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Objective. To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy. Methods. Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia ( T 0 ), after anesthesia ( T 1 ), and after surgery ( T 2 ). Results. Group A observed a longer extubation time and recovery time in PACU than group B (P < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of T 1 by comparison with those of T 0 (P < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR (P > 0.05), and there was no interaction effect of groups and time (P > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients (P > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all P < 0.05). Conclusion. Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery. [ABSTRACT FROM AUTHOR]

Cross talk among different tissues and organs is a hotspot in metabolic research. Recent studies have revealed the regulatory roles of a number of myokines in metabolism. Here, we report that female mice lacking muscle-specific histone methylase G9a (Ehmt2Ckmm knockout [KO] or Ehmt2HSA KO) are resistant to high-fat diet (HFD)-induced obesity and hepatic steatosis. Furthermore, we identified a significantly upregulated circulating level of musclin, a myokine, in HFD-fed Ehmt2Ckmm KO or Ehmt2HSA KO female mice. Similarly, upregulated musclin was observed in mice injected with two structurally different inhibitors for G9a methylase activity: BIX01294 and A366. Moreover, injection of recombinant full-length musclin or its functional core domain inhibited the HFD-induced obesity and hepatic steatosis in wild-type female and male mice. Mechanistically, G9a methylase activity-dependently regulated muscular musclin level by binding to its promoter, also by regulating phosphorylated-FOXO1/FOXO1 levels in vivo and in vitro. Collectively, these data suggest a critical role for G9a in the muscle-liver-fat metabolic axis, at least for female mice. Musclin may serve as a potential therapeutic candidate for obesity and associated diseases. [ABSTRACT FROM AUTHOR]

Objective: Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications.Research Design and Methods: In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis.Results: The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension.Conclusions: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19. [ABSTRACT FROM AUTHOR]

To investigate the difference between the sulfur hexafluoride (SF6) decomposition characteristics initiated by two sorts of insulation defects — free metal particles and metal protrusion defects — under negative DC partial discharge (PD), SF6 decomposition data was obtained under different DC voltages on the basis of constructing a SF6 decomposition experimental platform. The differences between the characteristic components and the characteristic ratios of the two defects at the same discharge quantity and voltage were systematically analyzed. Results show that the two defects have significant differences in the type of decomposition components, the yield sizes of the components, and the changes in the component ratios. This paper proposed c(CF4 + CS2)/c(CO2) and c(CF4)/c(SO2F2) as the characteristic ratios to characterize the fault severity of the two defects, and their physical nature were revealed. The combination of the above ratios with the existing c(SO2F2)/c(SOF2 + SO2) can construct a feature quantity for identifying the two defects. [ABSTRACT FROM AUTHOR]

As a minimally invasive surgery to treat atrial fibrillation (AF), catheter based ablation uses high radio-frequency energy to eliminate potential sources of abnormal electrical events, especially around the ostia of pulmonary veins (PV). Fusing a patient-specific left atrium (LA) model (including LA chamber, appendage, and PVs) with electro-anatomical maps or overlaying the model onto 2-D real-time fluoroscopic images provides valuable visual guidance during the intervention. In this work, we present a fully automatic LA segmentation system on nongated C-arm computed tomography (C-arm CT) data, where thin boundaries between the LA and surrounding tissues are often blurred due to the cardiac motion artifacts. To avoid segmentation leakage, the shape prior should be exploited to guide the segmentation. A single holistic shape model is often not accurate enough to represent the whole LA shape population under anatomical variations, e.g., the left common PVs vs. separate left PVs. Instead, a part based LA model is proposed, which includes the chamber, appendage, four major PVs, and right middle PVs. Each part is a much simpler anatomical structure compared to the holistic one and can be segmented using a model-based approach (except the right middle PVs). After segmenting the LA parts, the gaps and overlaps among the parts are resolved and segmentation of the ostia region is further refined. As a common anatomical variation, some patients may contain extra right middle PVs, which are segmented using a graph cuts algorithm under the constraints from the already extracted major right PVs. Our approach is computationally efficient, taking about 2.6 s to process a volume with 256\,\times\,256\,\times\,245 voxels. Experiments on 687 C-arm CT datasets demonstrate its robustness and state-of-the-art segmentation accuracy. [ABSTRACT FROM AUTHOR]

