Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance.

Acquired radioresistance is the primary contributor to treatment failure of radiotherapy, with ferroptosis is identified as a significant mechanism underlying cell death during radiotherapy. Although resistance to ferroptosis has been observed in both clinical samples of radioresistant cells and cell models, its mechanism remains unidentified. Herein, our investigation revealed that radioresistant cells exhibited greater tolerance to Glutathione Peroxidase 4 (GPX4) inhibitors and, conversely, increased sensitivity to ferroptosis suppressor protein 1 (FSP1) inhibitors compared to their sensitive counterparts. This observation suggested that FSP1 might play a dominant role in the development of radioresistance. Notably, the knockout of FSP1 demonstrated considerably superior efficacy in resensitizing cells to radiotherapy compared to the knockout of GPX4. To elucidate the driving force behind this functional shift, we conducted a metabolomic assay, which revealed an upregulation of Coenzyme Q (CoQ) synthesis and a downregulation of glutathione synthesis in the acquired radioresistance cells. Mechanistically, CoQ synthesis was found to be supported by aarF domain containing kinase 3-mediated phosphorylation of CoQ synthases, while the downregulation of Solute carrier family 7 member 11 led to decreased glutathione synthesis. Remarkably, our retrospective analysis of clinical response data further validated that the additional administration of statin during radiotherapy, which could impede CoQ production, effectively resensitized radioresistant cells to radiation. In summary, our findings demonstrate a dependency shift from GPX4 to FSP1 driven by altered metabolite synthesis during the acquisition of radioresistance. Moreover, we provide a promising therapeutic strategy for reversing radioresistance by inhibiting the FSP1-CoQ pathway.

Looking Beyond the Lens of Crimean-Congo Hemorrhagic Fever in Africa.

Crimean-Congo hemorrhagic fever (CCHF) is a lethal viral disease that has severe public health effects throughout Africa and a case fatality rate of 10%-40%. CCHF virus was first discovered in Crimea in 1944 and has since caused a substantial disease burden in Africa. The shortage of diagnostic tools, ineffective tick control efforts, slow adoption of preventive measures, and cultural hurdles to public education are among the problems associated with continued CCHF virus transmission. Progress in preventing virus spread is also hampered by the dearth of effective serodiagnostic testing for animals and absence of precise surveillance protocols. Intergovernmental coordination, creation of regional reference laboratories, multiinstitutional public education partnerships, investments in healthcare infrastructure, vaccine development, and a One Health approach are strategic methods for solving prevention challenges. Coordinated efforts and financial commitments are needed to combat Crimean-Congo hemorrhagic fever and improve all-around readiness for newly developing infectious illnesses in Africa.

Incidence, Risk Factors, and Temporal Trends of Small Intestinal Cancer: A Global Analysis of Cancer Registries.

BACKGROUND & AIMS: Small intestinal cancer is a rare cancer, with limited studies exploring its epidemiology. To our knowledge, this study is the first effort to comprehensively analyze the incidence, risk factors, and trends for small intestinal cancer by sex, age, and country. METHODS: Global Cancer Observatory, Cancer Incidence in Five Continents Plus, and Global Burden of Disease were accessed to estimate the age-standardized rates of small intestinal cancer incidence (International Classification of Diseases, 10th Revision, Clinical Modification: C17) and prevalence of lifestyle risk factors, metabolic risk factors, and inflammatory bowel disease (IBD). Risk factor associations were assessed by linear and logistic regressions. Average annual percent change was calculated using joinpoint regression. RESULTS: A total of 64,477 small intestinal cancer cases (age-standardized rate, 0.60 per 100,000) were estimated globally in 2020, with a higher disease burden found in North America (1.4). Higher small intestinal cancer incidence was associated with higher human development index; gross domestic product; and prevalence of smoking, alcohol drinking, physical inactivity, obesity, diabetes, lipid disorder, and IBD (ß = 0.008-0.198; odds ratios, 1.07-10.01). There was an overall increasing trend of small intestinal cancer incidence (average annual percent change, 2.20-21.67), and the increasing trend was comparable among the 2 sexes but more evident in the older population aged 50-74 years than in the younger population aged 15-49 years. CONCLUSION: There was a substantial geographic disparity in the burden of small intestinal cancer, with higher incidence observed in countries with higher human development index; gross domestic product; and prevalence of unhealthy lifestyle habits, metabolic disorders, and IBD. There was an overall increasing trend in small intestinal cancer incidence, calling for the development of preventive strategies.

