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Background: The Food and Drug Administration approved left atrial appendage occlusion with the Watchman device for patients who are at increased stroke risk and are suitable for oral anticoagulation but who have an appropriate reason to seek a nondrug alternative. These broad criteria raise the question of their interpretation in clinical practice. There is a lack of studies comprehensively evaluating the indications for Watchman implantation among a large series of patients from contemporary, real-world practice in the United States. Methods: We used the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry to identify Watchman procedures performed between 2016 and 2018. We assessed procedural indications for Watchman implantation in the United States and evaluated the association between procedural indications and in-hospital adverse events. Results: A total of 38 314 procedures were included. The mean patient age was 76.1±8.1 years, and 58.9% were men. The mean CHA 2 DS 2 -VASc score was 4.8±1.5, whereas the mean hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) score was 3.0±1.1. Prior stroke or transient ischemic attack was reported in 40.2% and prior bleeding in 70.1%, with gastrointestinal bleeding being most common (41.9%). The most common site-reported procedural indications for Watchman implantation were increased thromboembolic risk (64.8%) and history of major bleed (64.3%), followed by high fall risk (35.5%). Most (71.9%) had ≥2 procedural indications. Patients with high fall risk had increased risk of in-hospital adverse events (adjusted OR, 1.12; P =0.025), but no other differences were found in the risk of in-hospital adverse events by procedural indication. Conclusions: Among patients in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry, the most common procedural indications for Watchman implantation were increased thromboembolic risk, history of major bleed, and high fall risk. A majority of patients had multiple procedural indications. High fall risk conferred a modestly increased risk of in-hospital adverse events.

Acromegaly is characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), accompanied by a compromise in the perception of wellness. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) is relevant to assessing signs and symptoms but is mainly used to evaluate the efficacy of a pharmacological intervention. To explore the perioperative variation in symptom severity, the divergence between subgroups stratified according to clinical outcomes or treatment modalities, and the interaction between symptom scores and clinical indices, we prospectively recruited 106 patients with acromegaly from 2016 to 2018. Oral glucose tolerance and GH tests were performed, and PASQ was administered before treatment and 6 months postoperatively. Patients were divided into active (n = 49) and remission (n = 57) groups according to postoperative GH and IGF-1 levels. PASQ scores and GH and IGF-1 levels decreased significantly postoperatively in both groups. A significantly higher preoperative headache score and greater extent of decrease in arthralgia were seen in the active and remission groups, respectively. No significant variation in PASQ scores was found between patients receiving surgery alone and those receiving preoperative somatostatin analogs. Preoperative fasting GH (GH0) levels were positively correlated with preoperative excessive perspiration. Further regression analyses validated the variation in GH0 as a noteworthy determinant of the extent of change in soft-tissue swelling, excessive perspiration, fatigue, and total PASQ scores. Patient-reported symptoms were substantially alleviated after surgery, independent of endocrine remission or use of preoperative somatostatin. A GH level decrease was a notable coefficient for PASQ scores.

PLQE enhancement and emission manipulation have been achieved for zero-dimensional (MA)4InCl7 through a metal ion doping strategy. Cs+ or Mn2+ doping result in defect passivation and homogeneous crystals, while Sb3+ doping shift the emission center.

Clinical events committee (CEC) evaluation is the standard approach for end point adjudication in clinical trials. Due to resource constraints, large registries typically rely on site-reported end points without further confirmation, which may preclude use for regulatory oversight.We developed a novel automated adjudication algorithm (AAA) for end point adjudication in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion (LAAO) Registry using an iterative process using CEC adjudication as the "gold standard." A ≥80% agreement rate between automated algorithm adjudication and CEC adjudication was prespecified as clinically acceptable. Agreement rates were calculated.A total of 92 in-hospital and 127 post-discharge end points were evaluated between January 1, 2016 and June 30, 2019 using AAA and CEC. Agreement for neurologic events was90%. Percent agreement for in-hospital and post-discharge events was as follows: ischemic stroke 95.7% and 94.5%, hemorrhagic stroke 97.8% and 96.1%, undetermined stroke 97.8% and 99.2%, transient ischemic attack 98.9% and 98.4% and intracranial hemorrhage 100.0% and 94.5%. Agreement was80% for major bleeding (83.7% and 90.6%) and major vascular complication (89.1% and 97.6%). With this approach,1% of site reported end points require CEC adjudication. Agreement remained very good during the period after algorithm derivation.An AAA-guided approach for end point adjudication was successfully developed and validated for the LAAO Registry. With this approach, the need for formal CEC adjudication was substantially reduced, with accuracy maintained above an 80% agreement threshold. After application specific validation, these methods could be applied to large registries and clinical trials to reduce the cost of event adjudication while preserving scientific validity.

Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery, the causative molecular mechanisms are far from being fully defined. Therefore, more studies are needed to improve the current clinicopathological classification system, and advanced treatment strategies such as targeted therapy and immunotherapy are yet to be explored. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date for a cohort of 200 PitNET patients. Genomics data indicate that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion, and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. These identified molecular markers and alternations in various clusters/subtypes were further confirmed in an independent cohort of 750 PitNET patients. This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies.

