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In this paper, we propose a pose transfer framework that can deal with large body motion to generate dance videos. To solve the problem of body shape deformation from large movements, a Multiple Scale Region Extractor (MSRE) is proposed. The features of each body region can be extracted from multiple layers of the encoder according to the body key points and passed through shortcuts to the decoder to reduce the spatial information loss. We add a region style loss calculated by the style representations of the body regions to the loss function to improve the quality of the generated images. In addition, the concept of learnable region normalization is integrated in the proposed framework to prevent introducing undesired mean and variance shifts by the corrupted regions during normalization. The experiments have shown that the proposed system can significantly improve the pose generation results compared with existing methods, especially when there are large body movements in the dancing poses.

BACKGROUND Inhibition of the renin angiotensin aldosterone system (RAAS) improves survival and reduces adverse cardiac events in heart failure with reduced ejection fraction, but the benefit is not well-defined following left ventricular assist device (LVAD). METHODS We analyzed the ISHLT IMACS registry for adults with a primary, continuous-flow LVAD from January 2013 to September 2017 who were alive at postoperative month 3 without a major adverse event, and categorized patients according to treatment an angiotensin converting enzyme inhibitor (ACEI/ARB) or mineralocorticoid receptor antagonist (MRA). Propensity score matching was performed separately for ACEI/ARB vs none (n = 4,118 each) and MRA vs none (n = 3,892 each). RESULTS Of 11,494 patients included, 50% were treated with ACEI/ARB and 38% with MRA. Kaplan-Meier survival was significantly better for patients receiving ACEI/ARB (p < 0.001) but not MRA (p = 0.31). In Cox proportional hazards analyses adjusted for known predictors of mortality following LVAD, ACEI/ARB use (hazard ratio 0.81 [95% confidence interval 0.71-0.93], p < 0.0001) but not MRA use (hazard ratio 1.03 [95% confidence interval 0.88-1.21], p = 0.69) was independently associated with lower mortality. Among patients treated with an ACEI/ARB, there was a significantly lower unadjusted risk of cardiovascular death (p < 0.001), risk of gastrointestinal bleeding (p = 0.01), and creatinine level (p < 0.001). MRA therapy was associated with lower risk of gastrointestinal bleeding (p = 0.01) but higher risk of hemolysis (p < 0.01). Potential limitations include residual confounding and therapy crossover. CONCLUSION These findings suggest a benefit for ACEI/ARB therapy in patients with heart failure after LVAD implantation.

In this work, a day-ahead to week-ahead solar irradiance prediction mechanism based on convolutional Long Short-Term Memory (LSTM) model is proposed. The system takes hourly irradiance data from several days previous to the prediction day as the input. Then, features are extracted from the input data using one dimensional convolutional filters. The extracted features from different days are concatenated and serve as the input of the LSTM network. The output of the LSTM is further concatenated with selected original data to emphasize its importance and enhance the prediction results. Afterwards, a fully connected layer is used to produce the final prediction output. The proposed framework can be trained using a relatively small amount of training data within the duration of only two months. Therefore, it has the advantage of being applicable in the initial deployment phase when the amount of training data is limited. The proposed system has been validated using a highly challenging dataset collected in Taiwan with tropical and subtropical marine island climate.

OBJECTIVE Sulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction. RESEARCH DESIGN AND METHODS As an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions. RESULTS After establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction at a genome-wide scale (P < 5 × 10−8). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10−8), lower reduction in HbA1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10−58). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA1c (P = 4.80 × 10−8). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10−7), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor. CONCLUSIONS We have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.

This study was aimed to analyze the role of hepatocyte nuclear factor -1α (HNF-1α) in regulating migrative and invasive potentials in cervical cancer via the involvement of pyruvate kinase L/R (PKLR). The expression of HNF-1α and PKLR in cervical cancer tissues classified by tumor size and FIGO (Federation International of Gynecology and Obstetrics) stage were detected by qRT-PCR. The expression correlation between HNF-1α and PKLR in cervical cancer tissues was analyzed by Pearson correlation test. After intervening HNF-1α and PKLR levels in SiHa and Hela cells, their migratory and invasive abilities were examined by the Transwell assay. HNF-1α was upregulated in cervical cancer tissues, particularly those with large tumor size or advanced FIGO stage. PKLR was highly expressed in cervical cancer tissues as well, presenting a positive correlation with the HNF-1α level. Knockdown of HNF-1α attenuated migratory and invasive abilities in SiHa cells, whereas overexpression of HNF-1α enhanced migratory and invasive abilities in SiHa cells. PKLR was able to abolish the regulatory effects of HNF-1α on cervical cancer metastasis. HNF-1α and PKLR synergistically promote cervical cancer to migrate and invade.

BACKGROUND: Supervised exercise training improves outcomes in patients with pulmonary arterial hypertension (PAH). The effect of an unsupervised activity intervention has not been tested. RESEARCH QUESTION: Can a text-based mobile health intervention increase step counts in patients with PAH? STUDY DESIGN AND METHODS: We performed a randomized, parallel arm, single-blind clinical trial. We randomized patients to usual care or a text message-based intervention for 12 weeks. The intervention arm received three automated text messages per day with real-time step count updates and encouraging messages rooted in behavioral change theory. Individual step targets increased by 20% every 4 weeks. The primary end point was mean week 12 step counts. Secondary end points included the 6-min walk test, quality of life, right ventricular function, and body composition. RESULTS: Among 42 randomized participants, the change in raw steps between baseline and week 12 was higher in the intervention group (1,409 steps [interquartile range, –32 to 2,220] vs –149 steps [interquartile range, –1,010 to 735]; P = .02), which persisted after adjustment for age, sex, baseline step counts, and functional class (model estimated difference, 1,250 steps; P = .03). The intervention arm took a higher average number of steps on all days between days 9 and 84 (P < .05, all days). There was no difference in week 12 six-minute walk distance. Analysis of secondary end points suggested improvements in the emPHasis-10 score (adjusted change, –4.2; P = .046), a reduction in visceral fat volume (adjusted change, –170 mL; P = .023), and nearly significant improvement in tricuspid annular plane systolic excursion (model estimated difference, 1.2 mm; P = .051). INTERPRETATION: This study demonstrated the feasibility of an automated text message-based intervention to increase physical activity in patients with PAH. Additional studies are warranted to examine the effect of the intervention on clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT03069716; URL: www.clinicaltrials.gov

