Automated analysis of lymphocytic infiltration, tumor budding, and their spatial relationship improves prognostic accuracy in colorectal cancer

Funding: Medical Research Scotland, and Indica Labs, Inc. provided in-kind resource.Both immune profiling and tumor budding significantly correlate with colorectal cancer (CRC) patient outcome, but are traditionally reported independently. This study evaluated the association and interaction between lymphocytic infiltration and tumor budding, coregistered on a single slide, in order to determine a more precise prognostic algorithm for patients with stage II CRC. Multiplexed immunofluorescence and automated image analysis were used for the quantification of CD3+CD8+ T cells, and tumor buds (TBs), across whole slide images of three independent cohorts (training cohort: n = 114, validation cohort 1: n = 56, validation cohort 2: n = 62). Machine learning algorithms were used for feature selection and prognostic risk model development. High numbers of TBs (HR = 5.899, 95% CI, 1.875 - 18.55), low CD3+ 11 T cell density (HR = 9.964, 95% CI 3.156 - 31.46), and low mean number of CD3+CD8+ T cells within 50 μm of TBs (HR = 8.907, 95% CI 2.834 - 28.0) were associated with reduced disease-specific survival. A prognostic signature, derived from integrating TBs, lymphocyte infiltration, and their spatial relationship, reported a more significant cohort stratification (HR = 18.75, 95% CI 6.46–54.43), than TBs, Immunoscore, or pT stage. This was confirmed in two independent validation cohorts (HR = 12.27, 95% CI 3.524–42.73, HR = 15.61, 95% CI 4.692-51.91). The investigation of the spatial relationship between lymphocytes and TBs within the tumor microenvironment improves accuracy of prognosis of patients with stage II CRC through an automated image analysis and machine learning workflow.PostprintPeer reviewe

Compilation of algorithm-specific graph states for quantum circuits

We present a quantum circuit compiler that prepares an algorithm-specific graph state from quantum circuits described in high level languages, such as Cirq and Q#. The computation can then be implemented using a series of non-Pauli measurements on this graph state. By compiling the graph state directly instead of starting with a standard lattice cluster state and preparing it over the course of the computation, we are able to better understand the resource costs involved and eliminate wasteful Pauli measurements on the actual quantum device. Access to this algorithm-specific graph state also allows for optimisation over locally equivalent graph states to implement the same quantum circuit. The compiler presented here finds ready application in measurement based quantum computing, NISQ devices and logical level compilation for fault tolereant implementations

High-complexity extracellular barcoding using a viral hemagglutinin

While single-cell sequencing technologies have revealed tissue heterogeneity, resolving mixed cellular libraries into cellular clones is essential for many pooled screens and clonal lineage tracing. Fluorescent proteins are limited in number, while DNA barcodes can only be read after cell lysis. To overcome these limitations, we used influenza virus hemagglutinins to engineer a genetically encoded cell-surface protein barcoding system. Using antibodies paired to hemagglutinins carrying combinations of escape mutations, we developed an exponential protein barcoding system which can label 128 clones using seven antibodies. This study provides a proof of principle for a strategy to create protein-level cell barcodes that can be used in vivo in mice to track clonal populations

Assessment of immunological features in muscle-invasive bladder cancer prognosis using ensemble learning

Funding: This research received financial support from Definiens GmbH and the Industrial Centre for AI Research in digital Diagnostics (iCAIRD) which is funded by Innovate UK on behalf of UK Research and Innovation (UKRI) [project number: 104690].The clinical staging and prognosis of muscle-invasive bladder cancer (MIBC) routinely includes the assessment of patient tissue samples by a pathologist. Recent studies corroborate the importance of image analysis in identifying and quantifying immunological markers from tissue samples that can provide further insight into patient prognosis. In this paper, we apply multiplex immunofluorescence to MIBC tissue sections to capture whole-slide images and quantify potential prognostic markers related to lymphocytes, macrophages, tumour buds, and PD-L1. We propose a machine-learning-based approach for the prediction of 5 year prognosis with different combinations of image, clinical, and spatial features. An ensemble model comprising several functionally different models successfully stratifies MIBC patients into two risk groups with high statistical significance (p value < 1×10−5). Critical to improving MIBC survival rates, our method correctly classifies 71.4% of the patients who succumb to MIBC, which is significantly more than the 28.6% of the current clinical gold standard, the TNM staging system.Publisher PDFPeer reviewe

