bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate Decision-Making
Authors: Orlove Ben , Shwom Rachael , Markowitz Ezra , Cheong So-Min
Published: June 2020

Climate change decision-making has emerged in recent decades as an area of research and practice, expanding on an earlier focus on climate policy. Defined as the study of decisions relevant for climate change, it draws on developments in decision science, particularly advances in the study of cognitive and deliberative processes in individuals and organizations. The effects of climate, economic, social, and other framings on decision-making have been studied, often showing that nonclimate frames can be as effective as, or more effective than, climate frames in promoting decision-making and action. The concept of urgency, linked to the ideas of climate crisis and climate emergency, has taken on importance in recent years. Research on climate decision-making has influenced numerous areas of climate action, including nudges and other behavioral interventions, corporate social responsibility, and Indigenous decision-making. Areas of transformational change, such as strategic retreat in the face of sea-level rise, are emerging.
Sex-Based Harassment and Symbolic Compliance
Authors: Edelman Lauren B. , Cabrera Jessica
Published: June 2020

With the rise of the #MeToo movement, there has been a groundswell of attention to sex-based harassment. Organizations have pressured high-level personnel accused of harassment to resign, or fired them outright, and they have created or revised their anti-harassment policies, complaint procedures, and training programs. This article reviews social science and legal scholarship on sex-based harassment, focusing on definitions and understandings of sexual (and sex-based) harassment, statistics on its prevalence, the consequences of harassment both for those who are subjected to it and for organizations, and explanations for why sex-based harassment persists. We then discuss the various steps that organizations have taken to reduce sex-based harassment and the social science literature on the effectiveness of those steps. We conclude that many organizational policies prevent liability more than they prevent harassment, in part because courts often fail to distinguish between meaningful compliance and the merely symbolic policies and procedures that do little to protect employees from harassment.
Characterization of the endometrial transcriptome in early diestrus influencing pregnancy status in dairy cattle after transfer of in vitro-produced embryos
Authors: Mazzoni Gianluca , Pedersen Hanne S. , Rabaglino Maria B. , Hyttel Poul , Callesen Henrik , Kadarmideen Haja N.
Published: June 2020

Modifications of the endometrial transcriptome at day 7 of the estrus cycle are crucial to maintain gestation after transfer of in vitro-produced (IVP) embryos, although these changes are still largely unknown. The aim of this study was to identify genes, and their related biological mechanisms, important for pregnancy establishment based on the endometrial transcriptome of recipient lactating dairy cows that become pregnant in the subsequent estrus cycle, upon transfer of IVP embryos. Endometrial biopsies were taken from Holstein Friesian cows on day 6–8 of the estrus cycle followed by embryo transfer in the following cycle. Animals were classified retrospectively as pregnant (PR, n = 8) or nonpregnant (non-PR, n = 11) cows, according to pregnancy status at 26–47 days. Extracted mRNAs from endometrial samples were sequenced with an Illumina platform to determine differentially expressed genes (DEG) between the endometrial transcriptome from PR and non-PR cows. There were 111 DEG (false discovery rate < 0.05), which were mainly related to extracellular matrix interaction, histotroph metabolic composition, prostaglandin synthesis, transforming growth factor-β signaling as well as inflammation and leukocyte activation. Comparison of these DEG with DEG identified in two public external data sets confirmed the more fertile endometrial molecular profile of PR cows. In conclusion, this study provides insights into the key early endometrial mechanisms for pregnancy establishment, after IVP embryo transfer in dairy cows.
Effects of High‐Fat Diet and Exercise Intervention on the Metabolism Regulation of Infant Mice
Authors: Zhu Xiaofeng , Ma Yun , Ye Qun , Shi Yue
Published: June 2020

