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Background: It is proven that children have significantly milder COVID-19 disease compared to adults. Various immunological characteristics influence this age-related difference in protection against COVID-19. Pediatric COVID-19 in Jordan is extremely under reported. Objectives: The primary goal of this work is to identify the anti_S and anti_N antibody responses in a random group of children in Jordan and compare it to that of naturally infected-unvaccinated adults. Methods: 151 unvaccinated children, 4 days to 18 years old, were screened for anti_S and anti_N antibodies. History of COVID-19 infection or exposure to infection and symptom severity were reported by parents on a special questionnaire. Results: 78.9 % and 65.3 % of participants were seropositive for anti_S IgG and anti_N Abs, respectively. There was a remarkable association between age and anti_S IgG and anti_N IgG antibody titers, as children aged 12 years or older had increased anti_S IgG titers (mean = 19.3 BAU/mL) compared to younger groups (means of 10.15, 9.24, 7.91 BAU/mL for age groups 6-12, 1-6, less than 1 year, respectively). Gender did not show a statistically important role in anti_S and anti_N IgG seropositivity rates or titers. Children displayed significantly elevated anti_S titers (mean = 13.23 BAU/mL) compared to naturally infected adults (mean = 9.72 BAU/mL), in contrast, adults' anti_N titers (mean = 39.64 U/mL) were significantly higher compared to those of children (mean = 10.77 U/mL). Conclusions: The current work provides evidence of distinctly robust and persistent humoral immunity displayed by high anti_S and anti_N IgG in children, even >12 months post-infection. Age was the only factor that had a significant statistical impact on anti_S and anti_N Ab levels among the pediatric group in this study. Children exhibited significantly higher anti_S titers than naturally infected adults. In contrast, adults' anti_N titers were significantly higher. Such information can assist direct pediatric SARS-CoV-2 immunization programs, with implications for creating age-targeted strategies for diagnostic and population protection measures.
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Deletion of CDKN2A occurs in 50% of glioblastomas (GBM), and IFNA locus deletion in 25%. These genes reside closely on chromosome 9. We investigated whether CDKN2A and IFNA were co-deleted within the same heterogeneous tumour and their prognostic implications. We assessed CDKN2A and IFNA14 deletions in 45 glioma samples using an in-house three-colour FISH probe. We examined the correlation between p16INK4a protein expression (via IHC) and CDKN2A deletion along with the impact of these genomic events on patient survival. FISH analyses demonstrated that grades II and III had either wildtype (wt) or amplified CDKN2A/IFNA14, whilst 44% of GBMs harboured homozygous deletions of both genes. Cores with CDKN2A homozygous deletion (n = 11) were negative for p16INK4a. Twenty p16INK4a positive samples lacked CDKN2A deletion with some of cells showing negative p16INK4a. There was heterogeneity in IFNA14/CDKN2A ploidy within each GBM. Survival analyses of primary GBMs suggested a positive association between increased p16INK4a and longer survival; this persisted when considering CDKN2A/IFNA14 status. Furthermore, wt (intact) CDKN2A/IFNA14 were found to be associated with longer survival in recurrent GBMs. Our data suggest that co-deletion of CDKN2A/IFNA14 in GBM negatively correlates with survival and CDKN2A-wt status correlated with longer survival, and with second surgery, itself a marker for improved patient outcomes.
