tbuckley/cabot-search huggingface dataset:
Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial
Authors: Carlo Gambacorti-Passerini, Tim H. Brümmendorf, Elisabetta Abruzzese, Kevin R. Kelly, Vivian G. Oehler, Valentín García-Gutiérrez, Henrik Hjorth-Hansen, Thomas Ernst, Eric Leip, Simon Purcell, Gerald Luscan, Andrea Viqueira, Francis J. Giles, Andreas Hochhaus
Journal: Leukemia (2024)

This final analysis from the phase 4 BYOND trial reports outcomes with bosutinib in patients with previously treated chronic myeloid leukemia (CML); 163 patients with CML resistant/intolerant to previous tyrosine kinase inhibitors received bosutinib (starting dose: 500 mg QD). At study completion (median follow-up, 47.8 months), 48.1% (n = 75/156) of patients with Philadelphia chromosome–positive chronic phase CML were still receiving treatment. Among evaluable patients, 71.8% (95% CI, 63.9–78.9) and 59.7% (95% CI, 51.4–67.7) attained or maintained major molecular response (MMR) and molecular response (MR)4, respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib. Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR4 at 36 months were 87.2% (78.0–92.7) and 80.7% (69.4–88.1), respectively. At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8–92.6); there were 17 deaths, including 2 that were considered CML related. Long-term adverse events (AEs) were consistent with the known safety profile of bosutinib, and no new safety issues were identified. The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML. ClinicalTrials.gov, NCT02228382
Engineered mitochondria exert potent antitumor immunity as a cancer vaccine platform
Authors: Jingwen Luo, Fei Mo, Zhe Zhang, Weiqi Hong, Tianxia Lan, Yuan Cheng, Chunju Fang, Zhenfei Bi, Furong Qin, Jingyun Yang, Ziqi Zhang, Xue Li, Haiying Que, Jiayu Wang, Siyuan Chen, Yiming Wu, Li Yang, Jiong Li, Wei Wang, Chong Chen, Xiawei Wei
Journal: Cellular and Molecular Immunology (2024)

The preferable antigen delivery profile accompanied by sufficient adjuvants favors vaccine efficiency. Mitochondria, which feature prokaryotic characteristics and contain various damage-associated molecular patterns (DAMPs), are easily taken up by phagocytes and simultaneously activate innate immunity. In the current study, we established a mitochondria engineering platform for generating antigen-enriched mitochondria as cancer vaccine. Ovalbumin (OVA) and tyrosinase-related protein 2 (TRP2) were used as model antigens to synthesize fusion proteins with mitochondria-localized signal peptides. The lentiviral infection system was then employed to produce mitochondrial vaccines containing either OVA or TRP2. Engineered OVA- and TRP2-containing mitochondria (OVA-MITO and TRP2-MITO) were extracted and evaluated as potential cancer vaccines. Impressively, the engineered mitochondria vaccine demonstrated efficient antitumor effects when used as both prophylactic and therapeutic vaccines in murine tumor models. Mechanistically, OVA-MITO and TRP2-MITO potently recruited and activated dendritic cells (DCs) and induced a tumor-specific cell-mediated immunity. Moreover, DC activation by mitochondria vaccine critically involves TLR2 pathway and its lipid agonist, namely, cardiolipin derived from the mitochondrial membrane. The results demonstrated that engineered mitochondria are natively well-orchestrated carriers full of immune stimulants for antigen delivery, which could preferably target local dendritic cells and exert strong adaptive cellular immunity. This proof-of-concept study established a universal platform for vaccine construction with engineered mitochondria bearing alterable antigens for cancers as well as other diseases.
CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph nodes and blood following mRNA vaccination in humans
Authors: Nicholas Borcherding, Wooseob Kim, Michael Quinn, Fangjie Han, Julian Q Zhou, Alexandria J Sturtz, Aaron J Schmitz, Tingting Lei, Stefan A Schattgen, Michael K Klebert, Teresa Suessen, William D Middleton, Charles W Goss, Chang Liu, Jeremy Chase Crawford, Paul G Thomas, Sharlene A Teefey, Rachel M Presti, Jane A O'Halloran, Jackson S Turner, Ali H Ellebedy, Philip A Mudd
Journal: Nature Immunology (2024)
Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review
Authors: Alexander Troester, Romil Parikh, Bronwyn Southwell, Elizabeth Ester, Shahnaz Sultan, Edward Greeno, Elliot Arsoniadis, Timothy R Church, Timothy Wilt, Mary Butler, Paolo Goffredo
Journal: JNCI Journal of the National Cancer Institute (2024)

To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC).
Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial
Authors: Miao Yu, Yong Yang, Si-Lai Dong, Chen Zhao, Fen Yang, Yuan-Fan Yuan, Yu-Hua Liao, Shao-Lin He, Kun Liu, Fen Wei, Hai-Bo Jia, Bo Yu, Xiang Cheng
Journal: Circulation (2024)

