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This looks More Like that: Enhancing Self-Explaining Models by prototypical relevance propagation: This Looks More Like That

2022, Gautam, Srishti, Höhne, Marina M.-C., Hansen, Stine, Jenssen, Robert, Kampffmeyer, Michael

Current machine learning models have shown high efficiency in solving a wide variety of real-world problems. However, their black box character poses a major challenge for the comprehensibility and traceability of the underlying decision-making strategies. As a remedy, numerous post-hoc and self-explanation methods have been developed to interpret the models’ behavior. Those methods, in addition, enable the identification of artifacts that, inherent in the training data, can be erroneously learned by the model as class-relevant features. In this work, we provide a detailed case study of a representative for the state-of-the-art self-explaining network, ProtoPNet, in the presence of a spectrum of artifacts. Accordingly, we identify the main drawbacks of ProtoPNet, especially its coarse and spatially imprecise explanations. We address these limitations by introducing Prototypical Relevance Propagation (PRP), a novel method for generating more precise model-aware explanations. Furthermore, in order to obtain a clean, artifact-free dataset, we propose to use multi-view clustering strategies for segregating the artifact images using the PRP explanations, thereby suppressing the potential artifact learning in the models.

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Gas plasma–oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis

2022, Miebach, Lea, Freund, Eric, Clemen, Ramona, Kersting, Stephan, Partecke, Lars-Ivo, Bekeschus, Sander

Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma–derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma–oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H2O2 and NO32 in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte–derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma–generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma–oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.

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Reply to Bhowmik et al.: Democratic climate action and studying extreme climate risks are not in tension

2022, Kemp, Luke, Xu, Chi, Depledge, Joanna, Ebi, Kristie L., Gibbins, Goodwin, Kohler, Timothy A., Rockström, Johan, Scheffer, Marten, Schellnhuber, Hans Joachim, Steffen, Will, Lenton, Timothy M.

[no abstract available]

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The Planetary Health Academy—a virtual lecture series for transformative education in Germany

2023, Gepp, Sophie, Jung, Laura, Wabnitz, Katharina, Schneider, Frederick, v Gierke, Friederike, Otto, Hannah, Hartmann, Sylvia, Gemke, Theresa, Schulz, Christian, Gabrysch, Sabine, Fast, Marischa, Schwienhorst-Stich, Eva-Maria

The planetary crises require health professionals to understand the interlinkages between health and environmental changes, and how to reduce ecological harm (ie, ecological footprint) and promote positive change (ie, ecological handprint). However, health professions’ education and training are mostly lacking these aspects. In this Viewpoint, we report findings from the evaluation of the Planetary Health Academy, the first open online lecture series for transformative planetary health education in Germany. In a retrospective online survey, 458 of 3656 Planetary Health Academy participants reported on their emotions towards climate change, attitudes towards health professionals’ responsibilities, self-efficacy, and the contribution of the Planetary Health Academy to their knowledge and actions. Additionally, motivators and barriers to acting were assessed. Our findings provide insights that can inform future efforts for transformative education. Combined with network and movement building, education could act as a social tipping element toward actions to mitigate global environmental changes.

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Reply to Ruhl and Craig: Assessing and governing extreme climate risks needs to be legitimate and democratic

2022, Kemp, Luke, Xu, Chi, Depledge, Joanna, Ebi, Kristie L., Gibbins, Goodwin, Kohler, Timothy A., Rockström, Johan, Scheffer, Marten, Schellnhuber, Hans Joachim, Steffen, Will, Lenton, Timothy M.

[No abstract available]

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Analysis of riboflavin/ultraviolet a corneal cross-linking by molecular spectroscopy

2023, Melcher, Steven, Zimmerer, Cordelia, Galli, Roberta, Golde, Jonas, Herber, Robert, Raiskup, Frederik, Koch, Edmund, Steiner, Gerald

Corneal cross-linking (CXL) with riboflavin and ultraviolet A light is a therapeutic procedure to restore the mechanical stability of corneal tissue. The treatment method is applied to pathological tissue, such as keratoconus and induces the formation of new cross-links. At present, the molecular mechanisms of induced cross-linking are still not known exactly. In this study, we investigated molecular alterations within porcine cornea tissue after treatment with riboflavin and ultraviolet A light by surface enhanced Raman spectroscopy (SERS). For that purpose, after CXL treatment a thin silver layer was vapor-deposited onto cornea flaps. To explore molecular alterations induced by the photochemical process hierarchical cluster analysis (HCA) was used. The detailed analysis of SERS spectra reveals that there is no general change in collagen secondary structure while modifications on amino acid side chains are the most dominant outcome. The formation of secondary and aromatic amine groups as well as methylene and carbonyl groups were observed. Even though successful cross-linking could not be registered in all treated samples, Raman signals of newly formed chemical groups are already present in riboflavin only treated corneas.