Abstract: Configuring structured products poses new challenges to the solving technologies for product configuration. This paper presents a novel and direct approach to encoding configuration models into the Dynamic Constraint Satisfaction Problems (DCSP). In the presented approach, components are encoded as DCSP variables while structural relationships are represented as DCSP activity constraints. Furthermore, the configuration constraints such as the requisition and exclusion constraints are treated as DCSP compatibility constraints, which allow a low-level component to join in the solving process only after its high-level component is selected in the configuration. The presented method allows a more compact encoding representation, compared to CSP and generative CSP. Experimental study shows that the presented DCSP encoding approach makes a significant improvement in the performance of product configuration. [Copyright &y& Elsevier]

Abstract: We analyze a single removable and unreliable server in an M/G/1 queueing system operating under the 〈p, N〉-policy. As soon as the system size is greater than N, turn the server on with probability p and leave the server off with probability (1− p). All arriving customers demand the first essential service, where only some of them demand the second optional service. He needs a startup time before providing first essential service until there are no customers in the system. The server is subject to break down according to a Poisson process and his repair time obeys a general distribution. In this queueing system, the steady-state probabilities cannot be derived explicitly. Thus, we employ an improved maximum entropy method with several well-known constraints to estimate the probability distributions of system size and the expected waiting time in the system. By a comparative analysis between the exact and approximate results, we may demonstrate that the improved maximum entropy method is accurate enough for practical purpose, and it is a useful method for solving complex queueing systems. [Copyright &y& Elsevier]

Abstract: The problem addressed in this paper is to compare the minimum cost of the two randomized control policies in the M/G/1 queueing system with an unreliable server, a second optional service, and general startup times. All arrived customers demand the first required service, and only some of the arrived customers demand a second optional service. The server needs a startup time before providing the first required service until the system becomes empty. After all customers are served in the queue, the server immediately takes a vacation and the system operates the (, )-policy or (, )-policy. For those two policies, the expected cost functions are established to determine the joint optimal threshold values of (, ) and (, ), respectively. In addition, we obtain the explicit closed form of the joint optimal solutions for those two policies. Based on the minimal cost, we show that the optimal (, )-policy indeed outperforms the optimal (, )-policy. Numerical examples are also presented for illustrative purposes. [Copyright &y& Elsevier]

Background: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement.Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function.Conclusions: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research.Registration: URL: https://www.Clinicaltrials: gov. Unique identifier: NCT03284827. [ABSTRACT FROM AUTHOR]

Objectives: The patent linkage system upgraded patent challenges to an important factor in granting timely market approval for generic drugs. We aim to understand patent challenges and identify the factors that are associated with successful patent challengers under the patent linkage system in South Korea.Methods: We constructed a novel dataset that combined information on manufacturers with detailed data about their patent challenges after introduction of the patent linkage system. Based on the number of successful patent challenges, manufacturers were categorized into non-challengers, passive challengers, and aggressive challengers. Then, two types of logistic models were applied to identify the factors associated with successful and aggressive challengers.Findings: Only 39 active ingredients were challenged by 77 manufacturers from March 2015 to December 2019. Of 171 manufacturers, 94 (55 %) were non-challengers, 58 (34 %) were passive challengers who had succeeded in fewer than 4 patent challenges, and 19 (11 %) were aggressive challengers who had succeeded in 4 or more patent challenges. Higher sales, more employees, and a greater number of reimbursed drugs were associated with being a patent challenger, while a greater number of reimbursed drugs was associated with being an aggressive challenger.Conclusion: Some manufacturers utilize patent challenges to strengthen their product portfolios in the market. However, under the patent linkage system, the frequency of patent challenges is limited in South Korea compared to the United States. In particular, patent challenges against drugs in injection form and biologics are very rare. [ABSTRACT FROM AUTHOR]

Background and Objectives: We conducted this meta-analysis about the effects of Souvenaid on cognition and functional abilities, with the hypothesis that Souvenaid may have beneficial effects in certain groups and the goal of finding the outcome measures, disease states, and so on, applicable for further clinical trials.Methods and Study Design: We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library. Only double- blind randomized controlled trials were included. Outcome measurements were cognition, clinical global change, functional ability, and adverse events. The duration of treatment was not restricted, but trials performed in patients who did not have Alzheimer's disease (AD) were excluded.Results: This review using meta-analyses of 4 clinical trials showed that Souvenaid had no significant effects on cognition as measured by ADAS-Cog (MD=0.08, 95% CI=-0.71-0.88) and the neuropsychological test battery total scores (MD=0.05, 95% CI=-0,02- 0.12), on global clinical function as measured by CDR-SB (MD=-0.21, 95% CI=-0.47-0.06), or on functional ability as measured by ADCS-ADL (MD=0.36, 95% CI=-0.54-1.25). There were no differences in any adverse events (OR=0.84, 95% CI=0.63-1.12) or in serious adverse events (OR=0.95, 95% CI=0.66-1.36). However, Souvenaid may benefit the domains of cognition that are affected by AD (attention, memory, and executive function), and it may have greater potential for benefits earlier rather than later in the disease.Conclusions: The results of current clinical trials do not suggest that Souvenaid has any beneficial effects on cognition, functional ability, or global clinical change. Further studies with outcome measures suitable in patients with early stages of AD will be needed. [ABSTRACT FROM AUTHOR]