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc &gt;90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] μm versus 87.2 [95% CI, 69.9 to 104.5] μm; difference, 34.2 [95% CI, 9.7 to 58.6] μm; P =0.006), and reduced average lipid arc (–25.2° [95% CI, –30.6° to –19.9°] versus –35.7° [95% CI, –40.5° to –30.8°]; difference, –10.5° [95% CI, –17.7° to –3.4°]; P =0.004), mean angular extension of macrophages (–8.9° [95% CI, –13.3° to –4.6°] versus –14.0° [95% CI, –18.0° to –10.0°]; difference, –6.0° [95% CI, –11.8° to –0.2°]; P =0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P =0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P =0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P =0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04848857.
Do not underestimate the cognitive benefits of exercise
Authors: Olivier Dupuy, Sebastian Ludyga, Francisco B. Ortega, Charles H. Hillman, Kirk I. Erickson, Fabian Herold, Keita Kamijo, Chun-Hao Wang, Timothy P. Morris, Belinda Brown, Irene Esteban-Cornejo, Patricio Solis-Urra, Laurent Bosquet, Markus Gerber, Said Mekari, Nicolas Berryman, Louis Bherer, Ben Rattray, Teresa Liu-Ambrose, Claudia Voelcker-Rehage, Boris Cheval
Journal: Nature Human Behaviour (2024)
Contemporary prognostic signatures and refined risk stratification of gliomas: An analysis of 4400 tumors
Authors: Hia S Ghosh, Ruchit V Patel, Eleanor Woodward, Noah F Greenwald, Varun M Bhave, Eduardo A Maury, Gregory Cello, Samantha E Hoffman, Yvonne Li, Hersh Gupta, Gilbert Youssef, Liam F Spurr, Jayne Vogelzang, Mehdi Touat, Frank Dubois, Andrew D Cherniack, Xiaopeng Guo, Sherwin Tavakol, Gino Cioffi, Neal I Lindeman, Azra H Ligon, E Antonio Chiocca, David A Reardon, Patrick Y Wen, David M Meredith, Sandro Santagata, Jill S Barnholtz-Sloan, Keith L Ligon, Rameen Beroukhim, Wenya Linda Bi
Journal: Neuro-Oncology (2024)

Abstract Background With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received. Methods We assembled a cohort of patients with histopathologically diagnosed glioma from The Cancer Genome Atlas (TCGA), Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women’s Hospital. This incorporated retrospective clinical, histological, and molecular data alongside a prospective assessment of patient survival. Results Of 4400 gliomas were identified: 2195 glioblastomas, 1198 IDH1/2-mutant astrocytomas, 531 oligodendrogliomas, 271 other IDH1/2-wild-type gliomas, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma, respectively (all P &amp;lt; .01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received. Conclusions By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations.
Breaching Confidentiality in Genetic and Non-Genetic Cases: Two Problematic Distinctions
Authors: Madison K. Kilbride
Journal: The American Journal of Bioethics (2024)

Ethical questions about confidentiality arise when patients refuse to inform relatives who are at risk of a genetic condition. Specifically, healthcare providers may struggle with the permissibility of breaching confidentiality to warn patients' at-risk relatives. In exploring this issue, several authors have converged around the idea that genetic cases differ from non-genetic cases (e.g., involving a threat of violence or the spread of an infectious disease) along two related dimensions: (1) In genetic cases, the risk of harm is already present in an at-risk third party, whereas in non-genetic cases, it is not; and (2) In genetic cases, the patient does not create a risk of harm to a third party, whereas in non-genetic cases, the patient does. I argue that these distinctions do not exclusively differentiate genetic from non-genetic cases and should not bear on the permissibility of breaching confidentiality. Instead, such determinations should be based on other considerations.
Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications
Authors: Jia-Kun Li, Tong Tang, Hui Zong, Er-Man Wu, Jing Zhao, Rong-Rong Wu, Xiao-Nan Zheng, Heng Zhang, Yi-Fan Li, Xiang-Hong Zhou, Chi-Chen Zhang, Zi-Long Zhang, Yi-Hang Zhang, Wei-Zhe Feng, Yi Zhou, Jiao Wang, Qi-Yu Zhu, Qi Deng, Jia-Ming Zheng, Lu Yang, Qiang Wei, Bai-Rong Shen
Journal: Military Medical Research (2024)

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.
The role of microRNAs in the gastric cancer tumor microenvironment
Authors: Xianzhe Yu, Yin Zhang, Fengming Luo, Qinghua Zhou, Lingling Zhu
Journal: Molecular Cancer (2024)

