tbuckley/cabot-search huggingface dataset:
Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy
Authors: Ajay Subramanian, Neda Nemat-Gorgani, Timothy J. Ellis-Caleo, David G. P. van IJzendoorn, Timothy J. Sears, Anish Somani, Bogdan A. Luca, Maggie Y. Zhou, Martina Bradic, Ileana A. Torres, Eniola Oladipo, Christin New, Deborah E. Kenney, Raffi S. Avedian, Robert J. Steffner, Michael S. Binkley, David G. Mohler, William D. Tap, Sandra P. D’Angelo, Matt van de Rijn, Kristen N. Ganjoo, Nam Q. Bui, Gregory W. Charville, Aaron M. Newman, Everett J. Moding
Journal: Nature Cancer (2024)
The European Network for IgE-Mediated Autoimmunity and Autoallergy (ENIGMA) initiative
Authors: Pavel Kolkhir, Sabine Altrichter, Fariza Mishaal Saiema Badloe, Hafsa Belasri, Nicolas Charles, Shauni De Vriese, Jan Gutermuth, Lisa Huygen, Emek Kocatürk, Inge Kortekaas Krohn, Melba Muñoz, Sherezade Moñino-Romero, Laurent L. Reber, Jörg Scheffel, Carolin Steinert, Yi-Kui Xiang, Marcus Maurer
Journal: Nature Medicine (2024)
Highlighted research articles
Journal: Cancer Discovery (2024)

In This Issue| March 01 2024 Highlighted research articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2024 American Association for Cancer Research2024American Association for Cancer Research Cancer Discov (2024) 14 (3): 384–385. https://doi.org/10.1158/2159-8290.CD-14-3-ITI 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 March 1 2024 Citation Highlighted research articles. Cancer Discov 1 March 2024; 14 (3): 384–385. https://doi.org/10.1158/2159-8290.CD-14-3-ITI 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 Published analyses of peripheral analytes in advanced renal cell carcinoma (aRCC) are limited. In this study, Choueiri, Donahue, and colleagues present findings from integrated analyses of longitudinal blood samples and baseline tumor tissue from the JAVELIN Renal 101 trial (N = 886), which represents one of the largest data sets for aRCC to date. The findings demonstrate different immunomodulatory mechanisms associated with efficacy outcomes in patients treated with avelumab plus axitinib versus sunitinib and in subsets of patients with different tumor microenvironments and genotypes. Novel treatment-specific observations may prove to have prognostic or predictive significance in the treatment of aRCC. See article, p. 406. Neuroendocrine prostate cancer is an aggressive variant of advanced prostate cancer that is currently diagnosed by tumor biopsy. In this study, Franceschini and colleagues developed the NEuroendocrine MOnitoring (NEMO) targeted cell-free DNA (cfDNA) methylation assay, which provides a phenotype evidence score that captures diverse... You do not currently have access to this content.
A multi-ancestry genetic study of pain intensity in 598,339 veterans
Authors: Sylvanus Toikumo, Rachel Vickers-Smith, Zeal Jinwala, Heng Xu, Divya Saini, Emily E. Hartwell, Mirko Pavicic, Kyle A. Sullivan, Ke Xu, Daniel A. Jacobson, Joel Gelernter, Christopher T. Rentsch, Mirko Pavicic, Eli Stahl, Martin Cheatle, Hang Zhou, Stephen G. Waxman, Amy C. Justice, Rachel L. Kember, Henry R. Kranzler
Journal: Nature Medicine (2024)
A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy
Authors: Zhentang Lao, Ling-Wen Ding, Qiao-Yang Sun, Li Jia, Benedict Yan, Alvin Yu-Jin Ng, Sharah Mae Capinpin, Renwei Wang, Li Ying, Wee Joo Chng, H. Phillip Koeffler, Woon-Puay Koh, Jian-Min Yuan, Henry Yang, Yeow Tee Goh, Nicholas Grigoropoulos
Journal: Clinical Cancer Research (2024)

Abstract Purpose: DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. Experimental Design: We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development. Targeted deep sequencing and methylated DNA immunoprecipitation sequencing (MeDIP-seq) were performed on peripheral blood collected a median of 9.9 years before diagnosis of AML or MDS, together with age-matched still-healthy individuals as controls. Results: Sixty-six individuals who developed AML or MDS displayed significant DNA methylation changes in the peripheral blood compared with 167 age- and gender-matched controls who did not develop AML/MDS during the follow-up period. Alterations in methylation in the differentially methylation regions were associated with increased odds of developing AML/MDS. Conclusions: The epigenetic changes may be acquired independently and before somatic mutations that are relevant for AML/MDS development. The association between methylation changes and the risk of pre-AML/MDS in these individuals was considerably stronger than somatic mutations, suggesting that methylation changes could be used as biomarkers for pre-AML/MDS screening.
Burden of chickenpox complications in Poland, 2006 to 2021: A comprehensive registry-based study
Authors: Rafał Halik, Iwona Paradowska-Stankiewicz, Aneta Trochonowicz, Swavik Dittmer
Journal: Eurosurveillance (2024)