In this article, we propose a system for automatically classifying and cleaning location images in large-scale image databases uploaded by arbitrary users. Detecting incorrect scenes uploaded by users and maintaining the correctness of the database through automatic data cleaning are essential because human inspection is not feasible for verifying massive amounts of data. In this study, we compared different feature extractors using deep convolutional neural networks trained using big data. We designed a multilevel extractor to improve feature extraction. Moreover, a detector based on multiresolution dissimilarity calculation was designed to overcome the issue of large intraclass distances and successfully identify incorrect scenes. The proposed system was validated using a highly challenging dataset with 138,000 images collected from Google Places. The experiments show that the multilevel extractor and the detector based on multiresolution dissimilarity calculation can improve the accuracy in identifying incorrect scenes and achieve satisfying data cleaning results.

The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation.To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics.This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes).During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation.Observational design and a lack of a comparison group.Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Background Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood. Objectives We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma. Methods We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma. Results Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress–related metabolites. There were no significant associations between metabolites and allergic sensitization. Conclusions We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.

Chang Yu,1,&ast; Xiaojun Zhu,1,&ast; Chao Zheng,1 Yichun Luo,1 Fang Wang,1 Yueqiu Gao,1 Hailong Wu,2 Xuehua Sun,1 Xiaoni Kong1 1Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoni Kong; Xuehua SunCentral Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, 528 Zhangheng Road, Shanghai, 201203, People’s Republic of ChinaTel +86 21 20256838Email xiaoni-kong@126.com; susan_sxh@sina.comIntroduction: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.Methods: Four-week-old male C57BL/6 mice were fed with a high-methyl diet (HMD) or a regulator diet (RD) till the experiment time. Mice septic model was induced by Cecal ligation and puncture (CLP), lipopolysaccharide (LPS), or E.coli. Inflammatory cytokine was analyzed by ELISA and qRT-PCR. Immune cell infiltration was evaluated by H&E and IHC. The composition of gut microbiota was determined by 16S rRNA sequencing. The effect of gut microbiota on sepsis was further verified by fecal microbiome transplantation.Results: Our results showed that the diet riches in methyl donors exacerbated mortality, organ injury, and circulating levels of inflammatory mediators in CLP-induced septic mice model, compared to the control diet group. However, no significant differences have been observed in the inflammatory responses in the LPS-induced septic model and macrophages activation between the two groups of mice. There was a higher bacterial burden in CLP-induced HMD mice suggested that methyl diet might modulate gut microbiota. Bacterial 16S rRNA sequencing results showed that the composition of gut microbiota was altered. The high methyl donor diet reduced the abundance of Akkermansia and Lachnospiraceae, which were associated with protective effects in sepsis, in the gut. Moreover, fecal microbiome transplantation experiment showed that the transfer of feces, which obtained from high methyl diet mice, aggravated the mortality and inflammation responses in recipient mice.Discussion: Methyl diet enhanced CLP-induced septic mortality and inflammatory responses through altering the composition of gut microbiota. This result indicated that diet-based gut microbiota may be a new therapeutic strategy for sepsis patients.Keywords: sepsis, DNA methylation, gut microbiota, Akkermansia, Lachnospiraceae

Safety is a main reason for drug failures, and therefore, the detection of compound toxicity and potential adverse effects in the early stage of drug development is highly desirable. However, accurate prediction of many toxicity endpoints is extremely challenging due to low accessibility of sufficient and reliable toxicity data, as well as complicated and diversified mechanisms related to toxicity. In this study, we proposed the novel multitask graph attention (MGA) framework to learn the regression and classification tasks simultaneously. MGA has shown excellent predictive power on 33 toxicity data sets and has the capability to extract general toxicity features and generate customized toxicity fingerprints. In addition, MGA provides a new way to detect structural alerts and discover the relationship between different toxicity tasks, which will be quite helpful to mine toxicity information from large amounts of toxicity data.

With the development of distributed generation (DG) technologies, distributed energy resources (DERs) with low capacity and low inertia are highly penetrated in the islanded AC microgrid. This has highlighted the need for secondary control strategies to remedy frequency deviation and strongly limitation of the frequency synchronization rate, which are associated with the primary control. To solve this problem, an optimal condition, in terms of explicit synchronization rate formula, is derived. Then, a distributed event-triggered control strategy is proposed to synchronize the microgrid frequency to the nominal value and maximize the synchronization rate for the primary control process. To reduce the communication and computation burdens, an event-triggered mechanism that enables each agent to update its input based on discrete information from only one of its neighbors are provided. The stability of the event condition and event interval are also analyzed using Lyapunov method. Finally, the theoretical results are applied to a parallel-feeder test system consisting of fourteen DGs, which verifies the effectiveness of the proposed strategy.

