tbuckley/cabot-search huggingface dataset:
SLC44A2-mediated phenotypic switch of vascular smooth muscle cells contributes to aortic aneurysm
Authors: Mengen Xing, Wanqi Chen, Yachen Ji, Weihong Song
Journal: Journal of Clinical Investigation (2024)

The phenotypic switch of vascular smooth cells (VSMCs) from a contractile to a synthetic state is associated with the development and progression of aortic aneurysm (AA). However, the mechanism underlying this process remains unclear. In this issue of the JCI, Song et al. identified SLC44A2 as a regulator of the phenotypic switch in VSMCs. Inhibition of SLC44A2 facilitated the switch to the synthetic state, contributing to the development of AA. Mechanistically, SLC44A2 interacted with NRP1 and ITGB3 to activate the TGF-β/SMAD signaling pathway, resulting in VSMCs with a contractile phenotype. Furthermore, VSMC-specific SLC44A2 overexpression by genetic or pharmacological manipulation reduced AA in mouse models. These findings suggest the potential of targeting the SLC44A2 signaling pathway for AA prevention and treatment.
MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction
Authors: Natalie M. Walker, Yuta Ibuki, A. Patrick McLinden, Keizo Misumi, Dylan C. Mitchell, Gabriel G. Kleer, Alison M. Lock, Ragini Vittal, Nahum Sonenberg, Amanda L. Garner, Vibha N. Lama
Journal: Journal of Clinical Investigation (2024)

Tissue fibrosis remains unamenable to meaningful therapeutic interventions and is the primary cause of chronic graft failure after organ transplantation. Eukaryotic translation initiation factor (eIF4E), a key translational regulator, serves as convergent target of multiple upstream profibrotic signaling pathways that contribute to mesenchymal cell (MC) activation. Here, we investigate the role of MAP kinase-interacting serine/threonine kinase-induced (MNK-induced) direct phosphorylation of eIF4E at serine 209 (Ser209) in maintaining fibrotic transformation of MCs and determine the contribution of the MNK/eIF4E pathway to the pathogenesis of chronic lung allograft dysfunction (CLAD). MCs from patients with CLAD demonstrated constitutively higher eIF4E phosphorylation at Ser209, and eIF4E phospho-Ser209 was found to be critical in regulating key fibrogenic protein autotaxin, leading to sustained β-catenin activation and profibrotic functions of CLAD MCs. MNK1 signaling was upregulated in CLAD MCs, and genetic or pharmacologic targeting of MNK1 activity inhibited eIF4E phospho-Ser209 and profibrotic functions of CLAD MCs in vitro. Treatment with an MNK1/2 inhibitor (eFT-508) abrogated allograft fibrosis in an orthotopic murine lung-transplant model. Together these studies identify what we believe is a previously unrecognized MNK/eIF4E/ATX/β-catenin signaling pathway of fibrotic transformation of MCs and present the first evidence, to our knowledge, for the utility of MNK inhibitors in fibrosis.
LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes
Authors: Jingzhong Ding, Anh Tram Nguyen, Kurt Lohman, Michael T. Hensley, Daniel Parker, Li Hou, Jackson Taylor, Deepak Voora, Janet K. Sawyer, Elena Boudyguina, Michael P. Bancks, Alain Bertoni, James S. Pankow, Jerome I. Rotter, Mark O. Goodarzi, Russell P. Tracy, David M. Murdoch, Daniel Duprez, Stephen S. Rich, Bruce M. Psaty, David Siscovick, Christopher B. Newgard, David Herrington, Ina Hoeschele, Steven Shea, James H. Stein, Manesh Patel, Wendy Post, David Jacobs, John S. Parks, Yongmei Liu
Journal: Journal of Clinical Investigation (2024)
Mechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model
Authors: David Lagier, Congli Zeng, David W. Kaczka, Min Zhu, Kira Grogg, Sarah E. Gerard, Joseph M. Reinhardt, Gabriel C. Motta Ribeiro, Azman Rashid, Tilo Winkler, Marcos F. Vidal Melo
Journal: Science Translational Medicine (2024)

