tbuckley/cabot-search huggingface dataset:
Exosome Isolation Using Chitosan Oligosaccharide Lactate‐1‐Pyrenecarboxylic Acid‐Based <i>Self</i>‐Assembled Magnetic Nanoclusters
Authors: Minse Kim, Chi‐Yeon Song, Jin Sil Lee, Yu‐Rim Ahn, Jaewon Choi, Sang Hoon Lee, SoJin Shin, Hee Jun Na, Hyun‐Ouk Kim
Journal: Advanced Healthcare Materials (2024)

Abstract Exosomes are small extracellular vesicles that play a crucial role in intercellular communication and offer significant potential for a wide range of biomedical applications. However, conventional methods for exosome isolation have limitations in terms of purity, scalability, and preservation of exosome structural integrity. To address these challenges, an exosome isolation platform using chitosan oligosaccharide lactate conjugated 1‐pyrenecarboxylic acid (COL‐Py) based self‐assembled magnetic nanoclusters (CMNCs), is presented. CMNCs are characterized to optimize their size, stability, and interaction dynamics with exosomes. The efficiency of CMNCs in isolating exosomes is systematically evaluated using various analytical methods to demonstrate their ability to capture exosomes based on amphiphilic lipid bilayers. CMNC‐based exosome isolation consistently yields exosomes with structural integrity and purity similar to those obtained using traditional methods. The reusability of CMNCs over multiple exosome isolation cycles underscores their scalability and offers an efficient solution for biomedical applications. These results are supported by western blot analysis, which demonstrated the superiority of CMNC‐based isolation in terms of purity compared to conventional methods. By providing a scalable and efficient exosome isolation process that preserves both structural integrity and purity, CMNCs can constitute a new platform that can contribute to the field of exosome studies.
Induction immunochemotherapy followed by definitive chemoradiotherapy for unresectable locally advanced non‐small cell lung cancer: a multi‐institutional retrospective cohort study
Authors: Leilei Wu, Bo Cheng, Xiaojiang Sun, Zhenshan Zhang, Jingjing Kang, Yun Chen, Qinghua Xu, Shuangyan Yang, Yujie Yan, Shengxiang Ren, Caicun Zhou, Yaping Xu
Journal: MedComm (2024)

Abstract This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non‐small cell lung cancer (LA‐NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression‐free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone ( p &lt; 0.001). Patients with concurrent CRT demonstrated markedly improved PFS ( p = 0.012) and OS ( p = 0.017) than those undergoing sequential CRT. Additionally, those with a programmed‐death ligand 1 (PD‐L1) expression of 50% or higher showed significantly elevated ORRs (72.2% vs. 47.2%, p = 0.011) and superior OS (median 44.8 vs. 28.6 months, p = 0.004) compared to patients with PD‐L1 expression below 50%. Hematologic toxicities were the primary severe adverse events (grade ≥ 3) encountered, with no unforeseen treatment‐related toxicities. Thus, induction immunochemotherapy followed by definitive CRT demonstrated encouraging efficacy and tolerable toxicities for unresectable LA‐NSCLC.
Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy
Authors: Zhilin Li, Qianfeng Zhang, Zhiqian Li, Long Ren, Dayi Pan, Qiyong Gong, Zhongwei Gu, Hao Cai, Kui Luo
Journal: Acta Pharmaceutica Sinica B (2024)

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer
Tracking and mapping in medical computer vision: A review
Authors: Adam Schmidt, Omid Mohareri, Simon DiMaio, Michael C. Yip, Septimiu E. Salcudean
Journal: Medical Image Analysis (2024)