Objective Repetitive transcranial magnetic stimulation (rTMS) has been widely used in non-invasive treatments for different neurological disorders. Few biomarkers are available for treatment response prediction. This study aims to analyze the correlation between changes in long-term potentiation (LTP)-like cortical plasticity and cognitive function in patients with Alzheimer’s disease (AD) that underwent rTMS treatment. Methods A total of 75 AD patients were randomized into either 20 Hz rTMS treatment at the dorsolateral prefrontal cortex (DLPFC) group (n = 37) or a sham treatment group (n = 38) for 30 sessions over six weeks (five days per week) with a three-month follow-up. Neuropsychological assessments were conducted using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment-Cognitive Component (ADAS-Cog). The cortical plasticity reflected by the motor-evoked potential (MEP) before and after high-frequency repetitive TMS to the primary motor cortex (M1) was also examined prior to and after the treatment period. Results The results showed that the cognitive ability of patients who underwent the MMSE and ADAS-Cog assessments showed small but significant improvement after six weeks of rTMS treatment compared with the sham group. The cortical plasticity improvement correlated to the observed cognition change. Conclusions Cortical LTP-like plasticity could predict the treatment responses of cognitive improvements in AD patients receiving rTMS intervention. This warrants future clinical trials using cortical LTP as a predictive marker.

Objective To evaluated the clinical outcomes of periprosthetic joint infection (PJI) patients with destination joint spacer compared with that of two‐stage revision. Methods From January 2006 to December 2017, data of PJI patients who underwent implantation with antibiotic‐impregnated cement spacers in our center due to chronic PJI were collected retrospectively. The diagnosis of PJI was based on the American Society for Musculoskeletal Infection (MSIS) criteria for PJI. One of the following must be met for diagnosis of PJI: a sinus tract communicating with the prosthesis; a pathogenis isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; four of the following six criteria exist: (i) elevated ESR and CRP; (ii) elevate dsynovial fluid white blood cell (WBC) count; (iii) elevated synovial fluid neutrophil percentage (PMN%); (iv) presence of purulence in the affected joint; (v) isolation of a microorganism in one periprosthetic tissue or fluid culture; (vi) more than five neutrophilsper high‐power fields in five high‐power fields observed from histological analysis of periprosthetic tissue at ×400 magnification. Age, sex, body mass index (BMI), and laboratory test results were recorded. All patients were followed up regularly after surgery, the infection‐relief rates were recorded, Harris hip score (HHS) and knee society score (KSS) were used for functional evaluation, a Doppler ultrasonography of the lower limb veins was performed for complication evaluation. The infection‐relief rates and complications were compared between destination joint spacer group and two‐stage revision group. Results A total of 62 patients who were diagnosed with chronic PJI were enrolled, with an age of 65.13 ± 9.94 (39–88) years. There were 21 cases in the destination joint spacer group and 41 cases in the temporary spacer group, namely, two‐stage revision group (reimplantation of prosthesis after infection relief). The Charlson comorbidity index (CCI) in the destination joint spacer group was higher than that in the temporary spacer group, and this might be the primary reason for joint spacer retainment. As for infection‐relief rate, there were three cases of recurrent infection (14.29%) in the destination joint spacer group and four cases of recurrent infection (9.76%) in the two‐stage revision group, there were no significant differences with regard to infection‐relief rate. Moreover, there two patients who suffered from spacer fractures, three cases of dislocation, one case of a periarticular fracture, and three cases of deep venous thrombosis in destination joint spacer group, while there was only one case of periprosthetic hip joint fracture, one case of dislocation, and one patient suffered from deep venous thrombosis of the lower extremity in two‐stage revision. The incidence of complications in the destination joint spacer group was higher than that of two‐stage revision. Conclusions In summary, the present work showed that a destination joint spacer might be provided as a last resort for certain PJI patients due to similar infection‐relief rate compared with two‐stage revision., Diagram of destination joint spacer.

BACKGROUND. PI-RADS version 2.1 (v2.1) introduced a number of key changes to the assessment of transition zone (TZ) lesions. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement and diagnostic accuracy for detecting TZ prostate cancer (PCa) and clinically significant PCa (csPCa) by use of PI-RADS v2 and PI-RADS v2.1 among radiologists with different levels of experience. METHODS. This retrospective study included 355 biopsy-naive patients who from January 2017 to March 2020 underwent prostate MRI that showed a TZ lesion and underwent subsequent biopsy. PCa was diagnosed in 93 patients (International Society of Urological Pathology [ISUP] grade group 1, n = 34; ISUP grade group ≥ 2, n = 59) and non-cancerous lesions in 262 patients. Five radiologists with varying experience in prostate MRI scored lesions using PI-RADS v2 and PI-RADS v2.1 in sessions separated by at least 4 weeks. Interobserver agreement was evaluated with kappa and Kendall W statistics. ROC curve analysis was used to evaluate performance in detection of TZ PCa and csPCa. RESULTS. Interobserver agreement among all readers was higher for PI-RADS v2.1 than for PI-RADS v2 (mean weighted κ = 0.700 vs 0.622; Kendall W = 0.805 vs 0.728; p = .03). The pooled AUC values for detecting TZ PCa and csPCa were higher among all readers using PI-RADS v2.1 (0.866 vs 0.827 for TZ PCa; 0.929 vs 0.899 for TZ csPCa; p < .001). For detecting TZ PCa, the pooled sensitivity, specificity, and accuracy were 86.9%, 79.4%, and 75.4% among all readers for PI-RADS v2.1 compared with 79.4%, 71.8%, and 73.8% for PI-RADS v2. For detecting TZ csPCa, the pooled sensitivity, specificity, and accuracy were 84.8%, 90.9%, and 89.9% among all readers for PI-RADS v2.1 compared with 81.4%, 89.9%, and 88.5% for PI-RADS v2. Reader 1, who had the least experience, had the lowest sensitivity, specificity, and accuracy (78.0%, 89.2%, and 87.3%). Reader 5, who had the most experience, had the highest sensitivity, specificity, and accuracy (88.1%, 92.9%, and 92.1%) in detecting csPCa. CONCLUSION. PI-RADS v2.1 had better interobserver agreement and diagnostic accuracy than PI-RADS v2 for evaluating TZ lesions. Reader experience continues to affect the performance of prostate MRI interpretation with PI-RADS v2.1. CLINICAL IMPACT. PI-RADS v2.1 is more accurate and reproducible than PI-RADS v2 for the diagnosis of TZ PCa.

