MAMnet: detecting and genotyping deletions and insertions based on long reads and a deep learning approach.

Structural variations (SVs) play important roles in human genetic diversity; deletions and insertions are two common types of SVs that have been proven to be associated with genetic diseases. Hence, accurately detecting and genotyping SVs is significant for disease research. Despite the fact that long-read sequencing technologies have improved the field of SV detection and genotyping, there are still some challenges that prevent satisfactory results from being obtained. In this paper, we propose MAMnet, a fast and scalable SV detection and genotyping method based on long reads and a combination of convolutional neural network and long short-term network. MAMnet uses a deep neural network to implement sensitive SV detection with a novel prediction strategy. On real long-read sequencing datasets, we demonstrate that MAMnet outperforms Sniffles, SVIM, cuteSV and PBSV in terms of their F1 scores while achieving better scaling performance. The source code is available from https://github.com/micahvista/MAMnet.

Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

Visible-Light-Promoted Cascade Coupling of 2-Isocyanonaphthalenes with Elemental Sulfur and Amines to Construct Naphtho[2,1-d]thiazol-2-Amines.

A visible-light-induced strategy has been explored for the synthesis of naphtho[2,1-d]thiazol-2-amines through ortho-C-H sulfuration of 2-isocyanonaphthalenes with elemental sulfur and amines under external photocatalyst-free conditions. This three-component reaction, which utilizes elemental sulfur as the odorless sulfur source, molecular oxygen as the clean oxidant, and visible light as the clean energy source, provides a mild and efficient approach to construct a series of naphtho[2,1-d]thiazol-2-amines. Preliminary mechanistic studies indicated that visible-light-promoted photoexcitation of reaction intermediates consisting of thioureas and DBU might be involved in this transformation.

INSnet: a method for detecting insertions based on deep learning network.

BACKGROUND: Many studies have shown that structural variations (SVs) strongly impact human disease. As a common type of SV, insertions are usually associated with genetic diseases. Therefore, accurately detecting insertions is of great significance. Although many methods for detecting insertions have been proposed, these methods often generate some errors and miss some variants. Hence, accurately detecting insertions remains a challenging task. RESULTS: In this paper, we propose a method named INSnet to detect insertions using a deep learning network. First, INSnet divides the reference genome into continuous sub-regions and takes five features for each locus through alignments between long reads and the reference genome. Next, INSnet uses a depthwise separable convolutional network. The convolution operation extracts informative features through spatial information and channel information. INSnet uses two attention mechanisms, the convolutional block attention module (CBAM) and efficient channel attention (ECA) to extract key alignment features in each sub-region. In order to capture the relationship between adjacent subregions, INSnet uses a gated recurrent unit (GRU) network to further extract more important SV signatures. After predicting whether a sub-region contains an insertion through the previous steps, INSnet determines the precise site and length of the insertion. The source code is available from GitHub at https://github.com/eioyuou/INSnet . CONCLUSION: Experimental results show that INSnet can achieve better performance than other methods in terms of F1 score on real datasets.

Visible-Light-Initiated Multicomponent Reactions of α-Diazoesters to Access Organophosphorus Compounds.

A simple visible-light-initiated strategy has been established for the construction of organophosphorus compounds via aerobic multicomponent reaction of α-diazoesters, cyclic ethers, and P(O)H compounds under air. A number of phosphonates and phosphinates could be efficiently isolated in moderate to good yields without the use of photosensitizers and metal reagents. This multicomponent reaction has advantages of mild condition, simple operation, eco-friendly energy, good functional-group tolerance, and gram-scale synthesis.

Factors related to the absorption rate of benign thyroid nodules after image-guided microwave ablation: a 3-year follow-up.

PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.

BreakNet: detecting deletions using long reads and a deep learning approach.