Reception of the Herzog Stjepan Vukcic Kosaca in Herzegovina in the Second Half of the 20th Century

U radu se nastoji prikazati recepcija hercega Stjepana Vukčića Kosače u Hercegovini u drugoj polovici 20. stoljeća s posebnim naglaskom na razdoblje u kojemu je Bosna i Hercegovina bila jedna od republika bivše Jugoslavije. S obzirom na činjenicu da bi se barem početno znanje o hercegu Stjepanu trebalo steći tijekom osnovnoga i srednjoškolskoga obrazovanja, najprije je dat osvrt na nastavne planove i programe u kojima su, između ostaloga, naznačeni ciljevi (zadatci) nastave povijesti, a zatim se analiziraju tekstovi u udžbenicima povijesti koji su bili u uporabi u bh. školama (osnovnim i gimnazijama), u kojima se u određenim nastavnim jedinicama obrađuje djelovanje hercega Stjepana. Sudeći prema nastavnim planovima i programima, kao i sadržaju udžbenika iz druge polovice 20. stoljeća (barem nama dostupnima), mladež u Hercegovini u razmatranom razdoblju nije mogla mnogo saznati i naučiti o ovoj povijesnoj osobi, s čijom je titulom povezano ime prostora u kojemu žive. Na kraju istražuje se hercegova prisutnost u nazivima ulica, trgova i institucija u hercegovačkim gradovima i općinama. Istraživanje pokazuje da je tek u novije vrijeme evidentan interes nekih pojedinaca i institucija koje žele ovoj povijesnoj osobi dati značenje koje joj pripada. Naime, sve ulice u Hercegovini koje nose njegovo ime, kao i jedna institucija, imenovane su nakon 1990. godine.With the aim of presenting the reception of the Herzog Stjepan Vukcic Kosaca in Hercegovina in the second half of the 20th century, the paper analyzes the contents of history textbooks that write about the life and work of the Herzog Stjepan and his presence in the names of streets, squares and institutions in Herzegovinian towns and municipalities. Considering the second half of the 20th century, most attention is paid to the period in which Bosnia and Herzegovina was one of the republics of the former Yugoslavia. To illustrate the contents from medieval history, or the ones related to Stjepan, most important are school curricula, in which, apart from the teaching units and lessons, the teaching of history was particularly indicative, when during this period the constant task was "spreading fraternity and unity" or "developing patriotic awareness among students", the emphasis being on teaching history of the "newer period". Judging by the curricula and the content of textbooks from the second half of the 20th century (at least those available to us), the youth of Herzegovina in the mentioned period could not learn much about this historical person whose name is associated with the name of the area in which they live. Namely, by looking at the texts of the textbooks up to the 90s, it is evident that the texts in the textbooks differ, both in scope and emphasis on certain facts. What all the authors mention is taking of the \u27Herzog\u27 title in 1448 and the fall of Herzegovina under the Ottoman rule, whereas all the other facts about the Herzog Stjepan vary from one text to another. As there were no official textbooks in the region of Herzegovina in the 90s of the 20th century, the paper, as an example, presents the texts only from two textbooks (one for elementary school and the other for grammar school) used in some schools in Herzegovina which worked according to the Croatian curriculum, where we can find hardly any information about the Herzog Stjepan. Finally, the results of the research of the Herzog\u27s presence in the names of streets, squares and institutions of the Herzegovinian cities and municipalities show that the interest of some individuals and institutions, who want to give this historical person the significance he deserves, has only recently become evident. Namely, all the streets in Herzegovina named after the Herzog, as well as one institution, got this name after 1990

Spatial immune profiling of the colorectal tumor microenvironment predicts good outcome in stage II patients