H-1 antihistamines are commonly used in dermatological practice for itch and urticaria control. The widespread expression of H-1 receptor on different cells in the skin and various biologic functions of H-1 antihistamines indicate the possible treatment potentials of H-1 antihistamines in dermatology. A literature search was performed on PubMed and Embase, targeting articles reporting use of antihistamine for purposes other than itch and urticaria control in dermatological practice. Several off-label usages of antihistamines were identified, including alopecia, acne, Darier disease, eosinophilic dermatoses, paraneoplastic dermatoses, psoriasis, lichen nitidus, radiation dermatitis, skin dysesthesia, and cutaneous malignancies. Additional benefits were observed when H-1 antihistamines were used either alone or in combination with other therapeutic modalities. Although various novel uses of H-1 antihistamines have been uncovered, the evidence level of most included studies is weak. Further randomized control trials are warranted to better evaluate the efficacy and dosage of H-1 antihistamine for dermatological disorders.

TGR5 (G protein-coupled bile acid receptor 1, GPBAR-1) is a G protein-coupled receptor with seven transmembrane domains and is widely distributed in various organs and tissues. As an important bile acid receptor, TGR5 can be activated by primary and secondary bile acids. Increased expression of TGR5 is a risk factor for polycystic liver disease and hepatobiliary cancer. However, there is evidence that the anti-inflammatory effect of the TGR5 receptor and its regulatory effect on hydrophobic bile acid confer protective effects against most liver diseases. Recent studies have shown that TGR5 receptor activation can alleviate the development of diabetic liver fibrosis, regulate the differentiation of natural killer T cells into NKT10 cells, increase the secretion of anti-inflammatory factors, inhibit the invasion of hepatitis B virus, promote white adipose tissue browning, improve arterial vascular dynamics, maintain tight junctions between bile duct cells, and protect against apoptosis. In portal hypertension, TGR5 receptor activation can inhibit the contraction of hepatic stellate cells and improve intrahepatic microcirculation. In addition, the discovery of the regulatory relationship between the TGR5 receptor and miRNA-26a provides a new direction for further studies of the molecular mechanism underlying the effects of TGR5. In this review, we describe recent findings linking TGR5 to various liver diseases, with a focus on the mechanisms underlying its effects and potential therapeutic implications.

Background As a novel high magnification module (HMM) combining with OCT (OCT-HMM) is able to detect the microstructure of retina, we apply it to explore the ultrastructure of the macula after closure of the idiopathic macular hole (IMH) by surgery. Methods This is an observational case series study in which patients with full-thickness IMHs who had undergone successful macular closure by vitrectomy and internal limiting membrane peeling and healthy subjects were recruited. After comprehensive ophthalmic examinations, the images of macular area were obtained and collected by professional operators using OCT-HMM. Then images were independently analyzed by 4 masked vitreoretinal specialists. Results A total of 24 IMH eyes and 42 healthy eyes were examined. HMM images were obtained in 10 IMH eyes. Among them, 4 eyes whose macula closed completely with recovery of photoreceptor layer presented a dark arc nasal to the fovea, oriented to the optic, and the notch of arc faced temporally. Six eyes in which the macula closed incompletely with photoreceptor cells loss revealed a dark ring with uneven bright spots inside. The other 14 eyes failed to obtain clear images by OCT-HMM. The contra lateral eyes of the patients and the healthy subjects’ eyes succeeded to obtain the HMM images which displayed evenly grey background thickly covered with tiny bright dots that was in similar size and evenly and widely distributed and there no dark arc or ring. OCT B-scan and IR images could be acquired in all of the IMH and healthy eyes. Conclusion The preliminary application of HMM has supplied us a brand-new insight into the microstructure of closed IMH. A dark arc sign could be detected with OCT-HMM in the macula which was functionally closed after surgery that was probably the healing mark on a microstructure photoreceptors level. Its existence and shape indicated that the functional closure followed by a retinal displacement mainly horizontally from temporal side to nasal side but not symmetric centripetally.

ObjectivesSjögren’s syndrome (SS) is an autoimmune sialadenitis with unknown aetiology. Although extensive research implicated an abnormal immune response associated with lymphocytes, an initiating event mediated by salivary gland epithelial cell (SGEC) abnormalities causing activation is poorly characterised. Transcriptome studies have suggested alternations in lysosomal function are associated with SS, but a cause and effect linkage has not been established. In this study, we demonstrated that altered lysosome activity in SGECs by expression of lysosome-associated membrane protein 3 (LAMP3) can initiate an autoimmune response with autoantibody production and salivary dysfunction similar to SS.MethodsRetroductal cannulation of the submandibular salivary glands with an adeno-associated virus serotype 2 vector encoding LAMP3 was used to establish a model system. Pilocarpine-stimulated salivary flow and the presence of autoantibodies were assessed at several time points post-cannulation. Salivary glands from the mice were evaluated using RNAseq and histologically.ResultsFollowing LAMP3 expression, saliva flow was significantly decreased and serum anti-Ro/SSA and La/SSB antibodies could be detected in the treated mice. Mechanistically, LAMP3 expression increased apoptosis in SGECs and decreased protein expression related to saliva secretion. Analysis of RNAseq data suggested altered lysosomal function in the transduced SGECs, and that the cellular changes can chemoattract immune cells into the salivary glands. Immune cells were activated via toll-like receptors by damage-associated molecular patterns released from LAMP3-expressing SGECs.ConclusionsThese results show a critical role for lysosomal trafficking in the development of SS and establish a causal relationship between LAMP3 misexpression and the development of SS.

