Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach ...to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance.
We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predicting individual responses to immunotherapies. ELISE employed iterative univariable logistic regression to select genetic features of patients, using Monte Carlo Tree Search (MCTS) to tune hyperparameters. In each trial, ELISE selected multiple models for integration based on add or concatenate stacking strategies, including deep neural network, automatic feature interaction learning via self-attentive neural networks, deep factorization machine, compressed interaction network, and linear neural network, then adopted the best trial to generate a final approach. SHapley Additive exPlanations (SHAP) algorithm was applied to interpret ELISE, which was then validated in an independent test set.
Regarding prediction of responses to atezolizumab within esophageal adenocarcinoma (EAC) patients, ELISE demonstrated a superior accuracy (Area Under Curve AUC = 100.00%). AC005786.3 (Mean |SHAP value| = 0.0097) was distinguished as the most valuable contributor to ELISE output, followed by SNORD3D (0.0092), RN7SKP72 (0.0081), EREG (0.0069), IGHV4-80 (0.0063), and MIR4526 (0.0063). Mechanistically, immunoglobulin complex, immunoglobulin production, adaptive immune response, antigen binding and others, were downregulated in ELISE-neg EAC subtypes and resulted in unfavorable responses. More encouragingly, ELISE could be extended to accurately estimate the responsiveness of various immunotherapeutic agents against other cancers, including PD1/PD-L1 suppressor against metastatic urothelial cancer (AUC = 88.86%), and MAGE-A3 immunotherapy against metastatic melanoma (AUC = 100.00%).
This study presented deep insights into integrating ensemble deep learning with self-attention as a mechanism for predicting immunotherapy responses to human cancers, highlighting ELISE as a potential tool to generate reliable approaches to individualized treatment.
On the occasion of the 100th anniversary of the death of Elise Hall, a pioneering musician in the history of the saxophone. The saxophone is a globally popular instrument, often closely associated ...with renowned players such as Charlie Parker, John Coltrane, or more recently, Kenny G. Less well known, however, is the historical presence of women saxophonists in the nineteenth century, shortly after the instrument’s invention. Elise Hall (1853–1924), a prominent wealthy socialite in Boston at the turn of the twentieth century, defied social norms by mastering the saxophone, an unconventional instrument for a woman of her time. Despite her career’s profound impact, Elise Hall remains relatively obscure in broader music communities. Her untiring work as an impresario, patron, and performer made a significant mark on the history of the instrument. Yet these contributions have been historically undervalued, largely due to gender bias. This collection of essays, written by mainly women saxophonists/scholars, re-evaluates Elise Hall’s legacy beyond a discrete history, updating the narrative by highlighting the ways in which her identity and the saxophone itself have influenced historical accounts. By analyzing the sociocultural factors surrounding this innovative musician through a contemporary lens, the contributors challenge previously held narratives shaped by patriarchal structures and collectively affirm her place as one of the pioneers in the history of the saxophone. Ebook available in Open Access. This publication is GPRC-labeled (Guaranteed Peer-Reviewed Content).
Contributors: Andrew J. Allen (Georgia College & State University), Kurt Bertels (LUCA School of Arts - KU Leuven), Adrianne Honnold (Lewis University), Sarah McDonie (Indiana University Bloomington), Sarah V. Hetrick (University of Arkansas), Holly J. Hubbs (Ursinus College).
This paper provides a critical analysis of the public goods justification for national defense and empire. Social scientists have made a serious error in taking the public goods approach because they ...have drained economics from the exercise. Liberals who have embraced the Samuelsonian logic as the premise for liberal empire have likewise made a serious error because this approach overemphasizes the goods generated by empire while neglecting the significant bads. Further, in presenting the state as the source of domestic and international order through its military might, liberals have given up the game in terms of offering strong arguments against imperialism and militarism. This contributes to the persistence of the myth that imperialism and militarism are natural outgrowths of liberalism and capitalism. I present five challenges to the widely accepted view of government-provided defense and empire. I then discuss how we can constructively advance liberalism and peace.
Este trabajo se focaliza en el filme Pygmalion (1938) de Anthony Asquith y Leslie Howard, relacionado indirectamente con la Medicina y basado en la obra teatral del escritor irlandés George Bernard ...Shaw inspirada en el Libro X de Las metamorfosis de Ovidio. Empero, no es descartable que, entre otros, Shaw pudo haber sido también influido por el romance histórico entre el médico alemán Friedrich Gustav Jacob Henle y la costurera Elise Egloff, a través de la novela Die Frau Professorin de Berthold Auerbach. Su distinta ubicación en lugar y tiempo, el cambio desde el hecho escultórico original a una desigualdad socio-cultural y la llamativa identidad de nombres entre Elise y Eliza contribuyen a esta probabilidad.
The ITER neutral beam system will be equipped with radio-frequency (RF) negative ion sources, based on the IPP Garching prototype source design. Up to 100 kW at 1 MHz is coupled to the RF driver, out ...of which the plasma expands into the main source chamber. Compared to arc driven sources, RF sources are maintenance free and without evaporation of tungsten. The modularity of the driver concept permits to supply large source volumes. The prototype source (one driver) demonstrated operation in hydrogen and deuterium up to one hour with ITER relevant parameters. The ELISE test facility is operating with a source of half the ITER size (four drivers) in order to validate the modular source concept and to gain early operational experience at ITER relevant dimensions. A large variety of diagnostics allows improving the understanding of the relevant physics and its link to the source performance. Most of the negative ions are produced on a caesiated surface by conversion of hydrogen atoms. Cs conditioning and distribution have been optimized in order to achieve high ion currents which are stable in time. A magnetic filter field is needed to reduce the electron temperature and co-extracted electron current. The influence of different field topologies and strengths on the source performance, plasma and beam properties is being investigated. The results achieved in short pulse operation are close to or even exceed the ITER requirements with respect to the extracted ion currents. However, the extracted negative ion current for long pulse operation (up to 1 h) is limited by the increase of the co-extracted electron current, especially in deuterium operation.
The RF-driven negative ion source testbed ELISE at IPP Garching is being upgraded to allow for long-pulse beam operation, previously limited to 10 s beam pulses every 150 s. The improvements aim to ...extend the beam phase duration up to 1000s in H and 3600 s in D, in the framework of the ion source development for the ITER and DEMO NBI systems. The main upgrades comprise a recently commissioned steady-state HV power supply and a new long-pulse, actively cooled diagnostic calorimeter. The latter is made of copper plates with a total beam power measuring surface of 1.2 m x 1.2 m, placed at about 2.9 m from the ion source extraction grids. With respect to the previous inertially cooled beam dump, the new calorimeter has been designed to withstand a higher power load of up to 1.8 MW (maximum power density of 5 MW/m2) in continuous operation and with a higher spatial resolution (2400 points, spaced 30 mm H x 20 mm V) for 2D profile evaluation of beam power density. The measurement is enabled by small apertures (ø2 mm) in the copper plates that let a fraction of the beam pass through to be collected by thin (0.2 mm) copper “heat flux foils” attached to the back side of the plates. The power density evaluation is performed by mapping the temperature gradient in the heat flux foils with a high-resolution infrared camera, observing the calorimeter from the back side, which is calibrated by thermocouples attached to the copper plates.
Cooling channels embedded in the calorimeter plates are arranged in 8 separate circuits, each equipped with individual water calorimetry measurements for additional beam power evaluation capability.
This paper describes the design, manufacturing and commissioning of the new long pulse calorimeter for ELISE.
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