tbuckley/cabot-search huggingface dataset:
Customized Hydrogel Films for MicroRNA Super‐Resolution Imaging in Liquid Biopsies
Authors: Mirae Lee, Jiwon Woo, Kyoung‐Tae Kim, Seul‐A Moon, Hyeong Cheon Park, Tae Yeon Kim, Jeong‐Yoon Park
Journal: Advanced Healthcare Materials (2024)

Abstract Tissue biopsy for early diagnosis and monitoring comes with several challenges, such as its invasiveness, and issues related to tissue heterogeneity in sampling. To address these issues, researchers have proposed a noninvasive approach called liquid biopsy, which uses blood samples to detect specific noncoding RNA (microRNA, miRNA). However, the current process of isolating and amplifying miRNA can be time‐consuming and yield nonspecific results. In this study, a new super‐resolution imaging tool is introduced that utilizes a thin, hydrogel‐based liquid view (LV) film. This film can undergo a ninefold expansion and allows the analysis of cells obtained from liquid biopsy. The potential of the LV film is validated as a tool for early diagnosis and prognosis by testing biofluids derived from a variety of diseases. This method is confirmed to accurately analyze a greater number of miRNAs with higher sensitivity in a shorter time compared to other analytical methods. These findings suggest that the LV film provides high specificity, and multiplexing in detecting small amounts of miRNAs within cells, making it suitable for 3D implementation. It is proposed that liquid biopsy with LV films can be a solution to limitations related to the invasiveness, cost, and time‐consuming nature of molecular analysis.
Multiomic profiling of transcription factor binding and function in human brain
Authors: Jacob M. Loupe, Ashlyn G. Anderson, Lindsay F. Rizzardi, Ivan Rodriguez-Nunez, Belle Moyers, Katie Trausch-Lowther, Rashmi Jain, William E. Bunney, Blynn G. Bunney, Preston Cartagena, Adolfo Sequeira, Stanley J. Watson, Huda Akil, Gregory M. Cooper, Richard M. Myers
Journal: Nature Neuroscience (2024)
Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment
Authors: Kevin M. Tharp, Kelly Kersten, Ori Maller, Greg A. Timblin, Connor Stashko, Fernando P. Canale, Rosa E. Menjivar, Mary-Kate Hayward, Ilona Berestjuk, Johanna ten Hoeve, Bushra Samad, Alastrair J. Ironside, Marina Pasca di Magliano, Alexander Muir, Roger Geiger, Alexis J. Combes, Valerie M. Weaver
Journal: Nature Cancer (2024)
Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells
Authors: David K. Y. Zhang, Joshua M. Brockman, Kwasi Adu-Berchie, Yutong Liu, Yoav Binenbaum, Irene de Lázaro, Miguel C. Sobral, Rea Tresa, David J. Mooney
Journal: Nature Biomedical Engineering (2024)
High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection
Authors: Benjamin X. Wang, Dmitry Leshchiner, Lijuan Luo, Miles Tuncel, Karsten Hokamp, Jay C. D. Hinton, Denise M. Monack
Journal: Nature Genetics (2024)

Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi and Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.
When Lightning Strikes Twice: Routes to Second Malignancies in Young Patients
Authors: Clarissa N. Pacyna, Jyoti Nangalia
Journal: Cancer Discovery (2024)

Summary: Given the rarity of cancer in childhood, it should be even more uncommon for pediatric cancer survivors to develop a second, independent malignancy, yet they incur a greatly elevated risk after initial remission. In this issue of Cancer Discovery, Sánchez-Guixé and colleagues unpick the origins of second tumours in four children, and the potential role platinum-based chemotherapy may play in subsequent tumorigenesis. See related article by Sánchez-Guixé et al., p. 953 (8).
A Deep Learning Model for Cancer Type Prediction Sets a New Standard
Authors: Salil Garg
Journal: Cancer Discovery (2024)