Maternal exercise is crucial for promoting the health of the offspring. Previous studies showed that long‐term maternal exercise improves energy metabolism during pregnancy. Whether swimming exercise can reverse the metabolic disorders caused by high‐fat exposure in the early life of the offspring is yet to be elucidated. Three‐week‐old C57BL/6 female mice were randomly assigned to the standard chow diet group (SC), standard chow diet and exercise group (SC‐Ex), high‐fat diet group (HFD), and high‐fat diet and exercise group (HFD‐Ex). After swimming intervention for 13 weeks, male and female mice were caged, and the exercise intervention lasted until delivery. Then, the mothers were fed standard chow diet. A total of 8 offsprings/group were randomly selected after 4 weeks of lactation for GTT and ITT. After body composition analysis, the mice were sacrificed to obtain specimens. The levels of metabolism factors and IL‐6 were measured by suspension microarray. Subsequently, 15 min after starting the GTT and ITT, the curve detected significant difference between the HFD and other groups. The body fat percentage of the HFD‐Ex offspring was significantly lower than that of HFD offspring (p < 0.05) irrespective of the gender. The levels of IL‐6 and TG in the male offspring in the HFD‐Ex group were improved significantly (p < 0.05). Compared to the HFD offspring, serum glucose and GIP in the female offspring in the HFD‐Ex group was significantly reduced (p < 0.05). Long‐term exercise of the mother effectively improved the metabolic disorder caused by high‐fat exposure in the infant offspring. Thus, the metabolic inheritance of the offspring is gender‐dependent; the maternal metabolism can make male offspring genetically susceptible.
Credit Risk Assessment for Small and Microsized Enterprises Using Kernel Feature Selection-Based Multiple Criteria Linear Optimization Classifier: Evidence from China
Authors: Wang Yimeng , Zhang Yunqi
Published: June 2020

Credit risk assessment has gained increasing marked attention in the recent years by researchers, financial institutions, and banks, especially for small and microsized enterprises. Evidence shows that the core of small and microsized enterprises’ credit risk assessment is to construct a scientific credit risk indicator system, and the key is to establish an effective credit risk prediction model. Therefore, we analyze the factors that influence the credit risk of Chinese small and microsized enterprises and then construct a comprehensive credit risk indicator system by adding behaviour information, supervision information, and policy information. Furthermore, we improve the multiple criteria linear optimization classifier (MCLOC) by introducing the one-norm kernel feature selection and thereby establish the kernel feature selection-based multiple criteria linear optimization classifier (KFS-MCLOC). As for experiments, we use real business data from a Chinese commercial bank to test the performance of these models. The results show that (1) the proposed KFS-MCLOC has greater advantages in predictive accuracy, interpretability, and stability than other models; (2) the KFS-MCLOC selects 10 features from 53 original features and gives selected features their weight automatically; (3) the features selected by the KFS-MCLOC are further verified and compared by the features selected by the logistic regression model with stepwise parameter, and the indicators of “quick ratio; net operating cash flow; enterprises’ abnormal times of water, electricity, and tax fee; overdue days of enterprises’ loans; and mortgage and pledge status” are proved to be the most influencing credit risk factors.
A Node-Regulated Deflection Routing Framework for Contention Minimization
Authors: Nleya Bakhe , Mutsvangwa Andrew
Published: June 2020

Optical Burst Switching (OBS) paradigm coupled with Dense Wavelength Division Multiplexing (DWDM) has become a practical candidate solution for the next-generation optical backbone networks. In its practical deployment only the edge nodes are provisioned with buffering capabilities, whereas all interior (core) nodes remain buffer-less. In that way the implementation becomes quite simple as well as cost effective as there will be no need for optical buffers in the interior. However, the buffer-less nature of the interior nodes makes such networks prone to data burst contention occurrences that lead to a degradation in overall network performance as a result of sporadic heavy burst losses. Such drawbacks can be partly countered by appropriately dimensioning available network resources and reactively by way of deflecting excess as well as contending data bursts to available least-cost alternate paths. However, the deflected data bursts (traffic) must not cause network performance degradations in the deflection routes. Because minimizing contention occurrences is key to provisioning a consistent Quality of Service (QoS), we therefore in this paper propose and analyze a framework (scheme) that seeks to intelligently deflect traffic in the core network such that QoS degradations caused by contention occurrences are minimized. This is by way of regulated deflection routing (rDr) in which neural network agents are utilized in reinforcing the deflection route choices at core nodes. The framework primarily relies on both reactive and proactive regulated deflection routing approaches in order to prevent or resolve data burst contentions. Simulation results show that the scheme does effectively improve overall network performance when compared with existing contention resolution approaches. Notably, the scheme minimizes burst losses, end-to-end delays, frequency of contention occurrences, and burst deflections.
Efficacy of Thiamine in the Treatment of Postcardiac Arrest Patients: A Randomized Controlled Study
Authors: Pradita-ukrit Suntornwit , Vattanavanit Veerapong
Published: June 2020