Background Chickenpox, a vaccine-preventable disease caused by the varicella zoster virus, generally presents with mild symptoms but can cause complications necessitating hospitalisation. In Poland, since 2009, vaccination has been obligatory for children up to 12 years of age who are particularly vulnerable to infection and for children in their vicinity. Aim To examine the burden of chickenpox complications and the trends of hospitalisation arising from these complications over time in the Polish population. Methods Data spanning 2006–21 were sourced from the Polish Infectious Diseases Surveillance System, the Nationwide General Hospital Morbidity Study and the Statistics Poland death registry. Standardised and age-specific incidence rates, hospital discharge rates and number of deaths because of chickenpox were calculated. Moreover, the joinpoint regression model was used to analyse trends of annual hospital discharge rates. Results Over the analysed timeframe, 25,804 hospitalisations and 52 deaths attributable to chickenpox complications were documented, and 1.0% of chickenpox cases required hospitalisation because of chickenpox. Age-standardised hospitalisation rates varied between 2.3 and 9.6 per 100,000 population. The analysis revealed no statistically significant trend in overall hospital discharge rates from chickenpox complications. However, a notable increase in hospitalisation rates was observed in children aged 0–4 and among inhabitants of rural areas, with annual percentage changes of 4.9% and 3.4% respectively. Conclusions Our findings suggest that the implementation of a universal chickenpox immunisation programme, supported by health education, should be considered to reduce the number of hospitalisations and nearly eliminate deaths because of chickenpox.
The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Authors: Eranga R. Balasooriya, Qibiao Wu, Haley Ellis, Yuanli Zhen, Bryanna L. Norden, Ryan B. Corcoran, Adithi Mohan, Eric Martin, Aleksandra Franovic, John Tyhonas, Matthew Lardy, Kathryn B. Grandinetti, Robert Pelham, Liliana Soroceanu, Vanessa S. Silveira, Nabeel Bardeesy
Journal: Clinical Cancer Research (2024)

FGFR2 and FGFR3 show oncogenic activation in many cancer types, often through chromosomal fusion or extracellular domain mutation. FGFR2 and FGFR3 alterations are most prevalent in intrahepatic cholangiocarcinoma (ICC) and bladder cancers, respectively, and multiple selective reversible and covalent pan-FGFR tyrosine kinase inhibitors (TKI) have been approved in these contexts. However, resistance, often due to acquired secondary mutations in the FGFR2/3 kinase domain, limits efficacy. Resistance is typically polyclonal, involving a spectrum of different mutations that most frequently affect the molecular brake and gatekeeper residues (N550 and V565 in FGFR2).
Prostaglandin E2 in the Tumor Microenvironment, a Convoluted Affair Mediated by EP Receptors 2 and 4
Authors: Ana Santiso, Akos Heinemann, Julia Kargl
Journal: Pharmacological Reviews (2024)

<h3>Abstract</h3> The involvement of the prostaglandin E2 (PGE2) system in cancer progression has long been recognized. PGE2 functions as an autocrine and paracrine signaling molecule with pleiotropic effects in the human body. High levels of intratumoral PGE2 and overexpression of the key metabolic enzymes of PGE2 have been observed and suggested to contribute to tumor progression. This has been claimed for different types of solid tumors, including, but not limited to, lung, breast, and colon cancer. PGE2 has direct effects on tumor cells and angiogenesis that are known to promote tumor development. However, one of the main mechanisms behind PGE2 driving cancerogenesis is currently thought to be anchored in suppressed antitumor immunity, thus providing possible therapeutic targets to be used in cancer immunotherapies. EP2 and EP4, two receptors for PGE2, are emerging as being the most relevant for this purpose. This review aims to summarize the known roles of PGE2 in the immune system and its functions within the tumor microenvironment. <h3>Significance Statement</h3> Prostaglandin E2 (PGE2) has long been known to be a signaling molecule in cancer. Its presence in tumors has been repeatedly associated with disease progression. Elucidation of its effects on immunological components of the tumor microenvironment has highlighted the potential of PGE2 receptor antagonists in cancer treatment, particularly in combination with immune checkpoint inhibitor therapeutics. Adjuvant treatment could increase the response rates and the efficacy of immune-based therapies.
Abstract IA016: Molecular diversity of uterine serous carcinoma
Authors: Alessandro D. Santin
Journal: Clinical Cancer Research (2024)