The prediction of “sweet spot” of multi-lithology composite tight oil and gas reservoirs within mixed siliciclastic-carbonate sequences is a hot topic in oil and gas exploration. There are mixed lacustrine carbonate-siliciclastic rocks in the Da'anzhai Member of Ziliujing Formation in the Eastern Slope of western Sichuan Depression. The reservoir lithology is complex, and the main factors controlling the development of high-quality reservoirs are yet to be known. Based on a large number of drilling, core and thin section observation, well log and seismic data, this paper systematically studies the characteristics and factors controlling the development of the mixed siliciclastic-carbonate reservoir. The results show that the reservoir is composed primarily of coquina, sandstone, breccia and shale in lithology, and its development is mainly controlled by sedimentary microfacies, diagenesis, tectonism (fracturing) and paleogeomorphology during the sedimentary period. The effective fractures in reservoirs of the low-energy shell shoal facies are well developed with relatively good physical properties. With the change of sedimentary microfacies from low-energy shoal to high-energy shoal to arenaceous shoal, the hydrocarbon production capacity worsens step by step. Diagenesis, such as dissolution and fracturing, has a certain effect on reservoir physical properties. The palaeogeomorphic highs and slopes had well-developed fractures during the sedimentary period which are conducive to constructive dissolution, and thus they are favorable zones for reservoir development. The development of structural fractures further amplifies the influence of dissolution; thus the fracture zones are also favorable for the development of high-quality reservoirs. The favorable sedimentary facies zone and fracture development degree serve as the core factors for the formation of high-quality mixed reservoirs. The muddy limestone with certain dissolved pores and structural fractures deposited under the low-energy shell shoal setting is of relatively high-quality reservoir in the Da'anzhai Member.

ObjectiveOlder, relatively small studies identified female sex as a risk factor for adverse events after catheter ablation for atrial fibrillation (AF). We aimed to assess contemporary sex-based differences in baseline and procedural characteristics, adverse events, and quality of life among adults undergoing catheter ablation for AF.MethodsIn this observational cohort study, we evaluated those enrolled in the National Cardiovascular Data Registry AFib Ablation Registry between January 2016 and September 2020. Using logistic regression, we analysed the association between patient sex and in-hospital adverse events.ResultsAmong 58 960 adults (34.6% women) from 150 centres undergoing AF ablation by 706 physicians, women were older (68 vs 64 years, p1 day (adjusted OR (aOR) 1.41 (95% CI 1.33 to 1.49)), major adverse event (aOR 1.60 (95% CI 1.33 to 1.92)) and any adverse event (aOR 1.57 (95% CI 1.41 to 1.75)). Women had a higher risk of bradycardia requiring pacemaker, phrenic nerve damage, pericardial effusion, bleeding and vascular injury, but had no differences in death or acute pulmonary vein isolation.ConclusionsAmong almost 60 000 patients in the largest prospective registry of AF ablation procedures, female sex was independently associated with a higher risk of hospitalisation >1 day, adverse events, and reduced quality of life, although there were no differences in death or acute pulmonary vein isolation.

An increased risk of ocular hypertension was seen in Cushing's disease.Systemic steroid use is a significant risk factor for increased intraocular pressure (IOP). The incidence of ocular hypertension may rise to 30%-40% of the general population due to topical or systemic glucocorticoid usage. However, the incidence of ocular hypertension in endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to surgical resection, remain unknown.The IOP, visual field, and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing's disease (CD) admitted to a tertiary pituitary center for surgery from January to July 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period served as controls. We calculated the odds ratio (OR), identified the risk factors of developing ocular hypertension, and presented postoperative trends of the IOP.A total of 52 patients (38.4±12.4 y old) with CD were included. The IOP was higher in patients with CD (left 19.4±5.4 mm Hg and right 20.0±7.1 mm Hg) than in patients with acromegaly (left 17.5±2.3 mm Hg and right 18.6±7.0 mm Hg, P =0.033) and patients with NFPA (left 17.8±2.6 mm Hg and right 17.4±2.4 mm Hg, P =0.005). A total of 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension compared with 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The OR of developing ocular hypertension in patients with CD was 5.1 [95% confidence interval (CI), 1.3-25.1, P =0.029] and 6.6 (95% CI, 1.8-30.3, P =0.007) when compared with the 2 control groups. Among patients with CD, those with a higher urine-free cortisol were more likely to develop ocular hypertension (OR=19.4, 95% CI, 1.7-72.6). The IOP decreased at 1 month after surgery in patients with CD, and the change was sustained for 3 months after surgery.An increased risk of ocular hypertension was seen in CD and suggests that endogenous hypercortisolemia should be considered as part of the glaucoma assessment. This result warrants the discretion of both ophthalmologists and neuroendocrinologists.

Summary Since electromagnetic (EM) fields diffuse more smoothly to greater depth, it physically makes sense to apply fine discretization to model structure at near surface with an increasingly coarser grid both in horizontal and vertical directions as the depth increases for the numerical solution of EM fields. For finite difference magnetotelluric (MT) forward modeling on regular staggered grids, this can lead to difficulties in discretizing the curl-curl equation governing the EM diffusion in the earth at regions, where the grid resolution changes. In this paper, we propose an efficient algebraic multi-resolution sampling (MRS) method for MT forward modeling. In this method, we do not require the generation of physical subgrids and merely subsample the field components. The coefficient matrix for the subsampled components can be obtained by matrix multiplication based on the initial linear system of equations and field interpolation. To guarantee divergence free current during the iterative solution process at low frequencies, which is considered crucial for the development of efficient iterative solvers, our forward modeling is based a regularization equation obtained by augmenting the curl-curl equation with an equivalent scaled grad-div operator for electrical fields (explicitly enforcing the divergence free condition). The correctness of our algebraic MRS algorithm is examined based on a layered model. Its stability and efficiency is exploited by comparing our results with the forward modeling on unsampled staggered grids for the Dublin test model 1 (DTM1) and a complex model with realistic topography, indicating a time reduction of about 42 per cent-82 per cent.

