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- Global excess deaths associated with heatwaves in 2023 and the contribution of human-induced climate changePublication . Hundessa, Samuel; Huang, Wenzhong; Xu, Rongbin; Yang, Zhengyu; Zhao, Qi; Gasparrini, Antonio; Armstrong, Ben; Bell, Michelle L.; Huber, Veronika; Urban, Aleš; Coelho, Micheline; Sera, Francesco; Tong, Shilu; Royé, Dominic; Kyselý, Jan; de'Donato, Francesca; Mistry, Malcolm; Tobias, Aurelio; Íñiguez, Carmen; Ragettli, Martina S.; Hales, Simon; Achilleos, Souzana; Klompmaker, Jochem; Li, Shanshan; Guo, Yuming; Multi-Country Multi-City Collaborative Research NetworkAbstract: An unprecedented heatwave swept the globe in 2023, marking it one of the hottest years on record and raising concerns about its health impacts. However, a comprehensive assessment of the heatwave-related mortality and its attribution to human-induced climate change remains lacking. We aim to address this gap by analyzing high-resolution climate and mortality data from 2,013 locations across 67 countries/territories using a three-stage modeling approach. First, we estimated historical heatwave-mortality associations using a quasi-Poisson regression model with distributed lag structures, considering lag effects, seasonality, and within-week variations. Second, we pooled the estimates in meta-regression, accounting for spatial heterogeneity and potential changes in heatwave-mortality associations over time. Third, we predicted grid-specific (0.5 0.5) association in 2023 and calculated the heatwave-related excess deaths, death ratio, and death rate per million people. Attribution analysis was conducted by comparing heatwave-related mortality under factual and counterfactual climate scenarios. We estimated 178,486 excess deaths (95% empirical confidence interval [eCI], 159,892≥204,147) related to the 2023 heatwave, accounting for 0.73% of global deaths, corresponding to 23 deaths per million people. The highest mortality rates occurred in Southern (120, 95% eCI, 116≥126), Eastern (107, 95% eCI, 100≥114), and Western Europe (66, 95% eCI, 62≥70), where the excess death ratio was also higher. Notably, 54.29% (95% eCI, 45.71%≥61.36%) of the global heatwave-related deaths were attributable to human-induced climate change. These results underscore the urgent need for adaptive public health interventions and climate mitigation strategies to reduce future mortality burdens in the context of increasing global warming.
- Untargeted Multiomics of LNCaP Cell Line Treated with a Novel DNA Minor Groove Binder and/or Doxorubicin Using Mass SpectrometryPublication . Zenati, Ruba A.; Soares, Nelson C.; Alniss, Hasan Y.; Al-Hroub, Hamza M.; El-Awady, Raafat; Abuhelwa, Ahmad Y.; Ramadan, Wafaa S.; Aleidi, Shereen M.; El-Huneidi, Waseem; Abu-Gharbieh, Eman; Alzoubi, Karem H.; Bustanji, Yasser; Semreen, Mohammad H.Prostate cancer (PCa) remains a major global health concern, ranking among the most prevalent cancer in men worldwide. Despite the availability of various therapeutic options, the clinical efficacy of current anti-PCa agents is often compromised by drug resistance and adverse effects. DNA minor groove binders offer a potential therapeutic alternative, owing to their selective mechanism of action and favorable safety profiles. In the present study, we utilized a multiomics strategy to investigate the molecular impact of novel compound MGB4. LNCaP cells were treated with doxorubicin, MGB4, or a combination of both, followed by LC-MS/MS-based untargeted proteomics and metabolomics analyses. One-way ANOVA (p-value <0.05) revealed 55 significantly dysregulated proteins and 57 altered metabolites across treatments. Our findings indicate that both MGB4 and doxorubicin impacted key cellular pathways, including inhibition of translation and alterations in sphingolipid and amino acid metabolism, while doxorubicin and the combination therapy also reduced spermine and spermidine metabolism. Notably, the combined treatment exhibited synergistic effects, significantly impacting purine metabolism and reducing metabolite levels more than individual therapies. This study provides key molecular insights into MGB4 and doxorubicin's mechanisms, supporting MGB4 as a potential prostate cancer drug candidate.
- Direct costs with dementia hospitalization and its determinants in Portugal in 2018Publication . Madeira, Francisco; Moniz, Marta; Leite, Andreia; Alves, JoanaBackground/Objectives: Major neurocognitive disorders, as is the case of dementia, are characterised by a decline in cognitive abilities, leading to adverse health outcomes and deterioration in quality of life. The projected rise in diagnoses for the coming decades represent a public health concern, impacting patients and society, and placing a considerable financial burden on healthcare systems. This study aims to estimate hospitalisation costs with dementia in Portugal in 2018, and its determinants. Methods: We used inpatient data from the Portuguese publicly financed hospitals database (Base de Dados de Morbilidade Hospitalar, ACSS) for 2018. We selected hospitalization records (n = 25,830) with dementia-related diagnosis, either primary or non-primary, based on ICD-10. We computed average costs for inpatient cases, using tariffs from national legislation, stratifying by dementia type. We performed a multivariate regression analysis (gamma, log link) for assessing costs’ determinants (sex, age, region, number of comorbidities, type of dementia, medical or surgical inpatient, and destination after discharge). Results: The average cost per hospitalisation was 3,084 €. Stratifying by type of dementia, Alzheimer's patients accounted for 2,441 €, vascular dementia for 4,079 €, and other degenerative diseases (including Lewy body and frontotemporal dementia) for 2,515 €. This represented a national economic burden of 79.7 million €. Younger individuals (55-64, 65-74, and 75-84) incurred significantly higher inpatient costs of 1,042 €, 676 €, and 216 €, respectively, compared to 85+. Compared to unspecified dementia, Alzheimer's was associated with higher costs, while patients with other dementia showed no significant cost differences. The costs were higher (p < 0.001) with each additional comorbidity (+23 €) and severity level (+1,439 €). Compared to deceased (p < 0.001), patients discharged home had lower costs (-328 €), while those discharged to other settings incurred higher costs (+471 €). Non-surgical cases were 3,961€ less costly than surgical ones (p < 0.001). Conclusions/Recommendations: Dementia-related hospitalisations imposed a substantial financial burden on the Portuguese public healthcare system in 2018 and are expected to rise in the future. Costs were driven by key factors such as age, number of comorbidities, severity, destination of discharge, and hospitalisation type.