Global burden, risk factors, and temporal trends of ureteral cancer: a comprehensive analysis of cancer registries.

BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Incidence, risk factors, and temporal trends of penile cancer: a global population-based study.

OBJECTIVES: To examine the global disease burden and country-specific trends of penile cancer incidence by age group and investigate its associations with several factors. MATERIALS AND METHODS: The Global Cancer Observatory database was interrogated for penile cancer incidence. The 10-year cancer incidence rates were collected from the Cancer Incidence in Five Continents Plus. The country-specific data were extracted from the World Health Organization Global Health Observatory and Global Burden of Disease databases for conducting risk factors analysis. The penile cancer incidence was presented using age-standardised rates. Its associations with various factors were examined by linear regression, while the incidence trend was estimated using joinpoint regression and presented as average annual percentage change with 95% confidence intervals in different age groups. RESULTS: There were an estimated 36 068 new cases of penile cancer in 2020. There was a considerable geographical disparity in the disease burden of penile cancer, with South America reporting the highest incidence. Overall, alcohol drinking, human immunodeficiency virus (HIV) infection, and unsafe sex were positively associated with a higher penile cancer incidence, while circumcision was found to be a protective factor. There has been a mixed trend in penile cancer incidence overall, but an increasing trend was found among younger males. CONCLUSIONS: There was a global variation in the penile cancer burden associated with prevalence of alcohol drinking, HIV infection, unsafe sex, and circumcision. The increasing penile cancer incidence in the younger population is worrying and calls for early detection and preventive interventions.

Incidence distributions, risk factors and trends of vaginal cancer: A global population-based study.

OBJECTIVE: This study aimed to investigate the incidence, risk factors and trends for vaginal cancer. DESIGN: Retrospective observational design. SETTING: Data were collected from multiple sources, including the Global Cancer Observatory, Cancer Incidence in Five Continents Plus, Global Burden of Disease, World Bank and the United Nations. POPULATION: Individuals diagnosed with vaginal cancer. METHODS: The study collected data on vaginal cancer from the specified sources. The age-standardised rate (ASR) of vaginal cancer was calculated for different regions and age groups. Multivariable and univariable linear regression analyses were performed to examine the associations between risk factors and the incidence of vaginal cancer. Trend analysis was conducted using joinpoint regression analysis, and the average annual percentage change (AAPC) was calculated to quantify the temporal trend. MAIN OUTCOME MEASURES: The main outcome measures of the study were the incidence of vaginal cancer, risk factors associated with the disease and the trend of its incidence over time. RESULTS: There were 17 908 newly reported cases of vaginal cancer (ASR = 0.36, 95% CI 0.30-0.44) in 2020, with the highest ASRs reported in South-Central Asia and Southern Africa. Risk factors associated with a higher incidence of vaginal cancer included a higher prevalence of unsafe sex and human immunodeficiency virus (HIV) infection. The temporal trend showed an overall rising incidence globally, with Iceland (AAPC = 29.56, 95% CI 12.12-49.71), Chile (AAPC = 22.83, 95% CI 13.20-33.27), Bahrain (AAPC = 22.05, 95% CI 10.83-34.40) and the UK (AAPC = 1.40, 95% CI 0.41-2.39) demonstrating the most significant rising trends. CONCLUSIONS: The significant regional disparities and risk factors associated with vaginal cancer underscore the necessity for targeted interventions and education, particularly in regions with a lower human development index (HDI) and a higher prevalence of human papillomavirus (HPV) infection. The increasing incidence trend emphasises the need for enhanced HPV vaccination rates to prevent the development of vaginal cancer.