Artificial intelligence approaches to analyze pathological images (pathomic) for outcome prediction have not been sufficiently considered in the field of pituitary research. A total of 5,504 hematoxylineosin-stained pathology image tiles from 58 acromegalic patients with a good or poor outcome were integrated with other clinical and genetic information to train a low-rank fusion convolutional neural network (LFCNN). The model was externally validated in 1,536 patches from an external cohort. The primary outcome was the time to the first endocrine remission after stereotactic radiosurgery (SRS). The median time of initial endocrine remission was 43 months (interquartile range [IQR]: 13-60 months) after SRS, and the 24-month initial cumulative remission rate was 57.9% (IQR: 46.4-72.3%). The patient-wise accuracy of the LFCNN model in predicting the primary outcome was 92.9% in the internal test dataset, and the sensitivity and specificity were 87.5 and 100.0%, respectively. The LFCNN model was a strong predictor of initial cumulative remission in the training cohort (hazard ratio [HR] 9.58, 95% confidence interval [CI] 3.89-23.59; p 0.001) and was higher than that of established prognostic markers. The predictive value of the LFCNN model was further validated in an external cohort (HR 9.06, 95% CI 1.14-72.25; p = 0.012). In this proof-of-concept study, clinically and genetically useful prognostic markers were integrated with digital images to predict endocrine outcomes after SRS in patients with active acromegaly. The model considerably outperformed established prognostic markers and can potentially be used by clinicians to improve decision-making regarding adjuvant treatment choices. © 2022 The Pathological Society of Great Britain and Ireland.

A review of a collection of theoretical source spectral models revealed: (1) Despite the well-known variation in predicting static stress drop Δσs from the seismic moment and corner frequency, all models, especially the three conventional models, suggest that earthquakes radiate about half of the available strain energy into the surrounding medium. This similarity justifies a less model-dependent approach to estimate Δσs, though estimates for natural earthquakes rely on apparent seismic radiation efficiency (=2σa/Δσs; σa is apparent stress of an earthquake). (2) When one attempts to use Δσs and spectral models to make predictions, such as apparent stress σa, there is a model-dependent discrepancy between the σa inferred from theoretical energy partitioning and the σa predicted using spherical mean corner frequency. Their ratio cp varies significantly from 1.0 for the Brune (1970, 1971) model to 6.38 for the Madariaga (1976) model. If one uses spectral models to predict the ground motion, cp must be considered. (3) We infer that the constancy of the “stress parameter” (Δσ˜) found in engineering seismology (e.g., Boore, 1983; Atkinson and Beresnev, 1998) is similar to having constant apparent stress, σa (e.g., Ide and Beroza, 2001). The observation that Δσ˜ is generally larger than the average static stress drop Δσs for global M >5.5 shallow crustal earthquakes in active tectonic regions implies that these earthquakes radiate, on average, more seismic energy than predicted from the conventional dynamic crack models.

Seed storage proteins (SSPs) accumulated within plant seeds constitute the major protein nutrition sources for human and livestock. SSPs are synthesized on the endoplasmic reticulum and are then deposited in plant-specific protein bodies, including endoplasmic reticulum-derived protein bodies and protein storage vacuoles. Plant seeds have evolved a distinct endomembrane system to accomplish SSP transport. There are two distinct types of trafficking pathways contributing to SSP delivery to protein storage vacuoles: one is Golgi-dependent and the other is Golgi-independent. In recent years, molecular, genetic, and biochemical studies have shed light on the complex network controlling SSP trafficking, to which both evolutionarily conserved molecular machineries and plant-unique regulators contribute. In this review, we discuss current knowledge of protein body biogenesis and endomembrane-mediated SSP transport, focusing on endoplasmic reticulum export and post-Golgi traffic. This knowledge supports a dominant role for the Golgi-dependent pathways in SSP transport in Arabidopsis and rice. In addition, we describe cutting-edge strategies for dissecting the endomembrane trafficking system in plant seeds to advance the field.

Traditional Krylov subspace methods can be slow for electromagnetic modeling, particularly at lower frequencies. One of the commonly used remedies is to apply the divergence correction iteratively during the solution process, which requires solving an additional divergence correction equation. Alternatively, we have developed an efficient regularization technique to carry out the forward modeling of the anisotropic effect for 3D controlled-source electromagnetic data. Inside this scheme, we explicitly include the gradient of a scaled divergence correction term into the original curl-curl equation for general anisotropic conductivity structure. This inclusion leads to a significantly better-conditioned linear system of equations without changing the solution of the original system and avoids the solution of an additional equation. The correctness of the developed algorithm is examined based on a vertical transverse isotropic layered model with the semianalytical solution available. Then, we use a tilted transverse isotropic ocean canonical reservoir model and a general anisotropic 3D model to investigate the stability and efficiency of the algorithm. Numerical experiments demonstrate that the developed technique is 0.49–2.9 times faster than the standard algorithm at the considered frequencies.