Background. Thiamine administration has been shown to improve survival in a postcardiac arrest animal study. We aimed to evaluate the efficacy of thiamine in comatose out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation. Methods. A randomized, double-blinded, placebo-controlled study was conducted. Thirty-seven OHCA patients were randomly assigned to receive either thiamine 100 mg every 8 hours or a placebo. The primary outcome was 28-day all-cause mortality. Results. Over the course of 2 years, 37 patients were randomized to either receive thiamine (n = 20) or a placebo (n = 17). The primary outcome was not different between the groups: 10/20 (50%) in the thiamine group vs. 8/17 (47.1%) in the placebo group (P=0.93 by the log-rank test). There were no significant differences in secondary outcomes between the groups (good neurological outcome, lactate level, and S100B level). Conclusions. In this study, there were no significant differences in survival outcome. Further studies with a larger population are necessary to confirm these results.
Extensive Prostatic Abscess in an Elderly Patient Requiring Multidisciplinary Drainage
Authors: Nesemann John Michael , Huen Kathy , Bergman Jonathan
Published: June 2020

Background. Prostatic abscess is rare and mainly affects immunocompromised individuals, classically presenting with both systemic and lower urinary tract symptoms. Our case is unique as the patient presented with an exceptionally long duration of symptoms prior to seeing a health-care provider, had no systemic symptoms, and was managed via a multidisciplinary approach. Case Presentation. We present a case of a 70-year-old man with type-two diabetes who endured two months of lower urinary tract symptoms and constipation without systemic symptoms prior to seeking medical attention. He had a positive urinalysis and culture and was initially thought to have a urinary tract infection; however, computed tomography scan revealed a large, complex, and multiloculated prostatic abscess. Multidisciplinary drainage of the abscess was performed by interventional radiology and urology. A postoperative Foley catheter was left in place, and the patient recovered without complications. Discussion. Prostatic abscess is uncommon and presents almost exclusively in patients with immunocompromising conditions such as diabetes. Prior to the advent of antibiotics, the major causes were gonorrheal and Staphylococcus aureus infections, but with the advent of antibiotics, microbial culprits have shifted to gram-negative organisms. Patients typically present with lower urinary tract symptoms, perineal or lower back pain, and systemic symptoms. Management often consists of intravenous antibiotics and surgical drainage either by transrectal ultrasound-guided needle aspiration, or transurethral deroofing of the prostate. Our case highlights the following: (a) the importance of a high index of suspicion for a prostatic abscess in an immunocompromised patient with persistent leukocytosis and perineal pain after treatment with antibiotics and (b) the potential for an early multidisciplinary approach to draining extensive, loculated prostatic abscesses.
Cell Cycle Genes Are Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma
Authors: Liping Xu , Jia Li , Qi Chen , Liang Yang , Dongen Li , Jianshuai Jiang
Published: June 2020

Background. The cell cycle pathway genes are comprised of 113 members which are critical to the maintenance of cell cycle and survival of tumor cells. This study was performed to investigate the diagnostic and prognostic values of cell cycle gene expression in hepatocellular carcinoma (HCC) patients. Methods. Clinical features and cell cycle pathway gene expression data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Differentially expressed genes (DEGs) were determined by the student t‐test between HCC and noncancerous samples. Kaplan‐Meier survival, univariate, and multivariate survival analyses and validation analysis were performed to characterize the associations between cell cycle gene expression and patients’ overall survival and recurrence‐free survival. Results. 47 and 5 genes were significantly upregulated and downregulated genes in HCC samples, respectively. The high expression of BUB3, CDK1, and CHEK1 was associated with increased mortality (adjusted P value = 0.04, odds ratio (OR): 1.89 (95% confidence interval (CI): 1.04‐3.46); adjusted P value = 0.02, OR: 2.06 (95% CI:1.15‐3.75); and adjusted P value = 0.04, OR: 1.84 (%95 CI: 1.03‐3.32), respectively). The expression of PTTG2 and RAD21 was significantly associated with cancer recurrence (adjusted P value = 0.01, OR: 2.17 (95% CI: 1.24‐3.86); adjusted P value = 0.03, OR: 1.88[95% CI:1.08‐3.28], respectively), while the low expression of MAD1L1 was associated with cancer recurrence (adjusted P value = 0.03, OR: 0.53 (%95 CI: 0.3‐0.93)). Conclusions. The present study demonstrated that BUB3, CDK1, and CHEK1 may serve as a prognostic biomarker for HCC patients. PTTG2, RAD21, and MAD1L1 expression is a major factor affecting the recurrence of HCC patients.
Identification of 5 Gene Signatures in Survival Prediction for Patients with Lung Squamous Cell Carcinoma Based on Integrated Multiomics Data Analysis
Authors: Ma Hongxia , Tong Lihong , Zhang Qian , Chang Wenjun , Li Fengsen
Published: June 2020

