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Colorectal cancer (CRC) is among the most common gastrointestinal malignancies worldwide. eIF3a is highly expressed in a variety of cancer types, yet its role in CRC remains unclear. We introduced ectopic eIF3a expression in CRC cells to investigate its relevance to various malignant behaviors. Further, we silenced eIF3a to explore its effect on tumor growth in a nude mouse tumor xenograft model. Finally, the molecular mechanisms through which eIF3a regulates malignancy in CRC cells were explored through bioinformatics analysis combined with the use of a specific PI3K inhibitor (LY294002). eIF3a was highly expressed in the peripheral blood and cancer tissue of CRC patients. Malignancy and tumor growth were significantly inhibited by silencing eIF3a, while overexpression promoted malignant behaviors, with a positive correlation between PI3K/AKT activation and eIF3a expression. Taken together, eIF3a plays an oncogenic role in CRC by regulating PI3K/AKT signaling and is a potential biomarker for CRC diagnosis and prognostic monitoring.

The COVID-19 booster dose is considered an important adjunct for the control of the COVID-19 pandemic due to reports of reduced immunity in fully vaccinated individuals. The aims of this study were to assess healthcare workers' intention to receive the booster dose of COVID-19 vaccine and to identify predictive factors among healthcare workers. A cross-sectional study was conducted among healthcare workers selected in two provinces, Kasai Oriental, and Haut-Lomami. Data were collected using a questionnaire administered through structured face-to-face interviews, with respondents using a pre-tested questionnaire set up on the Open Data Kit (ODK Collect). All data were analyzed using SPSS v26.0 (IBM Corporation, Armonk, NY, USA). Vaccination coverage for COVID-19, considering declarations by health workers, is around 85.9% for the province of Kasai Oriental and 85.8% for Haut-Lomami. A total of 975 responses were collected, 71.4% of health workers at Kasai Oriental and 66.4% from Haut-Lomami declared a definite willingness to receive a COVID-19 vaccine booster. The duration of protection was the main reason for accepting a booster COVID-19 dose for 64.6% of the respondents. Logistic regression analysis showed that having chronic diseases (aOR = 2.95 [1.65-5.28]), having already received one of the COVID-19 vaccines (aOR = 2.72 [1.43-5. 19]); the belief that only high-risk individuals, such as healthcare professionals and elderly people suffering from other illnesses, needed a booster dose (aOR = 1.75 [1.10-2.81]). Considering the burden of COVID-19, a high acceptance rate for booster doses could be essential to control the pandemic. Our results are novel and could help policymakers design and implement specific COVID-19 vaccination programs to reduce reluctance to seek booster vaccination.

Circular RNA Ribonuclease P RNA Component H1 (circ_RPPH1) and microRNA (miRNA) miR-1296-5p play a crucial role in breast cancer (BC), but the molecular mechanism is vague. Evidence showed that miR-1296-5p can activate tripartite motif-containing 14 (TRIM14). Clinical indications of eighty BC patients were collected and the circ_RPPH1 expression was detected using real-time quantitative PCR. MCF-7 and MDA-MB-231 cells were transfected with overexpression or knockdown of circ_RPPH1, miR-1296-5p, or TRIM14. Cell counting kit-8, cell cloning formation, wound healing, Transwell, and flow cytometry assays were performed to investigate the malignant phenotype of BC. The dual-luciferase reporter gene analyses were applied to reveal the interaction between these target genes. Subcutaneous tumorigenic model mice were established with circ_RPPH1 overexpression MDA-MB-231 cells in vivo; the tumor weight and volume, levels of miR-1296-5 and TRIM14 mRNA were measured. Western blot and immunohistochemistry were used to detect TRIM14 in cells and mice. Circ_RPPH1 levels were notably higher in BC patients and have been found to promote cell proliferation, invasion, and migration of BC cells. Circ_RPPH1 altered cell cycle and hindered apoptosis. Circ_RPPH1 knockdown or miR-1296-5p overexpression inhibited the malignant phenotype of BC. Furthermore, miR-1296-5p knockdown reversed circ_RPPH1's promotion effects on BC. Interestingly, TRIM14 overexpression counteracts the inhibitory effects of miR-1296-5p overexpression and circ_RPPH1 silencing on BC. Moreover, in BC tumor-bearing mice, circ_RPPH1 overexpression led to increased TRIM14 expression and facilitated tumor growth. Circ_RPPH1 enhanced BC progression through miR-1296-5p/TRIM14 axis, indicating its potential as a biomarker and therapeutic target in BC.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and pneumonia-related hospitalizations. A new preventive monoclonal antibody (MAb), nirsevimab, has been launched in the United States, Luxembourg, and France, and was recently approved to be given in a population-based manner throughout Spain. This study aimed to have a first pre-immunization insight into the Spanish parental knowledge about bronchiolitis, RSV, and nirsevimab immunization. Parents in Murcia with children <2 years of age up to the date of September 1, 2023, were selected to complete a questionnaire. The primary endpoint was the parental knowledge about bronchiolitis, RSV, and nirsevimab. A total of 3,217 responses were analyzed. The majority (95.8%) were aware of bronchiolitis. Meanwhile, 46.6% of the respondents knew about RSV, most of them only after the first child's birth. Information about RSV or bronchiolitis was mainly obtained from family members, with only 4.8% reporting having been informed by Health care Professionals (HCPs). Only 11.2% of respondents were aware of nirsevimab. Nonetheless, these were not entirely satisfied with the information received (score of 3.3 out of 5) and shared that HCPs should be the primary source of information. The present survey then highlights the need for better and more efficient educational strategies directed to all parents/legal guardians. It also sheds some light on the different factors that should be considered to improve awareness of RSV immunization to decrease its burden in Spain and beyond.