Objective: Gonadal and sexual disturbances are commonly encountered in patients with Cushing’s disease. Nevertheless, the prevalence of hypogonadism in male Cushing’s disease, the risk factors as well as the recovery time have been scarcely reported. Therefore, we aimed to explore the prevalence of hypogonadism at baseline and its determinants. In addition, the recovery time of hypogonadism and risk factors for unrecovered gonadal axis in male Cushing’s disease with biochemical remission were investigated.Methods: We reviewed medical records of males with Cushing’s disease managed between 2010 and 2020. Fifty-two male patients were enrolled according to the criteria. Each case attained biochemical remission after transsphenoidal surgery. Demographic details, clinical features, 24-hour UFC, hormonal profile [serum PRL, FSH, LH, TT, ACTH, cortisol, TT4/FT4, TT3/ FT3, TSH and IGF-1] were measured at baseline and during follow-up. The maximal tumor diameter on MRI was recorded at diagnosis.Results: Hypogonadotropic hypogonadism was observed in thirty-nine patients (75%) at diagnosis. Total testosterone was negatively correlated with ACTH and 24-hour UFC. Midnight serum ACTH level at diagnosis was significantly associated with hypogonadism after adjusting for confounding factors. Thirty-two (80%) patients achieved eugonadism within 12 months after the surgery, of which twenty-eight (87.5%) achieved eugonadism within 3 months. Seven patients were persistently hypogonadal during the follow-up (>1 year), mainly due to the hypopituitarism as a complication of the therapies such as surgery.Conclusion: Hypogonadotropic hypogonadism is frequent in male Cushing’s disease, but it is reversible in most cases within one-year follow-up after remission.

Pivotal trials of percutaneous left atrial appendage occlusion (LAAO) used specific postprocedure treatment protocols.This study sought to evaluate patterns of postprocedure care after LAAO with the Watchman device in clinical practice and compare the risk of adverse events for different discharge antithrombotic strategies.We evaluated patients in the LAAO Registry of the National Cardiovascular Data Registry who underwent LAAO with the Watchman device between 2016 and 2018. We assessed adherence to the full postprocedure trial protocol including standardized follow-up, imaging, and antithrombotic agents and then evaluated the most commonly used antithrombotic strategies and compared the rates and risk of adverse events at 45 days and 6 months by means of multivariable COX frailty regression.Among 31,994 patients undergoing successful LAAO, only 12.2% received the full postprocedure treatment protocol studied in pivotal trials; the most common protocol deviations were with discharge antithrombotic medications. The most common discharge medication strategies were warfarin and aspirin (36.9%), direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin only (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (5.0%). In multivariable Cox frailty regression, the adjusted risk of any adverse event through the 45-day follow-up visit were significantly lower for discharge on warfarin alone (HR: 0.692; 95% CI: 0.569-0.841) and DOAC alone (HR: 0.731; 95% CI: 0.574-0.930) compared with warfarin and aspirin. Warfarin alone retained lower risk at the 6-month follow-up.In contemporary U.S. practice, practitioners rarely used the full U.S. Food and Drug Administration-approved postprocedure treatment protocols studied in pivotal trials of the Watchman device. Discharge after implantation on warfarin or DOAC without concomitant aspirin was associated with lower risk of adverse outcomes.

Implantable cardioverter-defibrillators (ICDs) are recommended for patients with cardiac sarcoidosis (CS) with an indication for pacing, prior ventricular arrhythmias, cardiac arrest, or left ventricular ejection fraction35%, but data on outcomes are limited.Using data from the National Cardiovascular Data Registry ICD Registry between April 1, 2010 and December 31, 2015, we evaluated a propensity matched cohort of CS patients implanted with ICDs versus non-ischemic cardiomyopathies (NICM). We compared mortality using Kaplan-Meier survival curves and Cox proportional hazards models.We identified 1,638 patients with CS and 8,190 propensity matched patients with NICM. The rate of death at 1 and 2 years was similar in patients with CS and patients with NICM (5.2% vs 5.4%, P = 0.75 and 9.0% vs 9.3%, P = 0.72, respectively). After adjusting for other covariates, patients with CS had similar mortality at 2 years after ICD implantations compared with NICM patients (RR 1.03, 95% CI 0.87-1.23). Among patients with CS, multivariable logistic regression identified 6 factors significantly associated with increased 2-year mortality: presence of heart failure (HR 1.92, 95% CI 1.44-3.22), New York Heart Association (NYHA) Class III heart failure (HR 1.68, 95% CI 1.16-2.45), NYHA Class IV heart failure (HR 3.08, 95% CI 1.49-6.39), atrial fibrillation/flutter (HR 1.66, 95% CI 1.17-2.35), chronic lung disease (HR 1.64, 95% CI 1.17-2.29), creatinine2.0 mg/dL (HR 4.07, 95% CI 2.63-6.30), and paced rhythm (HR 2.66, 95% CI 1.07-6.59).Mortality following ICD implantation was similar in CS patients compared with propensity matched NICM patients. Presence of heart failure, NYHA class, atrial fibrillation/flutter, chronic lung disease, renal dysfunction, and paced rhythm at time of implantation were all predictors of increased 2-year mortality among CS patients with ICDs.

Vesicular trafficking plays critical roles in cell expansion in yeast and mammals, but information linking vesicular trafficking and cell expansion in plants is limited. Here, we isolated and characterized a rice (Oryza sativa) mutant, decreased plant height 1-1 (dph1-1), which exhibited a wide spectrum of developmental phenotypes, including reduced plant height and smaller panicles and grains. Cytological analysis revealed that limited cell expansion was responsible for the dph1-1 mutant phenotype compared to the wild-type. Map-based cloning revealed that DPH1 encodes a plant-specific protein, OsSCD2, which is homologous to Arabidopsis (Arabidopsis thaliana) STOMATAL CYTOKINESIS DEFECTIVE2 (SCD2). Subcellular localization revealed that OsSCD2 is associated with clathrin. Confocal microscopy showed that the dph1-1 mutant has defective endocytosis and post-Golgi trafficking. Biochemical and confocal data indicated that OsSCD2 physically interacts with OsSCD1 and that they are associated with intracellular structures that colocalize with microtubules. Furthermore, we found that cellulose synthesis was affected in the dph1-1 mutant, evidenced by reduced cellulose synthase gene accumulation at the transcript and protein levels, most likely resulting from an impaired localization pattern. Our results suggest that OsSCD2 is involved in clathrin-related vesicular trafficking with an important role in maintaining plant growth in rice.