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack of reliable early detection techniques, a majority of patients have a poor prognosis. Therefore, identifying new tumor biomarkers and therapeutic targets is essential. This review aims to provide fresh insights into enhancing the prognosis of patients with GC by summarizing the processes through which microRNAs (miRNAs) regulate the tumor microenvironment (TME) and highlighting their critical role in the TME. A comprehensive literature review was conducted by focusing on the interactions among tumor cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, and immune cells within the GC TME. The role of noncoding RNAs, known as miRNAs, in modulating the TME through various signaling pathways, cytokines, growth factors, and exosomes was specifically examined. Tumor formation, metastasis, and therapy in GC are significantly influenced by interactions within the TME. miRNAs regulate tumor progression by modulating these interactions through multiple signaling pathways, cytokines, growth factors, and exosomes. Dysregulation of miRNAs affects critical cellular processes such as cell proliferation, differentiation, angiogenesis, metastasis, and treatment resistance, contributing to the pathogenesis of GC. miRNAs play a crucial role in the regulation of the GC TME, influencing tumor progression and patient prognosis. By understanding the mechanisms through which miRNAs control the TME, potential biomarkers and therapeutic targets can be identified to improve the prognosis of patients with GC.
Author Correction: Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer
Authors: Jacqulyne P. Robichaux, Yasir Y. Elamin, Zhi Tan, Brett W. Carter, Shuxing Zhang, Shengwu Liu, Shuai Li, Ting Chen, Alissa Poteete, Adriana Estrada-Bernal, Anh T. Le, Anna Truini, Monique B. Nilsson, Huiying Sun, Emily Roarty, Sarah B. Goldberg, Julie R. Brahmer, Mehmet Altan, Charles Lu, Vassiliki Papadimitrakopoulou, Katerina Politi, Robert C. Doebele, Kwok-Kin Wong, John V. Heymach
Journal: Nature Medicine (2024)

In the version of the article initially published, in Supplementary Fig. 7c, the ERK1/2 blot (afatinib treatment) was flipped with respect to the drug concentration.The corrected version is shown below as Fig. 1.The blots shown in Supplementary Fig. 10d were a repeat of the experiment and have now been corrected to show the membranes that correspond to Supplementary Fig. 7c.The corrected figure is shown below as Fig. 2.
Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice
Authors: Xiaoqiang Zhu, Xiaojuan Dai, Lijun Zhao, Jing Li, Yanhong Zhu, Wenjuan He, Xinlei Guan, Tao Wu, Li Liu, Hongping Song, Liang Lei
Journal: Gut Microbes (2024)

Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.
<scp>NRP1</scp> antagonism as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis
Authors: Roza Khalmuratova, Jae‐Sung Ryu, Ji Hyeon Hwang, Yi Sook Kim, Suha Lim, Ji‐Hun Mo, Jong‐Yeup Kim, Hyun‐Woo Shin
Journal: Allergy (2024)

Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP).
Current limitations in predicting mRNA translation with deep learning models
Authors: Niels Schlusser, Asier González, Muskan Pandey, Mihaela Zavolan
Journal: Genome biology (2024)

The design of nucleotide sequences with defined properties is a long-standing problem in bioengineering. An important application is protein expression, be it in the context of research or the production of mRNA vaccines. The rate of protein synthesis depends on the 5' untranslated region (5'UTR) of the mRNAs, and recently, deep learning models were proposed to predict the translation output of mRNAs from the 5'UTR sequence. At the same time, large data sets of endogenous and reporter mRNA translation have become available.
Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn
Authors: Eduard W. J. van der Vossen, Mark Davids, Bas Voermans, Koen Wortelboer, Annick V. Hartstra, Annefleur M. Koopen, Pieter de Groot, Evgeni Levin, Max Nieuwdorp
Journal: Gut Microbes (2024)

Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of
Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1highCD206+ pro-tumor macrophages mediated pre-metastatic niche formation in colorectal cancer liver metastasis
Authors: Jing Zhou, Qing Song, Haoze Li, Yicun Han, Yunzhou Pu, Ling Li, Wenqing Rong, Xiaodie Liu, Ziyuan Wang, Jian Sun, Yuqing Song, Xueyan Hu, Guanghao Zhu, Huirong Zhu, Liu Yang, Guangbo Ge, Hongshan Li, Qing Ji
Journal: Molecular Cancer (2024)

Information transmission between primary tumor cells and immunocytes or stromal cells in distal organs is a critical factor in the formation of pre-metastatic niche (PMN). Understanding this mechanism is essential for developing effective therapeutic strategy against tumor metastasis. Our study aims to prove the hypothesis that circ-0034880-enriched tumor-derived extracellular vesicles (TEVs) mediate the formation of PMN and colorectal cancer liver metastasis (CRLM), and targeting circ-0034880-enriched TEVs might be an effective therapeutic strategy against PMN formation and CRLM.