Mechanical ventilation exposes the lung to injurious stresses and strains that can negatively affect clinical outcomes in acute respiratory distress syndrome or cause pulmonary complications after general anesthesia. Excess global lung strain, estimated as increased respiratory system driving pressure, is associated with mortality related to mechanical ventilation. The role of small-dimension biomechanical factors underlying this association and their spatial heterogeneity within the lung are currently unknown. Using four-dimensional computed tomography with a voxel resolution of 2.4 cubic millimeters and a multiresolution convolutional neural network for whole-lung image segmentation, we dynamically measured voxel-wise lung inflation and tidal parenchymal strains. Healthy or injured ovine lungs were evaluated as the mechanical ventilation positive end-expiratory pressure (PEEP) was titrated from 20 to 2 centimeters of water. The PEEP of minimal driving pressure (PEEP DP ) optimized local lung biomechanics. We observed a greater rate of change in nonaerated lung mass with respect to PEEP below PEEP DP compared with PEEP values above this threshold. PEEP DP similarly characterized a breaking point in the relationships between PEEP and SD of local tidal parenchymal strain, the 95th percentile of local strains, and the magnitude of tidal overdistension. These findings advance the understanding of lung collapse, tidal overdistension, and strain heterogeneity as local triggers of ventilator-induced lung injury in large-animal lungs similar to those of humans and could inform the clinical management of mechanical ventilation to improve local lung biomechanics.
Acyl-CoA binding protein for the experimental treatment of anorexia
Authors: Hui Chen, Stéphanie Moriceau, Adrien Joseph, Francois Mailliet, Sijing Li, Virginie Tolle, Philibert Duriez, Roland Dardennes, Sylvère Durand, Vincent Carbonnier, Gautier Stoll, Allan Sauvat, Sylvie Lachkar, Fanny Aprahamian, Carolina Alves Costa Silva, Hui Pan, Léa Montégut, Gerasimos Anagnostopoulos, Flavia Lambertucci, Omar Motiño, Uxía Nogueira-Recalde, Mélanie Bourgin, Misha Mao, Yuhong Pan, Alexandra Cerone, Erwan Boedec, Zelia L. Gouveia, Federica Marmorino, Chiara Cremolini, Lisa Derosa, Laurence Zitvogel, Oliver Kepp, Carlos López-Otín, Maria Chiara Maiuri, Franck Perez, Philip Gorwood, Nicolas Ramoz, Franck Oury, Isabelle Martins, Guido Kroemer
Journal: Science Translational Medicine (2024)

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.
Deciphering the sex gap in global life expectancy: the impact of female-specific cancers 1990-2019
Authors: Sergi Trias-Llimós, Elisenda Rentería, Roberta Rutigliano, Ajay Aggarwal, Jennifer Moodley, Karla Unger-Saldaña, Isabelle Soerjomataram
Journal: JNCI Journal of the National Cancer Institute (2024)

Females live longer than males, which results in a sex gap in life expectancy. This study examines the contribution of female cancers to this differential by world region and country over the period 1990-2019 with special focus to the 15-69 years age group.
Is it Time to Resist using RECIST as a Primary Endpoint for Rare Tumors Trials?
Authors: Brian A. Van Tine, Sasha Haarberg
Journal: Clinical Cancer Research (2024)