Abstract Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer with a high recurrence rate and poor prognosis disproportionately affecting black women. Whole-exome-sequencing analysis revealed that up to 10% of USC harbor features of ultra/hypermutation due to a deficiency of polymerase e (POLE) and/or mismatched-repair genes (MMRd). These tumors are notable for having a high number of single nucleotide variants (SNV), no LOH segments or copy-number variants (CNV) and a peculiar genetic signature characterized by an increased rate of C &amp;gt; A transversions. In contrast, the overwhelming majority of USC (~ 90%) are POLE/MMR proficient, have a low number of SNV and demonstrate alteration in genes including TP53, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling-complex, and TAF1, an element of the core TFIID transcriptional machinery are also detected in a significant number of USC. Somatic CNVs, a sign of genomic instability, are identified in the majority of USC with multiple copy number gains and copy number losses, with the most frequent events taking place in pathways similar to those found from analysis of SNVs. In addition to loss of TP53, frequent deletion of a small segment of chromosome 19 containing MBD3, a member of the NuRD-chromatin-modification-complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (encoding for the HER2/neu receptor) and CCNE1 (a target of FBXW7-mediated ubiquitination) are commonly detected. Overall, these findings suggest that both somatic point mutations (SNV) and somatic CNV play a major role in the pathogenesis of USC. Importantly, the frequent mutation of DNA damage, chromatin remodeling, cell cycle and cell proliferation pathways in USC including the overexpression/amplification of HER2/neu, CCNE1 and the tumor-associated calcium signal transducer 2 (TACSTD2/TROP2) genes, suggest novel targets for therapy against this lethal variant of endometrial cancer. Citation Format: Alessandro D. Santin. Molecular diversity of uterine serous carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA016.
Correction: Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape–Driven Relapse in Multiple Myeloma
Journal: Blood Cancer Discovery (2024)

In the original version of this article (1), Fig. 2C, the left-most image in row 5 representing the day 30 time point for the group of mice treated with BCMA-41BBζ[2A]GPRC5D-CD28ζ was inadvertently duplicated to row 4 representing the same time point for the mice treated with GPRCD-BCMA-41BBζ.The error has been corrected in the latest online HTML and PDF versions of the article.The authors regret this error.
A gut microbial signature for combination immune checkpoint blockade across cancer types
Authors: Ashray Gunjur, Yan Shao, Timothy Rozday, Oliver Klein, Andre Mu, Bastiaan W. Haak, Ben Markman, Damien Kee, Matteo S. Carlino, Craig Underhill, Sophia Frentzas, Michael Michael, Bo Gao, Jodie Palmer, Jonathan Cebon, Andreas Behren, David J. Adams, Trevor D. Lawley
Journal: Nature Medicine (2024)

Abstract Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is a relationship between a cancer patient’s gut microbiota composition and clinical response to ICB; however, defining microbiome-based biomarkers that generalize across cohorts has been challenging. This may relate to previous efforts quantifying microbiota to species (or higher taxonomic rank) abundances, whereas microbial functions are often strain specific. Here, we performed deep shotgun metagenomic sequencing of baseline fecal samples from a unique, richly annotated phase 2 trial cohort of patients with diverse rare cancers treated with combination ICB ( n = 106 discovery cohort). We demonstrate that strain-resolved microbial abundances improve machine learning predictions of ICB response and 12-month progression-free survival relative to models built using species-rank quantifications or comprehensive pretreatment clinical factors. Through a meta-analysis of gut metagenomes from a further six comparable studies ( n = 364 validation cohort), we found cross-cancer (and cross-country) validity of strain–response signatures, but only when the training and test cohorts used concordant ICB regimens (anti-PD-1 monotherapy or combination anti-PD-1 plus anti-CTLA-4). This suggests that future development of gut microbiome diagnostics or therapeutics should be tailored according to ICB treatment regimen rather than according to cancer type.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2024)

Highlights| March 01 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 (5): 929. https://doi.org/10.1158/1078-0432.CCR-30-5-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 March 1 2024 Citation Selected Articles from This Issue. Clin Cancer Res 1 March 2024; 30 (5): 929. https://doi.org/10.1158/1078-0432.CCR-30-5-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 Addition of anti-PD-1 and PD-L1 immunotherapies to chemotherapy and radiation for the treatment of cervical cancer has had mixed clinical results. As TGF-β has been shown to promote tumor progression and immune escape in human papillomavirus (HPV)-associated cervical cancer, it has been suggested that targeting both the immunosuppressive TGF-β and PD-L1 pathways may improve patient outcomes. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of a TGF-β "trap" fused to a PD-L1 monoclonal antibody. In this phase Ib trial, Oaknin and colleagues evaluate the combination of bintrafusp alfa with cisplatin or carboplatin plus paclitaxel or radiation, with or without the VEGF-A monoclonal antibody bevacizumab in patients with locally advanced or persistent, recurrent, or metastatic (P/R/M) cervical cancer. The combination therapies were tolerable, with most adverse events being grade 1-2. The authors report promising activity, with an objective response rate of 75.0% in patients receiving bintrafusp alfa, cisplatin or carboplatin,... You do not currently have access to this content.
Contractile and Tensile Measurement of Molecular Artificial Muscles for Biohybrid Robotics
Authors: Yingzhe Wang, Kaoru Uesugi, Takahiro Nitta, Yuichi Hiratsuka, Keisuke Morishima
Journal: Cyborg and Bionic Systems (2024)