Summary: Classifying tumor types using machine learning approaches is not always trivial, particularly for challenging cases such as cancers of unknown primary. In this issue of Cancer Discovery, Darmofal and colleagues describe a new tool that uses information from a clinical sequencing panel to diagnose tumor type, and show that the model is particularly robust. See related article by Darmofal et al., p. 1064 (1).
L-arginine loading porous PEEK promotes percutaneous tissue repair through macrophage orchestration
Authors: Tong Zhao, Xingdan Liu, Zhuangzhuang Chu, Jing Zhao, Dongya Jiang, Xiaohua Dong, Ziyi Lu, Kelvin W.K. Yeung, Xuanyong Liu, Liping Ouyang
Journal: Bioactive Materials (2024)

Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results
Application of individual brain connectome in chronic ischemia: mapping symptoms before and after reperfusion
Authors: Yu Lei, Xin Zhang, Wei Ni, Chao Gao, Yanjiang Li, Heng Yang, Xinjie Gao, Ding Xia, Xia Zhang, Karol Osipowicz, Stephane Doyen, Michael E. Sughrue, Yuxiang Gu, Ying Mao
Journal: MedComm (2024)

Abstract How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC &gt; 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC &gt; 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.
Vaccines against extraintestinal pathogenic <i>Escherichia coli</i> (ExPEC): progress and challenges
Authors: Ling Qiu, Dylan Chirman, Justin R. Clark, Yikun Xing, Haroldo Hernandez Santos, Ellen E. Vaughan, Anthony W. Maresso
Journal: Gut Microbes (2024)

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria
Atomic force microscopy in the characterization and clinical evaluation of neurological disorders: current and emerging technologies
Authors: David T. She, Mui Hoon Nai, Chwee Teck Lim
Journal: Med-X (2024)

Abstract This review examines the significant role of Atomic Force Microscopy (AFM) in neurobiological research and its emerging clinical applications in diagnosing neurological disorders and central nervous system (CNS) tumours. AFM, known for its nanometre-scale resolution and piconewton-scale force sensitivity, offers ground breaking insights into the biomechanical properties of brain cells and tissues and their interactions within their microenvironment. This review delves into the application of AFM in non-clinical settings, where it characterizes molecular, cellular, and tissue-level aspects of neurological disorders in experimental models. This includes studying ion channel distribution, neuron excitability in genetic disorders, and axonal resistance to mechanical injury. In the clinical context, this article emphasizes AFM’s potential in early detection and monitoring of neurodegenerative diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS), through biomarker characterization in biofluids such as cerebrospinal fluid and blood. It also examines the use of AFM in enhancing the grading and treatment of CNS tumours by assessing their stiffness, providing a more detailed analysis than traditional histopathological methods. Despite its promise, this review acknowledges challenges in integrating AFM into clinical practice, such as sample heterogeneity and data analysis complexity, and discusses emerging solutions such as machine learning and neural networks to overcome these hurdles. These advancements, combined with commercial nanotechnology platforms, herald a new era in personalized treatment strategies for management, treatment and diagnosis of neurological disorders. Graphical Abstract
Influence of TP53 mutation on efficacy and survival in advanced EGFR‐mutant non‐small cell lung cancer patients treated with third‐generation EGFR tyrosine kinase inhibitors
Authors: Zhonghan Zhang, Jinhui Xue, Yunpeng Yang, Wenfeng Fang, Yan Huang, Shen Zhao, Fan Luo, Jiaxin Cao, Kangmei Zeng, Wenjuan Ma, Jianhua Zhan, Feiteng Lu, Li Zhang, Hongyun Zhao
Journal: MedComm (2024)

