Performance analysis of non-invasive prenatal testing for trisomy 13, 18, and 21: A large-scale retrospective study (2018-2021).

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi.

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Physical Grinding of Prefabricated Co3O4 and MCM-22 Zeolite for Fischer-Tropsch Synthesis: Impact of Pretreatment Procedure on the Dispersion and Catalytic Performance.

To improve the mess-specific activity of Co supported on zeolite catalysts in Fischer-Tropsch (FT) synthesis, the Co-MCM-22 catalyst was prepared by simply grinding the MCM-22 with nanosized Co3O4 prefabricated by the thermal decomposition of the Co(II)-glycine complex. It is found that this novel strategy is effective for improving the mess-specific activity of Co catalysts in FT synthesis compared to the impregnation method. Moreover, the ion exchange and calcination sequence of MCM-22 has a significant influence on the dispersion, particle size distribution, and reduction degree of Co. The Co-MCM-22 prepared by the physical grinding of prefabricated Co3O4 and H+-type MCM-22 without a further calcination process exhibits a moderate interaction between Co3O4 and MCM-22, which results in the higher reduction degree, higher dispersion, and higher mess-specific activity of Co. Thus, the newly developed method is more controllable and promising for the synthesis of metal-supported catalysts.

A retrospective single-center analysis of prenatal diagnosis and follow-up of 626 chinese patients with positive non-invasive prenatal screening results.

This study explored the diagnostic efficiency of different prenatal diagnostic approaches for women with positive non-invasive prenatal screening (NIPS) results by analyzing their clinical information and pregnancy outcomes. We collected data on 626 NIPS-positive pregnant women from January 2017 to June 2021 and arranged subsequent prenatal diagnostic operations for them after genetic counseling, along with long-term intensive follow-up. A total of 567 women accepted invasive prenatal diagnosis (IPD) (90.58%), and 262 cases were confirmed as true positives for NIPS. The positive predictive values for trisomies 21 (T21), 18 (T18), and 13 (T13); sex chromosome aneuploidies (SCAs); rare autosomal trisomies (RATs); and microdeletion and microduplication syndromes (MMS) were 81.13%, 37.93%, 18.42%, 48.83%, 18.37%, and 41.67%, respectively. Discordant results between NIPS and IPD were observed in 48 cases, with the discordance rate being 8.47%. Additionally, there were 43 cases with discordant results between karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing. Additional reporting of RATs and MMS with routine NIPS that only detects T21/T18/T13 and SCAs can yield more accurate diagnoses. However, NIPS cannot be used as a substitute for IPD owing to its high false positive rate and discordance with other diagnostic methods. Therefore, we recommend CMA combined with karyotyping as the preferred method for accurately diagnosing NIPS-positive women.

[Health economic evaluation of four prenatal screening strategies for Down syndrome in Changsha, China].

OBJECTIVE: To compare the clinical application and health economic values of non-invasive prenatal testing (NIPT) and second trimester serum screening (STSS). METHODS: A retrospective analysis was carried out on 54 026 singleton pregnant women undergoing NIPT and STSS from March 1, 2018 to December 31, 2019 in Changsha Maternal and Child Health Care Hospital. For pregnant women with high-risk results of NIPT, prenatal diagnosis and follow-up of pregnancy outcomes were conducted. The data was grouped to 4 screening models, and their cost-benefit was analyzed. RESULTS: The sensitivity, specificity and positive predictive value of NIPT were all higher than STSS. Screening models 1 to 4 have prevented the birth of 71, 29, 52 and 54 patients with Down syndrome, respectively. The safety index of screening models 1 to 4 were 0.0036, 0.3944, 02215 and 0.1281, respectively. When the price of NIPT was decreased to 600 RMB, the cost-benefit of the screening models 1 to 4 was 0.46, 0.65, 0.44 and 0.40 million RMB, respectively. CONCLUSION: NIPT has a better detection performance than STSS. When the price of NIPT is 600 RMB, screening model 1 has the best screening effect and the highest accuracy, safety index and health economical value.

Retrospective analysis of the risk factors associated with failure in obtaining effective noninvasive prenatal test results and pregnancy outcomes: a case-control study.