Practical application of 3D magnetotelluric inversion requires efficient forward modeling of electromagnetic (EM) fields in the earth. To resolve realistic 3D structures, large computational domains and extremely large linear systems of equations are required. The iterative solvers, which are almost exclusively used to solve these systems, can be inefficient due to the abundant null space of the curl-curl operator. Multigrid (MG) solvers are considered a potentially efficient technique for solving such problems. However, due to the abundant null solution space and existence of the air layer, MG solvers can still converge slowly or even diverge. We have developed an efficient MG solver for finite-difference frequency-domain EM solution. In this algorithm, the excellent smoothing property of an efficient four-color cell-block Gauss-Seidel (GS) is exploited to remove the short-range errors effectively, and the interpolation and prolongation operators are used to handle the long-range errors. They work as a whole to speed the convergence of our algorithm remarkably. Because all of the nodes for the four-color cell-block GS are grouped into four colors and the edge components attached to different nodes in each color are completely decoupled, this can be used to develop a highly vectorized or parallelized algorithm. Another important property is that our algorithm is locally current divergence free, effectively eliminating spurious solutions in the null space of the curl-curl operator. The accuracy and efficiency of the algorithm are verified by comparing the numerical solutions obtained with our MG solver to those from the biconjugate gradient stabilized solver with different preconditioners based on synthetic models and a model from 3D inversion. Comparisons, in terms of iteration number and computational time, indicate that our algorithm is extremely stable and efficient relative to the other solvers. Our MG algorithm will be suitable for massively parallel computing as well.

Efficient bifunctional OER/ORR catalysts are crucial for the further development of zinc-air battery. From a sustainable point of view, it is important that electrocatalysts are efficient, low cost, and composed of abundant resources instead of scarce metals. Due to their good conductivity, low cost, and strong durability, carbon-based materials are considered a promising alternative in the field of commercial zinc-air battery catalysts. Herein, we briefly introduce the zinc-air battery and then summarize recent progress in the development of carbon-based bifunctional catalysts by defect engineering, heteroatom doping and metal doping. Finally, we discuss the main challenges and prospects for the future development of carbon-based bifunctional oxygen catalysts.

MCF/PPy/MoS2 delivers high reversible capacity and long cycling stability as a potential anode for lithium-ion batteries.

Pseudomonas spp. had rich biological functions, including the degradation of mycotoxins. In this study, to reveal the reasons for the different AFB1 degradation abilities, three pseudomonas strains with distinct AFB1 degradation abilities were isolated and their genomes were sequenced and annotated. COG (Clusters of Orthologous Groups) and GO (Gene Ontology) annotations of the protein-coding genes show a conservation of genomewide protein functions in genus Pseudomonas. However, the AFB1-degrading strains HAI2 and HT3 harbor much more genes belonged to the pathway of xenobiotics biodegradation and metabolism than non-degrading strain 48. Besides, the enzyme families potentially involved in the AFB1 degradation of bacteria are more abundant in the two AFB1-degrading strains. A pan-genome profile was then formed by comparing the genomes against other reference genomes of the corresponding Pseudomonas species. Accordingly, a total of 1,528 genes were found to be specific in AFB1-degrading strains, and 65 genes of them are related to oxidoreductase activity. The two AFB1-degrading Pseudomonas strains HAI2 and HT3 harbor additional peroxidases compared to strain 48. However, none of these oxidoreductase activity-related genes is shared by all three AFB1-degrading strains. High AFB1-degrading strain HT3 is more diverse than those of strains 48 and HAI2 and harbored two cytochrome P450 genes, but homologous sequences could not be found in the other two strains. Moreover, the numbers of peroxidase in HT3 and strain HAI2 are higher than strain 48. These findings indicate that different Pseudomonas strains might earn the ability to degrade AFB1 by independently acquiring different catalytic proteins rather than sharing some core proteins. Differences in some oxidoreductases, such as P450 and Peroxidase, may be responsible for this difference in degradation ability in Pseudomonas strains.

New small molecules MDAN and EDAN are synthesized and found to be different in tuning the morphology of low-dimensional perovskite morphology.

Objective Patients with Cushing’s disease (CD) experienced transient central adrenal insufficiency (CAI) after successful surgery. However, the reported recovery time of hypothalamic-pituitary-adrenal (HPA) axis varied and the risk factors which could affect recovery time of HPA axis had not been extensively studied. This study aimed to analyze the duration of CAI and explore the risk factors affecting HPA axis recovery in post-operative CD patients with biochemical remission. Design and methods Medical records of diagnosis with CD in Huashan Hospital were reviewed between 2014 and 2020. 140 patients with biochemical remission and regular follow-up after surgery were enrolled in this retrospective cohort study according to the criteria. Demographic details, clinical and biochemical information at baseline and each follow-up (within 2 years) were collected and analyzed. Results Overall, 103 patients (73.6%) recovered from transient CAI within 2 years follow-up and the median recovery time was 12 months [95% confidence intervals (CI): 10–14]. The age and midnight ACTH at baseline were significantly lower, while the TT3 and FT3 levels were significantly higher in patients with recovered HPA compared to patients with CAI at 2-year follow-up(p

