tbuckley/cabot-search huggingface dataset:
Cancer screening with multicancer detection tests: A translational science review
Authors: Wendy S. Rubinstein, Christos Patriotis, Anthony Dickherber, Paul K. J. Han, Hormuzd A. Katki, Elyse LeeVan, Paul F. Pinsky, Philip C. Prorok, Amanda L. Skarlupka, Sarah M. Temkin, Philip E. Castle, Lori M. Minasian
Journal: CA A Cancer Journal for Clinicians (2024)

Abstract Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard‐of‐care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow‐up for patients with a positive test.
Digital twins for health: a scoping review
Authors: Evangelia Katsoulakis, Qi Wang, Huanmei Wu, Leili Shahriyari, Richard Fletcher, Jinwei Liu, Luke Achenie, Hongfang Liu, Pamela Jackson, Ying Xiao, Tanveer Syeda-Mahmood, Richard Tuli, Jun Deng
Journal: npj Digital Medicine (2024)

Abstract The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the industry, government, and military, DT4H is still in its early stages. This paper presents an overview of the current applications of DTs in healthcare, examines consortium research centers and their limitations, and surveys the current landscape of emerging research and development opportunities in healthcare. We envision the emergence of a collaborative global effort among stakeholders to enhance healthcare and improve the quality of life for millions of individuals worldwide through pioneering research and development in the realm of DT technology.
Cholecystectomy following EUS-guided gallbladder drainage in patients with acute cholecystitis at high surgical risk: friend or foe?
Authors: Alberto Larghi, Roy L J van Wanrooij, Michiel Bronswijk, Giuseppe Vanella, Rastislav Kunda, Manuel Pérez-Miranda, Jeanin E Van-Hooft, Marc A Barthet, Paolo Giorgio Arcidiacono, Schalk Willem Van der Merwe
Journal: Gut (2024)
An oral carbon monoxide–releasing molecule protects against acute hyperhemolysis in sickle cell disease
Authors: Kim Anh Nguyen, Alessandro Matte, Roberta Foresti, Enrica Federti, Laurent Kiger, Cécile Lefebvre, Hakim Hocini, Yanis Pelinski, Hiroaki Kitagishi, Laura Bencheikh, France Pirenne, Lucia de Franceschi, Roberto Motterlini, Pablo Bartolucci
Journal: Blood (2024)
Genomic imbalances analysis provides new insight into prognostic factors in adult and pediatric T-ALL
Authors: Estelle Balducci, Mathieu Simonin, Nicolas Duployez, Thomas Steimlé, Marie-Emilie Dourthe, Patrick Villarese, Stéphane Ducassou, Isabelle Arnoux, Jean-Michel Cayuela, Marie Balsat, Lucien Courtois, Guillaume P. Andrieu, Aurore Touzart, Françoise Huguet, Arnaud Petit, Norbert Ifrah, Herve Dombret, André Baruchel, Elizabeth A. Macintyre, Claude Preudhomme, Nicolas Boissel, Vahid Asnafi
Journal: Blood (2024)
Efficacy of far infrared functional glasses in the treatment of meibomian gland dysfunction‐related dry eye
Authors: Lei Tian, Yihan Guo, Silu Wang, Zhongying Li, Ningli Wang, Ying Jie
Journal: MedComm (2024)

Abstract Meibomian gland dysfunction (MGD)‐related dry eye disease (DED) is a significant subtype of DED. In this research, we investigate the effectiveness of far infrared (FIR) functional glasses in the treatment of MGD‐related DED. According to the TFO DEWS II diagnostic criteria, 61 eyes with MGD‐related DED were included. All participants wore functional FIR glasses throughout the day for a period of 4 weeks and were followed up three times during the treatment. All subjects were followed up thoroughly in accordance with the DED clinical examination procedure. Ultimately, the treatment's impact was assessed. We found the Visual Analogue Scale and Ocular Surface Disease Index scores after FIR treatment were significantly lower than the baseline values ( p &lt; 0.05). Compared with the baseline, fluorescein tear breakup time and corneal fluorescein staining score after FIR treatment were significantly improved ( p &lt; 0.05). The eyelid margin signs, meibum quality, and meibomian gland expressibility after the 4‐week treatment were significantly better than those at baseline ( p &lt; 0.05). We can see that wearing the FIR functional glasses significantly relieves the symptoms and signs of patients. We believe FIR therapy could be considered as a new method of MGD‐related DED.
Dickkopf‐1 drives perineural invasion via PI3K–AKT signaling pathway in head and neck squamous cancer
Authors: Jingyi Wang, Qianying Li, Faya Liang, Xin Du, Pan Song, Taowei Wu, Renhui Chen, Xiaorong Lin, Qinglian Liu, Hai Hu, Ping Han, Xiaoming Huang
Journal: MedComm (2024)

Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf-1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1-overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K–AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1-overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease-free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K–AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.
Abstract 4413: Identifying genome-wide histone profiles in patient derived models of AML for predictive biomarker development
Authors: Alysha Simmons, Eva Oswald, Georg Kuales, Michael Keogh, Vishnu U. Kumary, Eva Brill, Martis W. Cowles, Bryan Venters, Julia B. Schueler
Journal: Cancer Research (2024)

Abstract Acute myeloid leukemia (AML) is a complex disease with highly individualized treatment plans for patients. Mostly these are based on genetic and phenotypic markers of the disease, but the patient’s overall condition is playing a significant role as well. To develop innovative drugs for a broad patient cohort, it is essential to understand the biological implications of these differences and to model them preclinically. In this study, we are assessing the utility of EpiCypher’s CUT&amp;Tag-FFPE platform to characterize the epigenome of AML PDX samples. CUT&amp;Tag-FFPE is an epigenome profiling assay that is compatible with Formalin-Fixed Paraffin-Embedded (FFPE) samples, enabling robust genome-wide profiling of histone modifications from limited clinical samples. We derived PDX model LEXFAM 2799 (NPM1 wt; FLT3 wt, t(8;21)) and LEXFAM 2966 (NPM1 mut; FLT3 wt) from treatment naïve patients and established in immunocompromised NSG mice. LEXFAM 2799 is a fast-growing model with passaging times of 33 days, whereas LEXFAM 2966 displays a passaging time of 140 days. We next treated with Standard of Care (SoC) agents Decitabine, Cytarabine and all-trans-retinoic acid (ATRA): LEXF 2966 was highly sensitive towards Decitabine leading to complete remission. Cytarabine induced a partial remission and ATRA had only minor effect on tumor growth. In contrast LEXFAM 2799 was resistant towards treatment with ATRA and showed only partial remission under treatment with Cytarabine or Decitabine. Using the CUT&amp;Tag-FFPE platform we are analyzing FFPE slides from the above mentioned two AML PDX models to investigate differences in the genome-wide histone profile that relate to the different growth behavior as well as sensitivity towards SoC treatment. The goal of these studies is to identify tumor model specific profiles that correlated specifically with the sensitivity towards the hypomethylating agent Decitabine. In addition, we plan to analyze additional untreated as well as treated AML PD models to validate the identified signatures confirming them as predictive biomarkers for sensitivity towards current standard of care and prospectively as well innovative compounds. Citation Format: Alysha Simmons, Eva Oswald, Georg Kuales, Michael Keogh, Vishnu U. Kumary, Eva Brill, Martis W. Cowles, Bryan Venters, Julia B. Schueler. Identifying genome-wide histone profiles in patient derived models of AML for predictive biomarker development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4413.
Abstract 320: Development and automation of a streamlined targeted enrichment method for cancer mutation detection
Authors: Zhong Wu, Michelle Baird, Cornelia Mechlen, Peter Hahn, Jonathan M. Shaffer
Journal: Cancer Research (2024)

Abstract Next Generation Sequencing (NGS) of DNA is a powerful tool for the detection of genetic variations, including single nucleotide polymorphisms, copy number variation, and small insertions/deletions. Target enrichment technologies enhance DNA sequencing by enabling users to analyze specific regions of interest only, which helps to effectively increase sequencing depth and sample throughput while minimizing cost. However, many targeted DNA library construction workflows are not optimal for routine genetic testing needs due to inconsistent, lengthy workflow. This poses significant challenge to application like cancer mutation profiling that requires detection sensitivity down to 1% or below due to heterogeneous nature of tumor tissue. In addition, high throughput testing with minimal hands on time is desirable with the rapid advance of precision medicine. Magnetic bead separations are commonly used between the individual reactions of targeted DNA library preparation workflows for cleanup and size selection. These bead clean up reactions are not only labor-intensive and tedious procedures but can also greatly contribute to sample-to sample variation especially when employing automated library preparation procedures. With the sophisticated QIAseq Targeted DNA Pro, we developed a novel streamlined targeted DNA workflow that greatly reduces handling variation by replacing the majority of bead clean up steps with enzymatic reactions, which now can be finished in as little as six hours. In combination with the newly developed QIAseq Normalizer kit, the protocol has been successfully implemented on the Hamilton NGS Star liquid handling platform resulting in up to 96 highly uniform, complex and ready-to-sequence libraries that can be effortless generated in one run. This complete automated solution saves researcher up to four hours of hands-on time. When using commercial reference samples, cancer mutations down to 1% were consistently detected with this automated workflow. The presented data demonstrate that this integrated and streamlined workflow does not only provide an automation friendly workflow but also allows to reliably identify low frequent cancer mutations. The applications presented here are for research use only. Not for use in diagnostic procedures. Citation Format: Zhong Wu, Michelle Baird, Cornelia Mechlen, Peter Hahn, Jonathan M. Shaffer. Development and automation of a streamlined targeted enrichment method for cancer mutation detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 320.
Abstract 5217: Genome instability in renal tumors
Authors: Hanbyul Cho, Ginny X. Li, Rahul Mannan, Noshad Hosseini, Yi Hsiao, Yuping Zhang, Aniket Dagar, Chandan Kumar-Sinha, Marcin P. Cieslik, Saravana M. Dhanasekaran, Alexey I. Nesvizhskii, Arul M. Chinnaiyan, Clinical Proteomic Tumor Analysis Consortium
Journal: Cancer Research (2024)