Research on gas hydrates is relevant to many industrial issues including flow assurance in oil and gas production and transportation, exploitation of new energy deposits in the form of natural gas ...

Summary The Coronavirus disease 2019 (COVID-19) outbreak has been brought under control through a nationwide effort, and now it has become a global pandemic and the situation seems grim. We summarized the measures taken in Wuhan and analyzed the effects to comprehensively describe the factors involved in controlling the COVID-19 in China. In China, several measures such as the lockdown of Wuhan, restriction of traffic and communities, increasing hospital beds, nationwide support from medical staff, epidemic prevention equipment and supplies, and establishment of makeshift shelter hospitals have been taken. The lockdown of Wuhan reduced the propagation of cases to other cities in Hubei province and throughout China, traffic and community restrictions reduced the flow of population and the spread of disease, increasing wards and beds and medical personnel reduced the incidence of severe cases and mortality, the establishment of the Fangcang shelter hospitals provided a good isolation and monitoring environment, and further reduced the spread and fatality of the disease. The fact that China was able to control the spread of COVID-19 within three months without a specific drug or vaccine suggests that these measures are more adequate and effective.

This paper investigates the impact of board gender diversity on a firm’s investment inefficiency. We document that firms with gender-diverse boards have significantly less investment inefficiency than firms without gender-diverse board and the fraction of female directors on the board is sigificantly negative correlated with investment inefficiency. The instrumental variable approach indicates that the negative relation is robust after addressing endogeneity concerns. Subsample analysis indicates that the effect of board gender diversity on investment inefficiency is focused on firms with CEO- chairman duality and firms with longer CEO tenures. We also document that board independence is a channel for board gender diversity to reduce investment inefficiency.

Urban flooding is a major concern in many cities around the world. Together with continuous urbanization, extreme weather events are likely to increase the magnitude and frequency of flood hazards ...

Background Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Methods In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24–35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. Results In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants’ physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. Conclusions Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P

Two-dimensional (2D) materials have attracted significant attention in recent years owing to their exotic properties. Semiconducting p-type 2D crystals are crucial to the construction of versatile p–n junction-based nanoelectronic devices, and promising future optoelectronic applications. Herein, we reported the growth of high-quality p-type silicon telluride (Si2Te3) single crystals using the chemical vapor transport (CVT) technique. Few layered Si2Te3 nanosheets were obtained by mechanical exfoliation and used to fabricate a phototransistor device under a rigid silicon substrate. The Si2Te3 nanosheet-based transistor exhibits an outstanding device performance, such as a high photoresponsivity of approximately 1396 A W−1 and a larger specific detectivity of approximately 2.52 × 1012 Jones at a wavelength of 633 nm. The values obtained using the Si2Te3 single crystal are remarkably superior to those obtained for the other chalcogenide 2D crystals, such as Bi2Te3 and Sb2Te3. In addition, the normalized gain value of approximately 2.74 × 10−4 V−1 cm2 achieved using this field-effect transistor (FET) device is several orders higher than those of the other 2D single crystal-based FET devices. Our results suggest that the Si2Te3 single crystal could be a benchmark candidate for the integration of prospective p–n junction circuits and photo-sensing applications.

Background The treatment, genotyping, and phenotyping of patients with World Health Organization Group 1 pulmonary arterial hypertension (PAH) have evolved dramatically in the last decade. Research Question The United States Pulmonary Hypertension Scientific Registry was established as the first US PAH patient registry to investigate genetic information, reproductive histories, and environmental exposure data in a contemporary patient population. Study Design and Methods Investigators at 15 US centers enrolled consecutively screened adults diagnosed with Group 1 PAH who had enrolled in the National Biological Sample and Data Repository for PAH (PAH Biobank) within 5 years of a cardiac catheterization demonstrating qualifying hemodynamic criteria. Exposure and reproductive histories were collected by using a structured interview and questionnaire. The biobank provided genetic data. Results Between 2015 and 2018, a total of 499 of 979 eligible patients with clinical diagnoses of idiopathic PAH (IPAH) or familial PAH (n = 240 [48%]), associated PAH (APAH; n = 256 [51%]), or pulmonary venoocclusive disease/pulmonary capillary hemangiomatosis (n = 3 [1%]) enrolled. The mean age was 55.8 years, average BMI was 29.2 kg/m2, and 79% were women. Mean duration between symptom onset and diagnostic catheterization was 1.9 years. Sixty-six percent of patients were treated with more than one PAH medication at enrollment. Past use of prescription weight loss drugs (16%), recreational drugs (27%), and oral contraceptive pills (77%) was common. Women often reported miscarriage (37%), although PAH was rarely diagnosed within 6 months of pregnancy (1.9%). Results of genetic testing identified pathogenic or suspected pathogenic variants in 13% of patients, reclassifying 18% of IPAH patients and 5% of APAH patients to heritable PAH. Interpretation Patients with Group 1 PAH remain predominately middle-aged women diagnosed with IPAH or APAH. Delays in diagnosis of PAH persist. Treatment with combinations of PAH-targeted medications is more common than in the past. Women often report pregnancy complications, as well as exposure to anorexigens, oral contraceptives, and/or recreational drugs. Results of genetic tests frequently identify unsuspected heritable PAH.