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Phylodynamic signatures in the emergence of community-associated MRSA

2022, Steinig, Eike, Aglua, Izzard, Duchene, Sebastian, Meehan, Michael T., Yoannes, Mition, Firth, Cadhla, Jaworski, Jan, Drekore, Jimmy, Urakoko, Bohu, Poka, Harry, Wurr, Clive, Ebos, Eri, Nangen, David, Müller, Elke, Mulvey, Peter, Jackson, Charlene, Blomfeldt, Anita, Aamot, Hege Vangstein, Laman, Moses, Manning, Laurens, Earls, Megan, Coleman, David C., Greenhill, Andrew, Ford, Rebecca, Stegger, Marc, Syed, Muhammad Ali, Jamil, Bushra, Monecke, Stefan, Ehricht, Ralf, Smith, Simon, Pomat, William, Horwood, Paul, Tong, Steven Y. C., McBryde, Emma

Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.

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Reply to Burgess et al: Catastrophic climate risks are neglected, plausible, and safe to study

2022, Kemp, Luke, Xu, Chi, Depledge, Joanna, Ebi, Kristie L., Gibbins, Goodwin, Kohler, Timothy A., Rockström, Johan, Scheffer, Marten, Schellnhuber, Hans Joachim, Steffen, Will, Lenton, Timothy M.

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Hydrothermal carbonization as an alternative sanitation technology: Process optimization and development of low-cost reactor

2022, Chung, Jae Wook, Gerner, Gabriel, Ovsyannikova, Ekaterina, Treichler, Alexander, Baier, Urs, Libra, Judy, Krebs, Rolf

Background: The provision of safe sanitation services is essential for human well-being and environmental integrity, but it is often lacking in less developed communities with insufficient financial and technical resources. Hydrothermal carbonization (HTC) has been suggested as an alternative sanitation technology, producing value-added products from faecal waste. We evaluated the HTC technology for raw human waste treatment in terms of resource recovery. In addition, we constructed and tested a low-cost HTC reactor for its technical feasibility. Methods: Raw human faeces were hydrothermally treated in a mild severity range (≤ 200 °C and ≤ 1 hr). The total energy recovery was analysed from the energy input, higher heating value (HHV) of hydrochar and biomethane potential of process water. The nutrient contents were recovered through struvite precipitation employing process water and acid leachate from hydrochar ash. A bench-scale low-cost reactor (BLR) was developed using widely available materials and tested for human faeces treatment. Results: The hydrochar had HHVs (23.2 - 25.2 MJ/kg) comparable to bituminous coal. The calorific value of hydrochar accounted for more than 90% of the total energy recovery. Around 78% of phosphorus in feedstock was retained in hydrochar ash, while 15% was in process water. 72% of the initial phosphorus can be recovered as struvite when deficient Mg and NH 4 are supplemented. The experiments with BLR showed stable operation for faecal waste treatment with an energy efficiency comparable to a commercial reactor system. Conclusions: This research presents a proof of concept for the hydrothermal treatment of faecal waste as an alternative sanitation technology, by providing a quantitative evaluation of the resource recovery of energy and nutrients. The experiments with the BLR demonstrate the technical feasibility of the low-cost reactor and support its further development on a larger scale to reach practical implementation.

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Reply to Kelman: The foundations for studying catastrophic climate risks

2022, Kemp, Luke, Xu, Chi, Depledge, Joanna, Ebi, Kristie L., Gibbins, Goodwin, Kohler, Timothy A., Rockström, Johan, Scheffer, Marten, Schellnhuber, Hans Joachim, Steffen, Will, Lenton, Timothy M.