Abstract Genome instability (GI), a recognized cancer hallmark, encompasses CNV burden, tumor mutational burden (TMB), and microsatellite instability and is variably associated with several clinical/prognostic features in solid tumors. GI and intratumor mutational heterogeneity in clear cell renal cell carcinoma (ccRCC) were associated with poor prognosis in a large multi-site sequencing study. As 10-15% of renal tumors exhibit copy number burden associated GI, the development of proteogenomic biomarkers to identify this subset of tumors will be of high clinical value. In our in-depth analysis of CPTAC renal cancer cohorts namely, ccRCC discovery and rare RCC, we first estimated absolute copy number using CNVEX TPO analysis pipeline. Copy number burden-based genome instability was estimated by calculating whole genome instability index (wGII) from DNA sequencing data, in addition to the estimation of genome ploidy and purity of the tumors. Genome instability was associated with survival outcomes in both ccRCC and rare RCC (Ref. 1 and 2). Differential proteogenomic analysis identified IGF2BP3, IGF2BP1, PYCR1 RNA and protein, to be upregulated among high wGII tumors. High wGII tumors showed upregulation of cell proliferation and other cell cycle/proliferation concepts in gene set enrichment analysis. Interestingly, transcriptional module analysis revealed transcription factors and target genes specifically upregulated in GI cases and this pattern showed certain degree of overlap to 9p loss ccRCC tumors (another molecular ccRCC subset that is also associated with poor prognosis). Differential expression analysis also identified, kinases, phosphosites and co-regulated kinase-substrates that are dysregulated in genome instable renal tumors. IGF2BP3 immunohistochemistry staining showed specific overexpression in high wGII tumors and the high positivity was observed exclusivity in the tumor cells. Prognostic biomarkers IGF2BP3, IGF2BP1, PYCR1, and UCHL1 show great promise to be developed as clinical prognostic assays and warrants additional characterization. Citation Format: Hanbyul Cho, Ginny X. Li, Rahul Mannan, Noshad Hosseini, Yi Hsiao, Yuping Zhang, Aniket Dagar, Chandan Kumar-Sinha, Marcin P. Cieslik, Saravana M. Dhanasekaran, Alexey I. Nesvizhskii, Arul M. Chinnaiyan, Clinical Proteomic Tumor Analysis Consortium. Genome instability in renal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5217.
Abstract 7399: Development of a reproducible AI-based spatial biomarker of the tumor immune infiltrate on H&amp;E slides
Authors: Valentina Di Proietto, Jean El-Khoury, Benjamin Adjadj, Lucie Gillet, Ulysse Marteau, Kathryn Schutte, Katharina Von Loga
Journal: Cancer Research (2024)