The experimental study on the laminar flame speeds of the CH4/H2/CO/CO2/N2 mixture was carried out in oxygen-enriched air condition. The laminar flame propagation velocities of the blended gas were measured in a range of equivalence ratios (from 0.6 to 1.4) and oxygen concentrations (from 21 to 33%) using a Bunsen flame. Comparisons between the experiments and calculations show that the GRI Mech 3.0 mechanism can well predict the laminar flame speed of the blended gas in oxygen-enriched conditions. The laminar flame propagation velocities were enhanced by the increasing oxygen concentration, while the reaction pathway of fuel changed little. The effects of each species of the CH4/H2/CO/CO2/N2 mixture on the laminar flame speeds were discussed. Results show that the laminar flame speed is promoted by the increase of H2 and CO, while the laminar flame speed is decreased by the increasing CH4, CO2, and N2 concentrations. The inhibition effect of CO2 on the laminar flame speed is bigger than that of N2, which is due to the difference in the properties of CO2 and N2.

Treatment of gas and water for environmental applications requires a high-voltage, fast-rising pulse to act on the plasma gas or water treating reactor, but the existing stacked high-voltage pulse generator is arduous to use owing to its large size, high cost, and relatively slow pulse rise time. In this study, we propose a low-cost, small-volume pulsed power modulator that can significantly reduce the cost and volume of the device and shorten the pulse rise time to meet the requirements of gas and water treatment. The proposed pulsed power modulator is based on a discontinuous conduction mode (DCM) flyback converter, and it generates a high-voltage pulse through the resonance of the flyback transformer secondary side inductance and the parallel capacitor. A straightforward spark gap sharpens the generated high-voltage pulse. Finally, a fast-rising, high-voltage pulse with a narrow pulsewidth run on the load is generated. Through PSIM simulation and actual experiments, we validated the feasibility of the proposed pulse generator and obtained 23 kV, 500-Hz pulses with a width of 0.5- $\mu \text{s}$ width and rise time of 5 ns in actual experiments.

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.

Ultra-low field magnetic resonance imaging (ULF MRI) is an effective imaging technique that applies the ultrasensitive detector of superconducting quantum interference device (SQUID) sensor to detect the MR signal at a microtesla field range. In this work, we designed and developed a SQUID-based ULF MRI system with a frequency-adjustable measurement field, the performance of which was characterized via water phantoms. In order to enhance the MR signals, a 500 mT Halbach magnet was used to prepolarize the magnetization of the sample prior to excitation. The signal-to-noise-ratio (SNR) of the spin-echo- (SE-) based pulse sequence can reach up to 70 in a single scan. The images were then reconstructed successfully by using the maximum likelihood expectation maximization (MLEM) algorithm based on the backprojection imaging method. It was demonstrated that an in-plane resolution of 1.8 × 1.8 mm2 can be achieved which indicated the feasibility of SQUID-based MRI at the ULF.

BackgroundPercutaneous microwave ablation is clinically used for inoperable lung tumour treatment. Delivery of microwave ablation applicators to tumour sites within lung parenchyma under virtual bronchoscopy guidance may enable ablation with reduced risk of pneumothorax, providing a minimally invasive treatment of early-stage tumours, which are increasingly detected with computed tomography (CT) screening. The objective of this study was to integrate a custom microwave ablation platform, incorporating a flexible applicator, with a clinically established virtual bronchoscopy guidance system, and to assess technical feasibility for safely creating localised thermal ablations in porcine lungs in vivo.MethodsPre-ablation CTs of normal pigs were acquired to create a virtual model of the lungs, including airways and significant blood vessels. Virtual bronchoscopy-guided microwave ablation procedures were performed with 24–32 W power (at the applicator distal tip) delivered for 5–10 mins. A total of eight ablations were performed in three pigs. Post-treatment CT images were acquired to assess the extent of damage and ablation zones were further evaluated with viability stains and histopathologic analysis.ResultsThe flexible microwave applicators were delivered to ablation sites within lung parenchyma 5–24 mm from the airway wall via a tunnel created under virtual bronchoscopy guidance. No pneumothorax or significant airway bleeding was observed. The ablation short axis observed on gross pathology ranged 16.5–23.5 mm and 14–26 mm on CT imaging.ConclusionWe have demonstrated the technical feasibility for safely delivering microwave ablation in the lung parenchyma under virtual bronchoscopic guidance in an in vivo porcine lung model.

Recent empirical works on graph drawing have investigated visual properties of graph drawings created by users based on adjacency lists of graphs as well as drawing behaviors. This is mainly done by asking participants to sketch these graphs on a tablet computer so that they can freely express their interpretation. However, previous works did not consider weighted vertices, i.e., assigning a weight to a vertex to reflect its importance. Therefore, we conducted an empirical study on graphs with weighted vertices. More specifically, this work conducts an experiment and analyzes characteristics of the final graph layouts, participants’ drawing processes and strategies and their drawing preferences. Results indicated that minimizing the number of edge crossings was still the most important aesthetic for participants, and that participants preferred the aesthetic of creating grid-like drawings in the condition with weighted vertices. Hence, this work suggested that aesthetics of minimizing number of edge crossings and creating grid-like patterns should be the main consideration for designing a graph drawing software application.