International audience; Protein allergens is a health risk for consumption of soybeans. To understand allerginicity mechanism, T cell epitopes of 7 soybean allergens were predicted and screened by abilities to induce cytokine interleukin (IL) 4. The relationships among amino acid composition, properties, allergenicity, and pepsin hydrolysis sites were analyzed. Among the 138 T cell epitopes identified, YIKDVFRVIPSEVLS, KDVFRVIPSEVLSNS, DVFRVIPSEVLSNSY of Gly m 6.0501 (P04347), and AKADALFKAIEAYLL, ADALFKAIEAYLLAH of Gly m 4.0101 (P26987) were the most possible epitope candidates. In T cell epitopes pattern, the frequencies of amino acids Q, D, E, P, and G decreased, while F, I, N, V, K, H, A, L, and S increased. Hydrophobic residues at positions p1 and p2 and positively charged residues in positions p13 might contribute to allergenicity. Most of epitopes could be hydrolyzed by pepsin into small polypeptides within 12 residues length, and the anti-digestive epitope regions contained I, V, S, N, and Q residues. T cell epitopes EEQRQQEGVIVELSK from Gly m 5.03 (P25974) showed resistance to pepsin hydrolysis and would cause a higher Th2 cell response. This research provides basis for the development of hypoallergenic soybean products in the soybean industry as well as for the immunotherapy design for protein allergy.

Objectives This study analyzed the predictors of defibrillation safety margin (DSM) testing at the time of implantable cardioverter-defibrillator (ICD) insertion and factors associated with inadequate DSM in patients with congenital heart disease (CHD). Background There are few data about the prevalence and safety of DSM testing in those with CHD. Methods A retrospective analysis was performed of all patients with atrial or ventricular septal defect, tetralogy of Fallot, transposition of the great vessels, Ebstein anomaly, or common ventricle undergoing a transvenous ICD procedure in the National Cardiovascular Data Registry (NCDR) ICD Registry from April 2010 to March 2016, and DSM testing was assessed. Inadequate DSM was defined as a lowest successful energy tested Results Of all ICD recipients (N = 7,024), DSM testing was performed in 52.0% (n = 3,654). The mean lowest successful energy tested was 20.7 ± 7.3 J. Of those with DSM adequacy data available (n = 3,623), an inadequate DSM occurred in 13.8% (n = 501). After multivariable adjustment, DSM testing was not associated with in-hospital complications or death (odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.79 to 1.28) but was associated with lower odds of prolonged hospital stay (>3 days) (OR: 0.71; 95% CI: 0.60 to 0.84; p Conclusions DSM testing is being performed less frequently over time and seems safe in those with CHD. An inadequate DSM was not associated with worse in-hospital outcomes.

Coseismic surface fault displacement presents a serious potential hazard for structures and for lifeline infrastructure. Distributed lifeline infrastructure tends to cover large distances and may cross faults in multiple locations, especially in active tectonic regions like California. However, fault displacement measurements for engineering applications are quite sparse, rendering the development of predictive models extremely difficult and fraught with large uncertainties. Detailed fault surface rupture mapping products exist for a few documented cases, but they may not capture the full width of ground deformations that are likely to impact distributed infrastructure. The 2019 Ridgecrest earthquake sequence presented an ideal opportunity to collect data and evaluate the ability of different techniques to capture coseismic deformations on and near the fault ruptures. Both the M 6.5 and 7.1 events ruptured the surface in sparsely populated desert areas where little vegetation is present to obscure surficial features. Two study areas (~400 m × 500 m each) around the surface ruptures from the two events were selected. Teams of researchers were deployed and coordinated to gather data in three ways: field measurements and photographs, imagery from small uninhabited aerial systems, and imagery from airborne light detection and ranging. Each of these techniques requires different amounts of resources in terms of cost, labor, and time associated with the data collection, processing, and interpretation efforts. This article presents the data collection methods used for the two study areas, and qualitative and quantitative comparisons of the results interpretations. While all three techniques capture the key features that are important for displacement design of distributed infrastructure, the use of remote sensing methods in combination with field measurements presents an advantage over the use of any single technique.

Coseismic fault displacements in large earthquakes have caused significant damage to structures and lifelines on and near fault lines. Coseismic displacements represent a real threat, especially to distributed infrastructure systems. For infrastructure systems that can not avoid active faults, engineering displacement demands are defined using probabilistic fault-displacement hazard analyses (PFDHA). However, PFDHA models are sparse and poorly constrained partly due to the scarcity of detailed fault-displacement observations. Advancements in dynamic rupture simulation methods make them an attractive approach to address this important issue. Because fault displacements can be simulated for various geologic conditions as constrained by current knowledge about earthquake processes, they can be used to supplement the observation datasets. In addition to providing on-fault displacements, when used with appropriate constitutive models for the bulk medium, they can capture off-fault distributed inelastic deformations as well. For viable extrapolation, simulations must first be validated against data. In this article, we summarize the calibration and validation of the dynamic rupture model against the observations of the well-documented 1992 Landers earthquake. We defined a preferred model that reproduces several first-order fault-displacement metrics such as the on-fault partition of the total displacement, the mean fault-zone width, and the location of the peak displacement. Simulated ground motions consistent with the observations ensure that all physics important to modeling have been properly parameterized. For the extrapolation, we generated a suite of dynamic rupture models to quantify expected fault-displacement metrics, their intercorrelations, and magnitude dependencies, which are in part supported by the Landers and other recent earthquakes. Our validation and extrapolation exercise paves the way for using dynamic rupture modeling to quantitatively address fault-displacement hazard on a broader scale. The results are promising and are expected to be useful to inform PFDHA model development.