BACKGROUND: Structural variations (SVs) occupy a prominent position in human genetic diversity, and deletions form an important type of SV that has been suggested to be associated with genetic diseases. Although various deletion calling methods based on long reads have been proposed, a new approach is still needed to mine features in long-read alignment information. Recently, deep learning has attracted much attention in genome analysis, and it is a promising technique for calling SVs. RESULTS: In this paper, we propose BreakNet, a deep learning method that detects deletions by using long reads. BreakNet first extracts feature matrices from long-read alignments. Second, it uses a time-distributed convolutional neural network (CNN) to integrate and map the feature matrices to feature vectors. Third, BreakNet employs a bidirectional long short-term memory (BLSTM) model to analyse the produced set of continuous feature vectors in both the forward and backward directions. Finally, a classification module determines whether a region refers to a deletion. On real long-read sequencing datasets, we demonstrate that BreakNet outperforms Sniffles, SVIM and cuteSV in terms of their F1 scores. The source code for the proposed method is available from GitHub at https://github.com/luojunwei/BreakNet . CONCLUSIONS: Our work shows that deep learning can be combined with long reads to call deletions more effectively than existing methods.

BAP1 regulates AMPK-mTOR signalling pathway through deubiquitinating and stabilizing tumour-suppressor LKB1.

Liver kinase B1 (LKB1), a tumour suppressor, participates in many cellular processes, including cell survival, growth, apoptosis, transformation, and metabolism. Upon performing yeast two-hybrid screening, co-immunoprecipitation, and GST pull-down, we identified that BRCA1-associated protein 1 (BAP1), a deubiquitinase, interacts with LKB1. Immunoblotting was performed to examine the effect of BAP1 on the activation of 5' AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), downstream of LKB1. The relationship between BAP1 deficiency and cancer cell proliferation was examined using cell survival assay and soft agar assay. qRT-PCR and oil red O staining were performed to evaluate lipid synthesis. Our findings reveal that BAP1 deubiquitinates LKB1, inhibits its degradation, and stabilises it, thereby affecting AMPK activation and downstream mTOR activity. BAP1 deficiency may enhance cellular proliferation as well as lipid synthesis.

Ultrasound appears to be a reliable technique for the diagnosis of piriformis syndrome.

INTRODUCTION: Piriformis muscle syndrome (PS) is a disorder encompassing a constellation of symptoms, including buttock and hip pain. In this study we aimed to assess the value of ultrasound (US) in the diagnosis of PS. METHODS: Thirty-three clinically diagnosed PS patients and 26 healthy volunteers underwent a clinical PS scoring examination and US and MRI assessment of the bilateral piriformis muscles. The areas under the receiver operating characteristic curves (AUROCs) of the US parameters (i.e., increased thickness [iTh] and increased cross-sectional area [iCSA]) for piriformis muscle were evaluated. RESULTS: On US and MRI, the thickness and CSA were increased in PS patients. The AUROCs for the iTh and iCSA for discriminating stage 0 (healthy volunteers) from stage 1 through stage 3 (PS patients) were 0.88 and 0.95, respectively. DISCUSSION: US may be a reliable technique for the clinical diagnosis of PS. Muscle Nerve 59:411-416, 2019.

Incidence of second-time lateral patellar dislocation is associated with anatomic factors, age and injury patterns of medial patellofemoral ligament in first-time lateral patellar dislocation: a prospective magnetic resonance imaging study with 5-year follow-up.

PURPOSE: To examine the predictors of the second-time lateral patellar dislocation (LPD) in patients after acute first-time LPD in a 5-year follow-up. METHODS: Data were collected prospectively from patients after acute first-time LPD with conservative treatment. Factors included sex, age at the first-time LPD, anatomical variants [trochlear dysplasia, patellar height, tibial tuberosity-trochlear groove (TT-TG) distance], and injury patterns of medial patellofemoral ligament (MPFL) in acute first-time LPD. Logistic regression was carried out to identify the independent risk factors for the incidence of the second-time LPD. RESULTS: The incidence rate of a second-time LPD was 35.5% (59 of 166) in the 5-year follow-up. Univariate analysis revealed significant differences in the incidence rate of the second-time LPD among age at the first-time LPD (P = 0.04), trochlear dysplasia (P = 0.003), patella height (P = 0.017) and the TT-TG distance (P = 0.027). Risk factors for the second-time LPD were age < 18 years at the first-time LPD [odds ratio (OR) 4.088], low-grade trochlear dysplasia (OR 7.214), high-grade trochlear dysplasia (OR 18.945), patella alta (OR 8.416), elevated TT-TG distance (OR 12.742), complete MPFL tear at its isolated femoral-side (OR 6.04) and complete combined MPFL tear (OR 5.851). CONCLUSIONS: Trochlear dysplasia, elevated TT-TG distance, patella alta, age < 18 years at the first-time LPD, complete MPFL tear at its isolated femoral-side and complete combined MPFL tear in the first-time LPD are independently associated with a higher incidence rate of the second-time LPD. LEVEL OF EVIDENCE: III.