When distributed generation (DG) technologies are implemented in an islanded low-voltage microgrid (LVMG), the topological architecture directly affects the frequency synchronisability. Especially in cases of high DG penetration, the synchronisability of existing traditional topological architectures for LVMGs is very limited. However, a cobweb network topology, which combines the characteristics of several traditional topological architectures, has become a novel alternative for LVMGs. In this context, a compact criterion related to the Moore–Penrose inverse of the incidence matrix for the synchronisability of an LVMG is derived. Then, based on a linear transformation and Moore–Penrose inverse theory, a comparative analysis of the synchronisability of LVMG systems with different topological architectures is presented, the results of which indicate that the synchronisability can be significantly enhanced in a cobweb network topology and that the Braess paradox can also be effectively avoided during the corresponding topological transformation. The effectiveness of the proposed synchronisation criterion is validated based on the Iceland power network, modelled as a cobweb-based LVMG with large-scale DG integration, which exhibits excellent sychronisability.

Background Spontaneous pneumomediastinum (SPM) is more common in young adults, usually caused by external factors like trauma. It causes symptoms such as chest pain or dyspnea, but it is rare to see elderly patients who develop SPM. Here we report the case of an elderly patient diagnosed with coronavirus disease 2019 (COVID-19) who neither got mechanical ventilation nor had chest trauma but were found to develop SPM for unknown reason. Case summary A 62-year-old man complained of a 14-d history of fever accompanied by dry cough, shortness of breath, wheezing, myalgia, nausea, and vomiting. Real-time fluorescence polymerase chain reaction confirmed the diagnosis of COVID-19. The patient was treated with supplementary oxygen by nasal cannula and gamma globulin. Other symptomatic treatments included antibacterial and antiviral treatments. On day 4 of hospitalization, he reported sudden onset of dyspnea. On day 6, he was somnolent. On day 12, the patient reported worsening right-sided chest pain which eventually progressed to bilateral chest pain. He was diagnosed with SPM, with no clear trigger found. Conservative treatment was administrated. During follow-up, the pneumomediastinum had resolved and the patient recovered without other complications. Conclusion We presume that aging lung changes and bronchopulmonary infection play an important part in the onset of SPM in COVID-19, but severe acute respiratory syndrome may represent a separate pathophysiologic mechanism for pneumomediastinum. Although the incidence of SPM in elderly patients is low, clinicians should be alert to the possibility of SPM in those infected with severe acute respiratory syndrome coronavirus 2 for life-threatening complications such as cardiorespiratory arrest may occur.

Purpose To evaluate the level of human papilloma virus (HPV)-related knowledge and vaccination willingness of people in Fujian Province, and to explore the factors influencing doctors' recommendation of HPV vaccine. Methods We conducted two cross-sectional surveys in Fujian Province. The study cohort included 248 medical staff and medical students and 1001 community members. Descriptive statistics were used to identify the general demographics of the participants, along with their knowledge and attitudes regarding HPV and vaccination. Analyses were conducted to identify factors associated with willingness to vaccinate and willingness to recommend vaccination. Results The level of HPV knowledge in Fujian province was found to be low, but more than 80% of participants would like to accept HPV vaccine. Medical staff had a higher willingness to recommend HPV vaccine than students (OR= 4.696, CI: 2.698-8.175), which may be related to work experience and acceptance of vaccine price but not to knowledge level. Conclusion Knowledge of HPV in our community population appears to be lower than that in other regions in China. We suggest that a lack of knowledge may not be the main factor affecting the willingness to vaccinate, but we still needed to raise the level of knowledge about HPV to prevent misunderstandings. When the level of knowledge is high, education and per capita household income are not important factors influencing the willingness to vaccinate; only acceptance of vaccine prices significantly affects the willingness to vaccinate. Inclusion of the HPV vaccine in the national immunization program could help to alleviate public concerns regarding the vaccine to change present situation.

Coal bed methane has been considered as an important energy resource. One major difficulty of purifying coal bed methane comes from the similar physical properties of CH4 and N2. The ZIF-8/water-glycol slurry was used as a medium to separate coal bed methane by fluidifying the solid adsorbent material. The sorption equilibrium experiment of binary mixture (CH4/N2) and slurry was conducted. The selectivity of CH4 to N2 is within the range of 2–6, which proved the feasibility of the slurry separation method. The modified Langmuir equation was used to describe the gas-slurry phase equilibrium behavior, and the calculated results were in good agreement with the experimental data. A continuous absorption–adsorption and desorption process on the separation of CH4/N2 in slurry is proposed and its mathematical model is also developed. Sensitivity analysis is conducted to determine the operation conditions and the energy performance of the proposed process was also evaluated. Feed gas contains 30 mol% of methane and the methane concentration in product gas is 95.46 mol% with the methane recovery ratio of 90.74%. The total energy consumption for per unit volume of product gas is determined as 1.846 kWh Nm−3. Experimental results and process simulation provide basic data for the design and operation of pilot and industrial plant.

A low-power and small chip-area multi-rate human body communication (HBC) discontinuous-phase FSK (DPFSK) transceiver applied for wearable devices is presented. The transceiver is implemented in UMC $0.18~\mu \text{m}$ CMOS process with a small chip area of only 0.46 mm2. DPFSK modulation is adopted to reduce the hardware complexity of the transceiver. In the receiver, a direct-conversion front-end is adopted to eliminate polarization voltage of the electrode-skin interface. A delay line (DL)-based variable phase shifter used in the demodulator of the receiver is proposed for accomplishing of multi-rate DPFSK demodulation. In the transmitter, a digital frequency interpolator is adopted for achieving multi-rate DPFSK transmission. At a data rate of 1 Mb/s, the receiver and the transmitter consume the power of 1.79 mW and $700~{\boldsymbol{\mu }}\text{W}$ , respectively. Therefore, energy consumption per received and transmitted bit are 1.79 nJ/bit and 0.7 nJ/bit, respectively.

