Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Characteristics and feasibility of ambulatory respiratory assessment of paediatric neuromuscular disease: an observational retrospective study.

PURPOSE: To investigate the characteristics of respiratory involvement in Chinese paediatric neuromuscular disease (NMD) at early stage and to explore convenient monitoring methods. MATERIALS AND METHODS: Children with NMD (age < 18) diagnosed at a multidisciplinary joint NMD clinic at Peking University First Hospital from January 2016 to April 2021 were included. Overnight polysomnography (PSG) and pulmonary function test (PFT) data were analysed, and the characteristics of four groups: congenital muscular dystrophy (CMD), congenital myopathy, spinal muscular atrophy, and Duchenne muscular dystrophy (DMD) were compared. RESULTS: A total of 83 children with NMD were referred for respiratory assessment, of who 80 children underwent PSG; 41 performed spirometry and 38, both. The duration of pulse oxygen saturation (SpO2) <90% over apnoea and hypopnoea index (AHI) was lowest in DMD and significantly different from CMD (p = 0.033). AHI was positively correlated with the oxygen desaturation index (ODI) (r = 0.929, p = 0.000). The peak expiratory flow (PEF) were positively correlated with forced vital capacity (FVC), both as actual values and percent pred, respectively (r = 0.820, 0.719, p = 0.000). ROC derived sensitivity and specificity of prediction of AHI > 15/h or duration of SpO2<90% ≥ 60 min from FVC <51% pred was 75.8% and 85.7%, respectively. CONCLUSIONS: AHI and hypoxia burden were independent factors in children with NMD in PSG and attention needed to be paid in both. FVC might be a daytime predictor for significant sleep-disordered breathing or hypoxia. Nocturnal consecutive oximetry with diurnal peak flow measurement may be convenient and effective for home monitoring at early stage of respiratory involvement.

Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management.

The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.

Three-dimensional assessment of asymmetric mid-palatal suture expansion assisted by a customized microimplant-supported rapid palatal expander in non-growing patients: Uncontrolled Clinical Trial.

OBJECTIVES: The objective was to evaluate the magnitude, incidence and possible factors of asymmetric expansion with a customized microimplant-supported rapid palatal expander (MARPE) in non-growing patients. SETTING AND SAMPLE POPULATION: This retrospective study included a sample of 49 patients (mean age: 23.9 ± 3.9 years) treated with a customized microimplant-supported rapid palatal expander. Based on the symmetry of expansion, the sample was divided into Group S (symmetric expansion group, n = 26) and Group A (asymmetric expansion group, n = 23). METHODS: Pre- and post-treatment cone-beam computed tomography (CBCT) images were superimposed to assess skeletal change in both studied groups. Seven variables were tested: unilateral crossbite, maxillary base cant, chin deviation, the initial asymmetrical position of the mid-palatal suture, split pattern of frontomaxillary suture, Angle's classification and dental arch crowding. Paired t-test and logistic regression analyses were utilized to evaluate the possible factors behind the asymmetric expansion. RESULTS: There was a significant difference (P < .01) between the studied groups. The average expansion was 4.26 mm at the anterolateral maxillary walls (BB) and 3.83 mm at the greater palatine foramen region (GPF). The average expansion at the GPF was 90% of that at the BB. The frequency of asymmetric expansion was 46.9%. Among the seven tested variables, the presence of the initial asymmetric position of the mid-palatal suture is the only variable that showed correlation with asymmetric expansion. CONCLUSION: Initial asymmetric position of the mid-palatal suture is considered a contributing factor of skeletal asymmetric expansion following microimplant-supported rapid palatal expansion in skeletally comparable patients.

Safety assessment of a new benzoylphenylurea TXH09 and its efficacy against two borers Ostrinia furnacalis and Grapholitha molesta in field.

Benzoylphenylureas as an important type of insect growth regulators, acting on the moulting stage in immature insects, are highly effective and low toxic. The new benzoylphenylurea TXH09 [N-((2,6-dimethyl-4-(heptafluoropropyl-2-yl)phenyl)carbamoyl)-2,6-difluorobenzamide] has high efficacy against chewing insect pests harming vegetables and rice. In this paper, the efficacy of TXH09 against two intractable borers Ostrinia furnacalis and Grapholitha molesta were evaluated in field, and safety assessment by exploring the characteristics of photodegradation, cytotoxicity, micronucleus generation and chromosome aberration was performed. The results showed that TXH09 had good capability in preventing infested corn and reducing the population of O. furnacalis larvae, and maintained high efficacy on shoot protection and peach conservation against G. molesta larvae. There were no significant differences between the control effects of TXH09 and that of hexaflumuron or diflubenzuron at the same active dose. TXH09 photolysis in solvents N,N-dimethylformamide, toluene and methanol yielded two major products, and the photodegradation of TXH09 was more prone to occur in N,N-dimethylformamide. TXH09 and the mixture of its photoproducts showed higher cytotoxicity on insect Sf-9 cells than on human Hek293 cells. Moreover, TXH09 didn't show significant effects in inducing micronucleated cells in both male and female mice and chromosomal aberrations in mouse spermatocytes by its own. In conclusion, TXH09, as an effective insecticide, has good environmental safety performance against O. furnacalis and G. molesta in field.