We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.

Parent vaccine hesitancy (PVH) remains a significant public health concern, particularly emphasized during the COVID-19 pandemic. This study investigates PVH among parents of children with various psychiatric and neurodevelopmental conditions, such as attention deficit hyperactivity disorder (ADHD), anxiety disorders, and behavioral disturbances, extending previous research focused on autism spectrum disorder (ASD). We examined PVH in children aged 5-11 years with psychiatric and behavioral disorders excluding ASD. A cross-sectional questionnaire-based analysis was conducted in Qatar, involving 244 parents of neurodiverse children and 245 parents of neurotypical children as controls. The Parent Attitudes about Childhood Vaccines (PACV) survey assessed PVH. Results indicated a significantly higher prevalence of vaccine hesitancy among parents of children with psychiatric disorders (54.1%, 95% CI [47.8%, 60.4%], n = 132) compared to controls (11.7%, 95% CI [7.5%, 16.0%], n = 26), p < .001. The PACV total score was significantly higher in parents of children with a mental disorder. Higher education among parents and lower PACV scores significantly influenced the intent to vaccinate against COVID-19. Tailored interventions by child and adolescent mental healthcare professionals, such as harnessing artificial intelligence to fight disinformation, are crucial to addressing vaccine hesitancy, enhancing acceptance, and improving outcomes for children with psychiatric disorders.

This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg. After assessment of safety and immunogenicity of the 12 μg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 μg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3-73.3% across groups) and myalgia (36.9%; 13.3-56.7%). Unsolicited AEs were reported by 14.4% (6.7-26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7-30.0%) reported MAAEs, and 8.3% (0.0-13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.

Seasonal vaccination remains one of the best interventions to prevent morbidity and mortality from influenza in children. Understanding the characteristics of parents who vaccinate their children can inform communication strategies to encourage immunization. Using a cross-sectional study, we described parental characteristics of people who reported vaccinating their children against influenza during 2018/2019 in a cohort of Canadian digital immunization record users. Data was collected from a free, Pan-Canadian digital vaccination tool, CANImmunize. Eligible accounts contained at least one parental and one "child/dependent" record. Each parental characteristic (gender, age, family size, etc) was tested for association with pediatric influenza vaccination, and a multivariate logistic regression model was fit. A total of 6,801 CANImmunize accounts met inclusion criteria. After collapsing the dataset, the final sample contained 11,381 unique dyads. Influenza vaccination was reported for 32.3% of the children and 42.0% of the parents. In the multivariate logistic regression analysis, parents receiving the seasonal influenza vaccine were most strongly associated with reporting pediatric influenza vaccination (OR 17.05, 95% CI 15.08, 19.28). Having a larger family size and fewer transactions during the study period was associated with not reporting pediatric influenza vaccination. While there are several limitations to this large-scale study, these results can help inform future research in the area. Digital technologies may provide a unique and valuable source of vaccine coverage data and to explore associations between individual characteristics and immunization behavior. Policy makers considering digital messaging may want to tailor their efforts based on parental characteristics to further improve pediatric seasonal influenza vaccine uptake.

Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα.

A wide range of survey studies have explored vaccination hesitancy/resistance during the COVID-19 pandemic and provided evidence that this can be explained by several individual variables from the ideological, clinical, and socio-affective domain. However, evidence about which individual variables predict vaccine hesitancy in the post-pandemic state of COVID-19 is meager. We administered a battery of questionnaires to a group of 120 Italian participants with high and low scores on the adult vaccine hesitancy scale (aVHS) to investigate the predictive role of ideological (i.e. political orientation), clinical (i.e. anxiety, interoceptive accuracy), and socio-affective (i.e. alexithymia, disgust sensitivity/propensity, empathy) variables on vaccine hesitancy/resistance. This study provides evidence that lower interoceptive awareness and cognitive empathy are predictors of a greater hesitancy to get vaccinated in the post-pandemic COVID-19 state.