tbuckley/cabot-search huggingface dataset:
PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction
Authors: Richard Blake Ross, Jacob Gadwa, Justin Yu, Laurel B. Darragh, Michael W. Knitz, Diemmy Nguyen, Nicholas A. Olimpo, Khalid N.M. Abdelazeem, Alexander Nguyen, Sophia Corbo, Benjamin Van Court, Jessica Beynor, Brooke Neupert, Anthony J. Saviola, Angelo D'Alessandro, Sana D. Karam
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show that altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic and dietary modulation of FA catabolism will affect therapeutic efficacy. Experimental Design: We performed in vivo and in vitro experiments using PPARα agonism with fenofibrate (FF) or high oleic acid diets (OAD) with radiotherapy, generating metabolomic, proteomic, stable isotope tracing, extracellular flux analysis, and flow-cytometric data to investigate these alterations. Results: FF improved antitumor efficacy of high dose per fraction radiotherapy in HNC murine models, whereas the OAD reversed this effect. FF-treated mice on the control diet had evidence of increased FA catabolism. Stable isotope tracing showed less glycolytic utilization by ex vivo CD8+ T cells. Improved efficacy correlated with intratumoral alterations in eicosanoid metabolism and downregulated mTOR and CD36. Conclusions: Metabolic intervention with increased FA catabolism improves the efficacy of HNC therapy and enhances antitumoral immune response.
Erratum to “Cancer statistics, 2024”
Journal: CA A Cancer Journal for Clinicians (2024)

Multiple errors appear in Table 9.The first age column should be "1-19" (not "1-9" as originally published), and the second age column should be "20-39" (not "20-30").Additionally, cancer was left off as the fourth leading cause of death among men aged 40-59 years.The authors apologize for the oversight.
Letter to the editor: Further identification of a measles variant displaying mutations impacting molecular diagnostics, Northern Italy, 2024
Authors: Clara Fappani, Maria Gori, Silvia Bianchi, Marta Canuti, Daniela Colzani, Melissa Baggieri, Silvia Gioacchini, Emilio D’Ugo, Elisabetta Tanzi, Fabio Magurano, Antonella Amendola
Journal: Eurosurveillance (2024)

Preview this article: Letter to the editor: Further identification of a measles variant displaying mutations impacting molecular diagnostics, Northern Italy, 2024, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/29/7/eurosurv-29-7-6-1.gif
FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System
Authors: Bowen Li, Fangfang Liu, Xihui Chen, Tangdong Chen, Juan Zhang, Yifeng Liu, Yan Yao, Weihong Hu, Mengjie Zhang, Bo Wang, Liwen Liu, Kun Chen, Yuanming Wu
Journal: Circulation (2024)

Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease. Although HCM has been reported to be associated with many variants of genes involved in sarcomeric protein biomechanics, pathogenic genes have not been identified in patients with partial HCM. FARS2 (the mitochondrial phenylalanyl-tRNA synthetase), a type of mitochondrial aminoacyl-tRNA synthetase, plays a role in the mitochondrial translation machinery. Several variants of
Editor's Note: Combining EGFR and mTOR Blockade for the Treatment of Epithelioid Sarcoma
Authors: Xianbiao Xie, Markus P.H. Ghadimi, Eric D. Young, Roman Belousov, Quan-sheng Zhu, Juehui Liu, Gonzalo Lopez, Chiara Colombo, Tingsheng Peng, David Reynoso, Jason L. Hornick, Alexander J. Lazar, Dina Lev
Journal: Clinical Cancer Research (2024)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2024)

