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Background Plasma circular (circ)RNAs detected by droplet digital polymerase chain reaction (ddPCR) may be ideal markers for liquid biopsy. However, ddPCR detection of circRNAs in plasma for diagnosis of lung adenocarcinoma has been rarely reported. Methods An RNA sequencing analysis was performed in plasma from patients with early lung adenocarcinoma and healthy individuals. Droplet digital PCR was used to verify the differentially expressed genes. Results The copy numbers of circle RNA LZIC (circ LZIC)and circle RNA CEP350 (circ CEP350) in the plasma of lung adenocarcinoma patients were significantly higher than in plasma of healthy people, and the copy numbers in postoperative plasma of the same patients were significantly lower than those in preoperative plasma. Circ LZIC and circ CEP350 alone and in combination had diagnostic value in lung adenocarcinoma and early lung adenocarcinoma. Circ LZIC and circ CEP350 had more binding sites with multiple microRNAs. Their target genes were enriched in several signaling pathways. Conclusion The copy numbers of circ LZIC and circ CEP350 were higher in plasma of lung adenocarcinoma patients than in plasma of healthy controls, significantly correlated with tumor size and TNM stage, and closely related to the occurrence and development of tumors. These circRNAs may serve as molecular markers for the diagnosis of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte differentiation, and other changes. We tested the hypothesis that altered immune-inflammatory response system (IRS) and compensatory immune-regulatory reflex system (IRS/CIRS) dynamics are associated with reduced white matter integrity in patients with schizophrenia. Study Design Patients with schizophrenia (SCZ, 70M/50F, age = 40.76 ± 13.10) and healthy controls (HCs, 38M/27F, age = 37.48 ± 12.31) underwent neuroimaging and plasma collection. A panel of cytokines were assessed using enzyme-linked immunosorbent assay. White matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging using a 3-T Prisma MRI scanner. The cytokines were used to generate 3 composite scores: IRS, CIRS, and IRS/CIRS ratio. Study Results The IRS/CIRS ratio in SCZ was significantly higher than that in HCs (P  = .009). SCZ had a significantly lower whole-brain white matter average FA (P  < .001), and genu of corpus callosum (GCC) was the most affected white matter tract and its FA was significantly associated with IRS/CIRS (r  = 0.29, P  = .002). FA of GCC was negatively associated with negative symptom scores in SCZ (r  = −0.23, P  = .016). There was no mediation effect taking FA of GCC as mediator, for that IRS/CIRS was not associated with negative symptom score significantly (P  = .217) in SCZ. Conclusions Elevated IRS/CIRS might partly account for the severity of negative symptoms through targeting the integrity of GCC. [ABSTRACT FROM AUTHOR]

Aims To assess the additional prognostic significance of echocardiographic parameters of subpulmonary left ventricular (LV) size and function in patients with a systemic right ventricle (SRV). Methods and results All adults with an SRV who underwent transthoracic echocardiography in 2010–18 at a large tertiary centre were identified. Biventricular size and function were assessed at the most recent examination. The study endpoint was all-cause mortality or heart/heart–lung transplantation. We included 180 patients, with 100 (55.6%) males, with a mean age of 42.4 ± 12.3 years, of whom 103 (57.2%) had undergone Mustard/Senning operations and 77 (42.8%) had congenitally corrected transposition of great arteries. Over 4.9 (3.8–5.7) years, 28 (15.6%) patients died and 4 (2.2%) underwent heart or heart–lung transplantation. Univariable predictors of the study endpoint included age, New York Heart Association functional Class III or IV, history of atrial arrhythmias, presence of a pacemaker or cardioverter defibrillator, high B-type natriuretic peptide, and echocardiographic markers of SRV and subpulmonary LV size and function. On multivariable Cox analysis of echocardiographic variables, indexed LV end-systolic diameter [ESDi; hazard ratio (HR) 2.77 (95% confidence interval, CI) 1.35–5.68, P = 0.01], LV fractional area change [FAC; HR 0.7 (95% CI 0.57–0.85), P = 0.002), SRV basal diameter [HR 1.66 (95% CI 1.21–2.29), P = 0.005], and SRV FAC [HR 0.65 (95% CI 0.49–0.87), P = 0.008] remained predictive of mortality or transplantation. On receiver-operating characteristic analysis, subpulmonary LV parameters performed better than SRV markers in predicting adverse events. Conclusion SRV basal diameter, SRV FAC, LV ESDi, and LV FAC are significantly and independently associated with mortality and transplantation in adults with an SRV. Accurate echocardiographic assessment of both SRV and subpulmonary LV is, therefore, essential to inform risk stratification and management. [ABSTRACT FROM AUTHOR]