Epithelioid hemangioendothelioma is an ultra-rare cancer driven by YAP-CAMTA1 fusion. Based on the link of the fusion to the MEK pathway, SARC33 was performed. It is a phase 2 trial examining trametinib that missed its primary objective by RECIST but demonstrated patient-reported outcome benefits in improved pain. See related article by Schuetze et al., p. 4584.
Cancer Stemness Online: A Resource for Investigating Cancer Stemness and Associations with Immune Response
Authors: Weiwei Zhou, Minghai Su, Tiantongfei Jiang, Yunjin Xie, Jingyi Shi, Yingying Ma, Kang Xu, Gang Xu, Yongsheng Li, Juan Xu
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Cancer progression involves the gradual loss of a differentiated phenotype and the acquisition of progenitor and stem cell-like features, which are potential culprits of immunotherapy resistance. Although the state-of-the-art predictive computational methods have facilitated the prediction of cancer stemness, there remains a lack of efficient resources to accommodate various usage requirements. Here, we present the Cancer Stemness Online, an integrated resource for efficiently scoring cancer stemness potential at both bulk and single-cell levels. This resource integrates eight robust predictive algorithms as well as 27 signature gene sets associated with cancer stemness for predicting stemness scores. Downstream analyses were performed from five distinct aspects: identifying the signature genes of cancer stemness; exploring the associations with cancer hallmarks and cellular states; exploring the associations with immune response and the communications with immune cells; investigating the contributions to patient survival; and performing a robustness analysis of cancer stemness among different methods. Moreover, the pre-calculated cancer stemness atlas for more than 40 cancer types can be accessed by users. Both the tables and diverse visualizations of the analytical results are available for download. Together, Cancer Stemness Online is a powerful resource for scoring cancer stemness and expanding downstream functional interpretation, including immune response and cancer hallmarks. Cancer Stemness Online is freely accessible at http://bio-bigdata.hrbmu.edu.cn/CancerStemnessOnline.
Psychopathy and Impairments in Emotion Regulation: A systematic review and Meta-analysis
Authors: Patrizia Velotti, Serena Bruno, Guyonne Rogier, Sara Beomonte Zobel, Martina Vacchino, Carlo Garofalo, David S Kosson
Journal: Clinical Psychology Review (2024)

Considering the sparse but rapidly growing literature concerning the relationship between psychopathy and emotion regulation, taking stock of accumulating knowledge in a systematic review and meta-analysis of the existing results is needed. We performed a systematic search (up to May 30, 2024) following PRISMA guidelines of five scientific databases (PsycINFO, PsycARTICLES, MEDLINE, PubMed, Scopus and Web of Science). Also, gray literature was searched. After removing the duplicates, a total of 8.786 records were screened, and 73 articles were selected based on the inclusion criteria used for systematic review. The meta-analytic procedure was performed on 55 identified studies consistent with the criteria adopted, which overall comprised 29.856 individuals. The current systematic and meta-analysis review has clarified the association between impairments of emotional regulation abilities and facets of psychopathy. More specifically, analyses indicated that emotional dysregulation is associated with overall levels of psychopathic traits, as well as with both the lifestyle and affective components of psychopathy, which suggests the utility of assessing these features when designing interventions focused on modulating negative emotional states and enhancing regulation of impulsive behaviors.
Interactions between eosinophils and IL-5Rα–positive mast cells in nonadvanced systemic mastocytosis
Authors: Guillaume Lefèvre, Jean-Baptiste Gibier, Antonino Bongiovanni, Ludovic Lhermitte, Julien Rossignol, Emilie Anglo, Arnaud Dendooven, Romain Dubois, Louis Terriou, David Launay, Stéphane Barete, Stéphane Esnault, Laurent Frenzel, Clément Gourguechon, Thomas Ballul, Frédéric Dezoteux, Delphine Staumont-Salle, Marie-Christine Copin, Rachel Rignault-Bricard, Thiago Trovati Maciel, Gandhi Damaj, Meryem Tardivel, Marie Crinquette-Verhasselt, Patrice Dubreuil, Leila Maouche-Chrétien, Julie Bruneau, Olivier Lortholary, Nicolas Duployez, Hélène Behal, Thierry Jo Molina, Olivier Hermine
Journal: Journal of Allergy and Clinical Immunology (2024)
The key role of iroBCDN-lacking pLVPK-like plasmid in the evolution of the most prevalent hypervirulent carbapenem-resistant ST11-KL64 Klebsiella pneumoniae in China
Authors: Xinmiao Jia, Ying Zhu, Peiyao Jia, Cuidan Li, Xiaobing Chu, Tianshu Sun, Xiaoyu Liu, Wei Yu, Fei Chen, Yingchun Xu, Qiwen Yang
Journal: Drug Resistance Updates (2024)

