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Mitochondrial one-carbon metabolism provides carbon units to several pathways, including nucleic acid synthesis, mitochondrial metabolism, amino acid metabolism, and methylation reactions. Late-onset Alzheimer’s disease is the most common age-related neurodegenerative disease, characterised by impaired energy metabolism, and is potentially linked to mitochondrial bioenergetics. Here, we discuss the intersection between the molecular pathways linked to both mitochondrial one-carbon metabolism and Alzheimer’s disease. We propose that enhancing one-carbon metabolism could promote the metabolic processes that help brain cells cope with Alzheimer’s disease-related injuries. We also highlight potential therapeutic avenues to leverage one-carbon metabolism to delay Alzheimer’s disease pathology.

Purpose This paper aims to examine the short-term market reaction for the world’s 100 largest listed defence firms at and around the three recent largest threats to the global economy – Ukraine–Russia war, Fourth Taiwan Strait Crisis and the Hamas terrorist attack on Israel. Design/methodology/approach The author examine the impact of the three recent largest threats to the global economy in the largest listed defence firms using an event study methodology. Findings The results show a positive and statistically significant short-term reaction around the three geopolitical threats. The results also reveal the existence of higher abnormal returns for defence firms with greater weight of defence sales, in line with the captured regulator theory and for firms with higher research and development and capital expenditure intensity. Originality/value The effect of the war on stock markets has been relatively little examined in the financial theory. This study intends to fill this gap in the literature through the analysis of the three recent largest threats to the global economy.

Purpose The purpose of this study investigates the short-term market reaction of three commodity futures indices for four recent events of high geopolitical risk: the Ukraine–Russia war, the Taiwan Strait crisis and the Hamas terrorist attack on Israel. Design/methodology/approach The author examines three commodity futures indices at and around the beginning of four recent events of high geopolitical risk using an event study methodology. Findings The results show a positive abnormal return for the commodity futures indices for three of the four recent events considered in the analysis. The exception in terms of abnormal returns observed is the visit of US Speaker of the House Nancy Pelosi to Taiwan on August 2, 2022, which resulted in statistically significant negative abnormal returns in the commodity futures around the visit. The other three geopolitical events, by causing an increase of uncertainty level and supply-side constraints, led to a rise in the price of most commodity futures. This allowed commodity-exporting countries to achieve positive and statistically significant abnormal returns. Policy implications of our findings are discussed. Originality/value The effect of high geopolitical risk events on commodity futures indices has been relatively little examined in the financial theory. This study intends to fill this gap in the literature.

PurposeThis paper investigates the short-term market impact of the beginning of the military conflict between Russia and Ukraine (February 24, 2022) on a set of airline stocks listed.Design/methodology/approachThis study uses an event study methodology, cross-section analyses and interaction effects to study the effect of the war on airline stock prices and firm-specific characteristics that explain the cumulative abnormal return.FindingsThe authors observe a negative and statistically significant stock price reaction at and around the beginning of the military conflict between Russia and Ukraine, for 74 listed airlines. These results are consistent with investment portfolio rebalancing and asset pricing perspective. Moreover, this study's results show a higher negative stock market reaction for airlines based in Europe. Empirical evidence suggests the existence of a “proximity penalty” for European companies. Finally, this study's results provide insights into which airline-specific characteristics emerge as value drivers. Larger, well-capitalized (high liquidity and low debt) and profitable airlines firms with less institutional ownership have superior stock market returns and show more able to handle with the losses resulting from the war.Originality/valueThis paper fills a gap in the literature about the impact of the Russia–Ukraine war on the airline industry.

Purpose Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study was to assess the comparative safety profile (odds ratio) of ICIs and estimate the absolute rate of immune-related serious adverse events (irSAEs) in cancer patients undergoing treatment with ICIs. Methods We searched for randomized trials till February 2021, including all ICIs for all cancers. Primary outcome was overall irSAEs, and secondary outcomes were pneumonitis, colitis, hepatitis, hypophysitis, myocarditis, nephritis, and pancreatitis. We conducted Bayesian network meta-analyses, estimated absolute rates and ranked treatments according to the surface under the cumulative ranking curve (SUCRA). Results We included 96 trials (52,811 participants, median age 62 years). Risk of bias was high in most trials. Most cancers were non-small cell lung cancer (28 trials) and melanoma (15 trials). The worst-ranked ICI was ipilimumab (SUCRA 14%; event rate 848/10,000 patients) while the best-ranked ICI was atezolizumab (SUCRA 82%; event rate 119/10,000 patients). Conclusion Each ICI showed a unique safety profile, with certain events more frequently observed with specific ICIs, which should be considered when managing cancer patients.

