tbuckley/cabot-search huggingface dataset:
The SUMOylated RREB1 interacts with KDM1A to induce 5‐fluorouracil resistance via upregulating thymidylate synthase and activating DNA damage response pathway in colorectal cancer
Authors: Ya‐Nan Deng, Lan Huang, Shan Gao, Zenghua Sheng, Yinheng Luo, Nan Zhang, Samina Ejaz Syed, Ruiwu Dai, Qiu Li, Xianghui Fu, Shufang Liang
Journal: MedComm (2025)

Abstract Chemoresistance is one main cause of failure in colorectal cancer (CRC) treatment. The role of transcription factor Ras‐responsive element binding protein 1 (RREB1) remains unclarified in CRC chemoresistance. Herein, we reveal that RREB1 functions as an oncogene to promote cell proliferation and 5‐fluorouracil (5‐FU) chemoresistance in CRC, and SUMOylation is required for RREB1 to exert its oncogenic role in CRC. RREB1 induced cell cycle arrest at the S‐phase and a decreased apoptosis rate under 5‐FU exposure. Mechanistically, the interaction of RREB1 with lysine demethylase 1A (KDM1A) elevated expression of 5‐FU targeting proteins thymidylate synthase (TS) and thymidine kinase (TK1) to maintain the nucleotide pool balance under 5‐FU treatment, and enhanced activation of Chk1‐mediated DNA damage response (DDR) pathway. The deSUMOylation of RREB1 resulted in a reduced interaction of RREB1 with KDM1A, contributing to a downregulation of TS expression and a less activation of DDR pathway. Moreover, KDM1A knockdown improved the DNA damage and reduced RREB1‐mediated resistance to 5‐FU. These findings provide new insights into RREB1‐mediated chemotherapy responses in CRC and indicate RREB1 is a potential target for overcoming 5‐FU resistance.
Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody
Authors: Till Braun, Michael Rade, Maximilian Merz, Hanna Klepzig, Florian Große, David Fandrei, Nhu-Nguyen Pham, Markus Kreuz, Christina Katharina Kuhn, Florian Kuschel, Dennis Löffler, Jörn Meinel, Eva Heger, Viola Schweinsberg, Natali Pflug, Uwe Platzbecker, Michael Hallek, Udo Holtick, Ulrike Köhl, Christof Scheid, Kristin Reiche, Marco Herling, Tim Richardson
Journal: Nature Medicine (2025)
Protein palmitoylation: biological functions, disease, and therapeutic targets
Authors: Yan‐Ran Qian, Yu‐Jia Zhao, Feng Zhang
Journal: MedComm (2025)

Abstract Protein palmitoylation, a reversible post‐translational lipid modification, is catalyzed by the ZDHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases, regulating protein localization, accumulation, secretion, and function. Neurological disorders encompass a spectrum of diseases that affect both the central and peripheral nervous system. Recently, accumulating studies have revealed that pathological protein associated with neurological diseases, such as β‐amyloid, α‐synuclein, and Huntingtin, could undergo palmitoylation, highlighting the crucial roles of protein palmitoylation in the onset and development of neurological diseases. However, few preclinical studies and clinical trials focus on the interventional strategies that target protein palmitoylation. Here, we comprehensively reviewed the emerging evidence on the role of protein palmitoylation in various neurological diseases and summarized the classification, processes, and functions of protein palmitoylation, highlighting its impact on protein stability, membrane localization, protein–protein interaction, as well as signal transduction. Furthermore, we also discussed the potential interventional strategies targeting ZDHHC proteins and elucidated their underlying pathogenic mechanisms in neurological diseases. Overall, an in‐depth understanding of the functions and significances of protein palmitoylation provide new avenues for investigating the mechanisms and therapeutic approaches for neurological disorders.
Low coverage of hepatitis D virus testing in individuals with hepatitis B virus and HIV, the Netherlands, 2000 to 2022
Authors: Anders Boyd, Colette Smit, Annemiek A van der Eijk, Hans Zaaijer, Bart JA Rijnders, Berend van Welzen, Mark AA Claassen, Katalin Pogány, Theodora EMS de Vries-Sluijs, Eline Op de Coul, Marc van der Valk
Journal: Eurosurveillance (2025)