Background It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care. Objectives To describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS. Methods At 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods. Results Of the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty‐eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio‐oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety‐two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta‐blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P, The implementation and impact of cardiovascular screening recommendations in asymptomatic childhood cancer survivors is characterized based on survey responses from 50 academic medical centers. Heterogeneity in current clinical practice highlights the need for multidisciplinary alliances, standardization of care across institutions, and collaborative research programs to improve evidence‐based care for this population.

The efficacy of basal insulin (BI) for adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) has been well documented by randomized clinical trials. This post hoc analysis of the Observational Registry of Basal Insulin Treatment (ORBIT) study was performed to explore the 6-month dose of BI used in insulin-naïve T2DM patients achieving HbA1c target (7%) and determine the patient characteristics that affect the 6-month dose of BI in the setting of real-world clinics in China.This multicenter observational registry screened 19 894 adult T2DM patients with inadequately controlled hyperglycemia and treated with oral antidiabetic drugs (OADs) in China. Of these patients, 5191 who continued to receive BI after 6 months and achieved HbA1c target were analyzed. Patient characteristics including age, body weight, fasting plasma glucose (FPG), use of OADs, insulin (type and dose), and glycemic control were recorded at baseline and 6-month follow-ups.The 6-month dose of BI needed for effective glycemic control was 0.20 ± 0.08 U/kg/day. High body mass index, high FPG, young age, longer duration of diabetes or OAD treatment, a greater number of OADs at baseline, and allocation to detemir and glargine were significant independent predictors for high dose of BI at 6 months.This post hoc analysis of the ORBIT registry provides key information on the 6-month dose of BI needed for effective glycemic control in Chinese T2DM patients. Furthermore, it identified crucial patient characteristics that are significant determinants of the dose of BI in a real-world setting.背景: 基础胰岛素(BI)对2型糖尿病(T2DM)患者血糖控制的有效性已被随机对照临床试验所证实。这项来自ORBIT研究的事后分析旨在探讨既往未接受胰岛素治疗的中国T2DM患者, 在临床真实世界中接受基础胰岛素治疗6个月后, HbA1c达标(7%)患者的基础胰岛素剂量及其相关特征。 方法: ORBIT研究在中国采用多中心观察性研究方法, 共筛选入组19894例接受口服降糖药(OAD)治疗但血糖控制不佳的2型糖尿病患者。本研究对其中5191例持续接受BI治疗6个月且HbA1c达标(7%)的患者进行了分析。收集的患者特征包括基线和随访6个月时的年龄, 体重, 空腹血浆血糖(FPG), OAD使用情况, 胰岛素的类型和剂量以及血糖控制情况。 结果: 治疗6个月时血糖达标患者的BI剂量为0.20±0.08U/kg/d。高体重指数, 高FPG, 年龄小, 糖尿病病程或OAD治疗时间较长, 基线OAD种类多, 接受地特胰岛素或甘精胰岛素治疗是6个月时较高BI剂量的独立预测因素。 结论: 这项ORBIT研究的事后分析提供了启动基础胰岛素治疗6个月的中国2型糖尿病患者血糖控制达标所需BI剂量的关键信息。此外, 该研究明确了在临床真实世界中影响基础胰岛素剂量的患者特征。.

This paper applies the BEKK-GARCH model to construct a comparative analysis of the heterogeneous relationship between the oil prices and stock prices of oil-related firms in the US and China. We find the following results. First, the effects of oil prices on stock returns depend heavily on the subsector category of an oil firm. Second, the effect from stock returns to oil prices displays distinguished country-specific patterns. The stock returns of oil firms in the US affect oil price, whereas stock returns of oil companies in China have limited influence on the oil market. Third, compared to the US, fewer Chinese oil company stocks are subject to risk spillover from oil market, but more stocks transmit their risks to oil market.

Primary aldosteronism is a frequent cause of resistant hypertension and is associated with an increased risk of developing diabetes mellitus. Aldosterone impairs insulin secretion in isolated islets, and insulin secretion is increased in aldosterone synthase–deficient mice. We hypothesized that treatment for primary aldosteronism increases insulin secretion and insulin sensitivity in humans. We conducted a prospective cohort study in patients with primary aldosteronism, with assessment of glucose metabolism before and 3 to 12 months after treatment. Participants underwent treatment for primary aldosteronism with adrenalectomy or a mineralocorticoid receptor antagonist at the discretion of their treating physician. We assessed insulin secretion and insulin sensitivity by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively, on 2 study days after a 5-day standardized diet. After treatment, the C-peptide and insulin response during the hyperglycemic clamp increased compared with pretreatment (ΔC-peptide at 90–120 minutes +530.5±384.1 pmol/L, P =0.004; Δinsulin 90–120 minutes +183.0±122.6, P =0.004). During hyperinsulinemic-euglycemic clamps, insulin sensitivity decreased after treatment (insulin sensitivity index 30.7±6.2 versus 18.5±4.7 nmol·kg −1 ·min −1 ·pmol −1 ·L; P =0.02). Insulin clearance decreased after treatment (872.8±207.6 versus 632.3±178.6 mL/min; P =0.03), and disposition index was unchanged. We conclude that the insulin response to glucose increases and insulin clearance decreases after treatment for primary aldosteronism, and these effects were not due to alterations in creatinine clearance or plasma cortisol. These studies may provide further insight into the mechanism of increased diabetes mellitus risk in primary aldosteronism.