As computer vision algorithms increase in capability, their applications in clinical systems will become more pervasive. These applications include: diagnostics, such as colonoscopy and bronchoscopy; guiding biopsies, minimally invasive interventions, and surgery; automating instrument motion; and providing image guidance using pre-operative scans. Many of these applications depend on the specific visual nature of medical scenes and require designing algorithms to perform in this environment. In this review, we provide an update to the field of camera-based tracking and scene mapping in surgery and diagnostics in medical computer vision. We begin with describing our review process, which results in a final list of 515 papers that we cover. We then give a high-level summary of the state of the art and provide relevant background for those who need tracking and mapping for their clinical applications. After which, we review datasets provided in the field and the clinical needs that motivate their design. Then, we delve into the algorithmic side, and summarize recent developments. This summary should be especially useful for algorithm designers and to those looking to understand the capability of off-the-shelf methods. We maintain focus on algorithms for deformable environments while also reviewing the essential building blocks in rigid tracking and mapping since there is a large amount of crossover in methods. With the field summarized, we discuss the current state of the tracking and mapping methods along with needs for future algorithms, needs for quantification, and the viability of clinical applications. We then provide some research directions and questions. We conclude that new methods need to be designed or combined to support clinical applications in deformable environments, and more focus needs to be put into collecting datasets for training and evaluation.
Interleukin-6 classic and trans-signaling utilize glucose metabolism reprogramming to achieve anti- or pro-inflammatory effects
Authors: Shilei Xu, Ke-Qiong Deng, Chengbo Lu, Xin Fu, Qingmei Zhu, Shiqi Wan, Lin Zhang, Yu Huang, Longyu Nie, Huanhuan Cai, Qiming Wang, Hao Zeng, Yufeng Zhang, Fubing Wang, Hong Ren, Yu Chen, Huan Yan, Ke Xu, Li Zhou, Mengji Lu, Ying Zhu, Shi Liu, Zhibing Lu
Journal: Metabolism (2024)
Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy
Authors: Hongbin Zhuang, Zhiyuan Liang, Guanwei Ma, Ayesha Qureshi, Xiaoqian Ran, Chengyun Feng, Xukun Liu, Xi Yan, Liming Shen
Journal: MedComm (2024)

Abstract Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multi‐omics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. The non‐targeted omics and targeting studies of diagnostic markers for ASD were also reviewed. Moreover, we summarized the progress and methods of behavioral and educational interventions, intervention methods related to technological devices, and research on medical interventions and potential drug targets. This review highlighted the application of high‐throughput omics methods in ASD research and emphasized the importance of seeking homogeneity from heterogeneity and exploring the convergence of disease mechanisms, biomarkers, and intervention approaches, and proposes that taking into account individuality and commonality may be the key to achieve accurate diagnosis and treatment of ASD.
H<sub>2</sub>S donor S‐propargyl‐cysteine for skin wound healing improvement via smart transdermal delivery
Authors: Xiaoqing Zhao, Yao Chen, Zhongxiao Lin, Xinyang Jin, Bolun Su, Xiaotong Liu, Mao Yang, Keyuan Chen, Menglin Zhu, Lei Wang, Yi Zhun Zhu
Journal: MedComm (2024)

Abstract Hydrogen sulfide for wound healing has drawn a lot of attention recently. In this research, the S‐propargyl‐cysteine (SPRC), an endogenous H 2 S donor, was loaded on carbomer hydrogel, and a copper sheet rat burn model was developed. Pathological changes in rat skin tissue were examined using hematoxylin–eosin (HE) and Masson staining. The immunohistochemistry (IHC) staining was performed to detect the expression of Collagen I (Col I) and Collagen III (Col III). The mRNA levels of interleukin (IL)‐6, Col Iα2, Col IIIα1, tissue inhibitors of metalloproteinase (TIMP)‐1, matrix metalloproteinase (MMP)‐9, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)‐β1 were examined by quantitative real‐time chain polymerase reaction. The findings demonstrated that the collagen layer was thicker in the SPRC group during the proliferative phase, SPRC hydrogel promoted VEGF expression. In the late stage of wound healing, the expression of IL‐6, TIMP‐1, MMP‐9, and TGF‐β1 was inhibited, and the Col I content was closer to that of normal tissue. These results surface that SPRC hydrogel can promote wound healing and play a positive role in reducing scar formation. Our results imply that SPRC can facilitate wound healing and play a positive role in reducing scar formation.
Mitosis detection, fast and slow: Robust and efficient detection of mitotic figures
Authors: Mostafa Jahanifar, Adam Shephard, Neda Zamanitajeddin, Simon Graham, Shan E. Ahmed Raza, Fayyaz Minhas, Nasir Rajpoot
Journal: Medical Image Analysis (2024)