Disease burden, risk factors, and temporal trends of eye cancer: A global analysis of cancer registries.

BACKGROUND: This study aims to investigate the global disease burden, risk factors, and temporal trends of eye cancer by sex and age group. METHODS: Databases including Cancer Incidence in Five Continents volumes I-XI, the Nordic Cancer Registries, the Surveillance, Epidemiology, and End Results Program and the WHO IARC mortality database were accessed to extract incidence and mortality data. Joinpoint regression analyses were conducted to evaluate the Average Annual Percentage Change of the incidence and mortality. RESULTS: The age-standardised rates of eye cancer incidence and mortality were 0.49 and 0.08 globally in 2020. Higher incidence rates were observed in Sub-Saharan Africa (ASR = 4.06), Western Europe (ASR = 0.89), and Northern Europe (ASR = 0.84), but higher mortality was observed only in Sub-Saharan Africa (ASR = 1.59). Lower HDI, higher prevalence of UV exposure and lower prevalence of several lifestyle habits and metabolic syndromes were associated with higher incidence and mortality. There was an overall stable incidence trend and a decreasing mortality trend. Notably, all countries reporting decreasing trend in mortality were in the Asian or European region. CONCLUSIONS: Although higher incidence was observed in both African and European regions, only the Sub-Saharan Africa region reported high mortality, indicating inequity in the access of healthcare and treatment resource. Higher prevalence of UV exposure was associated with both higher incidence and mortality. Education should be provided to increase the awareness of eye protection. An overall declining mortality trend was found, but it was limited to only Asian and European countries.

Global incidence, risk factors and trends of vulvar cancer: A country-based analysis of cancer registries.

Vulvar cancer is an uncommon malignancy. Vulvar cancer alarmed the public health problem in terms of the cost of diagnostic and medical treatments and psychical health of females. Our study aims to provide a thorough analysis of the global disease burden, related risk factors and temporal incidence trends of vulvar cancer in population subgroups. Data from Global Cancer Observatory and the Cancer Incidence in Five Continents Plus were used for the vulvar cancer incidence. Age-standardized rates (ASR) were used to depict the incidence of vulvar cancer. The 10-year trend of incidence was assessed using joinpoint regression with average annual percentage change and 95% confidence intervals in various age groups, while its correlations with risk factors were investigated using linear regression. Higher ASR were found in Western Europe (2.4), Northern America (1.9), Northern Europe (1.9), Australia and New Zealand (1.8) and Eastern Africa (1.4). The associated risk factors of higher vulvar cancer incidence were gross domestic product per capita, Human Development Index, higher prevalence of smoking, alcohol drinking, unsafe sex and human immunodeficiency virus infection. The overall trend of vulvar cancer incidence was increasing. An increasing trend was found in older females while a mixed trend was observed in younger females. The disease burden of vulvar cancer follows a bimodal pattern according to its two histologic pathways, affecting women in both developed and developing regions. Smoking cessation, sex education and human papillomavirus vaccination programs should be promoted among the general population. Subsequent studies can be done to explore the reasons behind the increasing trend of vulvar cancer.

Global distribution, risk factors, and recent trends for cervical cancer: A worldwide country-level analysis.

