Complexity of the COVID-19 pandemic in Maringa

While extensive literature exists on the COVID-19 pandemic at regional and national levels, understanding its dynamics and consequences at the city level remains limited. This study investigates the pandemic in Maring\'a, a medium-sized city in Brazil's South Region, using data obtained by actively monitoring the disease from March 2020 to June 2022. Despite prompt and robust interventions, COVID-19 cases increased exponentially during the early spread of COVID-19, with a reproduction number lower than that observed during the initial outbreak in Wuhan. Our research demonstrates the remarkable impact of non-pharmaceutical interventions on both mobility and pandemic indicators, particularly during the onset and the most severe phases of the emergency. However, our results suggest that the city's measures were primarily reactive rather than proactive. Maring\'a faced six waves of cases, with the third and fourth waves being the deadliest, responsible for over two-thirds of all deaths and overwhelming the local healthcare system. Excess mortality during this period exceeded deaths attributed to COVID-19, indicating that the burdened healthcare system may have contributed to increased mortality from other causes. By the end of the fourth wave, nearly three-quarters of the city's population had received two vaccine doses, significantly decreasing deaths despite the surge caused by the Omicron variant. Finally, we compare these findings with the national context and other similarly sized cities, highlighting substantial heterogeneities in the spread and impact of the disease.Comment: 20 pages, 5 figures, supplementary information; accepted for publication in Scientific Report

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field