Cumulative Tsallis entropy based on power spectrum of financial time series.

The complexity of financial time series is an important issue for nonlinear dynamic systems. Generalized power spectrum cumulative Tsallis entropy (PSCTE) is a newly proposed model for measuring dissimilarities between different time series. It solves the problem of traditional Shannon entropy inconsistency. In addition, the power spectrum is used to calculate the probability in the algorithm. In this paper, PSCTE is applied to simulation data sets, and financial time series are used to verify PSCTE reliability. The results show that PSCTE can be worked as an effective tool to measure dissimilarities and help identify signal patterns. Finally, we also obtain the geographical division of the stock market.

Vascularity assessment of thyroid nodules by quantitative color Doppler ultrasound.

Our objective was to assess the role of quantitative Doppler vascularity in differentiating malignant and benign thyroid nodules. Color Doppler images of 100 nodules were analyzed for three metrics: vascular fraction area, mean flow velocity index and flow volume index in three regions (nodule center, nodule rim and surrounding parenchyma). Vascular fraction area and flow volume index were higher in malignant than benign nodules in both the central and rim regions, whereas flow velocity index was equivalent in both regions. Of the three vascularity metrics studied, the vascular fraction area of the central region was most effective in predicting malignancy, with a sensitivity of 0.90 ± 0.05, specificity of 0.88 ± 0.13, positive predictive value of 0.84 ± 0.14, negative predictive value of 0.92 ± 0.03 and accuracy of 0.89 ± 0.08. Quantitative Doppler vascularity of the nodule center yielded a high level of discrimination between benign and malignant nodules and, thus, has the greatest potential to contribute to gray-scale assessment of thyroid cancer.

Benchmark Dose Analysis via Nonparametric Regression Modeling.

Estimation of benchmark doses (BMDs) in quantitative risk assessment traditionally is based upon parametric dose-response modeling. It is a well-known concern, however, that if the chosen parametric model is uncertain and/or misspecified, inaccurate and possibly unsafe low-dose inferences can result. We describe a nonparametric approach for estimating BMDs with quantal-response data based on an isotonic regression method, and also study use of corresponding, nonparametric, bootstrap-based confidence limits for the BMD. We explore the confidence limits' small-sample properties via a simulation study, and illustrate the calculations with an example from cancer risk assessment. It is seen that this nonparametric approach can provide a useful alternative for BMD estimation when faced with the problem of parametric model uncertainty.

Nonparametric estimation of benchmark doses in environmental risk assessment.

An important statistical objective in environmental risk analysis is estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a pre-specified benchmark response in a dose-response experiment. In such settings, representations of the risk are traditionally based on a parametric dose-response model. It is a well-known concern, however, that if the chosen parametric form is misspecified, inaccurate and possibly unsafe low-dose inferences can result. We apply a nonparametric approach for calculating benchmark doses, based on an isotonic regression method for dose-response estimation with quantal-response data (Bhattacharya and Kong, 2007). We determine the large-sample properties of the estimator, develop bootstrap-based confidence limits on the BMDs, and explore the confidence limits' small-sample properties via a short simulation study. An example from cancer risk assessment illustrates the calculations.

Breeding of commercially acceptable allelopathic rice cultivars in China.

BACKGROUND: One promising area of paddy weed control is the potential for exploiting the weed-suppressing ability of rice. This study was conducted to develop commercially acceptable allelopathic rice cultivars using crosses between allelopathic rice variety PI312777 and commercial Chinese cultivars (N2S, N9S, Huahui354, Peiai64S and Tehuazhan35), and to assess their weed suppression and grain yield in paddy fields in relation to their parents. RESULTS: There was a positive dominance in the crosses Huahui354 × PI312777 and N2S × PI312777 but recessive or negative dominance in N9S × PI312777, Peiai64S × PI312777 and Tehuazhan35 × PI312777. Huahui354 × PI312777 and N2S × PI312777 showed stronger weed suppression than their parents and other crosses. Finally, an F8 line with an appearance close to Huahui354 and a magnitude of weed suppression close to PI312777 was obtained from Huahui354 × PI312777. This line, named Huagan-3, was released as a first commercially acceptable allelopathic rice cultivar in China. The grain yield and quality of Huagan-3 met the commercial standard of the local rice industry. Huagan-3 greatly suppressed paddy weeds, although suppression was influenced by year-to-year variation and plant density. There was no certain yield reduction in Huagan-3 even under a slight infestation of barnyard grass in paddy fields. CONCLUSION: The successful breeding of Huagan-3 with high yield and strong weed suppression may be incorporated into present rice production systems to minimise the amount of herbicide used.