OBJECTIVES: This study aimed to evaluate the most updated worldwide distribution, risk factors, and temporal trends of cervical cancer for different countries and age groups. METHODS: The Global Cancer Observatory database was retrieved for the age-standardized rates (ASRs, per 100,000 persons) for incidence and mortality of cervical cancer in 2018. The associations with risk factors were examined by multivariable regression analysis, adjusting for human development index (HDI) and gross domestic products (GDP) per capita. Joinpoint regression analysis was used to calculate the 10-year annual average percent change (AAPC) for incidence and mortality. RESULTS: A total of 568,847 new cases (ASR, 13.1) and 311,365 deaths (ASR, 6.9) of cervical cancer were reported globally in 2018. The highest incidence and mortality were observed in Southern Africa (ASRs, 43.1 and 20.0) and countries with low HDI (ASRs, 29.8 and 23.0). Countries with higher incidence and mortality had lower HDI (ß = -8.19, 95% CI -11.32 to -5.06, p < 0.001; ß = -7.66, CI -9.82 to -5.50; p < 0.001) but higher alcohol consumption (ß = 1.89, 95% CI 0.59 to 3.19, p = 0.005; ß = 0.98, CI 0.08 to 1.88; p = 0.033). An increasing trend of incidence was also observed in younger populations, with Cyprus (AAPC, 6.96), Sweden (AAPC, 4.88), and Norway (AAPC, 3.80) showing the most prominent. CONCLUSIONS: The burden of cervical cancer was highest in regions with low and medium HDI and was associated with higher prevalence of alcohol consumption. There was an overall decreasing burden of cervical cancer; however, an increase in incidence and mortality was observed in some populations. More intensive preventive strategies are recommended for these populations.

The impact of having a dedicated obstetrics and gynecology resident to provide contraceptive counseling on immediate postpartum family planning uptake: a "pre-post" study.

BACKGROUND: Providing effective, high quality, antenatal and postpartum contraceptive counseling can reduce unintended pregnancies, decrease maternal and fetal morbidity and mortality, and prevent unsafe abortions. The postpartum period is a critical time to address unmet family planning need and to reduce the risks of short interpregnancy interval. This study aimed at determining the impact of assigning a dedicated obstetrics and gynecology resident for postpartum family planning counselling on the uptake of immediate postpartum family planning. METHODS: A "pre-post" observational study was conducted at Saint Paul's Hospital Millennium Medical College (SPHMMC), in Addis Ababa-Ethiopia, from May 1, 2021 to June 30, 2021. Immediate postpartum family planning uptake between the months of June (when there was a dedicated resident assigned for postpartum family planning counselling and provison on weekdays) and May (when there was no such dedicated resident for similar purpose) were compared. Data was analyzed using SPSS version 20 software packages. Simple descriptive was used to describe baseline characteristics. Chi-square test of association was done to determine the correlation between dependent and independent variables. Multivariate regression analysis was applied to determine factors associated with uptake of family planning methods in the immediate postpartum period. Odds ratio, 95% CI, and p-value < 0.05 were used to describe results significance. RESULTS: Out of 776 mothers who delivered at SPHMMC in the month of June 2021, 158 (20.4%) of them used immediate postpartum family planning. This finding during the month of June is higher than a 15.4% immediate postpartum family planning uptake observed during the preceding month of May. Having a dedicated resident for postpartum family planning counselling was associated with an increase in immediate postpartum family planning use (AOR = 1.31, 95% CI [1.01, 1.69]). CONCLUSION: In this study, presence of a dedicated obstetrics and gynecology resident for postpartum family planning counselling was associated with an increase in the uptake of immediate postpartum family planning. This implies the importance of assigning a dedicated care provider for the purpose of postpartum family planning counselling within the immediate postpartum, which gives postpartum women another opportunity of adequate counselling before they are discharge from Hospitals or obstetric service centers.

