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AimsTo estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress.DesignRetrospective cohort study with longitudinal follow-up of self-reported health outcomes.SettingChildhood Cancer Survivor Study (CCSS), a 26-center study of ≥ 5-year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada.ParticipantsA total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress.MeasurementsSurvivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory-18 and the Posttraumatic Stress Diagnostic Scale.FindingsAfter adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1-1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1-1.5), anxiety (RR = 1.6; 95% CI = 1.3-2.1), and somatization (RR = 1.2; 95% CI = 1.1-1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4-2.3).ConclusionsDrinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer.

Background: Hemoptysis resulting from rupture of the pulmonary artery pseudoaneurysm (PAP) is massive and fatal, while factor contributing to the rupture of pseudoaneurysm remains elusive. This study aimed to elucidate the clinical and radiological features of PAP and identify the risk factors associated with rupture. Methods: Patients who developed hemoptysis with PAP were collected from January 2019 to December 2022 retrospectively. Clinical data of the demographic characteristics, radiological findings, treatment strategies, and prognosis were collected. A comparative analysis was performed on the characteristics in the ruptured and non-ruptured cases. Results: A total of 58 PAPs were identified in the 50 patients. The most common causes were infection (86%) and cancer (8%). The PAPs were located predominantly in the upper lobes of both lungs, and 57 (99.3%) were distributed in the segmental or subsegmental pulmonary arteries. The median diameter was 6.1(4.3–8.7) mm. A total of 29 PAPs were identified adjacent to pulmonary cavitations, with the median diameter of the cavity being 18.9 (12.4–34.8) mm. Rupture of pseudoaneurysm occurred in 21 cases (42%). Compared to unruptured group, the ruptured group had a significantly higher proportion of massive hemoptysis (57.1% vs. 6.9%, p < 0.001), larger pseudoaneurysm diameter (8.1 ± 3.2 mm vs. 6.0 ± 2.3 mm, p = 0.012), higher incidence of pulmonary cavitation (76.2% vs. 44.8%, p = 0.027), and larger cavitation diameters (32.9 ± 18.8 mm vs. 15.7 ± 8.4 mm, p = 0.005). The mean pulmonary artery pressure (mPAP) in the ruptured group was also significantly higher than that in the unruptured group [23.9 ± 7.4 mmHg vs. 19.2 ± 5.0 mmHg, p = 0.011]. Endovascular treatment was successfully performed in all 21 patients with ruptured PAP, of which the clinical success rate was 96.0%. Five patients experienced recurrent hemoptysis within one year. Conclusions: Massive hemoptysis, pseudoaneurysm diameter, pulmonary cavitation, and elevated mPAP were the risk factors for rupture of pseudoaneurysm. Our findings facilitate early identification and timely intervention of PAP at high risk of rupture. [ABSTRACT FROM AUTHOR]

A "signal-off" photoelectrochemical (PEC) sensing platform has been designed for the ultrasensitive detection of DNA methylation levels and multiple methylated sites. The platform employs tungsten trioxide and TpPa-1-COF loaded by gold nanoparticle (AuNPs@WO3@TpPa-1-COF) composite material as the photoactive component and p-type reduced graphene (rGO) as an efficient quencher. The PEC signal of AuNPs@WO3@TpPa-1-COF composite is effectively quenched in the presence of p-type rGO, because p-type rGO can compete with AuNPs@WO3@TpPa-1-COF to deplete light energy and electron donors. In addition, a hybrid strand reaction (HCR) amplification strategy fixes more target DNA and then combines with rGO-modified anti-5-methylcytosine antibody to facilitate ultrasensitive DNA methylation detection. Under optimal conditions, DNA methylation can be measured within a linear concentration range of 10–14 to 10–8 M, with an exceptionally low detection limit of 0.19 fM (S/N = 3). At the same time, the platform can conduct quantitative determination of multi-site methylation, with the linear equation △I = 44.19LogA + 61.43, and the maximum number of methylation sites is 5. The sensor demonstrates high sensitivity, excellent selectivity, and satisfactory stability. Furthermore, the proposed signal-off PEC strategy was successfully employed to detect DNA methylation in spiked human serum samples, with recoveries ranging from 93.17 to 107.28% and relative standard deviation (RSD) ranging from 1.15 to 5.49%. [ABSTRACT FROM AUTHOR]