Correlation analysis between injury patterns of medial patellofemoral ligament and vastus medialis obliquus after acute first-time lateral patellar dislocation.

PURPOSE: To evaluate the correlation between injury patterns of the medial patellofemoral ligament (MPFL) and vastus medialis obliquus (VMO) after acute first-time lateral patellar dislocation (LPD) in adults. METHODS: Magnetic resonance imaging (MRI) was prospectively performed in 132 consecutive adults with acute first-time LPD. Images were acquired and evaluated using standardized protocols. Injury patterns of MPFL were grouped by location and severity for analysis of the prevalence of VMO injury. RESULTS: MRI demonstrated VMO injury in 63 (47.7%) patients. Twenty (38.5%) and 43 cases (56.6%) were present in partial and complete MPFL tear subgroups, respectively. Compared with partial MPFL tears, complete tears showed a higher prevalence of VMO injury (P = 0.044). The mean coronal (28.5 mm) and mean sagittal VMO elevations (20.7 mm) were higher in the complete MPFL tear subgroup than in the partial tear subgroup (19.8 mm, P = 0.005; 11.9 mm, P < 0.001). No correlations were identified between the prevalence of VMO injury and location subgroups of MPFL injury (n.s.). Mean VMO elevations were higher in isolated femoral-side (FEM) and combined MPFL tear (COM) subgroups (mean coronal VMO elevation of 29 mm and mean sagittal VMO elevation of 20.8 mm in the FEM subgroup; mean coronal VMO elevation of 29.6 mm and mean sagittal VMO elevation of 23.1 mm in the COM subgroup) than in the isolated patellar-side MPFL tear (PAT) subgroup (P = 0.022, P < 0.001) (mean coronal VMO elevation of 20.7 mm and mean sagittal VMO elevation of 10.6 mm). CONCLUSIONS: Complete MPFL tear predisposes to VMO injury and has a higher elevation of torn VMO after acute first-time LPD in adults. Isolated femoral-side and combined MPFL tears predispose to higher elevation of torn VMO. LEVEL OF EVIDENCE: IV.

Low-intensity pulsed ultrasound in combination with SonoVue induces cytotoxicity of human renal glomerular endothelial cells via repression of the ERK1/2 signaling pathway.

OBJECTIVES: Low-intensity pulsed ultrasound (LIPUS) and SonoVue have been used widely for diagnosis and therapeutic treatment. The effects of LIPUS and SonoVue on the microvascular system and underlying molecular mechanisms have not been established. METHODS: Cultured human renal glomerular endothelial cells (HRGECs) were treated with 5-min ultrasonic irradiation, 20% SonoVue or the combination of both treatments. Cell proliferation, viablity, and apoptosis were measured by MTT assay, Trypan blue exclusion assay and flow cytometry, respectively. Activation of extracellular regulated protein kinases (ERK) were examined by Western blot. RESULTS: We found that LIPUS and SonoVue alone do not induce cytotoxicity of HRGECs; however, the combination of the two treatments reduces cell proliferation and increases cell death. In addition, the combination of LIPUS and SonoVue suppressed the activation of ERK 1/2 in HRGRCs. With pretreatment of the inhibitor of ERK1/2 signaling, PD98059, LIPUS, and SonoVue does not induce additional cell death and inhibition of proliferation. CONCLUSIONS: LIPUS combined with SonoVue induces cytotoxicity of HRGECs via repression of the ERK1/2 signaling pathway.

Injury patterns of medial patellofemoral ligament after acute lateral patellar dislocation in children: Correlation analysis with anatomical variants and articular cartilage lesion of the patella.

