in vitro and in vivo, accompanied by increased secretion of cytokines such as interferon gamma and tumor necrosis factor alpha. Furthermore, the in vivo experiments illustrated that ICOS-B7H3-CAR-T cells exhibited prolonged antitumor activity and could effectively eradicate metastases in a TNBC metastasis model, consequently extending survival. Importantly, manipulating the expression of ICOSL on TNBC cells through overexpression or KO significantly influenced the function of ICOS-B7H3-CAR-T cells. This suggests that the level of ICOSL expression on TNBC cells is critical for enhancing the potent antitumor effects of ICOS-B7H3-CAR-T cells. Conclusion Overall, our study highlights the potential clinical application of ICOS as a promising strategy for combating TNBC recurrence and metastasis.
Immunogenicity and cross-protective efficacy induced by delayed attenuated <i>Salmonella</i> with regulated length of lipopolysaccharide in mice
Authors: Xiaoping Bian, Qing Liu, Yaolin Chen, Wenjin Zhang, Mengru Li, Xiaofen Zhang, Liu Yang, Yonghong Liao, Qingke Kong
Journal: Gut Microbes (2024)

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