Machine Learning-Assisted Classification of Paraffin-Embedded Brain Tumors with Raman Spectroscopy.

Raman spectroscopy (RS) has demonstrated its utility in neurooncological diagnostics, spanning from intraoperative tumor detection to the analysis of tissue samples peri- and postoperatively. In this study, we employed Raman spectroscopy (RS) to monitor alterations in the molecular vibrational characteristics of a broad range of formalin-fixed, paraffin-embedded (FFPE) intracranial neoplasms (including primary brain tumors and meningiomas, as well as brain metastases) and considered specific challenges when employing RS on FFPE tissue during the routine neuropathological workflow. We spectroscopically measured 82 intracranial neoplasms on CaF2 slides (in total, 679 individual measurements) and set up a machine learning framework to classify spectral characteristics by splitting our data into training cohorts and external validation cohorts. The effectiveness of our machine learning algorithms was assessed by using common performance metrics such as AUROC and AUPR values. With our trained random forest algorithms, we distinguished among various types of gliomas and identified the primary origin in cases of brain metastases. Moreover, we spectroscopically diagnosed tumor types by using biopsy fragments of pure necrotic tissue, a task unattainable through conventional light microscopy. In order to address misclassifications and enhance the assessment of our models, we sought out significant Raman bands suitable for tumor identification. Through the validation phase, we affirmed a considerable complexity within the spectroscopic data, potentially arising not only from the biological tissue subjected to a rigorous chemical procedure but also from residual components of the fixation and paraffin-embedding process. The present study demonstrates not only the potential applications but also the constraints of RS as a diagnostic tool in neuropathology, considering the challenges associated with conducting vibrational spectroscopic analysis on formalin-fixed, paraffin-embedded (FFPE) tissue.

Model-based assessment of COVID-19 epidemic dynamics by wastewater analysis.

Continuous surveillance of COVID-19 diffusion remains crucial to control its diffusion and to anticipate infection waves. Detecting viral RNA load in wastewater samples has been suggested as an effective approach for epidemic monitoring and the development of an effective warning system. However, its quantitative link to the epidemic status and the stages of outbreak is still elusive. Modelling is thus crucial to address these challenges. In this study, we present a novel mechanistic model-based approach to reconstruct the complete epidemic dynamics from SARS-CoV-2 viral load in wastewater. Our approach integrates noisy wastewater data and daily case numbers into a dynamical epidemiological model. As demonstrated for various regions and sampling protocols, it quantifies the case numbers, provides epidemic indicators and accurately infers future epidemic trends. Following its quantitative analysis, we also provide recommendations for wastewater data standards and for their use as warning indicators against new infection waves. In situations of reduced testing capacity, our modelling approach can enhance the surveillance of wastewater for early epidemic prediction and robust and cost-effective real-time monitoring of local COVID-19 dynamics.

Performance of early warning signals for disease re-emergence: A case study on COVID-19 data.

Developing measures for rapid and early detection of disease re-emergence is important to perform science-based risk assessment of epidemic threats. In the past few years, several early warning signals (EWS) from complex systems theory have been introduced to detect impending critical transitions and extend the set of indicators. However, it is still debated whether they are generically applicable or potentially sensitive to some dynamical characteristics such as system noise and rates of approach to critical parameter values. Moreover, testing on empirical data has, so far, been limited. Hence, verifying EWS performance remains a challenge. In this study, we tackle this question by analyzing the performance of common EWS, such as increasing variance and autocorrelation, in detecting the emergence of COVID-19 outbreaks in various countries. Our work illustrates that these EWS might be successful in detecting disease emergence when some basic assumptions are satisfied: a slow forcing through the transitions and not-fat-tailed noise. In uncertain cases, we observe that noise properties or commensurable time scales may obscure the expected early warning signals. Overall, our results suggest that EWS can be useful for active monitoring of epidemic dynamics, but that their performance is sensitive to certain features of the underlying dynamics. Our findings thus pave a connection between theoretical and empirical studies, constituting a further step towards the application of EWS indicators for informing public health policies.

COVID-19 crisis management in Luxembourg: Insights from an epidemionomic approach.

We develop an epidemionomic model that jointly analyzes the health and economic responses to the COVID-19 crisis and to the related containment and public health policy measures implemented in Luxembourg. The model has been used to produce nowcasts and forecasts at various stages of the crisis. We focus here on two key moments in time, namely the deconfinement period following the first lockdown, and the onset of the second wave. In May 2020, we predicted a high risk of a second wave that was mainly explained by the resumption of social life, low participation in large-scale testing, and reduction in teleworking practices. Simulations conducted 5 months later reveal that managing the second wave with moderately coercive measures has been epidemiologically and economically effective. Assuming a massive third (or fourth) wave will not materialize in 2021, the real GDP loss due to the second wave will be smaller than 0.4 percentage points in 2020 and 2021.

Modelling COVID-19 dynamics and potential for herd immunity by vaccination in Austria, Luxembourg and Sweden.

Against the COVID-19 pandemic, non-pharmaceutical interventions have been widely applied and vaccinations have taken off. The upcoming question is how the interplay between vaccinations and social measures will shape infections and hospitalizations. Hence, we extend the Susceptible-Exposed-Infectious-Removed (SEIR) model including these elements. We calibrate it to data of Luxembourg, Austria and Sweden until 15 December 2020. Sweden results having the highest fraction of undetected, Luxembourg of infected and all three being far from herd immunity in December. We quantify the level of social interaction, showing that a level around 1/3 of before the pandemic was still required in December to keep the effective reproduction number Refft below 1, for all three countries. Aiming to vaccinate the whole population within 1 year at constant rate would require on average 1,700 fully vaccinated people/day in Luxembourg, 24,000 in Austria and 28,000 in Sweden, and could lead to herd immunity only by mid summer. Herd immunity might not be reached in 2021 if too slow vaccines rollout speeds are employed. The model thus estimates which vaccination rates are too low to allow reaching herd immunity in 2021, depending on social interactions. Vaccination will considerably, but not immediately, help to curb the infection; thus limiting social interactions remains crucial for the months to come.

Dynamical SPQEIR model assesses the effectiveness of non-pharmaceutical interventions against COVID-19 epidemic outbreaks.

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of different control strategies. In this paper, we tackle this question with an extended epidemic SEIR model, informed by a socio-political classification of different interventions. First, we inquire the conceptual effect of mitigation parameters on the infection curve. Then, we illustrate the potential of our model to reproduce and explain empirical data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lockdown is an effective pandemic mitigation measure, a combination of social distancing and early contact tracing can achieve similar mitigation synergistically, while keeping lower isolation rates. This quantitative understanding can support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model.