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Inibidor p16 de Quinase Dependente de Ciclina , Glioblastoma , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/genética , Deleção de Genes , Glioblastoma/patologia , Homozigoto , Deleção de SequênciaRESUMO
The long-term immunoglobulin responses of COVID-19 vaccinations is important to determine the efficacy of these vaccinations. This study aimed to investigate and compare the long-term immunoglobulin response of COVID-19 vaccination recipients, using anti-S IgG, anti-N IgG, and IgM titer levels. This study included 267 participants, comprising individuals who tested positive for COVID-19 through PCR testing (n = 125), and those who received the Pfizer (n = 133), Sinopharm (n = 112), AstraZeneca (n = 20), or Sputnik (n = 2) vaccines. Female participants comprised the largest share of this study (n = 147, 55.1%). This study found that most participants had positive IgG antibodies, with 96.3% having anti-S IgG and 75.7% having anti-N IgG. Most participants (90.3%) tested negative for anti-N IgM antibodies. Sinopharm-vaccinated individuals exhibited a notably lower rate of positive anti-S IgG (93.8%) and a significantly higher rate of positive anti-N IgG antibodies (91%). Anti-N IgG levels were significantly correlated with the number of prior COVID-19 infections (p = 0.015). Specifically, individuals with a history of four COVID-19 infections had higher anti-N IgG titers (14.1 ± 1.4) than those with only one experience of COVID-19 infection (9.4 ± 7.2). Individuals who were infected with COVID-19 after receiving the vaccine demonstrated higher levels of anti-N IgG, exhibiting a 25% increase in mean titer levels compared to those who were infected prior to vaccination. There was a statistically significant association between anti-N IgG positivity with age (p = 0.034), and smoking status (p = 0.006) of participants. Participants younger than 20 and older than 60 showed the highest positivity rate of anti-N (>90%). Smokers had a low positivity rate of anti-N (68.8%) compared to nonsmokers (83.6%). In conclusion, this study demonstrated that most COVID-19 vaccination recipients had positive IgG antibodies, with differences in the long-term immunoglobulin response depending on the type of vaccine administered and occurrence of COVID-19 infection.
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Immune checkpoint inhibitors are a novel class of immunotherapy drugs that have improved the prognosis of melanoma, renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma, and various other solid tumors. Nivolumab is an immune checkpoint inhibitor that acts by inhibiting programmed death. Its use is associated with significant immune-related adverse events, such as pneumonitis, thyroiditis, hepatitis, pruritus, vitiligo, and diarrhea. However, adrenal insufficiency and checkpoint inhibitor-related autoimmune diabetes mellitus are extremely rare adverse events related to nivolumab treatment. Here, we are highlighting cases of adrenal insufficiency and diabetes inspidus as a result of nivolumab. These rare adverse events in our case series are to raise awareness that this medication also may be the cause for this illness among oncologists, endocrinologists, internists, and other clinicians.
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Large-scale coronavirus disease 2019 (COVID-19) vaccination programs have been rolled out worldwide. Vaccines that are widely used globally include mRNA vaccines, adenoviral vector vaccines, and inactivated whole-virus vaccines. COVID-19 vaccines can lead to varying side effects. Among the most common of these adverse effects are pain at the injection site, fatigue, and headaches. Some side effects, however, are not very well documented, and these include joint-related adverse effects. In this review, we assess the epidemiology and clinical features of post-COVID-19 vaccination joint-related adverse effects based on the analysis of 16 patient case reports. Based on our analysis, we found that females formed the majority of the cases, accounting for 62.5% of patients, while 37.5% of the cases were males. The mean age of presentation among the patients was 54.8 years, with a standard deviation (SD) of 17.49 years. In 37.5% of the cases, patients received the Sinovac vaccine. The proportion of patients who received other vaccines was as follows: the Pfizer vaccine: 31.25%; Sputnik V: 12.5%; Moderna, AstraZeneca, and Covaxin: 6.25% each. The characteristics of joint-related adverse effects following COVID-19 vaccination were analyzed in this study. We identified several key findings related to factors such as age, gender, type of vaccine, clinical features, and diagnosis modality. Our analysis showed that more cases were reported among individuals who received the Sinovac vaccine, as compared to the others. Further research is required to examine the underlying cause of this association.
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BACKGROUND: Synchronous bilateral breast cancer (SBBC) provides a special condition where two independent breast tumors are exposed to cancer pharmacotherapy within a uniform pharmacokinetic milieu. Both senescence and apoptosis are established responses to therapy; however, they have potentially variable contributions to the overall outcome of treatment, which are yet to be determined. METHODS: In this report, we describe the clinicopathological picture of two SBBC cases that received standard anticancer treatment and assess their expression profile of several molecular hallmarks of senescence and apoptosis. RESULTS: Our analysis identified that synchronous tumors have variable expression profiles of both senescence- and apoptosis-associated biomarkers, despite comparable pathological responses to neoadjuvant chemotherapy and current survival rates. CONCLUSIONS: Our results highlight the variable expression of senescence- and apoptosis-associated markers in breast tumors (despite the shared somatic genetic background) and invites a large-scale assessment of both senescence and apoptosis in breast cancer tissue in vivo and their contribution to the pathological response and overall survival.