Abstract TP53 comutation is related to poor prognosis of non‐small cell lung cancer. However, there is limited study focusing on the structural influence of TP53 mutation on third‐generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) treatment. We retrospectively analyzed the clinical and molecular data of patients treated with third‐generation EGFR‐TKIs in two independent cohorts. A total of 117 patients from the Sun Yat‐sen University Cancer Center (SYSUCC) and 141 patients from the American Association for Cancer Research Project GENIE database were included. In the SYSUCC cohort, TP53 comutations were found in 59 patients (50.4%) and were associated with poor median progress‐free survival (mPFS) and median overall survival (mOS). The additional subtype analysis found that TP53 mutation in the alpha‐helix region had shorter mOS compared with those with TP53 mutations in other regions in the SYSUCC cohort (mOS, 12.2 vs. 21.7 months; p = 0.027). Similar findings were confirmed in the GENIE cohort. Specifically, the presence of TP53 mutation in the alpha‐helix region was an independent negative predictive factor for PFS [hazard ratio (HR) 2.05(1.01–4.18), p = 0.048] and OS [HR 3.62(1.60–8.17), p = 0.002] in the SYSUCC cohort. TP53 mutation in alpha‐helix region was related to inferior clinical outcomes in patients treated with third‐generation EGFR‐TKIs.
Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure: Design and rationale of the BioMEMS study
Authors: Youssra Allach, Mylene Barry‐Loncq de Jong, Pascal R.D. Clephas, Marco W.F. van Gent, Hans‐Peter Brunner‐La Rocca, Mariusz K. Szymanski, Vokko P. van Halm, M. Louis Handoko, Wouter E.M. Kok, Folkert W. Asselbergs, Roland R.J. van Kimmenade, Olivier C. Manintveld, Nicolas M.D.A. van Mieghem, Saskia L.M.A. Beeres, Michiel Rienstra, Marco C. Post, Loek van Heerebeek, C. Jan Willem Borleffs, Raymond Tukkie, Arend Mosterd, Gerard C.M. Linssen, Ruud F. Spee, Mireille E. Emans, Tom D.J. Smilde, Jan van Ramshorst, Charles J.H.J. Kirchhof, Margriet W. Feenema‐Aardema, Carlos A. da Fonseca, Mieke van den Heuvel, Ronald Hazeleger, J.W. Martijn van Eck, Eric Boersma, Isabella Kardys, Rudolf A. de Boer, Jasper J. Brugts
Journal: European Journal of Heart Failure (2024)

Abstract Aims Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF‐related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early‐stage intervention, since haemodynamic congestion precedes clinical symptoms. Methods The BioMEMS study, a substudy of the MONITOR‐HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR‐HF trial were collected at baseline, 3‐, 6‐, and 12‐month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS‐HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. Conclusion Since the prognostic value of single baseline measurements of biomarkers like N‐terminal pro‐B‐type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.
Archaea influence composition of endoscopically visible ileocolonic biofilms
Authors: Elisabeth Orgler, Maximilian Baumgartner, Stefanie Duller, Christina Kumptisch, Bela Hausmann, Doris Moser, Vineeta Khare, Michaela Lang, Thomas Köcher, Adrian Frick, Markus Muttenthaler, Athanasios Makristathis, Christine Moissl-Eichinger, Christoph Gasche
Journal: Gut Microbes (2024)

The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.
Untapped potential of gut microbiome for hypertension management
Authors: Kan Gao, Pu Xiu Wang, Xue Mei, Tao Yang, Kai Yu
Journal: Gut Microbes (2024)

The gut microbiota has been shown to be associated with a range of illnesses and disorders, including hypertension, which is recognized as the primary factor contributing to the development of serious cardiovascular diseases. In this review, we conducted a comprehensive analysis of the progression of the research domain pertaining to gut microbiota and hypertension. Our primary emphasis was on the interplay between gut microbiota and blood pressure that are mediated by host and gut microbiota-derived metabolites. Additionally, we elaborate the reciprocal communication between gut microbiota and antihypertensive drugs, and its influence on the blood pressure of the host. The field of computer science has seen rapid progress with its great potential in the application in biomedical sciences, we prompt an exploration of the use of microbiome databases and artificial intelligence in the realm of high blood pressure prediction and prevention. We propose the use of gut microbiota as potential biomarkers in the context of hypertension prevention and therapy.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2024)

