Modeling of large-scale hoxbb cluster deletions in zebrafish uncovers a role for segmentation pathways in atrioventricular boundary specification.

Hox genes orchestrate the segmental specification of the muscular circulatory system in invertebrates but it has not proven straightforward to decipher segmental parallels in the vertebrate heart. Recently, patients with HOXB gene cluster deletion were found to exhibit abnormalities including atrioventricular canal defects. Using CRISPR, we established a mutant with the orthologous hoxbb cluster deletion in zebrafish. The mutant exhibited heart failure and atrioventricular regurgitation at 5 days. Analyzing the four genes in the hoxbb cluster, isolated deletion of hoxb1b-/- recapitulated the cardiac abnormalities, supporting hoxb1b as the causal gene. Both in situ and in vitro data indicated that hoxb1b regulates gata5 to inhibit hand2 expression and ultimately is required to pattern the vertebrate atrioventricular boundary. Together, these data reveal a role for segmental specification in vertebrate cardiac development and highlight the utility of CRISPR techniques for efficiently exploring the function of large structural genomic lesions.

A robust microsatellite instability detection model for unpaired colorectal cancer tissue samples.

BACKGROUND: Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples. METHODS: From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR. RESULTS: We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes ( MLH1 , MSH2 , MSH6 , and PMS2 ). CONCLUSION: MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.

A Combination Scheme of Pure Strapdown and Dual-Axis Rotation Inertial Navigation Systems.

Compared with the strapdown inertial navigation system (SINS), the rotation strapdown inertial navigation system (RSINS) can effectively improve the accuracy of navigation information, but rotational modulation also leads to an increase in the oscillation frequency of attitude errors. In this paper, a dual-inertial navigation scheme that combines the strapdown inertial navigation system and the dual-axis rotation inertial navigation system is proposed, which can effectively improve the attitude error accuracy in the horizontal direction by using the high-position information of the rotation inertial navigation system and the stability characteristics of the attitude error of the strapdown inertial navigation system. Firstly, the error characteristics of the strapdown inertial navigation system and the rotation strapdown inertial navigation system are analyzed, and then the combination scheme and Kalman filter are designed according to the error characteristics, and finally, the simulation experiment shows that the pitch angle error of the dual inertial navigation system is reduced by more than 35% and the roll angle error is reduced by more than 45% compared with the rotation strapdown inertial navigation system. Therefore, the combination scheme of double inertial navigation proposed in this paper can further reduce the attitude error of the rotation strapdown inertial navigation system, and at the same time, the two sets of inertial navigation systems can also enhance the reliability of ship navigation.

An Improved Differential Evolution Adaptive Fuzzy PID Control Method for Gravity Measurement Stable Platform.

In the platform gravimeter, the stabilization accuracy of the gravimetric stabilization platform is crucial to improve the accuracy of gravity value measurements due to its uncertainties, such as mechanical friction, inter-device coupling interference, and nonlinear disturbances. These cause fluctuations in the gravimetric stabilization platform system parameters and present nonlinear characteristics. To resolve the impact of the above problems on the control performance of the stabilization platform, an improved differential evolutionary adaptive fuzzy PID control (IDEAFC) algorithm is proposed. The proposed enhanced differential evolution algorithm is used to optimize the initial control parameters of the system adaptive fuzzy PID control algorithm to achieve accurate online adjustments of the gravimetric stabilization platform's control parameters when it is subject to external disturbances or state changes and attain a high level of stabilization accuracy. The results of simulation tests, static stability experiments, and swaying experiments on the platform under laboratory conditions, as well as on-board experiments and shipboard experiments, all show that the improved differential evolution adaptive fuzzy PID control algorithm has a higher stability accuracy compared with the conventional control PID algorithm and traditional fuzzy control algorithm, proving the superiority, availability, and effectiveness of the algorithm.

Body mass index, C-reactive protein, and pancreatic cancer: A Mendelian randomization analysis to investigate causal pathways.

Aim: To explore whether C-reactive protein (CRP) mediates the risk of body mass index (BMI) in pancreatic cancer (PC) and calculate the mediate proportion of CRP in this possible mechanism. Methods: Based on two-sample Mendelian randomization (TSMR), a two-step Mendelian randomization (TM) model was conducted to determine whether CRP was a mediator of the causal relationship between BMI and PC. The multivariable Mendelian randomization (MVMR) study was designed for mediating analysis and to calculate the mediating proportion mediated by CRP. Results: BMI has a positive causal relationship with PC (n = 393 SNPs, OR = 1.484, 95% CI: 1.021-2.157, p< 0.05). BMI has a positive causal relationship with CRP (n = 179 SNPs, OR = 1.393, 95% CI: 1.320-1.469, p< 0.05). CRP has a positive causal relationship with PC (n = 54 SNPs, OR = 1.348, 95% CI: 1.004-1.809, p< 0.05). After adjusting CRP, BMI has no causal relationship with PC (n = 334 SNPs, OR = 1.341, 95% CI: 0.884-2.037, p< 0.05). After adjusting BMI, there was still a positive causal relationship between CRP and PC (n = 334 SNPs, OR = 1.441, 95% CI: 1.064-1.950, p< 0.05). The mediating effect of CRP was 29%. Conclusions: In clinical practice, while actively advocating for weight loss among obese patients, we should focus on chronic inflammation levels in obese patients as well. In addition, anti-inflammatory dietary patterns and appropriate physical activity are important in preventing PC.