Background Since 2009, European guidelines recommend individuals with hepatitis B virus (HBV) and HIV be tested for hepatitis D virus (HDV). Aim To analyse HDV testing in individuals with HBV/HIV during routine practice in the Netherlands. Methods We assessed data from the ATHENA cohort of people with HIV who were ever HBV surface antigen-positive, aged ≥ 18 years and attended one of 24 HIV treatment centres in the Netherlands during 2000–22. Using longitudinal analysis, we estimated the percentage of individuals ever tested for HDV (antibody or RNA test) over time. In cross-sectional analysis, determinants for ever being tested by end of follow-up were assessed using relative risk regression. Results We identified 1,715 individuals with HBV/HIV; 1,460 (85.1%) and 255 (14.9%) were male and female at birth, respectively (median age: 52 years; IQR: 42–59). Only 249 (14.5%) had an HDV test. The percentage tested increased from 5.0% (95% CI: 3.4–7.3) in 2000 to 17.0% (95% CI: 14.9–19.3) in 2022. In 2022, 16.2% (95% CI: 13.7–19.1) of men who have sex with men, 25.0% (95% CI: 9.7–50.9) of persons who inject(ed) drugs and 18.1% (95% CI: 14.6–22.3) of heterosexual/others were tested. In multivariable analysis, ever having an HDV test was associated with detectable HBV DNA viral load (p &lt; 0.001), ever presenting with elevated alanine aminotransferase (ALT) levels (p = 0.023), advanced fibrosis/cirrhosis (p = 0.001) and being overweight/obese (p = 0.043). Conclusions HDV testing coverage in the Netherlands is low for individuals with HBV/HIV. Although testing was more common in those with advanced liver disease, a considerable proportion at risk of HDV still need testing.
Interim 2024/25 influenza vaccine effectiveness: eight European studies, September 2024 to January 2025
Authors: Angela MC Rose, Héloïse Lucaccioni, Kimberly Marsh, Freja Kirsebom, Heather Whitaker, Hanne-Dorthe Emborg, Amanda Bolt Botnen, Mark G O’Doherty, Francisco Pozo, Safraj Shahul Hameed, Nick Andrews, Mark Hamilton, Ramona Trebbien, Karina Lauenborg Møller, Diogo FP Marques, Siobhan Murphy, Ross McQueenie, Jamie Lopez-Bernal, Simon Cottrell, Magda Bucholc, Esther Kissling
Journal: Eurosurveillance (2025)

The 2024/25 influenza season in Europe is currently characterised by co-circulation of influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses, with influenza A(H1N1)pdm09 predominating. Interim vaccine effectiveness (VE) estimates from eight European studies (17 countries) indicate an all-age influenza A VE of 32–53% in primary care and 33–56% in hospital settings, with some signals of lower VE by subtype and higher VE against influenza B (≥ 58% across settings). Where feasible, influenza vaccination should be encouraged and other prevention measures strengthened.
Influenza vaccine effectiveness against detected infection in the community, France, October 2024 to February 2025
Authors: François Blanquart, Vincent Vieillefond, Benoit Visseaux, Claire Nour Abou Chakra, Marta C Nunes, Alexandra Jacques, Stephanie Haim-Boukobza, Laurence Josset, Valentin Wehrle, Guillaume Deleglise, Thomas Duret, Marie Anne Rameix-Welti, Bruno Lina, Vincent Enouf, Antonin Bal
Journal: Eurosurveillance (2025)

Influenza circulates at high levels in Europe since November 2024. Using a test-negative study based on data from French community laboratories between October 2024 and February 2025, we estimated vaccine effectiveness (VE) against PCR-detected influenza infection (44,420/15,052; positive/negative individuals). For all age groups, the overall VE was 42% (95% CI: 37–46%), with 26% (95% CI: 18–34%) against influenza A and 75% (95% CI: 66–82%) against influenza B. Among individuals ≥ 65-year-olds VE was 22% (95% CI: 13–30%) and among 0–64-year-olds, 60% (95% CI: 56–65%).
Adenovirus type 7d outbreak associated with severe clinical presentation, Finland, February to June 2024
Authors: Santtu Heinonen, Elina Erra, Richard Lundell, Aino Nyqvist, Pilvi Hepo-oja, Laura Mannonen, Hanna Jarva, Raisa Loginov, Erika Lindh, Leif Lakoma, Petri Kangaspunta, Ilkka Laaksi, Marjaana Pitkäpaasi, Carita Savolainen-Kopra, Simo Nikkari, Hanna Nohynek, Otto Helve, Eeva Ruotsalainen, Niina Ikonen
Journal: Eurosurveillance (2025)