Background. Lung squamous cell carcinoma (LSCC) is a frequently diagnosed cancer worldwide, and it has a poor prognosis. The current study is aimed at developing the prediction of LSCC prognosis by integrating multiomics data including transcriptome, copy number variation data, and mutation data analysis, so as to predict patients’ survival and discover new therapeutic targets. Methods. RNASeq, SNP, CNV data, and LSCC patients’ clinical follow‐up information were downloaded from The Cancer Genome Atlas (TCGA), and the samples were randomly divided into two groups, namely, the training set and the validation set. In the training set, the genes related to prognosis and those with different copy numbers or with different SNPs were integrated to extract features using random forests, and finally, robust biomarkers were screened. In addition, a gene‐related prognostic model was established and further verified in the test set and GEO validation set. Results. We obtained a total of 804 prognostic‐related genes and 535 copy amplification genes, 621 copy deletions genes, and 388 significantly mutated genes in genomic variants; noticeably, these genomic variant genes were found closely related to tumor development. A total of 51 candidate genes were obtained by integrating genomic variants and prognostic genes, and 5 characteristic genes (HIST1H2BH, SERPIND1, COL22A1, LCE3C, and ADAMTS17) were screened through random forest feature selection; we found that many of those genes had been reported to be related to LSCC progression. Cox regression analysis was performed to establish 5‐gene signature that could serve as an independent prognostic factor for LSCC patients and can stratify risk samples in training set, test set, and external validation set (p < 0.01), and the 5‐year survival areas under the curve (AUC) of both training set and validation set were > 0.67. Conclusion. In the current study, 5 gene signatures were constructed as novel prognostic markers to predict the survival of LSCC patients. The present findings provide new diagnostic and prognostic biomarkers and therapeutic targets for LSCC treatment.
Assessment of Knowledge and Attitude of Tuberculosis Patients in Direct Observation Therapy Program towards Multidrug-Resistant Tuberculosis in Addis Ababa, Ethiopia: A Cross-Sectional Study
Authors: Kusheno Firew Tadesse , Nguse Teklehaimanot Mezgebe , Gebretekle Gebremedhin Beedemariam
Published: June 2020

Background. Multidrug-resistant tuberculosis (MDR-TB) is becoming a major challenge of tuberculosis (TB) control program globally but more serious in developing countries like Ethiopia. In 2013, a survey result showed that in Ethiopia, tuberculosis patients from new cases and retreatment cases had resistance to at least isoniazid and rifampicin with a significant increase over time. Inadequate knowledge and wrong perception about MDR-TB by patients were detrimental to TB control programs. The study aimed at assessing the knowledge and attitude of TB patients of direct observation therapy program towards multidrug-resistant tuberculosis in health centres of Addis Ababa, Ethiopia. Methods. A cross-sectional study was conducted in 10 health centres of Addis Ababa which were selected by simple random sampling technique. A total of 422 TB patients were included in the study, and participants from each health centres were taken proportional to the number of clients in each health centres. Data was entered and analyzed using SPSS version 20. Association between outcome and independent variables was explored using logistic regression. Results. The level of knowledge of TB patients about MDR-TB was poor and only 55.0% of TB patients attained good overall knowledge. A significant association was found between good knowledge and attending tertiary level of education (AOR=4.3, 95%CI=1.9, 9.8), gender (AOR=1.62, 95%CI=1.1, 2.4), income of respondents’ family (OR=0.4, 95%CI=0.2, 0.9), and sleeping practice (AOR=8.0, 95%CI=4.0, 15.7). Nearly three-fourths (73.5%) of TB patients had a favourable attitude towards MDR-TB. Occupational status (AOR=4.4, 95%CI=2.5, 7.6) and sleeping practices (AOR=2.4, 95%CI=1.2, 5.0) were significantly associated with the attitude of the TB patients. Conclusions. Knowledge of TB patients toward MDR-TB was poor. Although a large proportion of patients had a favourable attitude, it still needs to be improved. Hence, efforts should be made to implementing health education to improve awareness of TB patients about MDR-TB.
Effect of the Abnormal Expression of BMP‐4 in the Blood of Diabetic Patients on the Osteogenic Differentiation Potential of Alveolar BMSCs and the Rescue Effect of Metformin: A Bioinformatics‐Based Study
Authors: Liang Chao , Sun Rongxin , Xu Yifan , Geng Wei , Li Jun
Published: June 2020