OBJECTIVE: To explore the pregnancy outcomes of women who couldn't obtain effective results from noninvasive prenatal testing (NIPT) and examine the factors leading to test failure. METHODS: From April 2017 to December 2019, 120,041 pregnant women enrolled for voluntary NIPT. The case group comprised of 274 (274/120,041) women who failed to obtain effective NIPT results, and the control group (n = 540) was from the same population who obtained effective NIPT results and matched by age at a 1:2 ratio. Abnormal pregnancy rates between the two groups were analyzed using Chi-square analysis. NIPT failure risk factors were analyzed using logistic regression analysis. RESULTS: Logistic regression analysis showed that increased maternal age (OR = 0.988; 95% CI = 0.982-0.994), increased pregnancy age (OR = 0.989; 95%CI = 0.988-0.991), and decreased cell-free fetal DNA concentration (OR = 1.050; 95%CI = 1.043-1.058) were independent risk factors for NIPT failure. Fifteen cases showed fetus loss in cases of NIPT failure. There was a significant difference in abnormal pregnancy rate between the NIPT success and failure groups (χ2 = 50.943, P < 0.05). EXPERT COMMENTARY: The specific interventions, guidance, and precautions are needed for pregnant women who have no effective NIPT results.

Cell-Free DNA Screening for Sex Chromosome Abnormalities and Pregnancy Outcomes, 2018-2020: A Retrospective Analysis.

To evaluate the efficacy of non-invasive prenatal screening (NIPT) for detecting fetal sex chromosome abnormalities, a total of 639 women carrying sex chromosome abnormalities were selected from 222,107 pregnant women who participated in free NIPT from April 2018 to December 2020. The clinical data, prenatal diagnosis results, and follow-up pregnancy outcomes of participants were collected. The positive predictive value (PPV) was used to analyze the performance of NIPT. Around 235 cases were confirmed with sex chromosome abnormalities, including 229 cases with sex chromosome aneuploidy (45, X (n = 37), 47, XXX (n = 37), 47, XXY (n = 110), 47, XYY (n = 42)) and 6 cases with structural abnormalities. The total incidence rate was 0.11% (235/222,107). The PPV of NIPT was 45.37% (235/518). NIPT accuracy for detecting sex chromosome polysomes was higher than that for sex chromosome monomers. The termination of pregnancy rate for fetal diagnosis of 45, X, and 47, XXY was higher than that of 47, XXX, and 47, XYY. The detection rate of fetal sex chromosome abnormalities was higher in 2018-2020 than in 2010-2012 (χ2 = 69.708, P < 2.2 × 10-16), indicating that NIPT is greatly efficient to detect fetal sex chromosome abnormalities.

Boosting the Efficiency of Non-fullerene Organic Solar Cells via a Simple Cathode Modification Method.

This work demonstrates a simple yet effective method to significantly improve the power conversion efficiency (PCE) of highly efficient non-fullerene organic solar cells by mixing two electron transport materials. The new electron transport layer shows an energy level better aligned with the active layer and an improved morphology that could reduce the active layer-electrode contact. These improvements lead to enhanced charge extraction, better charge selectivity, suppressed exciton recombination, and finally a boosted PCE in the PM6:Y6-based solar cells. When applied in conjunction with the non-halogenated solvent-processed PM6:PY-IT-based active layer, the mixed ETL also gives rise to a leading result for binary all-polymer solar cells (PCE of >16%) with a concurrent increase in VOC, JSC, and FF.

Correction: Ding, S., et al. NNB-Type Tridentate Boryl Ligands Enabling a Highly Active Iridium Catalyst for C⁻H Borylation. Molecules 2019, 24, 1434.

The authors wish to make the following corrections to this paper [...].

NNB-Type Tridentate Boryl Ligands Enabling a Highly Active Iridium Catalyst for C⁻H Borylation.

Boryl ligands play a very important role in catalysis because of their very high electron-donating property. In this paper, NNB-type boryl anions were designed as tridentate ligands to promote aryl C-H borylation. In combination with [IrCl(COD)]2, they generate a highly active catalyst for a broad range of (hetero)arene substrates, including highly electron-rich and/or sterically hindered ones. This work provides a new NNB-type tridentate boryl ligand to support homogeneous organometallic catalysis.

Unsymmetrical Diboron Reagents: Application in Borylation Reactions of Unsaturated Bonds.

In the past decades, borylation reactions have received extensive research interest and have developed into effective tools in the synthesis of versatile organoboron compounds. Boranes and symmetrical diboron compounds are commonly utilized as borylating reagents in these transformations, especially in the borylation reactions of unsaturated bonds. More recently, several types of unsymmetrical diboron reagents have been synthesized and applied in these borylation reactions, allowing for complementary chemo- and regioselectivity. This review aimed to highlight the recent development in this rising research field, focusing on new reactivity and selectivity that originates from the use of these unsymmetrical diboron reagents.

Direct Transformation from Arylamines to Aryl Naphthalene-1,8-diamino Boronamides: A Metal-Free Sandmeyer-Type Process.

A direct metal-free transformation from arylamines to aryl naphthalene-1,8-diamino boronamides, a type of masked boronic acid, has been developed based on Sandmeyer-type reactions. A nonsymmetrical diboron reagent, B(pin)-B(dan), was utilized as the borylating reagent, and the B(dan) moiety was transferred to the aim products selectively. This conversion tolerated a series of functional groups, including chloro, bromo, fluoro, ester, hydroxy, cyano and amide.