We report an adenovirus outbreak with unusually severe clinical presentation, particularly in military conscripts and their close contacts. During 1 February–30 June 2024, 129 patients with adenovirus infection were hospitalised, 30 were admitted to ICU, 10 required ECMO treatment and six died. Cases consisted of 75 conscripts (58.1%) and 54 civilians (41.9%). Most samples were type 7 (97/108; 89.8%); all 24 sequenced samples were subtype 7d. During 1 August–30 November 2024, 274 additional hospitalised cases were identified from registries.
Early vaccine effectiveness estimates against medically attended laboratory-confirmed influenza based on influenza surveillance, Beijing, China, 2024/25 season
Authors: Ying Sun, Weixian Shi, Daitao Zhang, Chunna Ma, Zhaomin Feng, Jiaojiao Zhang, Dan Wu, Li Zhang, Jia Li, Wei Duan, Yingying Wang, Jiaxin Ma, Lu Zhang, Xiaodi Hu, Peng Yang, Quanyi Wang
Journal: Eurosurveillance (2025)

We estimated early influenza vaccine effectiveness (VE) for the 2024/25 season in outpatients, in Beijing using a test-negative design. A(H1N1)pdm09 dominated (99.3%), all sequenced strains (n = 38) clustered in clade 6B.1A.5a.2a, and 37 of 38 antigenically similar to the vaccine strain. VE against any influenza virus infection was 48.5% (95% CI: 34.8–59.5) and 48.7% (95% CI: 35.1–59.7) against A(H1N1)pdm09. Vaccination in the current or previous season against any influenza showed a VE of 52.5% to 54.9%, compared to no vaccination in both seasons.
Outbreak of listeriosis associated with consumption of deli meats in a hospital, Germany, February to March 2023
Authors: Lena Feige, Nicole Walter, Ahmad Fawzy, Tilman Schultze, Melanie Hassel, Manfred Vogt, Philipp Zanger, Anja Schoeps
Journal: Eurosurveillance (2025)

Listeria monocytogenes can cause severe illness in individuals with weakened immune systems. In March 2023, L. monocytogenes was isolated from blood (n = 2) or pleural fluid (n = 1) of three febrile patients receiving synthetic glucocorticoids in a tertiary hospital in Germany. Food supply records suggested sliced parboiled sausage as the likely source, and L. monocytogenes was isolated from four samples of sealed packaged sliced sausages and ham from one manufacturer. The patient and food isolates clustered within 0–4 allelic differences. Counts of L. monocytogenes in all four food samples were &lt; 100 colony-forming units (CFU)/g, a threshold in the European Union legislation for ready-to-eat products with specific conditions. Our findings, aligned with previous evidence, highlight that persons with weakened immune systems should not be exposed to L. monocytogenes in food. We advocate for a clear communication of deli meats as high-risk foods, so individuals with weakened immune systems can adjust their diet to reduce their risk for invasive listeriosis. We recommend an update of dietary and hygiene guidelines for care settings and private homes where food is prepared, handled and stored for persons with weakened immune systems.
A short-term, high-caloric diet has prolonged effects on brain insulin action in men
Authors: Stephanie Kullmann, Lore Wagner, Robert Hauffe, Anne Kühnel, Leontine Sandforth, Ralf Veit, Corinna Dannecker, Jürgen Machann, Andreas Fritsche, Nobert Stefan, Hubert Preissl, Nils B. Kroemer, Martin Heni, André Kleinridders, Andreas L. Birkenfeld
Journal: Nature Metabolism (2025)

Abstract Brain insulin responsiveness is linked to long-term weight gain and unhealthy body fat distribution. Here we show that short-term overeating with calorie-rich sweet and fatty foods triggers liver fat accumulation and disrupted brain insulin action that outlasted the time-frame of its consumption in healthy weight men. Hence, brain response to insulin can adapt to short-term changes in diet before weight gain and may facilitate the development of obesity and associated diseases.
STIM1-mediated NFAT signaling synergizes with STAT1 to control T-bet expression and TH1 differentiation
Authors: Li Zhong, Yin-Hu Wang, Sascha Kahlfuss, Miki Jishage, Maxwell McDermott, Jun Yang, Anthony Y. Tao, Ke Hu, Lucile Noyer, Dimitrius Raphael, Devisha Patel, Tristan E. Knight, Meera Chitlur, Khaled Machaca, Stefan Feske
Journal: Nature Immunology (2025)
Pyruvate Kinase Function Correlates With Red Blood Cell Properties and Clinical Manifestations in Sickle Cell Disease
Authors: M. J. M. Traets, J. F. Bos, S. van der Veen, L. van Pelt, M. J. van Dijk, B. A. van Oirschot, J. R. A. de Wilde, J. J. Jans, W. W. van Solinge, S. E. M. Schols, M. N. Lauw, M. H. Cnossen, E. Nur, B. J. Biemond, A. W. Rijneveld, E. J. van Beers, R. van Wijk, M. A. E. Rab
Journal: American Journal of Hematology (2025)