The postpartum period is a critical time to address unmet family planning need and to reduce the risks of short interpregnancy interval and unintended pregnancies, which translates in to a decrease in maternal and fetal morbidity and mortality. In this study, postpartum women who were counselled for family planning by dedicated obstetrics and gynecology resident were more likely to use immediate postpartum family planning (PPFP) compared to women who were not counselled by such care provider. This study aimed at determining the impact of assigning a dedicated obstetrics and gynecology resident for postpartum family planning counselling, by comparing immediate PPFP (family planning provided after delivery and before discharge of mothers from Hospital) uptake between the months of June (when there was a dedicated resident) and May (when there was no dedicated resident), in 2021. Out of 908 deliveries during the month of May, the uptake of immediate PPFP was 15.4%, which was significantly lower than an uptake of 20.4% in the following month of June. Mothers who delivered during the month of June were 1.3 times more likely to use immediate PPFP than mothers who delivered in the preceding month of May. In conclusion, presence of a dedicated obstetrics and gynecology resident for postpartum family planning counselling was associated with an increase in the uptake of immediate postpartum family planning.

Will people in conflict affected zones in Africa have access to COVID-19 vaccine? A case of Nigeria.

Vaccination is an important and cost-effective disease prevention and control strategy. Over the years, milestone discoveries in vaccine research and development as well as vaccine delivery systems, have contributed to expanded immunisation coverage and reduction in morbidity and mortality associated with vaccine-preventable diseases. While this outstanding development in vaccine delivery continues, there are considerable gaps in access to vaccines among populations living in fragile and conflict-affected zones which appeared to be the fault line of limited vaccine coverage. Despite progress in coronavirus disease 2019 (COVID-19) vaccine development, there are concerns about the feasibility of African countries affected by armed conflict and violence to effectively deliver COVID-19 vaccines at the unprecedented level required to fight against the virus. In this article we discuss the feasibility of access to COVID-19 vaccine among populations in conflict affected areas in Nigeria including methods that can be applied to reach and vaccinate populations in these settings.

Second wave of COVID-19 in Nigeria: Lessons from the first wave.

The COVID-19 pandemic struck the world unawares. The virus is now spreading as never before, despite the initial progress recorded by several countries towards kerbing the pandemic. As the pandemic continues to spread across Africa, there is a need for countries in the continent to re-evaluate, re-strategise, and re-invigorate their COVID-19 responses and efforts based on lessons from the first wave, and Nigeria is no exception. Before the second wave was officially announced by the health authorities on 17 December 2020, there were 78,434 confirmed cases and 1221 deaths reported with a case fatality rate (CFR) of 1.6%. To ensure that Nigeria achieves total pandemic control and reacts better given the possibility of a second wave, we propose workable recommendations to strengthen our preparedness and readiness efforts. Here, we argue that lessons learnt from the first wave of the COVID-19 pandemic can help Nigeria better react to the second wave.

Impact of COVID-19 on access to healthcare in low- and middle-income countries: Current evidence and future recommendations.

The COVID-19 pandemic continues to be a major public health threat globally and low- and middle-income countries (LMICs) are not an exception. The impact of the COVID-19 pandemic is far-reaching on many areas including but not limited to global health security, economic and healthcare delivery with a potential impact on access to healthcare in LMICs. We evaluate the impact of the COVID-19 pandemic on access to healthcare in LMICs, as well as plausible strategies that can be put in place to ensure that the delivery of healthcare is not halted. In order to mitigate the devastating effect of the COVID-19 pandemic on the already weak health systems in LMICs, it is much necessary to reinforce and scale up interventions and proactive measures that will ensure that access to healthcare is not disrupted even in course of the pandemic.

COVID-19 and progress towards achieving universal health coverage in Africa: A case of Nigeria.

Universal Health Coverage (UHC) 2030 is a global health target, and countries are making efforts to convert plans into tangible results. Nigeria, the most populated country in Africa, has made commitments towards UHC2030 target but is underperforming across many building blocks of health and progress has been slow. The arrival of COVID-19 poses additional pressure on the already feeble health system causing the government to direct focus towards containing the pandemic. However, existing gaps in health workforce density, weak primary health care infrastructure and inadequate budgetary allocation have resulted in inequitable access to basic healthcare services. This situation weighs most heavily on the poor who are mostly part of the informal economy thereby pushing people further into poverty. On the other hand, COVID-19 has provided valuable insights into Nigeria's current health system status which hopefully can be helpful in strengthening efforts towards building resilient health system and preparing the country towards future pandemic. The pandemic has highlighted the importance of essential health services and the need to strengthen primary healthcare system. It is, therefore, important that stakeholders in Nigeria and other African countries carry out situation analysis of the current health systems towards achieving UHC2030.