Pretreatment neutrophil-lymphocyte count ratio may associate with gastric cancer presence.

BACKGROUND: Inflammation plays a pivotal role in cancer development and progression. Neutrophil-lymphocyte count ratio (NLR) is an indicator of systemic inflammatory response which is supposedly associated with gastric cancer (GC) development and progression. Since this parameter can be easily obtained from routine blood examination, it will be a great economic relief to gastric patients if we can bring it into clinical application. OBJECTIVE: The current study aims to evaluate the pretreatment NLR in gastric cancer patients through retrospectively reviewing the medical records. METHODS: A total of 327 patients hospitalized on a tertiary care hospital were retrospectively investigated and divided into two groups. Gastric cancer group were composed of patients with newly diagnosed, pathologically confirmed GC and the control group were patients with gastric polyp or benign gastric stromal tumor. The value of NLR in the presence and stage of gastric cancer was investigated in the entire gastric cancer group. RESULTS: Our study showed levels of NLR were significantly higher in gastric cancer cohort (2.17 (1.63-3.09) versus 1.62 (0.85-2.32), p< 0.001). After all the known confounders were excluded, NLR was an independent predicator of GC (OR = 1.446, 95%CI (1.121-1.866), and P= 0.005). Area under ROC curve (AUC) of NLR was 0.694. In addition, the results of Spearman's correlation showed NLR may have a positive correlation with size of tumor, N-stage, distant metastasis, and overall stage (r = 0.256, 0.256, 0.161 and 0.171, resp., all p < 0.05). CONCLUSIONS: The current study demonstrated that pre-treatment NLR may be a useful biomarker in the health care of gastric cancer patients.

Application of failure mode and effects analysis in a clinical chemistry laboratory.

BACKGROUND: Timely delivery of correct results has long been considered as the goal of quality management in clinical laboratory. With increasing workload as well as complexities of laboratory testing and patient care, the traditional technical adopted like internal quality control (IQC) and external quality assessment (EQA) may not enough to cope with quality management problems for clinical laboratories. We applied failure mode and effects analysis (FMEA), a proactive tool, to reduce errors associated with the process beginning with sample collection and ending with a test report in a clinical chemistry laboratory. Our main objection was to investigate the feasibility of FMEA in a real-world situation, namely the working environment of hospital. METHODS: A team of 8 people (3 laboratory workers, 2 couriers, 2 nurses, and 1 physician) from different departments who were involved in the testing process were recruited and trained. Their main responsibility was to analyze and score all possible clinical chemistry laboratory failures based on three aspects: the severity of the outcome (S), the likeliness of occurrence (O), and the probability of being detected (D). These three parameters were multiplied to calculate risk priority numbers (RPNs), which were used to prioritize remedial measures. Failure modes with RPN≥200 were deemed as high risk, meaning that they needed immediate corrective action. After modifications that were put, we compared the resulting RPN with the previous one. RESULTS: A total of 33 failure modes were identified. Many of the failure modes, including the one with the highest RPN (specimen hemolysis) appeared in the pre-analytic phase, whereas no high-risk failure modes (RPN≥200) were found during the analytic phase. High-priority risks were "sample hemolysis" (RPN, 336), "sample delivery delay" (RPN, 225), "sample volume error" (RPN, 210), "failure to release results in a timely manner" (RPN, 210), and "failure to identify or report critical results" (RPN, 200). The corrective measures that we took allowed a decrease in the RPN, especially for the high-priority risks. The maximum reduction was approximately 70%, as observed for the failure mode "sample hemolysis". CONCLUSIONS: FMEA can effectively reduce errors in clinical chemistry laboratories.

Site-differentiated polyboron arenes prepared by direct C-H borylation and their highly selective Suzuki-Miyaura cross-coupling reactions.

Di- and polyboron (hetero)arenes, site-differentiated with MIDA boronyl (MIDA=N-methyliminodiacetic acid) and pinacolato boronyl (Bpin), were prepared by an iridium-catalyzed direct CH borylation of readily available (hetero)aryl MIDA boronates. The excellent synthetic uses of these multisite nucleophiles were demonstrated by the high-yield production of a variety of multifunctionalized poly(hetero)arenes with the highly chemoselective Suzuki-Miyaura coupling (SMC) of the Bpin moiety being an essential step.

Tracking of vessels in intra-operative microscope video sequences for cortical displacement estimation.