A printable artificial muscle assembled from biomolecular motors, which we have recently developed, showed great potential in overcoming the design limitations of conventional biohybrid robots as a new bio-actuator. Characterizing its contractility for extending its applicability is important. However, conventional measurement methods are composed of complex operations with poor reproducibility, flexibility, and real-time responsiveness. This study presents a new method for measuring the contractile force generated by artificial muscles. A measurement system was constructed, wherein artificial muscles were patterned by UV laser scanning in an oil-sealed microchamber, and the contractile force was measured in real time using a microforce sensor extended by a 3D-printed microcantilever. The measurement accuracy of the sensor was ensured through calibration and correction. For demonstration purposes, a series of contractile measurements were carried out using the proposed system. The relationship between contractile force and the dimensions of the activation space of the artificial muscles, as well as the tensile properties of the contracted muscle chain were evaluated. The results will help characterize the contractile properties of the artificial muscle and lay the foundations for its further application in biohybrid robotics.
Sedentary behavior and lifespan brain health
Authors: Liye Zou, Fabian Herold, Boris Cheval, Michael J. Wheeler, Dominika M. Pindus, Kirk I. Erickson, David A. Raichlen, Gene E. Alexander, Notger G. Müller, David W. Dunstan, Arthur F. Kramer, Charles H. Hillman, Mats Hallgren, Ulf Ekelund, Silvio Maltagliati, Neville Owen
Journal: Trends in Cognitive Sciences (2024)
Integrating Fluorescence and Magnetic Resonance Imaging in Biocompatible Scaffold for Real‐Time Bone Repair Monitoring and Assessment (Adv. Healthcare Mater. 6/2024)
Authors: Ai Yang, Yue Wang, Qian Feng, Kanwal Fatima, Qianqian Zhang, Xiaojun Zhou, Chuanglong He
Journal: Advanced Healthcare Materials (2024)
Micro‐Vessels‐Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma‐Endothelial Cells Co‐Culture Models (Adv. Healthcare Mater. 6/2024)
Authors: Qais Akolawala, Floor Keuning, Marta Rovituso, Wouter van Burik, Ernst van der Wal, Henri H. Versteeg, Araci M. R. Rondon, Angelo Accardo
Journal: Advanced Healthcare Materials (2024)
Introducing Specific Iodine Ions in Perovskite‐Based Nanocomplex to Cater for Versatile Biomedical Imaging and Tumor Radiotherapy (Adv. Healthcare Mater. 6/2024)
Authors: Yumeng Yue, Haoran Xu, Liwen Jiang, Xiaomin Zhao, Dawei Deng
Journal: Advanced Healthcare Materials (2024)
Injective Programmable Proanthocyanidin‐Coordinated Zinc‐Based Composite Hydrogel for Infected Bone Repair (Adv. Healthcare Mater. 6/2024)
Authors: Yue Wang, Yitao Zhao, Shiyuan Ma, Meimei Fu, Min Wu, Jintao Li, Keke Wu, Xiuli Zhuang, Zhihui Lu, Jinshan Guo
Journal: Advanced Healthcare Materials (2024)

Programmable antimicrobial and osteogenicIn article 2302690, Jinshan Guo and co-workers show that by compositing proanthocyanidin (PC)-coordinated ZnO with thioether-grafted sodium alginate, injective programmable proanthocyanidin-coordinated zinc-based composite hydrogels are developed, which can response to high endogenous ROS microenvironment in infected bone defects to trigger hydrogel disintegration and fast release of antimicrobial components, the concurrently released anti-oxidant PC scavenges excess ROS, enhances the immunomodulatory and osteoinductive properties of Zn 2+ , programmably promote infected bone repair.
Sexually dimorphic control of affective state processing and empathic behaviors
Authors: Shunchang Fang, Zhengyi Luo, Zicheng Wei, Yuxin Qin, Jieyan Zheng, Hongyang Zhang, Jianhua Jin, Jiali Li, Chenjian Miao, Shana Yang, Yonglin Li, Zirui Liang, Xiao-Dan Yu, Xiao Min Zhang, Wei Xiong, Hongying Zhu, Wen-Biao Gan, Lianyan Huang, Boxing Li
Journal: Neuron (2024)

Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.