Cervical cancer (CC) arises as a result of chronic and persistent female infection by different oncogenic human papillomaviruses (HPV). The incidence of this disease is still high in developing countries, such as Brazil, where diagnosis is often made in advanced stages. HPV 16 is the most common Papillomavirus genotype in CC worldwide. Studies regarding the association of different HPV 16 lineages with overall and disease-free CC survival rates can contribute to further understanding the behavior of different HPV 16 lineages concerning the prognosis of CC cases. To assess the CC prognosis of patients treated in a Brazilian institution concerning HPV16 lineages. Data were obtained from a prospective cohort of 334 patients with CC recruited between July 2011 and March 2014 and treated at the Brazilian National Cancer Institute (INCA), in Rio de Janeiro, Brazil. HPV 16 lineages were identified in tumor tissue samples. Genetic HPV 16 diversity comprised 218 cases of lineage A, 10 of lineage B, 10 of lineage C, and 96 of lineage D. In addition to HPV 16 lineages, age, histopathological type, staging, and treatment completion were evaluated as predictors of CC prognosis. The median patient age was 48 years. The most common histopathological type was squamous cell carcinoma (82.3%), followed by adenocarcinoma. Locally advanced disease staging was the most frequently detected, represented by similar stage II and III percentages (36.2% and 37.7%), followed by initial stage I (19.2%) and stage IV (6.9%). Two hundred two patients completed CC treatment. Age, histological type, staging, and treatment completion were associated with a higher risk of death, which was not observed for the HPV 16 lineage variable. With regard to age, an increase in each year of life led to approximately a 1% increase in the risk of death. Other histopathological types (poorly differentiated carcinoma, adenosquamous, neuroendocrine, and sarcoma) were associated with a higher risk of death compared with adenocarcinoma. Patients diagnosed in advanced stages exhibited a higher risk of death, and those who did not complete treatment exhibited an over 2-fold increased risk of death. This study found no associations between HPV 16 lineages A, B, C, and D and CC prognosis.

PurposeThis paper aims to highlight the role of the CEO’s background in the stock market reaction to a product recall. Based on the upper echelons theory and the crisis management literature, we argue that the CEO’s background influences the expected response in a product harm crisis and the updating of investors’ expectations following a product recall announcement. We test if the CEO’s background influences the abnormal stock market returns around product recalls and how it affects the way investors interpret the recall strategy and severity.Design/methodology/approachWe use an event study, for a sample of 2,576 product recalls in the US automobile industry, between January 2010 and June 2021.FindingsWe observe that the stock market’s reaction is less negative if the firm’s CEO presents a core specialist background and for firms led by insider CEOs. This result is in line with our argument that in the presence of a crisis that requires operational and firm-specific knowledge, such as product recalls, the best alignment in terms of the CEO’s background occurs when the CEO was recruited inside and is a core specialist. Finally, we also find that the CEO’s background has a moderating effect on the impact of the recall strategy and severity on the stock market reaction to a recall announcement. In particular, a recall with high severity has a more negative stock market reaction when the CEO is a core specialist as such an event is not expected by the market.Practical implicationsThese results have important implications for practitioners and scholars working in the areas of product quality and corporate governance. Given the high frequency and high costs for firms to carry out these operations in the automobile industry, we recommend a careful analysis of the CEO’s background before their appointment as well as careful planning to prevent and to adequately react appropriately to product quality problems. While there is a common tendency among executives to cut discretionary expenditures such as spending on product safety, our results regarding the stock market reaction to product recall announcements suggest that investors expect firms led by insider and core specialist CEOs to be more likely to ensure product quality and to respond to product quality crisis.Originality/valueWe extend knowledge of product recalls by studying the role of the CEO’s background on the stock market reaction to product recall announcements.

The tourism sector in Madeira represents 26.6% of the regional GDP and 16.7% of employment in the region. However, the sector is a source of adverse environmental impacts. One of the environmental repercussions of tourism, regarded as an externality, is the generation of solid waste. This paper aims to estimate the impact of tourist activities on solid waste generation in Madeira for the period 1996–2018. We used a fully modified ordinary least squares (FMOLS) model, including annual tourism inflows data. The results show that tourist activities are responsible for 41.9% to 46.6% of solid waste generation per resident in Madeira. The empirical results also support the hypothesis that there is a non-linear effect of tourism on the generation of solid waste. The importance of internalising this negative externality caused by tourism with the implementation of appropriate economic instruments and policies is the main policy implication of the study.

Alzheimer’s disease is the most common age-related neurodegenerative disorder. Familial forms of Alzheimer’s disease associated with the accumulation of a toxic form of amyloid-β (Aβ) peptides are linked to mitochondrial impairment. The coenzyme nicotinamide adenine dinucleotide (NAD + ) is essential for both mitochondrial bioenergetics and nuclear DNA repair through NAD + -consuming poly (ADP-ribose) polymerases (PARPs). Here we analysed the metabolomic changes in flies overexpressing Aβ and showed a decrease of metabolites associated with nicotinate and nicotinamide metabolism, which is critical for mitochondrial function in neurons. We show that increasing the bioavailability of NAD + protects against Aβ toxicity. Pharmacological supplementation using NAM, a form of vitamin B that acts as a precursor for NAD + or a genetic mutation of PARP rescues mitochondrial defects, protects neurons against degeneration and reduces behavioural impairments in a fly model of Alzheimer’s disease. Next, we looked at links between PARP polymorphisms and vitamin B intake in patients with Alzheimer’s disease. We show that polymorphisms in the human PARP1 gene or the intake of vitamin B are associated with a decrease in the risk and severity of Alzheimer’s disease. We suggest that enhancing the availability of NAD + by either vitamin B supplements or the inhibition of NAD + -dependent enzymes such as PARPs are potential therapies for Alzheimer’s disease.

Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson’s disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity. Suppressing Shmt2 or Nmdmc caused motor impairment and mitochondrial defects in flies. Epistatic analyses showed that suppressing the upregulation of Shmt2 or Nmdmc deteriorates the phenotype of pink1 or parkin mutants. Conversely, the genetic enhancement of these one-carbon metabolism genes in pink1 or parkin mutants was neuroprotective. We conclude that mitochondrial dysfunction caused by mutations in the Pink1/Parkin pathway engages ATF4-dependent activation of one-carbon metabolism as a protective response. Our findings show a central contribution of ATF4 signalling to PD that may represent a new therapeutic strategy. A video abstract for this article is available at https://youtu.be/cFJJm2YZKKM .