This study was funded by Medical Research Scotland and Indica Labs, Inc., who also provided in-kind resource.Cellular subpopulations within the colorectal tumor microenvironment (TME) include CD3+ and CD8+ lymphocytes, CD68+ and CD163+ macrophages, and tumor buds (TBs), all of which have known prognostic significance in stage II colorectal cancer. However, the prognostic relevance of their spatial interactions remains unknown. Here, by applying automated image analysis and machine learning approaches, we evaluate the prognostic significance of these cellular subpopulations and their spatial interactions. Resultant data, from a training cohort retrospectively collated from Edinburgh, UK hospitals (n = 113), were used to create a combinatorial prognostic model, which identified a subpopulation of patients who exhibit 100% survival over a 5-year follow-up period. The combinatorial model integrated lymphocytic infiltration, the number of lymphocytes within 50-μm proximity to TBs, and the CD68+/CD163+ macrophage ratio. This finding was confirmed on an independent validation cohort, which included patients treated in Japan and Scotland (n = 117). This work shows that by analyzing multiple cellular subpopulations from the complex TME, it is possible to identify patients for whom surgical resection alone may be curative.Publisher PDFPeer reviewe

Automated tumour budding quantification by machine learning augments TNM staging in muscle-invasive bladder cancer prognosis

Tumour budding has been described as an independent prognostic feature in several tumour types. We report for the first time the relationship between tumour budding and survival evaluated in patients with muscle invasive bladder cancer. A machine learning-based methodology was applied to accurately quantify tumour buds across immunofluorescence labelled whole slide images from 100 muscle invasive bladder cancer patients. Furthermore, tumour budding was found to be correlated to TNM (p = 0.00089) and pT (p = 0.0078) staging. A novel classification and regression tree model was constructed to stratify all stage II, III, and IV patients into three new staging criteria based on disease specific survival. For the stratification of non-metastatic patients into high or low risk of disease specific death, our decision tree model reported that tumour budding was the most significant feature (HR = 2.59, p = 0.0091), and no clinical feature was utilised to categorise these patients. Our findings demonstrate that tumour budding, quantified using automated image analysis provides prognostic value for muscle invasive bladder cancer patients and a better model fit than TNM staging.Publisher PDFPeer reviewe

DECISIVE Test Methods Handbook: Test Methods for Evaluating sUAS in Subterranean and Constrained Indoor Environments, Version 1.1

This handbook outlines all test methods developed under the Development and Execution of Comprehensive and Integrated Subterranean Intelligent Vehicle Evaluations (DECISIVE) project by the University of Massachusetts Lowell for evaluating small unmanned aerial systems (sUAS) performance in subterranean and constrained indoor environments, spanning communications, field readiness, interface, obstacle avoidance, navigation, mapping, autonomy, trust, and situation awareness. For sUAS deployment in subterranean and constrained indoor environments, this puts forth two assumptions about applicable sUAS to be evaluated using these test methods: (1) able to operate without access to GPS signal, and (2) width from prop top to prop tip does not exceed 91 cm (36 in) wide (i.e., can physically fit through a typical doorway, although successful navigation through is not guaranteed). All test methods are specified using a common format: Purpose, Summary of Test Method, Apparatus and Artifacts, Equipment, Metrics, Procedure, and Example Data. All test methods are designed to be run in real-world environments (e.g., MOUT sites) or using fabricated apparatuses (e.g., test bays built from wood, or contained inside of one or more shipping containers).Comment: Approved for public release: PAO #PR2022_4705

DECISIVE Benchmarking Data Report: sUAS Performance Results from Phase I

This report reviews all results derived from performance benchmarking conducted during Phase I of the Development and Execution of Comprehensive and Integrated Subterranean Intelligent Vehicle Evaluations (DECISIVE) project by the University of Massachusetts Lowell, using the test methods specified in the DECISIVE Test Methods Handbook v1.1 for evaluating small unmanned aerial systems (sUAS) performance in subterranean and constrained indoor environments, spanning communications, field readiness, interface, obstacle avoidance, navigation, mapping, autonomy, trust, and situation awareness. Using those 20 test methods, over 230 tests were conducted across 8 sUAS platforms: Cleo Robotics Dronut X1P (P = prototype), FLIR Black Hornet PRS, Flyability Elios 2 GOV, Lumenier Nighthawk V3, Parrot ANAFI USA GOV, Skydio X2D, Teal Golden Eagle, and Vantage Robotics Vesper. Best in class criteria is specified for each applicable test method and the sUAS that match this criteria are named for each test method, including a high-level executive summary of their performance.Comment: Approved for public release: PAO #PR2023_74172; arXiv admin note: substantial text overlap with arXiv:2211.0180