The premise of analyzing and researching robot technology is to establish a proper mathematical model and then to solve it with kinematics. In this study, a self-developed humanoid hydraulically driven dual-arm robot is taken as the research object, and the DH (Denavit–Hartenberg) parameter method and the rotational exponential formula (POE) are used to solve the kinematics of the robot. The calculation results are verified by simulation. The advantages and disadvantages of the two methods are analyzed. The differences between the two methods are compared. It lays a foundation for other scholars to choose mathematical models when analyzing the mechanism in the future. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) are difficult to diagnose early and have risk factors that are easy to overlook. Early prediction and personalization of treatment through the use of artificial intelligence (AI) may help clinicians and patients manage CVDs more effectively. However, to apply AI approaches to CVDs data, it is necessary to establish and curate a specialized database based on electronic health records (EHRs) and include pre-processed unstructured data.Methods: To build a suitable database (CardioNet) for CVDs that can utilize AI technology, contributing to the overall care of patients with CVDs. First, we collected the anonymized records of 748,474 patients who had visited the Asan Medical Center (AMC) or Ulsan University Hospital (UUH) because of CVDs. Second, we set clinically plausible criteria to remove errors and duplication. Third, we integrated unstructured data such as readings of medical examinations with structured data sourced from EHRs to create the CardioNet. We subsequently performed natural language processing to structuralize the significant variables associated with CVDs because most results of the principal CVD-related medical examinations are free-text readings. Additionally, to ensure interoperability for convergent multi-center research, we standardized the data using several codes that correspond to the common data model. Finally, we created the descriptive table (i.e., dictionary of the CardioNet) to simplify access and utilization of data for clinicians and engineers and continuously validated the data to ensure reliability.Results: CardioNet is a comprehensive database that can serve as a training set for AI models and assist in all aspects of clinical management of CVDs. It comprises information extracted from EHRs and results of readings of CVD-related digital tests. It consists of 27 tables, a code-master table, and a descriptive table.Conclusions: CardioNet database specialized in CVDs was established, with continuing data collection. We are actively supporting multi-center research, which may require further data processing, depending on the subject of the study. CardioNet will serve as the fundamental database for future CVD-related research projects. [ABSTRACT FROM AUTHOR]

Dysfunction of primary cilia is related to dyshomeostasis, leading to a wide range of disorders. The ventromedial hypothalamus (VMH) is known to regulate several homeostatic processes, but those modulated specifically by VMH primary cilia are not yet known. In this study, we identify VMH primary cilia as an important organelle that maintains energy and skeletal homeostasis by modulating the autonomic nervous system. We established loss-of-function models of primary cilia in the VMH by either targeting IFT88 (IFT88-KOSF-1) using steroidogenic factor 1-Cre (SF-1-Cre) or injecting an adeno-associated virus Cre (AAV-Cre) directly into the VMH. Functional impairments of VMH primary cilia were linked to decreased sympathetic activation and central leptin resistance, which led to marked obesity and bone-density accrual. Obesity was caused by hyperphagia, decreased energy expenditure, and blunted brown fat function and was also associated with insulin and leptin resistance. The effect of bone-density accrual was independent of obesity, as it was caused by decreased sympathetic tone resulting in increased osteoblastic and decreased osteoclastic activities in the IFT88-KOSF-1 and VMH primary cilia knockdown mice. Overall, our current study identifies VMH primary cilia as a critical hypothalamic organelle that maintains energy and skeletal homeostasis. [ABSTRACT FROM AUTHOR]