Assessing the causality between thyroid and breast neoplasms: A bidirectional Mendelian randomization study.

Aim: This study aimed to evaluate the association between thyroid neoplasms (TN) and the risk of developing breast neoplasms (BN) by assessing data on single nucleotide polymorphisms (SNPs) obtained from the Deutsches Krebsforschungszentrum (DKFZ) and Breast Cancer Association (BCAC). Methods: Data on SNPs associated with TN and BN were obtained from DKFZ and BCAC, respectively. Secondary data analysis of all pooled data from genome-wide association studies (GWAS) was performed to identify the genetic loci closely associated with TN or BN as instrumental variables (IVs). To evaluate the causal relationship between TN and BN, a bidirectional Mendelian randomization (MR) analysis was performed using MR Egger regression, weighted median, inverse variance weighted (IVW) random effects model, simple mode, weighted mode, maximum likelihood, penalized weighted median, IVW radial, IVW fixed effects, and robust adjusted profile scores (RAPS) method. Results: The MR in this study demonstrated a modest reverse causal relationship between TN and BN but a significant positive causal relationship between BN and TN. Conclusions: The MR of this study provided genetic evidence suggesting an association between BN and TN; however, further research is warranted to explore the potential mechanism of interaction between these two malignancies. Moreover, general breast screening should be performed in individuals with TN, but TN screening should be reinforced in individuals with BN.

An Improved System-Level Calibration Scheme for Rotational Inertial Navigation Systems.

The system-level calibration technology of rotational inertial navigation is one of the main methods to improve the accuracy of inertial navigation, and the design of the calibration scheme is the key to calibration technology. By the establishment of the error model of inertial navigation system, a 30-position calibration scheme is designed in this study. Based on the 30-dimensional Kalman filter, the constant errors, scale factor errors and installation error of gyroscope and accelerometer are identified. Comparing the traditional schemes and the 30-position scheme with the simulation experiment, the observability of the 30-position scheme is higher, the residual error of the estimated sensor is smaller and the navigation positioning accuracy after the estimated inertial sensor error parameter compensation is higher, which verifies the feasibility of the 30-position scheme. Finally, the measured experiment uses the 30-position scheme to estimate the error of a certain type of IMU sensor, and the calibration curve of the error parameter is well converged before the end of the calibration experiment, so it has certain practical value.

Genetic algorithm based fast alignment method for strap-down inertial navigation system with large azimuth misalignment.

In order to shorten the alignment time and eliminate the small initial misalignment limit for compass alignment of strap-down inertial navigation system (SINS), which is sometimes not easy to satisfy when the ship is moored or anchored, an optimal model based time-varying parameter compass alignment algorithm is proposed in this paper. The contributions of the work presented here are twofold. First, the optimization of compass alignment parameters, which involves a lot of trial-and-error traditionally, is achieved based on genetic algorithm. On this basis, second, the optimal parameter varying model is established by least-square polynomial fitting. Experiments are performed with a navigational grade fiber optical gyroscope SINS, which validate the efficiency of the proposed method.

[Retrograde locked intramedullary nail for the treatment of middle or distal fractures of humeral shaft].

OBJECTIVE: To study therapeutic effects of retrograde locked intramedullary nail for the treatment of middle or distal fractures of humeral shaft. METHODS: From October 2002 to February 2005, 21 patients with middle or distal fractures of humeral shaft were treated with AO retrograde locked intramedullary nail. Among the patients, 13 patients were male and 8 patients were female, ranging in age from 23 to 56 years, with an average of 34.5 years. Nineteen patients were fresh fractures, and 2 patients were old fractures. Eleven patients had middle fractures of humeral shaft, and other 10 patients had distal fractures of humeral shaft. Two patients with old fractures were non-union and treated with autoallergic bone grafting; 5 patients combined with radial nerve injury underwent exploration. The therapeutic effects were evaluated according to Constant-Murley shoulder score and Mayo elbow score. RESULTS: All the patients were followed up, ranging from 18 to 24 months, with an average of 20.8 months. The fractures were healed except 1 patient with old fracture and 1 patient with extremely distal acute fracture. The shoulders and elbows had satisfactory recovery except 1 patient with old fracture. The mean Constant-Murley score was (83.6 +/- 13.4) points (50-97), 12 patients got an excellent result, 5 good, 4 fair and no bad; the mean Mayo elbow score was (88.6 +/- 9.8) points (65-95), 13 patients got an excellent result, 5 good, 3 fair and no bad. CONCLUSION: The retrograde locked intramedullary nail offers an ideal treatment method for middle and distal fractures of humeral shaft. Strict operative indication, precise surgical techniques and stable locking are the keys to a successful treatment results.