Highlights| February 16 2024 Selected Articles from This Issue Author & Article Information Online ISSN: 1557-3265 Print ISSN: 1078-0432 ©2024 American Association for Cancer Research2024American Association for Cancer Research Clin Cancer Res (2024) 30 (4): 647. https://doi.org/10.1158/1078-0432.CCR-30-4-HI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record February 16 2024 Citation Selected Articles from This Issue. Clin Cancer Res 15 February 2024; 30 (4): 647. https://doi.org/10.1158/1078-0432.CCR-30-4-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Advanced progressive dedifferentiated liposarcoma (DDLS) tumors frequently harbor copy number alterations in chromosome 12q, which encompasses CDK4. Phase II clinical trials assessing CDK4/6 inhibitors have shown modest success in extending progression-free survival (PFS) in patients with liposarcoma, potentially by inducing cell senescence or enhancing antigen presentation in tumor cells. In this phase II trial, Gleason and colleagues evaluate the efficacy of the CDK4/6 inhibitor abemaciclib in patients with DDLS and investigate the mechanism by which abemaciclib exerts its antitumoral effects. The authors note a median PFS of 33 weeks, with 76.7% of patients progression-free at 12 weeks and no new adverse events. Additional preclinical work in liposarcoma cell lines identified ANGPTL4 as a regulator of cell progression from quiescence to senescence and inflammation. The authors found that senescence modulates the immune tumor microenvironment as demonstrated by an increase in CD4+ leukocyte infiltration, yet patients with both senescence and... You do not currently have access to this content.
A Whole-Brain Topographic Ontology
Authors: Michael Arcaro, Margaret Livingstone
Journal: Annual Review of Neuroscience (2024)

It is a common view that the intricate array of specialized domains in the ventral visual pathway is innately prespecified. What this review postulates is that it is not. We explore the origins of domain specificity, hypothesizing that the adult brain emerges from an interplay between a domain-general map-based architecture, shaped by intrinsic mechanisms, and experience. We argue that the most fundamental innate organization of cortex in general, and not just the visual pathway, is a map-based topography that governs how the environment maps onto the brain, how brain areas interconnect, and ultimately, how the brain processes information.
Harmony in the Molecular Orchestra of Hearing: Developmental Mechanisms from the Ear to the Brain
Authors: Sonja J. Pyott, Gabriela Pavlinkova, Ebenezer N. Yamoah, Bernd Fritzsch
Journal: Annual Review of Neuroscience (2024)

Auditory processing in mammals begins in the peripheral inner ear and extends to the auditory cortex. Sound is transduced from mechanical stimuli into electrochemical signals of hair cells, which relay auditory information via the primary auditory neurons to cochlear nuclei. Information is subsequently processed in the superior olivary complex, lateral lemniscus, and inferior colliculus and projects to the auditory cortex via the medial geniculate body in the thalamus. Recent advances have provided valuable insights into the development and functioning of auditory structures, complementing our understanding of the physiological mechanisms underlying auditory processing. This comprehensive review explores the genetic mechanisms required for auditory system development from the peripheral cochlea to the auditory cortex. We highlight transcription factors and other genes with key recurring and interacting roles in guiding auditory system development and organization. Understanding these gene regulatory networks holds promise for developing novel therapeutic strategies for hearing disorders, benefiting millions globally.
Aire in Autoimmunity
Authors: Corey N. Miller, Michael R. Waterfield, James M. Gardner, Mark S. Anderson
Journal: Annual Review of Immunology (2024)

The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis.
The Immunobiology and Treatment of Food Allergy
Authors: Suzanne Barshow, Jyothi Tirumalasetty, Vanitha Sampath, Xiaoying Zhou, Hana Seastedt, Jackson Schuetz, Kari Nadeau
Journal: Annual Review of Immunology (2024)

IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper T cell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several host-related and environmental factors impacting the risk of IgE-FA development have been identified. Mounting evidence supports the role of an impaired epithelial barrier in the development of IgE-FA, with exposure of allergens through damaged skin and gut epithelium leading to the aberrant production of alarmins and activation of TH2-type allergic inflammation. The treatment of IgE-FA has historically been avoidance with acute management of allergic reactions, but advances in allergen-specific immunotherapy and the development of biologics and other novel therapeutics are rapidly changing the landscape of food allergy treatment. Here, we discuss the pathogenesis and immunobiology of IgE-FA in addition to its diagnosis, prognosis, and treatment.
TET Enzymes in the Immune System: From DNA Demethylation to Immunotherapy, Inflammation, and Cancer
Authors: Isaac F. López-Moyado, Myunggon Ko, Patrick G. Hogan, Anjana Rao
Journal: Annual Review of Immunology (2024)

Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). All three epigenetic modifications are intermediates in DNA demethylation. TET proteins are recruited by transcription factors and by RNA polymerase II to modify 5mC at enhancers and gene bodies, thereby regulating gene expression during development, cell lineage specification, and cell activation. It is not yet clear, however, how the established biochemical activities of TET enzymes in oxidizing 5mC and mediating DNA demethylation relate to the known association of TET deficiency with inflammation, clonal hematopoiesis, and cancer. There are hints that the ability of TET deficiency to promote cell proliferation in a signal-dependent manner may be harnessed for cancer immunotherapy. In this review, we draw upon recent findings in cells of the immune system to illustrate established as well as emerging ideas of how TET proteins influence cellular function.
Priming and Maintenance of Adaptive Immunity in the Liver
Authors: Keigo Kawashima, Francesco Andreata, Cristian Gabriel Beccaria, Matteo Iannacone
Journal: Annual Review of Immunology (2024)

The liver's unique characteristics have a profound impact on the priming and maintenance of adaptive immunity. This review delves into the cellular circuits that regulate adaptive immune responses in the liver, with a specific focus on hepatitis B virus infection as an illustrative example. A key aspect highlighted is the liver's specialized role in priming CD8+ T cells, leading to a distinct state of immune hyporesponsiveness. Additionally, the influence of the liver's hemodynamics and anatomical features, particularly during liver fibrosis and cirrhosis, on the differentiation and function of adaptive immune cells is discussed. While the primary emphasis is on CD8+ T cells, recent findings regarding the involvement of B cells and CD4+ T cells in hepatic immunity are also reviewed. Furthermore, we address the challenges ahead and propose integrating cutting-edge techniques, such as spatial biology, and combining mouse models with human sample analyses to gain comprehensive insights into the liver's adaptive immunity. This understanding could pave the way for novel therapeutic strategies targeting infectious diseases, malignancies, and inflammatory liver conditions like metabolic dysfunction-associated steatohepatitis and autoimmune hepatitis.
Not All Parafibromin Deficiency Relates to Parathyroid Carcinoma: The Role of Morphological Assessment
Authors: C. Christofer Juhlin
Journal: Endocrine Pathology (2024)

A male in his early thirties, without any prior medical history, presented with a history of fatigue.Upon examination, mild hypercalcemia and elevated levels of parathyroid hormone (PTH) were observed.The patient was subsequently referred to our endocrine surgery department.Ultrasound and sestamibi scintigraphy revealed an enlarged right superior parathyroid gland measuring 20 mm.The patient had no family history suggestive of parathyroid disease or MEN1related manifestations.A focused parathyroidectomy was performed.
Editor's Note: Cyclin-Dependent Kinase 5 Decreases in Gastric Cancer and its Nuclear Accumulation Suppresses Gastric Tumorigenesis
Authors: Longlong Cao, Jiechao Zhou, Junrong Zhang, Sijin Wu, Xintao Yang, Xin Zhao, Huifang Li, Ming Luo, Qian Yu, Guangtan Lin, Huizhong Lin, Jianwei Xie, Ping Li, Xiaoqing Hu, Chaohui Zheng, Guojun Bu, Yun-wu Zhang, Huaxi Xu, Yongliang Yang, Changming Huang, Jie Zhang
Journal: Clinical Cancer Research (2024)
Estimation of antimicrobial resistance of Mycoplasma genitalium, Belgium, 2022
Authors: Irith De Baetselier, Hilde Smet, Kaat Kehoe, Imelda Loosen, Marijke Reynders, Iqbal Mansoor, Lorenzo Filippin, Mathieu Cauchie, Ellen Van Even, Nadia Makki, Gilberte Schiettekatte, Wouter Vandewal, Bart Glibert, Veerle Matheeussen, Yolien Van der Beken, Reinoud Cartuyvels, Sophia Steyaert, Ann Lemmens, Maria-Grazia Garrino, Henry Paridaens, Elena Lazarova, Bénédicte Lissoir, Marine Deffontaine, Amélie Heinrichs, Veroniek Saegeman, Elizaveta Padalko, Amaryl Lecompte, Wim Vanden Berghe, Chris Kenyon, Dorien Van den Bossche
Journal: Eurosurveillance (2024)