Objective: To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)‐directed therapies. Methods: A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS‐treated]; median age [range] = 25.5 years [18–48]; time since diagnosis = 17.7 years [6.8–30.2]) and 8039 without CNS‐directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal care needs, ability to work/attend school, attainment of driver's license, marital/partner status). Multivariable regression models, adjusted for age, sex, race/ethnicity, and chronic health conditions, estimated odds ratios (OR) or relative risks (RR) for associations between neurologic morbidity, functional independence, and emotional distress. Results: Among CNS‐treated survivors, three classes of independence were identified: (1) moderately independent, never married, and non‐independent living (78.7%); (2) moderately independent, unable to drive (15.6%); and (3) non‐independent (5.7%). In contrast to 50% of non‐CNS‐treated survivors and 60% of siblings, a fourth fully independent class of CNS‐treated survivors was not identified. History of stroke (OR = 2.50, 95% CI: 1.70–3.68), seizure (OR = 9.70, 95% CI: 7.37–12.8), neurosensory deficits (OR = 2.67, 95% CI: 2.16–3.31), and focal neurologic dysfunction (OR = 3.05, 95% CI: 2.40–3.88) were associated with non‐independence among CNS‐treated survivors. Non‐independence was associated with emotional distress symptoms. Interpretation: CNS‐treated survivors do not attain full independence comparable to non‐CNS‐treated survivors or siblings. Interventions to promote independence may be beneficial for survivors with treatment‐related neurological sequalae. [ABSTRACT FROM AUTHOR]

To improve robust estimation performance of fully correlated nonlinear error-in-variables model, three median robust estimate methods are discussed on base of Nonlinear Weighted Total Least Squares (NWTLS), namely, median parameter method, median parameter initial value method and median variance method. After the discussion of the median robust estimation theory and the derivation of the calculation formula of the three median robust estimation methods, three iterative algorithms are developed. Through two nonlinear regression examples, four schemes including no artificial outliers, different location of outliers, different degrees of correlation, and different ratios of outliers are adopted, which proves the feasibility and effectiveness of the proposed algorithm. The experimental results show that from the statistical point of view, although the three median methods have different antioutlier effects for different nonlinear models, they are more effective than RNWTLS and NWTLS; the robust estimation results of three median methods are related to the functional model. [ABSTRACT FROM AUTHOR]

Objective: Allergic asthma is a growing burden on national public health services due to its high prevalence. The aim of this experiment was to investigate whether miR-26a-5p affects cellular fibrosis and thus airway remodeling in asthmatic mice through the regulation of target genes. Methods: Screening for differentially expressed miRNAs in asthma model mice was carried out by constructing a mouse model of allergic asthma. qRT-PCR was performed to determine candidate miRNAs in each group of bronchial tissues. Western blot detection of the expression levels of predicted candidate target genes in each group of bronchial tissues was conducted. A dual luciferase assay was performed to validate the binding of miR-26a-5p to target genes. Fibronectin, a marker of cellular fibrosis, was detected via flow cytometry. CCK8 and BrdU staining were used to detect the proliferation ability of each group of cells. Results: miR-26a-5p is able to target and bind to ABL2 3′-UTR, MMP16 3′-UTR and PDE7A 3′-UTR sequences. After interference with miR-26a-5p, improved bronchial histopathology and reduced peribronchial collagen deposition were found. Compared with the model group, interference with miR-26a-5p reduced lung fibrosis, decreased fibroblasts and increased apoptosis in mouse bronchial tissues; overexpression of miR-26a-5p decreased apoptosis in mouse bronchial tissues. Compared with the model group, the serum levels of IL-4, IL-5, IL-13 and I IFN-γ were decreased in the miR-26a-5p inhibitor group and increased in the miR-26a-5p mimic group. The immunohistochemical results showed that the expression of ABL2, MMP16 and PDE7A was significantly reduced after intervention with miR-26a-5p. Compared with the model group, the apoptosis rate of cells in the miR-26a-5p inhibitor group of the allergic asthma model was upregulated, the levels of IL-4, IL-5, IL-13, IFN-γ and ROS were decreased, the expression of the miRNA and proteins of ABL2, MMP16 and PDE7A was decreased, the expression of LC3A and P62 was significantly increased and the expression of LC3B, Beclin1, Atg5 and fibrosis markers collagen I and α-SMA was decreased. Conclusion: miR-26a-5p affects cellular fibrosis and thus airway remodeling in asthmatic mice by regulating target genes. [ABSTRACT FROM AUTHOR]