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP), coharboring hypervirulence and carbapenem-resistance genes mediated by plasmids, causes infections with extremely high mortality and seriously impacts public health. Exploring the transfer mechanisms of virulence/carbapenem-resistance plasmids, as well as the formation and evolution pathway of hv-CRKP is of great significance to the control of hv-CRKP infections.
Author Correction: Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Authors: Samira Parhizkar, Thomas Arzberger, Matthias Brendel, Gernot Kleinberger, Maximilian Deussing, Carola Focke, Brigitte Nuscher, Monica Xiong, Alireza Ghasemigharagoz, Natalie Katzmarski, Susanne Krasemann, Stefan F. Lichtenthaler, Stephan A. Müller, Alessio Colombo, Laura Sebastian Monasor, Sabina Tahirovic, Jochen Herms, Michael Willem, Nadine Pettkus, Oleg Butovsky, Peter Bartenstein, Dieter Edbauer, Axel Rominger, Ali Ertürk, Stefan A. Grathwohl, Jonas J. Neher, David M. Holtzman, Melanie Meyer-Luehmann, Christian Haass
Journal: Nature Neuroscience (2024)

We have identified an accidental duplication of the representative image of IBA1 stain in Supplementary Fig. 2a (APPPS1/TREM2 -/-and APPPS1/TREM2 p
Breastfeeding may reduce the effects of maternal smoking on lung cancer mortality in adult offspring: a prospective cohort study
Authors: Hang Yin, Yixue Wang, Siyu Wang, Shijie Zhang, Xiaodong Ling, Tianshu Han, Changhao Sun, Jianqun Ma, Wei Wei, Jinhong Zhu, Xiaoyuan Wang
Journal: International Journal of Surgery (2024)

Background: Although previous research has indicated a correlation between smoking and the mortality rate in patients with lung cancer, the impact of early life factors on this relationship remains unclear and requires further investigation. This study aimed to investigate the hypothesis that breastfeeding reduces the risk of lung cancer-related death. Methods The authors conducted a prospective cohort study involving 501 859 participants recruited from the United Kingdom Biobank to explore the potential association between breastfeeding and the risk of lung cancer mortality using a Cox proportional hazards model. Subsequently, the polygenic risk score for lung cancer was calculated to detect interactions between genes and the environment. Results: Over a median follow-up duration of 11.8 years, encompassing a total of 501 859 participants, breastfeeding was found to reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This association remained consistent after stratification. Furthermore, the influence of maternal smoking and breastfeeding on the risk of lung cancer mortality was significant at a high genetic risk level. Conclusion: Breastfeeding can reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This correlation has the potential to reduce the probability of lung-cancer-related deaths in subsequent generations.
Research hotspots and frontiers of neoadjuvant therapy in triple-negative breast cancer: a bibliometric analysis of publications between 2002 and 2023
Authors: Chuang Yang, Hui Liu, Xing Feng, Han Shi, Yuchan Jiang, Junfeng Li, Jinxiang Tan
Journal: International Journal of Surgery (2024)

Triple negative breast cancer (TNBC) is a highly aggressive type of breast cancer with poor prognosis, and neoadjuvant therapy (NAT) has emerged as an important component in managing advanced-stage patients by providing surgical opportunities and improving survival outcomes. A search of publications on NAT for TNBC from 2002 to 2023 was conducted through the Web of Science core collection. A comprehensive bibliometric analysis was conducted on the data using CiteSpace, VOSviewer, and Bibliometrix. The analysis revealed a continuous and steady growth in the number of articles published in this field over the past 20 years. The United States has made significant contributions to this field, with The University of Texas MD Anderson Cancer Center publishing the most articles. Loibl, S. from Germany was found to be the most published author with 54 articles. Analysis of the journals showed that the Journal of Clinical Oncology is the most cited journal. Combined with the keyword co-occurrence analysis and clustering analysis, current research topic focuses on treatment regimens and disease prognosis. Dual-map overlay of the journals indicates that the research trend is gradually shifting from molecular biology and genetics to immunology and clinical research. Combination therapy, including immunotherapy, may be the future direction for NAT treatment of TNBC. Overall, this study provides valuable insights into the current research status, latest advancements, and emerging development trend of NAT for TNBC.
Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer
Authors: Lei Li, Hongbin Wang, Shiyuan Zhang, Song Gao, Xiuxin Lu, You Pan, Wei Tang, Rong Huang, Kun Qiao, Shipeng Ning
Journal: International Journal of Surgery (2024)