The monitoring of data anomaly identification is an important basis for dam safety online monitoring and evaluation. In this research, a cluster of anomaly identification models for dam safety monitoring data was constructed, and a three-stage online anomaly identification method was proposed to discriminate outliers. The proposed method combined anomaly detection for measured values based on a single-point time series simulation, measurement error reduction based on remote retesting and spatio-temporal analysis, and environmental response mutation recognition. It brought about efficient and accurate detection for data mutation and online classified identification for its inducement. Additionally, problems such as missing outliers, misjudging normal values induced by the environmental response, and difficulty in online identification for measurement errors were effectively solved. The research productions were applied to the online monitoring system for the safety risk of reservoirs and dams in the Dadu River Basin. The results showed that the proposed method could effectively improve the accuracy of anomaly identification and reduce the misjudgment and omission rate to less than 2%. It could also successfully recognize and subtract nonstructural anomalies such as accidental errors, instrument faults, and environmental responses online, which provided reliable data for online dam safety monitoring.

Tight sandstone reservoir is characterized by ultra-low porosity, complex microporous structure and water residues, which shows different gas storage and transport mechanism from conventional reservoirs. Therefore, effective development of tight sandstone gas reservoirs is faced with technical challenges. Microporous structures, distribution mechanism of fluid is a basic issue in gas reservoir evaluation. In this work, we take gas reservoir in the 2nd member of Xujiahe Formation in Yuanba area as an example to analyze the microscopic feature of pore structure and fluid distribution. The three-dimensional digital core has been applied to represent the real microporous structure. Specifically, a digital core reconstruction method based on SEM and casting slice images has been proposed. Ultimately, the mechanism of distribution, mode of occurrence of water residues in tight sandstone reservoirs has been simulated and quantitatively analyzed. The results show that the water residues could been visualized and categorized into three modes, water mass in corner, water film on surface, and water column in throat. The water residues could cause dramatic influence on pore structures, active pore size could be decreased with rising residual water saturation, the magnitude falls by over 50%. In addition, grain size would affect the distribution of water residues, which shows different percentage in medium and fine sand. Pore connectivity is another characteristic factor to describe the microporous structures. In this study, cluster marking algorithm has been applied to obtain the pore connectivity in tight sandstone with different grain size. In medium sand, the pore connectivity is dramatically decreased with rising water saturation, the downward trend become slower when water saturation reaches to 60%. Compared to fine sand, the tendency variation appears when water saturation reaches to 40%. This paper provides an applicable method to reveal the micro-scale reservoir properties and fluid distribution mechanisms in tight sandstone gas reservoirs.

Background Standardization of risk is critical in benchmarking and quality improvement efforts for percutaneous coronary interventions (PCIs). In 2018, the CathPCI Registry was updated to include additional variables to better classify higher-risk patients. Objectives This study sought to develop a model for predicting in-hospital mortality risk following PCI incorporating these additional variables. Methods Data from 706,263 PCIs performed between July 2018 and June 2019 at 1,608 sites were used to develop and validate a new full and pre-catheterization model to predict in-hospital mortality, and a simplified bedside risk score. The sample was randomly split into a development cohort (70%, n = 495,005) and a validation cohort (30%, n = 211,258). The authors created 1,000 bootstrapped samples of the development cohort and used stepwise selection logistic regression on each sample. The final model included variables that were selected in at least 70% of the bootstrapped samples and those identified a priori due to clinical relevance. Results In-hospital mortality following PCI varied based on clinical presentation. Procedural urgency, cardiovascular instability, and level of consciousness after cardiac arrest were most predictive of in-hospital mortality. The full model performed well, with excellent discrimination (C-index: 0.943) in the validation cohort and good calibration across different clinical and procedural risk cohorts. The median hospital risk-standardized mortality rate was 1.9% and ranged from 1.1% to 3.3% (interquartile range: 1.7% to 2.1%). Conclusions The risk of mortality following PCI can be predicted in contemporary practice by incorporating variables that reflect clinical acuity. This model, which includes data previously not captured, is a valid instrument for risk stratification and for quality improvement efforts.

Background We aimed to characterize the occurrence of major adverse cardiovascular and limb events (MACE and MALE) among patients with peripheral artery disease (PAD) undergoing peripheral vascular intervention (PVI), as well as associated factors in patients with chronic limb threatening ischemia (CLTI). Methods and Results Patients undergoing PVI in the American College of Cardiology’s (ACC) National Cardiovascular Data Registry’s PVI Registry who could be linked to Centers for Medicare and Medicaid Services data were included. The primary outcomes were MACE, MALE, and readmission within 1 month and 1 year following index CLTI‐PVI or non‐CLTI‐PVI. Cox proportional hazards regression was used to identify factors associated with the development of the primary outcomes among patients undergoing CLTI‐PVI. There were 1758 (49.7%) patients undergoing CLTI‐PVI and 1779 (50.3%) undergoing non‐CLTI‐PVI. By 1 year, MACE occurred in 29.5% of patients with CLTI (n=519), and MALE occurred in 34.0% of patients with CLTI (n=598). By 1 year, MACE occurred in 8.2% of patients with non‐CLTI (n=146), and MALE occurred in 26.1% of patients with non‐CLTI (n=465). Predictors of MACE at 1 year in CLTI‐PVI included end‐stage renal disease on hemodialysis, congestive heart failure, prior CABG, and severe lung disease. Predictors of MALE at 1 year in CLTI‐PVI included treatment of a prior bypass graft, profunda femoral artery treatment, end‐stage renal disease on hemodialysis, and treatment of a previously treated lesion. Conclusions Patients ≥65 years old undergoing PVI experience high rates of MACE and MALE. A range of modifiable and non‐modifiable patient factors, procedural characteristics, and medications are associated with the occurrence of MACE and MALE following CLTI‐PVI.