Rethinking 'Bacha Bazi', a culture of child sexual abuse in Afghanistan.

The global pandemic appears to be a never ending challenge. With the authorities' reach shrinking, we can assume that Bacha Bazi is celebrated more than before. Perpetrators not only harass individuals but also put public health in peril by organizing gathering and parties. With both individual and public health and rights at stake, this pandemic could also be a chance to contain Bacha Bazi practices. It may be early to say this and we definitely need to collect more information before we reach any conclusion, but most importantly, we, from healthcare workers and youth workers to policymakers, need to take action. Awareness is the spark of our mobilization. As citizens we can be more critical towards traditions involving any kind of abuse. As healthcare workers, we can be alert when treating boys, adolescents and young adults. We can probably spot a hidden case of abuse and refer the victim accordingly. As citizens we can support policymakers who are committed to take action against harassment of this, and any other, kind and this can also be a crucial chance to address the shadows haunting our societies once and for all.

Rural communities in Africa should not be forgotten in responses to COVID-19.

Rural areas in Africa make up a large proportion of the continent. Since the emergence of COVID-19 on the continent, major attention and responses have been placed on urban areas. Rural areas are typified by certain challenges which may serve as limitations to the provision of resources and tools for COVID-19 responses in these areas. These major challenges include limited access to these areas due to poor road networks which may hamper the possibility of conveying resources and manpower. Shortage of healthcare workforce in these areas, poor health facilities/structures and limited access to COVID-19 diagnostics services may also make containment challenging. It is therefore important that investment should be made in these areas towards providing the necessary tools, resources, and manpower to ensure effective containment of COVID-19 and to alleviate the plight caused by the pandemic in rural Africa. Rural communities in Africa should not be left behind in COVID-19 responses.

Speckle-Type POZ Protein Down-Regulates Matrix Metalloproteinase 2 Expression via Sp1/PI3K/Akt Signaling Pathway in Colorectal Cancer.

BACKGROUND: Elevated expression of matrix metalloproteinases (MMPs) is correlated with invasion and metastasis of colorectal cancer (CRC). Recently, a previous study has suggested that speckle-type POZ protein (SPOP) could inhibit cancer cell proliferation and migration through down-regulation of MMP2 and MMP7, with a mechanism remaining unknown. AIM: In this study, we, by using both CRC cells and normal colorectal cells, aimed to investigate the causal relationship between SPOP and MMP2, as well as the potential signaling pathways. METHODS: The causal relationship between SPOP and MMP2 was determined by both RT-PCR and Western blot in cells with SPOP expression or siRNA interference. The signaling pathway involved in MMP2 down-regulation by SPOP was subsequently identified by determination on the expression and phosphorylation of key signaling pathway proteins. Transcription factor involving in this MMP2 regulation was identified by determination on expression, phosphorylation, and nuclear translocation of key transcription factors. RESULTS: SPOP overexpression could significantly decrease MMP2 expression, while the knockdown of SPOP, in contrast, resulted in enhanced MMP2 level. Measurement of expression and phosphorylation of key signaling pathway proteins revealed that SPOP could inhibit PI3K and p-Akt level. Further tests on transcription factors showed that SPOP could inhibit SP1 phosphorylation and nuclear translocation. CONCLUSIONS: SPOP could down-regulate MMP2 expression in CRC, and this regulation is mediated by inhibiting SP1 phosphorylation and nuclear translocation through PI3K/Akt signaling pathway. Our findings in this study provide understanding of MMP2 regulation in CRC and may also shed lights on the development of anti-CRC treatments.