Background. Although immunomodulators are increasingly used in Crohn’s disease (CD), a significant number of gastroenterologists still use 5-aminosalicylate (5-ASA) in combination with azathioprine (AZA) or 6-mercaptopurine (6-MP); there is limited evidence regarding the benefit of concomitant 5-ASA with AZA/6-MP compared with AZA/6-MP monotherapy for the treatment of CD. Study Design. A total of 106 patients who received AZA/6-MP for more than 3 months between January 1991 and May 2014 were identified retrospectively. Each patient was matched with 3 randomly selected controls who were treated with concomitant therapy during the same period. Results. The cumulative probabilities of steroid use at 5 and 10 years were 24.9% and 75.8% in the 5-ASA + AZA/6-MP group and 31.2% and 87.8% in the AZA/6-MP group, respectively (P=0.187). The cumulative probabilities of anti-TNF use, resectional surgery, and disease-related hospitalization were comparable between the groups. The younger age and the use of lower doses of immunomodulators were associated with higher requirement of rescue therapy. Conclusions. This study did not demonstrate that the concomitant use of 5-ASA with AZA/6-MP showed the proof or effect in terms of steroid requirements, anti-TNF use, resectional surgery, or disease-related hospitalization compared with that of AZA/6-MP alone. [ABSTRACT FROM AUTHOR]

Study Question: What is the influence of copy number variation (CNV) in functional RNA binding motif protein Y-linked family 1 (RBMY1) on spermatogenic phenotypes?Summary Answer: The RBMY1 functional copy dosage is positively correlated with sperm motility, and dosage insufficiency is an independent risk factor for asthenozoospermia.What Is Known Already: RBMY1, a multi-copy gene expressed exclusively in the adult testis, is one of the most important candidates for male infertility in the azoospermia factor (AZF) region of the Y-chromosome. RBMY1 encodes an RNA-binding protein that serves as a pre-mRNA splicing regulator during spermatogenesis, and male mice deficient in Rbmy are sterile.Study Design, Size, Duration: A total of 3127 adult males were recruited from 2009 to 2016; of this group, the dosage of RBMY1 functional copy were investigated in 486 fertile males. In the remaining 2641 males with known spermatogenesis status, 1070 Y-chromosome haplogroup (Y-hg) O3* or O3e carriers without chromosomal aberration or known AZF structure mutations responsible for spermatogenic impairment, including 506 men with normozoospermia and 564 men with oligozoospermia or/and asthenozoospermia, were screened, and the RBMY1 functional copy dosage and copy conversion were determined to explore their associations with sperm phenotypes. The correlation between RBMY1 dosage and its mRNA level or RBMY1 protein level and the correlation between sperm RBMY1 level and motility were analysed in 15 testis tissue samples and eight semen samples. Ten additional semen samples were used to confirm the subcellular localization of RBMY1 in individual sperm.Participants/materials, Setting, Methods: All the Han volunteers donating whole blood, semen and testis tissue were from southwest China. RBMY1 copy number, copy conversion, mRNA/protein amount and protein location in sperm were detected using the AccuCopy® assay method, paralog ratio test, quantitative PCR, western blotting and immunofluorescence staining methods, respectively.Main Results and the Role Of Chance: This study identified Y-hg-independent CNV of functional RBMY1 in the enrolled population. A difference in the distribution of RBMY1 copy number was observed between the group with normal sperm motility and the group with asthenozoospermia. A positive correlation between the RBMY1 copy dosage and sperm motility was identified, and the males with fewer than six copies of RBMY1 showed an elevated risk for asthenozoospermia relative to those with six RBMY1 copies, the most common dosage in the population. The RBMY1 copy dosage was positively correlated with its mRNA and protein level in the testis. Sperm with high motility were found to carry more RBMY1 protein than those with relatively low motility. The RBMY1 protein was confirmed to predominantly localize in the neck and mid-piece region of sperm as well as the principal piece of the sperm tail. Our population study completes a chain of evidence suggesting that RBMY1 influences the susceptibility of males to asthenozoospermia by modulating sperm motility.Limitations Reasons For Caution: High sequence similarity between the RBMY1 functional copies and a large number of pseudogenes potentially reduces the accuracy of the copy number detection. The mechanism underlying the CNV in RBMY1 is still unclear, and the effect of the structural variations in the RBMY1 copy cluster on the copy dosage of other protein-coding genes located in the region cannot be excluded, which may potentially bias our observations.Wider Implications Of the Findings: Asthenozoospermia is a multi-factor complex disease with a limited number of proven susceptibility genes. This study identified a novel genomic candidate independently contributing to the condition, enriching our understanding of the role of AZF-linked genes in male reproduction. Our finding provides insight into the physiological and pathological characteristics of RBMY1 in terms of sperm motility, supplies persuasive evidence of the significance of RBMY1 copy number analysis in the clinical counselling of male infertility resulting from asthenozoospermia.Study Funding/competing Interest(s): This work was funded by the National Natural Science Foundation of China (Nos. 81370748 and 30971598). The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]