Counting of mitotic figures is a fundamental step in grading and prognostication of several cancers. However, manual mitosis counting is tedious and time-consuming. In addition, variation in the appearance of mitotic figures causes a high degree of discordance among pathologists. With advances in deep learning models, several automatic mitosis detection algorithms have been proposed but they are sensitive to domain shift often seen in histology images. We propose a robust and efficient two-stage mitosis detection framework, which comprises mitosis candidate segmentation (Detecting Fast) and candidate refinement (Detecting Slow) stages. The proposed candidate segmentation model, termed EUNet, is fast and accurate due to its architectural design. EUNet can precisely segment candidates at a lower resolution to considerably speed up candidate detection. Candidates are then refined using a deeper classifier network, EfficientNet-B7, in the second stage. We make sure both stages are robust against domain shift by incorporating domain generalization methods. We demonstrate state-of-the-art performance and generalizability of the proposed model on the three largest publicly available mitosis datasets, winning the two mitosis domain generalization challenge contests (MIDOG21 and MIDOG22). Finally, we showcase the utility of the proposed algorithm by processing the TCGA breast cancer cohort (1,124 whole-slide images) to generate and release a repository of more than 620K potential mitotic figures (not exhaustively validated).
Loss-of-phosphorylation of IKZF1 results in gain-of-function associated with immune dysregulation
Authors: Akihiro Hoshino, Benoît Heid Picard, Sophia Polychronopoulou, Charikleia Kelaidi, Saba Azarnoush, Sven Kracker, Frédéric Rieux-Laucat, David Boutboul, Sylvain Latour
Journal: Journal of Allergy and Clinical Immunology (2024)

Immune dysregulation often presents as autoimmunity, inflammation, and/or lymphoproliferation. Several germline genetic defects have been associated with immune dysregulation; they include heterozygous gain-of-function (GOF) mutations in IKZF1, an essential transcription factor for hematopoiesis containing zinc finger domains (ZFs). However, in a large percentage of patients, the genetic origin of their immunedysregulation remains undetermined.
Novel molecular subtypes of intracranial germ cell tumors expand therapeutic opportunities
Authors: Bo Li, Shuang Zhao, Shouwei Li, Chunde Li, Wei Liu, Lin Li, Bowen Cui, Xing Liu, Huiyuan Chen, Jing Zhang, Yin Ren, Fei Liu, Ming Yang, Tao Jiang, Yu Liu, Xiaoguang Qiu
Journal: Neuro-Oncology (2024)

Abstract Background Intracranial germ cell tumors (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumors (NGGCTs). Previous studies have found that somatic mutations involving the mitogen-activated protein kinase/mTOR signaling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking. Methods We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing. Results We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: Immune-hot, MYC/E2F, and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signaling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumors showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs. Conclusions Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.
Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling
Authors: Zhengnan Cai, Wan Li, Sonja Hager, Jayne Louise Wilson, Leila Afjehi-Sadat, Elke H. Heiss, Thomas Weichhart, Petra Heffeter, Wolfram Weckwerth
Journal: Cellular and Molecular Immunology (2024)

