Gamma-Ray Bursts from Primordial Quark Objects in Space

We investigate the possibility that gamma-ray bursts originate in a concentric spherical shell with a given average redshift and find that this is indeed compatible with the data from the third BATSE (3B) catalog. It is also shown that there is enough freedom in the choice of unknown burst properties to allow even for extremely large distances to the majority of bursts. Therefore, we speculate about an early, and very energetic, origin of bursts, and suggest that they come from phase transitions in massive objects of pure quark matter, left over from the Big Bang.Comment: 11 pages, Latex, 3 postscript figures, to be publ in the Proc of the Joint Meeting of the Networks 'The Fundamental Structure of Matter' and 'Tests of the Electroweak Symmetry Breaking', Ouranoupolis, Greece, May 199

Contribution value of akt, c-myc, cip2a, and pp2a genes expression in leukemogenesis: A bright perspective on the molecular pattern of patients with acute myeloid leukemia (aml)

Background: The heterogeneous nature of acute myeloid leukemia (AML) and the hurdle to find a suitable treatment strategy for this malignancy put this type of leukemia at the top of the list of the priorities for finding a valuable biomarker to improve its treatment and predict the outcome of the patients. Objectives: Given the involvement of the variety of signaling pathways, foremost the PI3K axis in the pathogenesis of human can-cers, we aimed to investigate the expression of the most important downstream targets of this pathway to propose a plausible mechanism underlying AML pathogenesis. Methods: In this case-control study, the blood samples from 30 patients diagnosed with AML were collected and after extracting their RNAs, the expression levels of Akt, c-Myc, CIP2A, and PP2A were evaluated using qRT-PCR analysis. For the control group, we also collected blood samples from 10 healthy volunteers. Afterward, by applying statistical analysis, we determined the probable correlation between the expressions of the aforementioned genes. Results: There was a significant elevation in the expression levels of Akt, c-Myc, and CIP2A coupled with the meaningful reduction in the expression level of PP2A in AML samples. However, we failed to find any significant association between the expression level of the indicated genes and age, sex, and the percentage of the blasts. Conclusions: As the most straightforward interpretation of our results, we propose that probably the association between PI3K and c-Myc which is built through the interaction between CIP2A and PP2A may play a pivotal role in the pathogenies of AML and any component of this axis could serve as a potential new target for more profound treatment strategy. However, further detailed inves-tigations in this field are required to clarify the exact role of this interesting testis-specific pathway in the context of hematological malignancies, in particular AML. © 2020, Author(s)

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021

Background Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings In 2021, the global prevalence of anaemia across all ages was 24·3% (95% uncertainty interval [UI] 23·9–24·7), corresponding to 1·92 billion (1·89–1·95) prevalent cases, compared with a prevalence of 28·2% (27·8–28·5) and 1·50 billion (1·48–1·52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52·0 million (35·1–75·1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422·4 [95% UI 286·1–612·9]), haemoglobinopathies and haemolytic anaemias (89·0 [58·2–123·7]), and other neglected tropical diseases (36·3 [24·4–52·8]), collectively accounting for 84·7% (84·1–85·2) of anaemia YLDs. Interpretation Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding Bill & Melinda Gates Foundation

Supplementary Material for: Breast Cancer and Chronic Lymphocytic Leukemia and Renal Cell Carcinoma: A Case Report of a Rare Cancer Combination

Introduction: The incidence of second malignancies in breast cancer survivors has increased because of early detection and improved cancer treatment modalities. The synchronous occurrence of chronic lymphocytic lymphoma (CLL) and renal cell carcinoma (RCC) in the same patient is higher than in the general population. Several factors, including the history of chemotherapy with alkylating agents, genetic alteration, and long-term survival of breast cancer patients may explain this condition, but further research is needed. Case Presentation: In the present report, we discussed the case of a 48-year-old female who had clear cell RCC; 5 months after the diagnosis of CLL and 15 years after invasive ductal carcinoma. Conclusion: Considering the continued elevated risk of second cancers in patients with breast cancer and CLL in a clinical setting, clinicians should be made aware of ongoing medical surveillance

c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis

Backgrounds: Although ATO is widely used to treat acute promelocytic leukemia (APL), the appropriate effects of the drug as a single agent are achieved in high doses which are not clinically achievable without the risk of side effects; highlighting the necessity of its application in a combined-modality. Herein, we aimed to investigate whether c-Myc inhibition could reinforce the anti-leukemic effect of ATO, while reducing its concentration in APL cells. Methods: NB4 cells were treated with the relevant concentrations of 10058-F4 (c-Myc inhibitor) and ATO, and then the survival of the cells was evaluated using trypan blue, MTT and BrdU assays. Moreover, the mechanism of action of the agents were evaluated using Flow cytometry, qRT-PCR and western blot analysis. Results: We found that the inhibition of c-Myc using 10058-F4 could enhance the anti-leukemic effect of ATO in APL cells through reducing the phosphorylation of IκB, decreasing the expression of the anti-apoptotic genes and in turn, inducing a caspase-3-dependent apoptotic cell death. Moreover, the combination of 10058-F4 and ATO abrogated the activation of the PI3K pathway, while neither agent had significant suppressive impact on this pathway; suggesting for the first time that probably the companionship of c-Myc inhibitor may be an appealing strategy for shifting the resistance condition toward a chemo-sensitive phenotype, without the necessity to elevate the effective dose of ATO. Conclusion: Given the efficacy of 10058-F4 in adjuvanting approaches, we suggest this small molecule inhibitor as an impressing agent to be used alongside ATO in the treatment of APL. © 2020 IMS