Background: In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people’s attention. Statin use may be potentially associated with a reduced risk of breast cancer. Objective: To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer. Methods: Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium’s low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth. Results: Data from about 3.8 million cancer patients and approximately 1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction ( P = 0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8 + T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy. Conclusion: The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8 + T-cell activity and leads to better prognostic characteristics.
Impaired Glucose Metabolism, Primary Cilium Defects, and Kidney Cystogenesis in Glycogen Storage Disease Type Ia
Authors: Laure Monteillet, Gwendoline Perrot, Félicie Evrard, Alexane Miliano, Marine Silva, Alicia Leblond, Clément Nguyen, Fabiola Terzi, Gilles Mithieux, Fabienne Rajas
Journal: Journal of the American Society of Nephrology (2024)

Key Points Metabolism adaptations due to glucose-6 phosphate accumulation in glycogen storage disease type Ia kidneys, toward a Warburg-like metabolism, promoted cell proliferation. Metabolic perturbations directly affected primary cilium structure and cystogenesis in glycogen storage disease type Ia kidneys. Background Glycogen storage disease type Ia (GSDIa) is a rare metabolic disorder caused by mutations in the catalytic subunit of glucose-6 phosphatase (G6PC1). This leads to severe hypoglycemia, and most young patients with GSDIa develop CKD. The kidney pathology is characterized by the development of cysts, which typically occur at an advanced stage of CKD. Methods To elucidate the molecular mechanisms responsible for cyst formation, we characterized renal metabolism, molecular pathways involved in cell proliferation, and primary cilium integrity using mice in which G6pc1 was specifically deleted in the kidney from an in utero stage. Results GSDIa mice exhibited kidney fibrosis, high inflammation, and cyst formation, leading to kidney dysfunction. In addition, the loss of G6PC1 led to the ectopic accumulation of glycogen and lipids in the kidneys and a metabolic shift toward a Warburg-like metabolism. This metabolic adaptation was due to an excess of glucose-6 phosphate, which supports cell proliferation, driven by the mitogen-activated protein kinase/extracellular signal–regulated kinases and protein kinase B/mammalian target of rapamycin pathways. Treatment of GSDIa mice with rapamycin, a target of the mammalian target of rapamycin pathway, reduced cell proliferation and kidney damage. Our results also identified lipocalin 2 as a contributor to renal inflammation and an early biomarker of CKD progression in GSDIa mice. Its inactivation partially prevented kidney lesions in GSDIa. Importantly, primary cilium defects were observed in the kidneys of GSDIa mice. Conclusions Metabolic adaptations because of glucose-6 phosphate accumulation in GSDIa renal tubules, toward a Warburg-like metabolism, promoted cell proliferation and cyst formation in a similar manner to that observed in various cystic kidney diseases. This was associated with downregulation of primary cilium gene expression and, consequently, altered cilium morphology.
Evaluating the association between time to skin grafting for truncal burn patients and complications: a comparative cohort study using the National Trauma Data Bank
Authors: Szu-Han Wang, Chih-Ying Chien, Chih-Yuan Fu, Faran Bokhari
Journal: International Journal of Surgery (2024)

The split-thickness skin graft (STSG) procedure is frequently used in the reconstruction of burn-injured patients. This study assessed the impact of graft timing on associated skin complications in patients with torso burns using a comprehensive national database.