Introduction Most studies reporting posterior pituitary tumors (PPTs) are small case series or single cases. Methods Patients with a histological diagnosis of PPT from January 2010 to December 2021 in a tertiary center were identified. We reported clinical symptoms, endocrine assessments, radiological and pathological features, and surgical outcomes of PPTs. Results A total of 51 patients (23 males, 51.3 ± 10.3 years old) with PPT were included in this study. Major symptoms were visual defects, headache, and hypopituitarism, while diabetes insipidus was uncommon (9.8%). The typical radiological feature was homogeneous enhancement (84.3%) of a regular-shaped mass on T1 contrast imaging without cystic change, calcification, or cavernous sinus invasion. We achieved gross total resection in 38/51 patients (74.5%). Pathologically, all tumors showed thyroid transcription factor 1 immunoreactivity. Among 29 patients with suprasellar PPTs, postoperative hemorrhage due to tumor residue was encountered in 2/15 cases in the transcranial group and 0/14 in the endoscopy group. Patients with spindle cell oncocytoma (SCO) were more likely to be surgically treated (25% vs 0%, P = 0.018), harbor a higher Ki-67 index (16.7% vs 0% > 5% P = 0.050), and present a lower 2-year recurrence-free survival rate (67.5% vs 90.9%) compared with patients with pituicytoma or granular cell tumor. Conclusion PPTs should be considered in the differential diagnosis of patients with sellar and suprasellar masses with a regular lesion with homogeneous enhancement. SCOs had high proliferation activity and risk of recurrence.

Protein storage vacuoles (PSVs) are unique organelles that accumulate storage proteins in plant seeds. Although morphological evidence points to the existence of multiple PSV-trafficking pathways for storage protein targeting, the molecular mechanisms that regulate these processes remain mostly unknown. Here, we report the functional characterization of the rice (Oryza sativa) glutelin precursor accumulation7 (gpa7) mutant, which over-accumulates 57-kDa glutelin precursors in dry seeds. Cytological and immunocytochemistry studies revealed that the gpa7 mutant exhibits abnormal accumulation of storage prevacuolar compartment-like structures, accompanied by the partial mistargeting of glutelins to the extracellular space. The gpa7 mutant was altered in the CCZ1 locus, which encodes the rice homolog of Arabidopsis (Arabidopsis thaliana) CALCIUM CAFFEINE ZINC SENSITIVITY1a (CCZ1a) and CCZ1b. Biochemical evidence showed that rice CCZ1 interacts with MONENSIN SENSITIVITY1 (MON1) and that these proteins function together as the Rat brain 5 (Rab5) effector and the Rab7 guanine nucleotide exchange factor (GEF). Notably, loss of CCZ1 function promoted the endosomal localization of vacuolar protein sorting-associated protein 9 (VPS9), which is the GEF for Rab5 in plants. Together, our results indicate that the MON1–CCZ1 complex is involved in post-Golgi trafficking of rice storage protein through a Rab5- and Rab7-dependent pathway.

Compared with the conventional servo press, the direct drive press even has no transmission mechanism, so it has advantages in controllability, precision and energy management. But, the forging capacity of the direct drive press is limited by the power of the linear motor. In this paper, a novel press driven by a tubular permanent magnet linear motor (TPMLM) is presented, and a symmetrical toggle booster mechanism is specially proposed to enhance the forging capacity. The mathematical model of the toggle booster mechanism is established, The TPMLM is designed, and the experimental prototype of the novel press is manufactured. The forging capacity and dynamic characteristics of the press are studied theoretically and experimentally. The results show that the introduction of the symmetrical toggle booster mechanism enriches the dynamic characteristic curve of the press and enhances the forging capacity. Therefore, the structural parameters of the toggle mechanism and the working position of the slider can be adjusted to meet different technological requirements. In addition, based on the research work, three directions are proposed to improve the forging capacity of the novel press. The research contributes to the performance optimization and development of direct drive press.

The processing efficiency of dentures is generally quite low due to the complex profile form and high brittleness of the dentures. However, there is little research for efficient path optimization and look-ahead speed control algorithm in denture machining field, which hinders the improvement of the machining efficiency and denture quality. In this work, an optimization method for both straight transition and curve paths was proposed, and look-ahead speed control algorithms for different machining paths were designed. The anomalous points were deleted according to the preprocessing algorithm before the path optimization. The straight transition path and curve path were fitted by the quasi-parabola model and cubic B-spline curve, respectively. The error between the optimized path and original path was analyzed, and the results demonstrated that the path optimization methods were reliable. A look-ahead speed control model based on S-type speed control was proposed, and the boundary conditions for different paths were calculated. The simulated and experimental results indicated that optimized algorithm significantly improved the machining efficiency and reduced the vibration of the machine tool. The accuracy and surface roughness of the denture processed using the optimized algorithm met the medical standard. This work can provide a theoretical guidance for high-efficiency and precision machining of dentures of glass ceramics.

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.