Conventional and frugal methods of estimating COVID-19-related excess deaths and undercount factors.

Across the world, the officially reported number of COVID-19 deaths is likely an undercount. Establishing true mortality is key to improving data transparency and strengthening public health systems to tackle future disease outbreaks. In this study, we estimated excess deaths during the COVID-19 pandemic in the Pune region of India. Excess deaths are defined as the number of additional deaths relative to those expected from pre-COVID-19-pandemic trends. We integrated data from: (a) epidemiological modeling using pre-pandemic all-cause mortality data, (b) discrepancies between media-reported death compensation claims and official reported mortality, and (c) the "wisdom of crowds" public surveying. Our results point to an estimated 14,770 excess deaths [95% CI 9820-22,790] in Pune from March 2020 to December 2021, of which 9093 were officially counted as COVID-19 deaths. We further calculated the undercount factor-the ratio of excess deaths to officially reported COVID-19 deaths. Our results point to an estimated undercount factor of 1.6 [95% CI 1.1-2.5]. Besides providing similar conclusions about excess deaths estimates across different methods, our study demonstrates the utility of frugal methods such as the analysis of death compensation claims and the wisdom of crowds in estimating excess mortality.

The Role of Endoplasmic Reticulum Stress Response in Liver Regeneration.

Exposure to hepatotoxic chemicals is involved in liver disease-related morbidity and mortality worldwide. The liver responds to damage by triggering compensatory hepatic regeneration. Physical agent or chemical-induced liver damage disrupts hepatocyte proteostasis, including endoplasmic reticulum (ER) homeostasis. Post-liver injury ER experiences a homeostatic imbalance, followed by active ER stress response signaling. Activated ER stress response causes selective upregulation of stress response genes and downregulation of many hepatocyte genes. Acetaminophen overdose, carbon tetrachloride, acute and chronic alcohol exposure, and physical injury activate the ER stress response, but details about the cellular consequences of the ER stress response on liver regeneration remain unclear. The current data indicate that inhibiting the ER stress response after partial hepatectomy-induced liver damage promotes liver regeneration, whereas inhibiting the ER stress response after chemical-induced hepatotoxicity impairs liver regeneration. This review summarizes key findings and emphasizes the knowledge gaps in the role of ER stress in injury and regeneration.