Background Lenvatinib is a first-line agent for advanced hepatocellular carcinoma (HCC), but individual responses to treatment are highly heterogeneous. The aim of this study was to investigate the clinical parameters that influence the efficacy of Lenvatinib and to develop a prognostic model. Methods We retrospectively enrolled 333 Lenvatinib-treated patients with HCC with a median age of 57 years. Two hundred nd sixty-three of these patients had BCLC (2022) stage C. The median overall survival (mOS) time within the cohort was 12.1 months, and the median progression-free survival (mPFS) time was 4.7 months. Univariate Cox regression, best subset regression, and Lasso regression were used to screen primary variables for possible contribution to OS, multivariate Cox analysis was used to fit selected models, and the final model was selected using the maximum area under the curve (AUC) and minimum AIC. Receiver operating curves (ROC), calibration curves, and decision curve analysis were plotted to assess model performance, and 5-fold cross-validation was performed for internal validation. X-tile software was used to select the best cutoff points and to divide the study cohort into 3 different risk groups. Results Seven variables were included in the final model: BCLC stage, prior transarterial chemoembolization and immunotherapy history, tumor number, prognostic nutritional index, log (alpha-fetoprotein), and log (platelet-to-lymphocyte ratio). We named this final model the "multivariate prognostic model for Lenvatinib" (MPML), and a nomogram was constructed to predict the probability of survival at 6, 9, and 12 months. The MPML had good discrimination, calibration, and applicability. Cross-validation showed mean AUC values of 0.7779, 0.7738, and 0.7871 at 6, 9, and 12 months, respectively. According to nomogram points, mOS time was 21.57, 8.70, and 5.37 months in the low, medium, and high-risk groups, respectively (P <.001), and these differences were also observed in the PFS survival curve (P <.001). Conclusions The MPML stratified patients according to baseline clinical characteristics had a strong performance in predicting Lenvatinib efficacy and has the potential for use as an auxiliary clinical tool for individualized decision-making. [ABSTRACT FROM AUTHOR]

Objectives Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). Methods Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups—coSMZ and non-coSMZ—based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. Results Compared with the non-coSMZ group (n  = 93), the coSMZ group (n  = 121) had lower mortality (18.8% vs 51.1%; P   <  0.001) and a lower incidence of PJP (6.8% vs 15.2%; P  = 0.040) and fatal infection (16.1% vs 3.3%; P  = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102–0.878), P  = 0.028]. Conclusion Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP. [ABSTRACT FROM AUTHOR]

Background Laboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed. Methods This observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without human immunodeficiency virus (HIV) and to evaluate their diagnostic performance in neurosyphilis compared with CSF. Results Serum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cutoff levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms' sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively. Conclusions To avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objective Our aim was to investigate the association between gene polymorphisms in catalase (CAT), a well-known oxidative stress regulator, and susceptibility to idiopathic nephrotic syndrome (INS) or responses to steroid therapy in a Chinese pediatric population. Methods We analyzed 3 CAT single-nucleotide polymorphisms (SNVs; rs7943316, rs769217, and rs12270780) using multi-polymerase chain reaction combined with next-generation sequencing in 183 INS patients and 100 healthy controls. Results For the allele and genotype frequencies of the CAT SNVs, no significant differences were observed between INS patients and controls. Patients with C allele of CAT rs769217 had a higher risk of developing steroid-dependent nephrotic syndrome than the steroid-sensitive nephrotic syndrome patients (P = 0.018; odds ratio = 1.76). Conclusion Our data suggests that genetic variations in CAT were unlikely to confer susceptibility to INS in Chinese children, whereas the C allele of the CAT rs769217 polymorphism showed a strong association with steroid-dependent responses in Chinese INS children. [ABSTRACT FROM AUTHOR]

Aims To investigate contraction patterns of the systemic right ventricle (SRV) in patients with transposition of great arteries (TGA) post-atrial switch operation and with congenitally corrected transposition of great arteries (ccTGA). Methods and results Right ventricular (RV) volumes and ejection fraction (EF) were measured by three-dimensional echocardiography in 38 patients with the SRV (24 TGA and 14 ccTGA; mean age 45 ± 12 years, 63% male), and in 38 healthy volunteers. The RV contraction was decomposed along the longitudinal, radial, and anteroposterior directions providing longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their contributions to total right ventricular ejection fraction (LEFi, REFi, and AEFi, respectvely). SRV was significantly larger with lower systolic function compared with healthy controls. SRV EF and four-chamber longitudinal strain strongly correlated with B-type natriuretic peptide (BNP) level (Rho −0.73, P < 0.0001 and 0.70, P < 0.0001, respectively). In patients with TGA, anteroposterior component was significantly higher than longitudinal and radial components (AEF 17 ± 4.5% vs. REF 13 ± 4.9% vs. LEF 10 ± 3.3%, P < 0.0001; AEFi 0.48 ± 0.09 vs. REFi 0.38 ± 0.1 vs. LEFi 0.29 ± 0.08, P < 0.0001). In patients with ccTGA, there was no significant difference between three SRV components. AEFi was significantly higher in TGA subgroup compared with ccTGA (0.48 ± 0.09 vs. 0.36 ± 0.08, P = 0.0002). Conclusion Contraction patterns of the SRV are different in TGA and ccTGA. Anteroposterior component is dominant in TGA providing compensation for impaired longitudinal and radial components, while in ccTGA all components contribute equally to the total EF. SRV EF and longitudinal strain demonstrate strong correlation with BNP level and should be a part of routine echocardiographic assessment of the SRV. [ABSTRACT FROM AUTHOR]

Background The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. Methods National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. Results A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI]: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI:.95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs. [ABSTRACT FROM AUTHOR]