Pyruvate kinase (PK) is a key enzyme involved in the final step of glycolysis, essential to produce adenosine triphosphate (ATP). Relatively decreased red blood cell (RBC) PK activity (reflected by a lower PK/hexokinase [HK] ratio) and PK thermostability (PK activity after exposure to heat) were recently identified as pathophysiological features of sickle cell disease (SCD). In this study, we investigated whether impaired PK function is associated with sickle RBC properties and SCD-related clinical manifestations. This study included 97 non-transfused patients with SCD (88 HbSS, 9 HbS/β0 thalassemia). PK thermostability was correlated with RBC parameters such as reticulocyte count (r = -0.402, p < 0.0001) and hemoglobin F (r = 0.394, p < 0.0001), and indicators of impaired functional properties of sickle RBCs, such as the point of sickling (r = -0.417, p < 0.0001), oxygen affinity (r = 0.408, p < 0.001) and RBC adhesion to laminin (r = -0.322, p = 0.024). Additionally, a low PK/HK ratio correlated with decreased PK thermostability (r = 0.308, p = 0.002), decreased RBC deformability (r = 0.268, p = 0.009), and elevated 2,3-diphosphoglycerate levels (r = -0.244, p = 0.016). Multivariate Poisson regression analysis demonstrated that reduced PK thermostability and PK/HK ratio were associated with a higher incidence of SCD-related clinical complications. For every 10-unit decrease in PK thermostability and 1-unit decrease in PK/HK ratio, the incidence of SCD-related clinical complications increased by 11% (p = 0.012) and 10% (p = 0.019), respectively. Altogether, these findings indicate that impaired PK function is related to compromised sickle RBC properties and SCD-related clinical manifestations. This supports the relevance and underlines the potential of PK activation therapy.
Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis
Authors: Lingfeng Bi, Xin Wang, Jiayi Li, Weimin Li, Zhoufeng Wang
Journal: MedComm (2025)

Abstract The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellular balance if overexploited, and the need for maintaining key gene expressions in therapeutic applications. This review highlights the promise and challenges of using liquid biopsy and epigenetic markers for early‐stage lung cancer diagnosis, with a focus on optimizing treatment strategies for personalized and precision medicine.
A Molecular Array for 10-second Diagnosis of Common Spinal Tumour Types with Picosecond Infrared Laser Mass Spectrometry
Authors: Alexa Fiorante, Michael Woolman, David G Munoz, Taira Kiyota, Lan Anna Ye, Yasmine Farahmand, Darah Vlaminck, Francis O Talbot, Sunit Das, Sorcha Kellett, Christine Giuffrida, Gelareh Zadeh, Howard J Ginsberg, Ahmed Aman, Arash Zarrine-Afsar
Journal: Neuro-Oncology (2025)

Abstract Background Improving the surgical outcomes for commonly occurring spinal neoplasms of extradural and intradural extramedullary origins requires precise intraoperative diagnosis provided by highly trained neuropathologists. Methods Through a retrospective study of n=319 patient specimens, verified where appropriate by learning curve analysis to be sufficient for statistically significant observations, we aimed to assess the utility of 10-second picosecond infrared laser mass spectrometry (PIRL-MS) for non-subjective diagnosis of major spinal tumour types of metastatic carcinoma, schwannoma and meningiomas. Results The sensitivity and specificity values of spinal tumour type diagnosis (based on n=182 independent specimens) were (93±1)% and (97±2)%, respectively. This classification utilizes n=41 cellular lipids including phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, and ceramides whose identities were established using high-resolution tandem mass spectrometry. Furthermore, the accuracy of diagnosis of a model that contained n=97 meningioma and n=106 schwannoma was not drastically influenced by the presence of n=54 additional intradural extramedullary spinal neoplasms of myxopapillary ependymoma, neurofibroma, paraganglioma and solitary fibrous tumour types in the differential diagnosis, confirming the generalizability and robustness of the identified molecular array in rendering correct classification even in the presence of data not seen previously by the model. Conclusions The identified lipids form a ‘molecular array’ for robust diagnosis of meningioma and schwannoma tumours by non-pathologists in a manner similar to genomic, transcriptomic or methylomic arrays used to diagnose brain cancer types, albeit on a much faster timescale of seconds as opposed to hours.
Design, molecular characterization and therapeutic investigation of a novel CCR8 peptide antagonist that attenuates acute liver injury by inhibiting infiltration and activation of macrophages
Authors: Eline Geervliet, Sahil Arora, Dagmara Donohue, Carlos Antonio de Albuquerque Pinheiro, Leon W.M.M. Terstappen, Richard Schasfoort, Julieta Paez, Raj Kumar, Ruchi Bansal
Journal: Acta Pharmaceutica Sinica B (2025)
A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma
Authors: Hu Chen, Yongfu Xiong, Minglei Teng, Yesen Li, Deliang Zhang, Yongjun Ren, Zheng Li, Hui Liu, Xiaofei Wen, Zhenjie Li, Yang Zhang, Syed Faheem Askari Rizvi, Rongqiang Zhuang, Jinxiong Huang, Suping Li, Jingsong Mao, Hongwei Cheng, Gang Liu
Journal: Acta Pharmaceutica Sinica B (2025)
When I use a word . . . The most beautiful medical words
Authors: Jeffrey K Aronson
Journal: BMJ (2025)