This article presents a method designed to automatically track cortical vessels in intra-operative microscope video sequences. The main application of this method is the estimation of cortical displacement that occurs during tumor resection procedures. The method works in three steps. First, models of vessels selected in the first frame of the sequence are built. These models are then used to track vessels across frames in the video sequence. Finally, displacements estimated using the vessels are extrapolated to the entire image. The method has been tested retrospectively on images simulating large displacement, tumor resection, and partial occlusion by surgical instruments and on 21 video sequences comprising several thousand frames acquired from three patients. Qualitative results show that the method is accurate, robust to the appearance and disappearance of surgical instruments, and capable of dealing with large differences in images caused by resection. Quantitative results show a mean vessel tracking error (VTE) of 2.4 pixels (0.3 or 0.6 mm, depending on the spatial resolution of the images) and an average target registration error (TRE) of 3.3 pixels (0.4 or 0.8 mm).

Intraoperative brain shift compensation: accounting for dural septa.

Biomechanical models that describe soft tissue deformation provide a relatively inexpensive way to correct registration errors in image-guided neurosurgical systems caused by nonrigid brain shift. Quantifying the factors that cause this deformation to sufficient precision is a challenging task. To circumvent this difficulty, atlas-based methods have been developed recently that allow for uncertainty, yet still capture the first-order effects associated with deformation. The inverse solution is driven by sparse intraoperative surface measurements, which could bias the reconstruction and affect the subsurface accuracy of the model prediction. Studies using intraoperative MR have shown that the deformation in the midline, tentorium, and contralateral hemisphere is relatively small. The dural septa act as rigid membranes supporting the brain parenchyma and compartmentalizing the brain. Accounting for these structures in models may be an important key to improving subsurface shift accuracy. A novel method to segment the tentorium cerebelli will be described, along with the procedure for modeling the dural septa. Results in seven clinical cases show a qualitative improvement in subsurface shift accuracy making the predicted deformation more congruous with previous observations in the literature. The results also suggest a considerably more important role for hyperosmotic drug modeling for the intraoperative shift correction environment.

A fast and efficient method to compensate for brain shift for tumor resection therapies measured between preoperative and postoperative tomograms.

In this paper, an efficient paradigm is presented to correct for brain shift during tumor resection therapies. For this study, high resolution preoperative (pre-op) and postoperative (post-op) MR images were acquired for eight in vivo patients, and surface/subsurface shift was identified by manual identification of homologous points between the pre-op and immediate post-op tomograms. Cortical surface deformation data were then used to drive an inverse problem framework. The manually identified subsurface deformations served as a comparison toward validation. The proposed framework recaptured 85% of the mean subsurface shift. This translated to a subsurface shift error of 0.4 +/- 0.4 mm for a measured shift of 3.1 +/- 0.6 mm. The patient's pre-op tomograms were also deformed volumetrically using displacements predicted by the model. Results presented allow a preliminary evaluation of correction both quantitatively and visually. While intraoperative (intra-op) MR imaging data would be optimal, the extent of shift measured from pre- to post-op MR was comparable to clinical conditions. This study demonstrates the accuracy of the proposed framework in predicting full-volume displacements from sparse shift measurements. It also shows that the proposed framework can be extended and used to update pre-op images on a time scale that is compatible with surgery.

Semiautomatic registration of pre- and postbrain tumor resection laser range data: method and validation.

This paper presents a semiautomatic method for the registration of images acquired during surgery with a tracked laser range scanner (LRS). This method, which relies on the registration of vessels that can be visualized in the pre- and the postresection images, is a component of a larger system designed to compute brain shift that occurs during tumor resection cases. Because very large differences between pre- and postresection images are typically observed, the development of fully automatic methods to register these images is difficult. The method presented herein is semiautomatic and requires only the identification of a number of points along the length of the vessels. Vessel segments joining these points are then automatically identified using an optimal path finding algorithm that relies on intensity features extracted from the images. Once vessels are identified, they are registered using a robust point-based nonrigid registration algorithm. The transformation computed with the vessels is then applied to the entire image. This permits establishment of a complete correspondence between the pre- and post-3-D LRS data. Experiments show that the method is robust to operator errors in localizing homologous points and a quantitative evaluation performed on ten surgical cases shows submillimetric registration accuracy.

Estimation of intra-operative brain shift using a tracked laser range scanner.

Intra-operative brain shift limits the usefulness of image-guided neurosurgery systems (IGNS), which are based on pre-operative images. Methods that are being developed to address this problem need intra-operative measurements as input. In this work, we present an intra-operative surface shift measurement technique that relies on a tracked 3D laser range scanner. This scanner acquires both 3D range data and 2D images, which are co-registered. We compare two methods to derive displacements at every point in the field of view. The first one relies on the registration of the 2D images; the second relies on the direct 3D registration of the 3D range data. Our results, based on five data sets, show that the 2D method is preferable.