Highlights| June 03 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 (11): 2295. https://doi.org/10.1158/1078-0432.CCR-30-11-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 June 3 2024 Citation Selected Articles from This Issue. Clin Cancer Res 1 June 2024; 30 (11): 2295. https://doi.org/10.1158/1078-0432.CCR-30-11-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 Preclinical studies have shown that androgen receptor-mediated CDK4/6 activation potentiates cell proliferation and endocrine therapy resistance in prostate cancer models, and CDK4/6 inhibition leads to tumor growth inhibition. The CDK4/6 inhibitor abemaciclib has been shown to significantly increase endocrine therapy efficacy in metastatic breast cancer, suggesting its potential as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). In the phase II CYCLONE 1 study, Agarwal and colleagues evaluate the clinical activity of abemaciclib in heavily pretreated patients with refractory mCRPC. The authors report an objective response rate of 6.8% and a disease control rate of 45.5%, with a median time to PSA progression of 6.5 months, a 2.7-month median radiographic progression-free survival (rPFS), a 6-month rPFS rate of 24.9%, and an 8.4-month overall survival. Abemaciclib was well tolerated, with no treatment-related grade 4 or 5 adverse events. Overall, abemaciclib showed initial clinical activity in this heavily pretreated patient... You do not currently have access to this content.
Unlocking the Next Frontier in Precision Oncology: Addressing Drug-Tolerant Residual Disease
Authors: Jessica J. Lin, Justin F. Gainor, Vincent K. Lam, Christine M. Lovly
Journal: Cancer Discovery (2024)

Summary: Drug-tolerant residual disease (DTRD) after the initial maximal response to a systemic therapy can serve as a tumor reservoir for the development of acquired drug resistance and represents a major clinical challenge across various cancers and types of therapies. To unlock the next frontier in precision oncology, we propose a fundamental paradigm shift in the treatment of metastatic cancers with a sharpened focus towards defining, monitoring, and therapeutically targeting the DTRD state.
The Cell Cycle: a Key to Unlock EZH2-targeted Therapy Resistance
Authors: Rachel L. Paolini, George P. Souroullas
Journal: Cancer Discovery (2024)

Summary: In this issue, a study by Kazansky and colleagues explored resistance mechanisms after EZH2 inhibition in malignant rhabdoid tumors (MRT) and epithelioid sarcomas (ES). The study identified genetic alterations in EZH2 itself, along with alterations that converge on RB1-E2F–mediated cell-cycle control, and demonstrated that inhibition of cell-cycle kinases, such as Aurora Kinase B (AURKB) could bypass EZH2 inhibitor resistance to enhance treatment efficacy. See related article by Kazansky et al., p. 965 (6).
Optimus-Era Dose Finding for Rare Cancers
Authors: Yonina R. Murciano-Goroff, Sean M. Devlin, Alexia Iasonos, Alexander Drilon
Journal: Cancer Discovery (2024)

Summary: Advances in cancer biology and diagnostics have led to the recognition of a multitude of rare cancer subtypes, emphasizing the pressing need for strategies to accelerate drug development for patients with these cancers. This paper addresses the unique challenges of dose finding in trials that accrue small numbers of patients with rare cancers; strategies for dose optimization are proposed, in line with evolving approaches to dose determination in the age of the US Food and Drug Administration's Project Optimus.
Advances in the isolation, cultivation, and identification of gut microbes
Authors: Meng-Qi Xu, Fei Pan, Li-Hua Peng, Yun-Sheng Yang
Journal: Military Medical Research (2024)

Abstract The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.
Correction: Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma
Authors: Weiwei Liu, Lu zheng, Rongguiyi Zhang, Ping Hou, Jiakun Wang, Linquan Wu, Jing Li
Journal: Molecular Cancer (2024)

After the