Abstract Background: The immune infiltrate in the tumor microenvironment (TME) has been shown to be associated with prognosis in several studies. However, a comprehensive assessment of the TME composition is not performed in routine practice due to the lack of standardized methods and tools for quantification. The aim of our study is to develop a reproducible, artificial intelligence (AI)-based, spatial biomarker of the tumor related immune response to predict patients outcome on routine Hematoxylin &amp; Eosin (H&amp;E) slides. To the best of our knowledge, this is the first study that implements a robust H&amp;E pipeline to assess, across multiple cohorts, the prognostic power and the added-value of a spatial marker in comparison to non-spatial measures such as the overall lymphocytes density on the slide. Methods: We trained AI models on both publicly available (NuCLS and Lizard) and proprietary datasets to automatically detect cells and tissue types on H&amp;E stained Whole Slide Images of cancers from different origins. We used these models on TCGA COAD and TCGA BRCA and computed spatial measures related to the lymphocyte densities in the tumor core versus the invasive margin as well as the immune infiltration in the tumor stroma (in between tumor islets) versus in the tumor islets themselves. Univariate and multivariate survival analysis is performed through repeated cross-validation. A log-rank test on the stratified groups is performed for each evaluated marker, using the median value as cutoff. Preliminary results on TCGA-COAD and TCGA-BRCA show that spatial markers of the tumor-related immune response are individually associated with overall survival, reinforcing findings from prior studies emphasizing the importance of the spatial relationship between tumor and immune cells. Multivariate analysis with both linear and non-linear models is currently ongoing across selected cohorts. Citation Format: Valentina Di Proietto, Jean El-Khoury, Benjamin Adjadj, Lucie Gillet, Ulysse Marteau, Kathryn Schutte, Katharina Von Loga. Development of a reproducible AI-based spatial biomarker of the tumor immune infiltrate on H&amp;E slides [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7399.
Abstract 7075: Global epitranscriptomic and transcriptomic footprint revealed upregulation of methylated single minded 2-small variant (meSIM2-SV) in colorectal cancer (CRC) by NTMT1(METTL11A) via m6A-YTHDF1-dependent manner
Authors: Sudhir Kumar Rai, Ting Gong, Zitong Gao, Yujia Qin, Matthew Huo, Ken Nakastu, Hua Yang, Yuanyuan Fu, Lang Wu, Mayumi Jijiwa, Masaki Nasu, Shaoqiu Chen, Gang Huang, Peiwen Fei, Youping Deng
Journal: Cancer Research (2024)

Abstract Establishing global footprint of altered m6A mRNA is a unique method to identify the new prognostics biomarkers. Altered N6-methyladenosine(m6A) RNA methylation regulates cancer progression with uncharacterized mechanism. Here, we present novel link between m6A modification on 5’-UTR SIM2-SV contribution in colorectal cancer progression. MeRIP and RNA-seq data from 68 fresh frozen CRC samples revealed 13,843 altered m6A methylated peaks and found highest in chromosomes 1, 2, and 3. Analysis uncovered 119 overlapping genes and clusters into 32 up-regulated genes with 56 up-hyper peaks, 8 up-regulated genes with 9 up-hypo peaks, 12 down-regulated genes with 14 down-hyper peaks, and 28 down-regulated genes with 40 down-hypo peaks. A significant increase in the SIM2 m6A and RNA level led us to perform correlation analysis between the SIM2SV and m6A RNA regulators. SIM2SV was significantly correlated with YTHDF1 m6A-readers and m6A-NTMT1 writer, suggesting important roles of SIM2SV in CRC oncogenicity. m6A-sequencing identified m6A enrichment in 5’-UTR of SIM2SV gene which further verified. siNTMT1 and siYTHDF1 manipulation in HCT116 and RKO cell lines verified a decrease in SIM2SV gene/protein expression, and m6A level. Knockdown effects also showed decrease in cell proliferation, clonogenicity and induced cell cycle arrest in the G2/M phase for NTMT1 and YTHDF1 versus SIM2 Knockdown showed cell cycle arrest in S/G2 phase. Our investigation revealed the role of new writer NTMT1 for methylated SIM2SV gene expression in colorectal cancer proliferation via m6A-YTHDF1(as “decoder”) dependent manner. Further investigation on m6A modification specifically on SIM2 mRNA revealed the essential roles of its writer NTMT1 and its reader YTHDF1 in CRC development, evidently supporting the importance of the unique landscape of m6A epigenetic modification in colorectal neoplasm, which not only advance our understanding of CRC pathobiology but also provides a new set of molecular targets for building up effective tools to fight CRC. Citation Format: Sudhir Kumar Rai, Ting Gong, Zitong Gao, Yujia Qin, Matthew Huo, Ken Nakastu, Hua Yang, Yuanyuan Fu, Lang Wu, Mayumi Jijiwa, Masaki Nasu, Shaoqiu Chen, Gang Huang, Peiwen Fei, Youping Deng. Global epitranscriptomic and transcriptomic footprint revealed upregulation of methylated single minded 2-small variant (meSIM2-SV) in colorectal cancer (CRC) by NTMT1(METTL11A) via m6A-YTHDF1-dependent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7075.