RESUMEN
Genomic instability is one of the main drivers of tumorigenesis and the development of hematological malignancies. Cancer cells can remedy chemotherapeutic-induced DNA damage by upregulating DNA-repair genes and ultimately inducing therapy resistance. Nevertheless, the association between the DNA-repair genes, drug resistance, and disease relapse has not been well characterized in acute lymphoblastic leukemia (ALL). This study aimed to explore the role of the DNA-repair machinery and the molecular mechanisms by which it is regulated in early- and late-relapsing pediatric ALL patients. We performed secondary data analysis on the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-ALL expansion phase II trial of 198 relapsed pediatric precursor B-cell ALL. Comprehensive genetic and epigenetic investigations of 147 DNA-repair genes were conducted in the study. Gene expression was assessed using Microarray and RNA-sequencing platforms. Genomic alternations, methylation status, and miRNA transcriptome were investigated for the candidate DNA-repair genes. We identified three DNA-repair genes, ALKBH3, NHEJ1, and PARP1, that were upregulated in early relapsers compared to late relapsers (p < 0.05). Such upregulation at diagnosis was significantly associated with disease-free survival and overall survival in precursor-B-ALL (p < 0.05). Moreover, PARP1 upregulation accompanied a significant downregulation of its targeting miRNA, miR-1301-3p (p = 0.0152), which was strongly linked with poorer disease-free and overall survivals. Upregulation of DNA-repair genes, PARP1 in particular, increases the likelihood of early relapse of precursor-B-ALL in children. The observation that PARP1 was upregulated in early relapsers relative to late relapsers might serve as a valid rationale for proposing alternative treatment approaches, such as using PARP inhibitors with chemotherapy.
RESUMEN
Background Autism spectrum disorder (ASD) is a psychopathologic disorder caused by several factors. The early signs include poor interaction and communication, delayed milestones, and repeated behavior patterns. This study aimed to assess the relationship between screen time and ASD severity and investigate the types of electronic devices associated with ASD in children aged four to six years in Arar City, Kingdom of Saudi Arabia (KSA). Methodology A cross-sectional study was conducted in primary healthcare centers (PHCs) in Arar City, KSA. The study enrolled all parents with children aged four to six years attending the PHCs in Arar City, KSA. Results The total sample size was 199 participants. Regarding the relationship between screen time exposure and ASD, there were variable screen time exposure durations, with 22.6% of children exposed for less than an hour, 30.7% for one to two hours, and 46.7% for more than two hours. Moreover, the type of electronic devices to which children were exposed varied, with smartphones being the most prevalent (68.3%). In terms of the age of children since exposure to electronic devices, the data indicated that 30.2% were exposed before the age of two, 35.2% between two and three years, and 34.7% after three years of age. Regarding the relationship with sociodemographic characteristics, there was a statistically significant relationship with the mother's age at birth (p = 0.050), mother's education level (p = 0.009), father's education level (p = 0.049), whether the child was suffering from any chronic or neurological disease (p = 0.008), age since the child was exposed to electronic devices (p = 0.049), and screen time exposure duration (p = 0.040). Conclusions The study highlights the significant association between screen time exposure and the development of ASD in children. Public awareness of this associated risk among caregivers is recommended to follow the protective guidelines. Further research and interventions are needed to better understand and address the impact of screen media use on children's neurodevelopment and overall well-being.
RESUMEN
The low bandgap antimony selenide (Sb2Se3) and wide bandgap organic solar cell (OSC) can be considered suitable bottom and top subcells for use in tandem solar cells. Some properties of these complementary candidates are their non-toxicity and cost-affordability. In this current simulation study, a two-terminal organic/Sb2Se3 thin-film tandem is proposed and designed through TCAD device simulations. To validate the device simulator platform, two solar cells were selected for tandem design, and their experimental data were chosen for calibrating the models and parameters utilized in the simulations. The initial OSC has an active blend layer, whose optical bandgap is 1.72 eV, while the initial Sb2Se3 cell has a bandgap energy of 1.23 eV. The structures of the initial standalone top and bottom cells are ITO/PEDOT:PSS/DR3TSBDT:PC71BM/PFN/Al, and FTO/CdS/Sb2Se3/Spiro-OMeTAD/Au, while the recorded efficiencies of these individual cells are about 9.45% and 7.89%, respectively. The selected OSC employs polymer-based carrier transport layers, specifically PEDOT:PSS, an inherently conductive polymer, as an HTL, and PFN, a semiconducting polymer, as an ETL. The simulation is performed on the connected initial cells for two cases. The first case is for inverted (p-i-n)/(p-i-n) cells and the second is for the conventional (n-i-p)/(n-i-p) configuration. Both tandems are investigated in terms of the most important layer materials and parameters. After designing the current matching condition, the tandem PCEs are boosted to 21.52% and 19.14% for the inverted and conventional tandem cells, respectively. All TCAD device simulations are made by employing the Atlas device simulator given an illumination of AM1.5G (100 mW/cm2). This present study can offer design principles and valuable suggestions for eco-friendly solar cells made entirely of thin films, which can achieve flexibility for prospective use in wearable electronics.
RESUMEN
OBJECTIVES: Left ventricular diastolic dysfunction (LVDD) in patients undergoing transcatheter aortic valve replacement (TAVR) is associated with poor outcomes; however, the effect of its severity is controversial. We sought to assess the impact of diastolic dysfunction on hospital outcomes and survival after TAVR and identify prognostic factors. METHODS: We included patients who underwent TAVR for severe aortic stenosis with preexisting LVDD from 2009 to 2018 (n = 325). Patients with prior mitral valve surgery (n = 4), atrial fibrillation (n = 39), missing or poor baseline diastolic dysfunction assessment (n = 36) were excluded. The primary endpoint was all-cause mortality. 246 patients were included in the study. RESULTS: The median age was 80 years (25th and 75th percentiles:75-86.7), 154 (62.6%) were males and the median EuroSCORE II was 4.3 (2.2-8). Patients with severe LVDD had significantly higher EuroSCORE, and lower ejection fraction (p < 0.001). There was no difference in post-TAVR new atrial fibrillation (p = 0.912), pacemaker insertion (p = 0.528), stroke (p = 0.76), or hospital mortality (p = 0.95). Patients with severe LVDD had longer hospital stay (p = 0.036). The grade of LVDD did not affect survival (log-rank = 0.145) nor major adverse cardiovascular events (log-rank = 0.97). Predictors of mortality were; low BMI (HR: 0.95 (0.91-0.99); p = 0.019), low sodium (0.93 (0.82-2.5); p = 0.021), previous PCI (HR: 1.6 (1.022-2.66); p = 0.04), E-peak (HR: 1.01 (1.002-1.019); p = 0.014) and implantation of more than one device (HR: 3.55 (1.22-10.31); p = 0.02). CONCLUSION: Transcatheter aortic valve replacement is feasible in patients with diastolic dysfunction, and the degree of diastolic dysfunction did not negatively affect the outcome. Long-term outcomes in those patients were affected by the preoperative clinical state and procedure-related factors.