Some English words are more euphonious than others, and there are many lists of words that their collectors have labelled "the most beautiful words in English." I have analysed 372 of these and have described their characteristics, summarising the important features that result in their being considered beautiful. Fifteen of them may be regarded as the most beautiful of all, appearing as they do in the largest numbers of lists: aurora, effervescent, elixir, eloquence, ephemeral, epiphany, ethereal, gossamer, halcyon, mellifluous, onomatopoeia, quintessential, serendipity, sonorous, and surreptitious. Eighteen words on the list have some medical relevance: bibliotherapy, depigmentation, effervescent, eidetic, elixir, embrocation, emollient, euphoria, hallucinate, histamine, kakorrhaphiophobia, lassitude, melancholy, narcissist, nexus, oleander, olfactory, and panacea.
Efficacy and safety of GLS4 with entecavir vs entecavir alone in chronic hepatitis B patients: a multicenter clinical trial
Authors: Mingyuan Zhang, Yanhang Gao, Fei Kong, Haibing Gao, Yongxiang Yi, Chao Wu, Yongning Xin, Sujun Zheng, Jiajie Lu, Tao Han, Yingren Zhao, Peng Hu, Xiaorong Mao, Qing Xie, Jie Zhang, Jinlin Hou, Zhiliang Gao, Jianqi Lian, Liang Chen, Jia Shang, Wen Xie, Mao Mu, Zhenjing Jin, Maorong Wang, Shide Lin, Huiying Rao, Dongliang Yang, Huanyu Gong, Lin Luo, Yunfu Chen, Yulei Zhuang, Yingjun Zhang, Robert G Gish, Youwen Tan, Jiming Zhang, Junqi Niu
Journal: Journal of Infection (2025)
Centromere protein U mediates the ubiquitination and degradation of RPS3 to facilitate temozolomide resistance in glioblastoma
Authors: Jinmin Sun, Wenyu Zhao, Lei Zhang, Sicheng Wu, Senrui Xue, Haowei Cao, Biao Xu, Xinmiao Li, Nan Hu, Tao Jiang, Yixin Xu, Zhifei Wang, Chao Zhang, Jing Ren
Journal: Drug Resistance Updates (2025)
siRNA micelleplexes-mediated glutamine metabolism re-engineering for vascular normalization-boosted photo-immunotherapy
Authors: Yunfei Yi, Zhangwen Peng, Yuanqi Liu, Huisong Hao, Liu Yu, Simin Wen, Shengjie Sun, Jianlin Shi, Meiying Wu, Lin Mei
Journal: Acta Pharmaceutica Sinica B (2025)
Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production
Authors: Sandra Tobón-Cornejo, Monica Sanchez-Tapia, Rocio Guizar-Heredia, Laura Velázquez Villegas, Lilia G. Noriega, Janette Furuzawa-Carballeda, Rogelio Hernández-Pando, Natalia Vázquez-Manjarrez, Omar Granados-Portillo, Adriana López-Barradas, Rosa Rebollar-Vega, Otoniel Maya, Aaron W. Miller, Aurora Serralde, Martha Guevara-Cruz, Nimbe Torres, Armando R. Tovar
Journal: Gut Microbes (2025)

Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1α in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.