Background Antimicrobial resistance (AMR) of Mycoplasma genitalium (MG) is a growing concern worldwide and surveillance is needed. In Belgium, samples are sent to the National Reference Centre of Sexually Transmitted Infections (NRC-STI) on a voluntary basis and representative or robust national AMR data are lacking. Aim We aimed to estimate the occurrence of resistant MG in Belgium. Methods Between July and November 2022, frozen remnants of MG-positive samples from 21 Belgian laboratories were analysed at the NRC-STI. Macrolide and fluoroquinolone resistance-associated mutations (RAMs) were assessed using Sanger sequencing of the 23SrRNA and parC gene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioural variables via Fisher’s exact test and logistic regression analysis. Results Of the 244 MG-positive samples received, 232 could be sequenced for macrolide and fluoroquinolone RAMs. Over half of the sequenced samples (55.2%) were resistant to macrolides. All sequenced samples from men who have sex with men (MSM) (24/24) were macrolide-resistant. Fluoroquinolone RAMs were found in 25.9% of the samples and occurrence did not differ between socio-demographic and sexual behaviour characteristics. Conclusion Although limited in sample size, our data suggest no additional benefit of testing MG retrieved from MSM for macrolide resistance in Belgium, when making treatment decisions. The lower occurrence of macrolide resistance in other population groups, combined with emergence of fluoroquinolone RAMs support macrolide-resistance testing in these groups. Continued surveillance of resistance in MG in different population groups will be crucial to confirm our findings and to guide national testing and treatment strategies.
Epidemiology of reported cases of leptospirosis in the EU/EEA, 2010 to 2021
Authors: Julien Beauté, Francesco Innocenti, Aristos Aristodimou, Michaela Špačková, Caroline Eves, Natalia Kerbo, Ruska Rimhanen-Finne, Mathieu Picardeau, Mirko Faber, Georgios Dougas, Anna Margrét Halldórsdóttir, Sarah Jackson, Viktorija Leitēna, Anne Vergison, Maria Louise Borg, Roan Pijnacker, Małgorzata Sadkowska-Todys, João Vieira Martins, Lavinia Cipriana Rusu, Eva Grilc, Rosa M Estévez-Reboredo, Taina Niskanen, Therese Westrell
Journal: Eurosurveillance (2024)

Background Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira . Humans are infected by exposure to animal urine or urine-contaminated environments. Although disease incidence is lower in Europe compared with tropical regions, there have been reports of an increase in leptospirosis cases since the 2000s in some European countries. Aim We aimed to describe the epidemiology of reported cases of leptospirosis in the European Union/European Economic Area (EU/EEA) during 2010−2021 and to identify potential changes in epidemiological patterns. Methods We ran a descriptive analysis of leptospirosis cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease during 2010−2021. We also analysed trends at EU/EEA and national level. Results During 2010–2021, 23 countries reported 12,180 confirmed leptospirosis cases corresponding to a mean annual notification rate of 0.24 cases per 100,000 population. Five countries (France, Germany, the Netherlands, Portugal and Romania) accounted for 79% of all reported cases. The highest notification rate was observed in Slovenia with 0.82 cases per 100,000 population. Overall, the notification rate increased by 5.0% per year from 2010 to 2021 (95% CI: 1.2–8.8%), although trends differed across countries. Conclusion The notification rate of leptospirosis at EU/EEA level increased during 2010−2021 despite including the first 2 years of the COVID-19 pandemic and associated changes in population behaviours. Studies at (sub)national level would help broaden the understanding of differences at country-level and specificities in terms of exposure to Leptospira , as well as biases in diagnosis and reporting.
Editor's Note: Eph-B2/Ephrin-B2 Interaction Plays a Major Role in the Adhesion and Proliferation of Waldenstrom's Macroglobulinemia
Authors: Feda Azab, Abdel Kareem Azab, Patricia Maiso, Teresa Calimeri, Ludmila Flores, Yang Liu, Phong Quang, Aldo M. Roccaro, Antonio Sacco, Hai T. Ngo, Yong Zhang, Brittany L. Morgan, Ruben D. Carrasco, Irene M. Ghobrial
Journal: Clinical Cancer Research (2024)
Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes
Authors: Xiaojing Sun, Hon-Chi Lee, Tong Lu
Journal: Circulation Research (2024)

