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1. Sex differences in adult famine mortality in medieval London

   https://doi.org/10.1002/ajpa.23930  

   DeWitte, Sharon_N; Yaussy, Samantha_L (October 2019, American Journal of Physical Anthropology)

   Abstract ObjectivesRecurrent famine events during the medieval period might have contributed to excess mortality during the Black Death in London, England (c. 1349–1350). Previous research using conventional methods of age estimation revealed that adult males experienced lower risks of mortality under “normal” (attritional) but not famine mortality conditions following the Black Death. However, given the biases inherent in conventional age estimation methods, this study reassesses sex differences in risks of medieval adult famine mortality using ages estimated via transition analysis, which avoids some of the limitations of conventional age estimation methods. Materials and MethodsWe apply hazards analysis (the Gompertz model of adult mortality) to ages estimated for human skeletal remains (n= 1245) from London cemeteries dated to the pre‐Black Death (c. 1000–1250 CE) and post‐Black Death (c. 1350–1540 CE) periods. ResultsThe results reveal no sex differences in risks of mortality before the Black Death but indicate that adult males faced lower risks of mortality after the Black Death during conditions of normal and famine mortality. ConclusionsThese findings largely support those of our previous research, which suggested that selective mortality during the Black Death or sex‐biased improvements in standard of living following the epidemic reduced risk of mortality for adult males in the post‐Black Death period under normal mortality conditions. However, the use of transition analysis age estimates also revealed a reduced risk of mortality for post‐Black Death adult males under famine conditions. 

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2. Association between social vulnerability and place of death during the first 2 years of COVID-19 in Massachusetts

   https://doi.org/10.1093/ageing/afae018  

   Charpignon, Marie-Laure; Onofrey, Shauna; Chen, Yea-Hung; Rewegan, Alex; Glymour, Medellena_Maria; Klevens, R_Monina; Majumder, Maimuna_Shahnaz (February 2024, Age and Ageing)

   Abstract We investigated the relationship between individual-level social vulnerability and place of death during the infectious disease emergency of the COVID-19 pandemic in Massachusetts. Our research represents a unique contribution by matching individual-level death certificates with COVID-19 test data to analyse differences in distributions of place of death. 

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3. Complexity of human death: its physiological, transcriptomic, and microbiological implications

   https://doi.org/10.3389/fmicb.2023.1345633  

   Javan, Gulnaz T.; Singh, Kanhaiya; Finley, Sheree J.; Green, Robert L.; Sen, Chandan K. (January 2024, Frontiers in Microbiology)

   Human death is a complex, time-governed phenomenon that leads to the irreversible cessation of all bodily functions. Recent molecular and genetic studies have revealed remarkable experimental evidence of genetically programmed cellular death characterized by several physiological processes; however, the basic physiological function that occurs during the immediate postmortem period remains inadequately described. There is a paucity of knowledge connecting necrotic pathologies occurring in human organ tissues to complete functional loss of the human organism. Cells, tissues, organs, and organ systems show a range of differential resilience and endurance responses that occur during organismal death. Intriguingly, a persistent ambiguity in the study of postmortem physiological systems is the determination of the trajectory of a complex multicellular human body, far from life-sustaining homeostasis, following the gradual or sudden expiry of its regulatory systems. Recent groundbreaking investigations have resulted in a paradigm shift in understanding the cell biology and physiology of death. Two significant findings are that (i) most cells in the human body are microbial, and (ii) microbial cell abundance significantly increases after death. By addressing the physiological as well as the microbiological aspects of death, future investigations are poised to reveal innovative insights into the enigmatic biological activities associated with death and human decomposition. Understanding the elaborate crosstalk of abiotic and biotic factors in the context of death has implications for scientific discoveries important to informing translational knowledge regarding the transition from living to the non-living. There are important and practical needs for a transformative reestablishment of accepted models of biological death (i.e., artificial intelligence, AI) for more precise determinations of when the regulatory mechanisms for homeostasis of a living individual have ceased. In this review, we summarize mechanisms of physiological, genetic, and microbiological processes that define the biological changes and pathways associated with human organismal death and decomposition. 

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4. Quorum sensing orchestrates parallel cell death pathways in Vibrio cholerae via Type 6 secretion-dependent and -independent mechanisms

   https://doi.org/10.1073/pnas.2412642121  

   Mashruwala, Ameya A; Bassler, Bonnie L (November 2024, Proceedings of the National Academy of Sciences)

   Quorum sensing (QS) is a cell-to-cell communication process that enables bacteria to coordinate group behaviors. InVibrio choleraecolonies, a program of spatial-temporal cell death is among the QS-controlled traits. Cell death occurs in two phases, first along the colony rim, and subsequently, at the colony center. Both cell death phases are driven by the type 6 secretion system (T6SS). Here, we show that HapR, the master QS regulator, does not controlt6ssgene expression nor T6SS-mediated killing activity. Nonetheless, a ΔhapRstrain displays no cell death at the colony rim. RNA-Sequencing (RNA-Seq) analyses reveal that HapR activates expression of an operon containing four genes of unknown function,vca0646-0649.Epistasis and overexpression studies show that two of the genes,vca0646andvca0647, are required to drive cell death in both a ΔhapRand a ΔhapRΔt6ssstrain. Thus,vca0646-0649are regulated by HapR but act independently of the T6SS machinery to cause cell death, suggesting that a second, parallel pathway to cell death exists inV. cholerae. 

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5. Risk of death during acute infection is accelerating across diverse host-pathogen systems and consistent with multiple models of host-pathogen interaction

   https://doi.org/10.1128/msphere.00953-24  

   O'Sullivan, Tim; Karakoç, Canan; Wollein_Waldetoft, Kristofer; Brown, Sam P (May 2025, mSphere)

   Buchler, Nicolas E (Ed.)

   ABSTRACT Infectious diseases remain a major cause of global mortality, yet basic questions concerning the relationship between within-host processes governing pathogen burden (pathogen replication, immune responses) and population-scale (epidemiological) patterns of mortality remain obscure. We use a structured literature review to leverage the extensive biomedical data generated by controlled host infections to address the epidemiological question of whether infection-induced mortality is constant, accelerating, or follows some other pattern of change and to infer the within-host mechanistic basis of this pattern. We show that across diverse lethal infection models, the risk of death increases approximately exponentially in time since infection, in a manner phenomenologically similar to the dynamics of all-cause death. We further show that this pattern of accelerating risk is consistent with multiple alternate mechanisms of pathogen growth and host-pathogen interaction, underlining the limitations of current experimental approaches to connect within-host processes to epidemiological patterns. We review critical experimental questions that our work highlights, requiring additional non-invasive data on pathogen burden throughout the course of infection.IMPORTANCEHere, we ask a simple question: what are the dynamics of pathogen-induced death? Death is a central phenotype in both biomedical and epidemiological infectious disease biology, yet very little work has attempted to link the biomedical focus on pathogen dynamics within a host and the epidemiological focus on populations of infected hosts. To systematically characterize the dynamics of death in controlled animal infections, we analyzed 209 data sets spanning diverse lethal animal infection models. Across experimental models, we find robust support for an accelerating risk of death since the time of infection, contrasting with conventional epidemiological models that assume a constant elevated risk of death. Using math models, we show that multiple processes of growth and virulence are consistent with accelerating risk of death, and we end with a discussion of critical experiments to resolve how within-host biomedical processes map onto epidemiological patterns of disease. 

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