Phosphoglycerate dehydrogenase (PHGDH) has emerged as a crucial factor in macromolecule synthesis, neutralizing oxidative stress, and regulating methylation reactions in cancer cells, lymphocytes, and endothelial cells. However, the role of PHGDH in tumor-associated macrophages (TAMs) is poorly understood. Here, we found that the T helper 2 (Th2) cytokine interleukin-4 and tumor-conditioned media upregulate the expression of PHGDH in macrophages and promote immunosuppressive M2 macrophage activation and proliferation. Loss of PHGDH disrupts cellular metabolism and mitochondrial respiration, which are essential for immunosuppressive macrophages. Mechanistically, PHGDH-mediated serine biosynthesis promotes α-ketoglutarate production, which activates mTORC1 signaling and contributes to the maintenance of an M2-like macrophage phenotype in the tumor microenvironment. Genetic ablation of PHGDH in macrophages from tumor-bearing mice results in attenuated tumor growth, reduced TAM infiltration, a phenotypic shift of M2-like TAMs toward an M1-like phenotype, downregulated PD-L1 expression and enhanced antitumor T-cell immunity. Our study provides a strong basis for further exploration of PHGDH as a potential target to counteract TAM-mediated immunosuppression and hinder tumor progression.
Population-level incidence of human papillomavirus–positive oropharyngeal, cervical, and anal cancers, by smoking status
Authors: Sameer V Gopalani, Mona Saraiya, Bin Huang, Thomas C Tucker, Jacqueline M Mix, Anil K Chaturvedi
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract We estimated the population-level incidence of human papillomavirus (HPV)–positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention’s Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer were among individuals who ever smoked. The population-level incidence rate was higher among individuals who ever smoked than among those who never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence rate ratio = 2.6), cervical (13.7 vs 6.8; adjusted incidence rate ratio = 2.0), and anal (3.9 vs 1.6; adjusted incidence rate ratio = 2.5) cancers. These findings indicate that smoking is associated with increased risk of HPV-positive oropharyngeal, cervical, and anal cancers, and the population-level burden of these cancers is higher among individuals who ever smoked.
Unveiling cutaneous adverse events and prognosis in immunotherapy for melanoma and squamous cell carcinoma
Authors: Simone Ribero, Pietro Quaglino, Gabriele Roccuzzo
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof Unveiling cutaneous adverse events and prognosis in immunotherapy for melanoma and squamous cell carcinoma Get access Simone Ribero, Simone Ribero Conceptualization Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy Correspondence: Simone Ribero. Email: simone.ribero@unito.it Search for other works by this author on: Oxford Academic Google Scholar Pietro Quaglino, Pietro Quaglino Conceptualization Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy Search for other works by this author on: Oxford Academic Google Scholar Gabriele Roccuzzo Gabriele Roccuzzo Conceptualization Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy https://orcid.org/0000-0001-7126-5506 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae092, https://doi.org/10.1093/bjd/ljae092 Published: 29 February 2024 Article history Received: 24 February 2024 Accepted: 26 February 2024 Published: 29 February 2024 Corrected and typeset: 18 March 2024
Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective
Authors: Ravi Ramessur, Nick Dand, Sinéad M Langan, Jake Saklatvala, Marie-Christine Fritzsche, Suzi Holland, Bernd W M Arents, Helen McAteer, Andrew Proctor, David McMahon, Michelle Greenwood, Alena M Buyx, Tamara Messer, Nina Weiler, Alexandra Hicks, Peter Hecht, Stephan Weidinger, Matladi N Ndlovu, Dai Chengliang, Matthias Hübenthal, Alexander Egeberg, Lavinia Paternoster, Lone Skov, Elke M G J De Jong, Maritza A Middelkamp-Hup, Satveer K Mahil, Jonathan N Barker, Carsten Flohr, Sara J Brown, Catherine H Smith
Journal: British Journal of Dermatology (2024)

Abstract More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.
Gender differences in referral trends and clinical characteristics in the evaluation of stable coronary artery disease by myocardial perfusion scintigraphy: a 20-year analysis from a tertiary referral centre
Authors: Suvasini Lakshmanan, Paolo Frumento, Stefano Dalmiani, Assuero Giorgetti, Alessia Gimelli
Journal:  (2024)

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality in women, 1 with reports of sex differences in risk profile and symptoms at presentation, that may impact 2 provider assessments, referrals and management.Despite targeted efforts on women's 3 cardiovascular (CV) health in last several significant gender based differences persist
Fitness Effects of Phenotypic Mutations at Proteome-Scale Reveal Optimality of Translation Machinery
Authors: Cedric Landerer, Jonas Poehls, Agnes Toth-Petroczy
Journal: Molecular Biology and Evolution (2024)

Abstract Errors in protein translation can lead to non-genetic, phenotypic mutations, including amino acid misincorporations. While phenotypic mutations can increase protein diversity, the systematic characterization of their proteome-wide frequencies and their evolutionary impact has been lacking. Here, we developed a mechanistic model of translation errors to investigate how selection acts on protein populations produced by amino acid misincorporations. We fitted the model to empirical observations of misincorporations obtained from over a hundred mass spectrometry datasets of E. coli and S. cerevisiae. We found that on average 20% to 23% of proteins synthesized in the cell are expected to harbor at least one amino acid misincorporation, and that deleterious misincorporations are less likely to occur. Combining misincorporation probabilities and the estimated fitness effects of amino acid substitutions in a population genetics framework, we found 74% of mistranslation events in E. coli and 94% in S. cerevisiae to be neutral. We further show that the set of available synonymous tRNAs is subject to evolutionary pressure, as the presence of missing tRNAs would increase codon–anticodon cross-reactivity and misincorporation error rates. Overall, we find that the translation machinery is likely optimal in E. coli and S. cerevisiae and that both local solutions at the level of codons and a global solution such as the tRNA pool can mitigate the impact of translation errors. We provide a framework to study the evolutionary impact of codon-specific translation errors and a method for their proteome-wide detection across organisms and conditions.