OBJECTIVES: To assess the relationship between injury patterns of medial patellofemoral ligament (MPFL) and anatomical variants and patellar cartilage lesions after acute lateral patellar dislocation (LPD) in children. METHODS: MR images were obtained in 140 children with acute LPD. Images were acquired and evaluated using standardised protocols. RESULTS: Fifty-eight cases of partial MPFL tear and 75 cases of complete MPFL tear were identified. Injuries occurred at an isolated patellar insertion (PAT) in 52 cases, an isolated femoral attachment (FEM) in 42 cases and an isolated mid-substance (MID) in five cases. More than one site of injury was identified in 34 cases. Compared with Wiberg patellar type C, Wiberg patellar type B predisposed to complete MPFL tear (P = 0.042). No correlations were identified between injury patterns of MPFL and trochlear dysplasia, patellar height and tibial tuberosity-trochlear groove distance (P > 0.05). Compared with partial MPFL tear, complete MPFL tear predisposed to Grade-IV and Grade-V patellar chondral lesion (P = 0.02). There were no correlations between incidence of patellar cartilage lesion and injury locational-subgroups of MPFL (P = 0.543). CONCLUSIONS: MPFL is most easily injured at the PAT in children. Wiberg patellar type B predisposes to complete MPFL tear. Complete MPFL tear predisposes to a higher grade of patellar chondral lesion. KEY POINTS: • MPFL is most easily injured at its patellar insertion in children. • Wiberg patellar type B predisposes to complete MPFL tear. • No correlations between injury patterns of MPFL and other three anatomical variants. • Complete MPFL tear predisposes to higher grade patellar chondral lesion. • No correlations between injury locations of MPFL and patellar cartilage lesion.

The Sonographic Features of an Oral Lymphoma.

The gastrointestinal tract is the most commonly involved extranodal site in non-Hodgkin lymphomas (NHL). Oral cavity as primary site constitutes only 2% of all extranodal non-Hodgkin lymphomas. The oral buccal mucosa involvement by lymphoma is very rare. Here, the authors report a case of primary mucosa-associated lymphoid tissue lymphoma of the oral mucosa. The sonographic features of the mass are described in depth.

Evaluation of medial patellofemoral ligament tears after acute lateral patellar dislocation: comparison of high-frequency ultrasound and MR.

OBJECTIVES: The purpose of this study was to compare the diagnostic performance of high-frequency ultrasound with MR in the evaluation of medial patellofemoral ligament (MPFL) lesions after acute lateral patellar dislocation (LPD). METHODS: High-frequency ultrasound and MR images were prospectively obtained in 97 consecutive patients with acute LPD. Images were acquired using standardised protocols and were independently evaluated by two radiologists. The MPFL was assessed at three sites (patellar insertion, femoral attachment, and mid-substance) for signs of injury. RESULTS: Of a total of 291 sites in 97 MPFLs, 127 showed proven MPFL tear at surgery, including 51 sites of complete tear and 76 sites of partial tear. In a site-based analysis, the sensitivity, specificity, and accuracy of high-frequency ultrasound was 90.8%, 96.3%, and 94.6%, respectively, for partial MPFL tear and 86.3%, 96.3%, and 94%, respectively, for complete tear. For MR, the sensitivity, specificity, and accuracy was 81.6%, 95.7%, and 91.3%, respectively, for partial MPFL tear and 80.4%, 95.7%, and 92.1%, respectively, for complete tear. There was no statistical difference between high-frequency ultrasound and MR in the assessment of partial (P = 0.1, 0.777, 0.155) or complete (P = 0.425, 0.777, 0.449) MPFL lesions. Interobserver agreement was very good for high-frequency ultrasound and good for MR. CONCLUSIONS: Data suggest that high-frequency ultrasound and MR have similar diagnostic performance in the evaluation of MPFL lesions after acute LPD. KEY POINTS: • High-frequency ultrasound and MR were able to detect MPFL lesions after acute lateral patellar dislocation. • High-frequency ultrasound and MR showed similarly high accuracy in diagnosing MPFL lesions. • Interobserver agreement was very good for high-frequency ultrasound and good for MR.

Transcatheter closure of atrial septal defect associated with arrhythmogenic right ventricular cardiomyopathy: a case report and literature review.

Arrhythmogenic right ventricular cardiomyopathy is characterised by progressive, fibrofatty replacement of myocardium, and ventricular arrhythmias, and its prognosis is usually poor. Arrhythmogenic right ventricular cardiomyopathy associated with atrial septal defect is very rare, and this combination may make the diagnosis, treatment, and prognosis difficult. We present a case of a patient with this association who underwent interventional treatment with a septal defect occluder. Transcatheter closure of atrial septal defect in a patient with arrhythmogenic right ventricular cardiomyopathy is hitherto unreported. During a 3-year follow-up he remained relatively stable. We also review the cases reported in the medical literature describing this uncommon association between arrhythmogenic right ventricular cardiomyopathy and atrial septal defect or patent foramen ovale.