BACKGROUND: Vascular large conductance Ca 2+ -activated K + (BK) channel, composed of the α-subunit (BK-α) and the β1-subunit (BK-β1), is a key determinant of coronary vasorelaxation and its function is impaired in diabetic vessels. However, our knowledge of diabetic BK channel dysregulation is incomplete. The Sorbs2 (Sorbin homology [SoHo] and Src homology 3 [SH3] domains-containing protein 2), is ubiquitously expressed in arteries, but its role in vascular pathophysiology is unknown. METHODS: The role of Sorbs2 in regulating vascular BK channel activity was determined using patch-clamp recordings, molecular biological techniques, and in silico analysis. RESULTS: Sorbs2 is not only a cytoskeletal protein but also an RNA-binding protein that binds to BK channel proteins and BK-α mRNA, regulating BK channel expression and function in coronary smooth muscle cells. Molecular biological studies reveal that the SH3 domain of Sorbs2 is necessary for Sorbs2 interaction with BK-α subunits, while both the SH3 and SoHo domains of Sorbs2 interact with BK-β1 subunits. Deletion of the SH3 or SoHo domains abolishes the Sorbs2 effect on the BK-α/BK-β1 channel current density. Additionally, Sorbs2 is a target gene of the Nrf2 (nuclear factor erythroid-2-related factor 2), which binds to the promoter of Sorbs2 and regulates Sorbs2 expression in coronary smooth muscle cells. In vivo studies demonstrate that Sorbs2 knockout mice at 4 months of age display a significant decrease in BK channel expression and function, accompanied by impaired BK channel Ca 2+ -sensitivity and BK channel-mediated vasodilation in coronary arteries, without altering their body weights and blood glucose levels. Importantly, Sorbs2 expression is significantly downregulated in the coronary arteries of db/db type 2 diabetic mice. CONCLUSIONS: Sorbs2, a downstream target of Nrf2, plays an important role in regulating BK channel expression and function in vascular smooth muscle cells. Vascular Sorbs2 is downregulated in diabetes. Genetic knockout of Sorbs2 manifests coronary BK channelopathy and vasculopathy observed in diabetic mice, independent of obesity and glucotoxicity.
Gonorrhoea on the rise in Denmark since 2022: distinct clones drive increase in heterosexual individuals
Authors: Thomas Roland Pedersen, Maria Wessman, Mikkel Lindegaard, Søren Hallstrøm, Casper Westergaard, Inger Brock, Esad Dzajic, Dennis Back Holmgaard, Christian Salgård Jensen, Ulrik Stenz Justesen, Jette Brommann Kornum, Turid Snekloth Søndergaard, Marianne Kragh Thomsen, Henrik Westh, Claus Østergaard, Steen Hoffmann, Marc Stegger
Journal: Eurosurveillance (2024)

A surge in gonorrhoea in Denmark has occurred since 2022, a 46% increase from 2021. National surveillance, leveraging mandatory reporting and epidemiological data, highlights three distinct clades linked to heterosexual transmission. Despite the rise, these exhibit high susceptibility, contrasting MSM-associated strains. Geographical hotspots and age-specific patterns further illuminate transmission dynamics. The combination of genomic and epidemiological data provides novel insights into the evolving landscape of gonorrhoea, indicating potential shifts in infection dynamics and transmissibility.
Editor's Note: Mechanisms of Activity of the TORC1 Inhibitor Everolimus in Waldenstrom Macroglobulinemia
Authors: Aldo M. Roccaro, Antonio Sacco, Xiaojing Jia, Ranjit Banwait, Patricia Maiso, Feda Azab, Ludmila Flores, Salomon Manier, Abdel Kareem Azab, Irene M. Ghobrial
Journal: Clinical Cancer Research (2024)