Simultaneous hybrid revascularization versus off-pump coronary artery bypass for multivessel coronary artery disease.

BACKGROUND: This study sought to compare early and midterm clinical outcomes of a simultaneous hybrid coronary revascularization procedure with those in a propensity-matched subset of patients undergoing conventional off-pump coronary artery bypass grafting. METHODS: From June 2007 through December 2009, 104 consecutive patients (mean age 61.8 ± 10.2 years) with multivessel coronary artery disease underwent elective simultaneous coronary revascularization at Fuwai Hospital. Using propensity score methodology, these patients were matched with 104 patients who had undergone off-pump coronary artery bypass grafting through median sternotomy during the same period. We compared these groups' in-hospital clinical outcomes and freedom from major adverse cardiac or cerebrovascular events at a mean follow-up of 18 ± 7.9 months. RESULTS: The hybrid procedure required longer operative time and incurred higher in-hospital costs, but had shorter median intubation time (11.6 ± 6.3 vs 13.8 ± 6.8 hours, p = 0.02), intensive care unit length of stay (34.5 ± 35.6 vs 55.3 ± 46.4 hours, p < 0.001), and postoperative in-hospital length of stay (8.2 ± 2.6 vs 9.5 ± 4.5 days, p = 0.01). The hybrid group had significantly less chest tube drainage (789 ± 389 vs 834 ± 285 mL, p = 0.005) and need for blood transfusion (28.8% vs 51.9%, p > 0.001). At a mean follow-up of 18 months, the freedom from major adverse cardiac or cerebrovascular events is in favor of the hybrid group (99.0% vs 90.4%; p = 0.03). CONCLUSIONS: Compared with conventional off-pump coronary artery bypass grafting, simultaneous hybrid coronary revascularization shortens recovery time and has superior outcomes at a mean follow-up of 18 months. Simultaneous hybrid coronary revascularization provides a safe and reproducible alternative for selected patients with multivessel coronary artery diseases.

[Surface modification and DNA-binding assessment of nano-hydroxyapatite].

OBJECTIVE: To evaluate the impact of surface modification on the DNA-binding ability of nano-hydroxyapatite (nHA). METHODS: Chemical co-precipitation-hydrothermal synthesis was utilized to prepare the nHA particles, and polyethylenimine (PEI) was used for surface modification of the nHA. Transmission electron microscopic (TEM) observation and zeta potential detection of the nHA were carried out before and after surface modification. The abilities of the nanoparticles, at different pH values and different concentrations, for DNA-binding and DNA protection against nuclease digestion were assessed before and after surface modification by electrophoresis. RESULTS: TEM observation showed a short rod-like morphology of PEI-modified nHA with uniform particle size and good dispersion; the nHA without the modification tended to aggregate with poor dispersion. With a positive zeta potential, the PEI-modified nHA showed an obviously enhanced ability of DNA binding at different pH values and concentrations, with strong capacity to protect the DNA against Dnase I digestion. At the concentration of 250 µg/ml and a pH value of 7.0, the nHA-PEI showed an optimal efficiency of DNA-binding and DNA protection. CONCLUSION: nHA with surface modification by PEI can serve as an effective vector for DNA binding and transfer.

Reducing seclusion and restraint: questionnaire for organizational assessment.

Mental health organizations that have successfully reduced or, in some cases, eliminated use of seclusion and restraint report that they have primarily focused on organizational factors to facilitate this process. The purpose of this paper is to describe the development of an instrument that measures staff perceptions of organizational activities to reduce seclusion and restraint as well as staff attitudes toward the use of these interventions. Consequently, the instrument can be used diagnostically to identify areas in need of improvement and can also be used as an outcome measure to assess shifts in staff perceptions reflective of organizational change. This article describes validation of the instrument, information on its administration, and analysis and use of data obtained with it.

Transitive closure and metric inequality of weighted graphs: detecting protein interaction modules using cliques.

We study transitivity properties of edge weights in complex networks. We show that enforcing transitivity leads to a transitivity inequality which is equivalent to ultra-metric inequality. This can be used to define transitive closure on weighted undirected graphs, which can be computed using a modified Floyd-Warshall algorithm. These new concepts are extended to dissimilarity graphs and triangle inequalities. From this, we extend the clique concept from unweighted graph to weighted graph. We outline several applications and present results of detecting protein functional modules in a protein interaction network.