Composition Design Strategy for High Entropy Amorphous Alloys.

High entropy amorphous alloys (HEAAs) are materials that have received much attention in recent years. They exhibit many unique properties; however, research on their composition design method has not been deep enough. In this paper, we summarized some effective composition design strategies for HEAAs. By adjusting the atomic ratio from quinary bulk metallic glasses, Ti20Zr20Cu20Ni20Be20 HEAA with a high fracture strength of 2315 MPa was designed. By similar element addition/substitution, a series of Ti-(Zr, Hf, Nb)-Cu-Ni-Be HEAAs was developed. They possess good glass-forming ability with a maximum critical diameter of 30 mm. Combining elements from those ternary/quaternary bulk metallic glasses has also proved to be an effective method for designing new HEAAs. The effect of high entropy on the property of the alloy, possible composition design methods, and potential applications were also discussed. This paper may provide helpful inspiration for future development of HEAAs.

Improving power ramp rate of a coal-fired power plant by a bypass steam accumulator.

The increasing penetration of high-volatility renewable energy sources in the power system presents higher demands for flexibility from coal-fired power plant (CFPP). To enhance the flexibility of CFPPs, researchers have conducted a significant amount of thermal-system-level research in recent years on increasing system peak shaving depth. However, the load ramp rate of CFPPs under deep peak shaving is rarely discussed, despite its significance to the overall flexibility performance of CFPPs. This paper proposes a steam accumulator storage system integrating to the turbine's bypass system. The steam accumulator charges directly with working fluid from the live steam or reheat systems and discharge to the turbine, responding quickly to power ramp commands. A steady state model and a dynamic model of the proposed system were built and validated, and the calculation shows that the proposed scheme provides a load change of +2.13 % Pe and -8.3%Pe during a round-trip with a power efficiency of 63.6 % at a unit load of 40 % THA. The unit's load increase rate under coordinated control was enhanced by 1.5 % Pe/min, reaching 3 % Pe/min, using the proposed steam accumulator without revising the original controls, and the load decrease rate reached at least 5 % Pe/min. The results indicate that the proposed system provides a straightforward, easy-to-implement, and efficient solution for enhancing the load ramp rate of CFPPs at low loads.

Insight into spatial variations of DOM fractions and its interactions with microbial communities of shallow groundwater in a mesoscale lowland river watershed.

Dissolved organic matter (DOM) plays a crucial role in driving biogeochemical processes and determining water quality in shallow groundwater systems, where DOM could be susceptible to dynamic influences of surface water influx. This study employed fluorescence excitation-emission matrix (EEM) spectroscopy combined with principal component coefficients, parallel factor analysis (PARAFAC), co-occurrence network analysis and structural equation modeling (SEM) to examine changes of DOM fractions from surface water to shallow groundwater in a mesoscale lowland river basin. Combining stable isotope and hydrochemical parameters, except for surface water (SW), two groups of groundwater samples were defined, namely, deeply influenced by surface water (IGW) and groundwater nearly non-influenced by surface water (UGW), which were 50.34 % and 19.39 % recharged by surface water, respectively. According to principal component coefficients, reassembled EEM data of these categories highlighted variations of the tyrosine-like peak in DOM. EEMs coupled with PARAFAC extracted five components (C1-C5), i.e. C1, protein-like substances, C2 and C4, humic-like substances, and C3 and C5, microbial-related substances. The abundance of the protein-like was SW > IGW > UGW, while the order of the humic-like was opposite. The bacterial communities exhibited an obvious cluster across three regions, which hinted their sensitivity to variations in environmental conditions. Based on co-occurrence, SW represented the highest connectivity between bacterial OTUs and DOM fractions, followed by IGW and UGW. SEM revealed that microbial activities increased bioavailability of the humic-like in the SW and IGW, whereas microbial compositions promoted the evolution of humic-like substances in the UGW. Generally, these results could be conducive to discern dissimilarity in DOM fractions across surface water and shallow groundwater, and further trace their interactions in the river watershed.