The success rate of oral implants is lower in type 2 diabetes mellitus (T2DM) patients than in nondiabetic subjects; functional impairment of bone marrow‐derived mesenchymal stem cells (BMSCs) is an important underlying cause. Many factors in the blood can act on BMSCs to regulate their biological functions and influence implant osseointegration, but which factors play important negative roles in T2DM patients is still unclear. This study is aimed at screening differentially expressed genes in the blood from T2DM and nondiabetic patients, identifying which genes impact the osteogenic differentiation potential of alveolar BMSCs in T2DM patients, exploring drug intervention regimens, and providing a basis for improving implant osseointegration. Thus, a whole‐blood gene expression microarray dataset (GSE26168) of T2DM patients and nondiabetic controls was analyzed. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results, differentially expressed genes and signaling pathways related to BMSC osteogenic differentiation were screened, and major risk genes were extracted based on the mean decrease Gini coefficient calculated using the random forest method. Bone morphogenetic protein‐4 (BMP‐4), with significantly low expression in T2DM blood, was identified as the most significant factor affecting BMSC osteogenic differentiation potential. Subsequently, metformin, a first‐line clinical drug for T2DM treatment, was found to improve the osteogenic differentiation potential of BMSCs from T2DM patients via the BMP‐4/Smad/Runx2 signaling pathway. These results demonstrate that low BMP‐4 expression in the blood of T2DM patients significantly hinders the osteogenic function of BMSCs and that metformin is effective in counteracting the negative impact of BMP‐4 deficiency.
The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (‐8C>G) on the Development and Outcome of Multiple Myeloma
Authors: Zmorzyński S. , Popek-Marciniec S. , Styk W. , Wojcierowska-Litwin M. , Korszeń-Pilecka I. , Szudy-Szczyrek A. , Chocholska S. , Hus M. , Filip A. A.
Published: June 2020

Introduction. Multiple myeloma (MM) is a hematological malignancy characterized by genetic variety. The 3020insC variant of the NOD2/CARD15 gene results in the upregulation of proinflammatory cytokines. Chronic inflammation and abnormal function of the proteasome system may lead to MM development. The polymorphism (‐8C>G) in the PSMA6 gene affects proteasome activity. The aim of our study was to analyze the possible relationship of NOD/CARD15 and PSMA6 genes with the risk of development and outcome of MM, as well as the sensitivity to bortezomib (proteasome inhibitor) in cell cultures derived from MM patients. Objects and Methods. Genomic DNA from 100 newly diagnosed MM patients and 100 healthy blood donors was analyzed by methods such as PCR‐RFLP (for PSMA6 genotyping) and automated DNA sequencing (for NOD2/CARD15 genotyping). In a subgroup of 50 MM patients, nucleated bone marrow cells were treated with bortezomib in vitro. Results. Patients with PSMA6 CG+GG genotypes had higher chances for progressive disease (OR = 5.0, 95% CI 1.07‐23.16, p = 0.05), shorter overall survival taking into account the type of treatment (p = 0.039), and increased risk of death due to MM at the level of tendency (OR = 4.74, 95% CI 1.02‐21.97, p = 0.06). The presence of NOD2/CARD15 3020insC decreased the risk of renal dysfunction in MM (OR = 0.23, 95% CI 0.07‐0.74, p = 0.009). The analyzed changes in NOD2/CARD15 and PSMA6 genes did not impact the MM risk. In an in vitro study, bortezomib increased the number of apoptotic cells at 8 nM and 12 nM between wild‐type and 3030insC variants of NOD2/CARD15 (p = 0.018 and p = 0.03, respectively). Conclusion. The presented results suggest a possible impact of PSMA6 CG+GG genotypes on the MM outcome and the association of the NOD2/CARD15 variant with bortezomib in vitro sensitivity.
Clinical Features and Prognostic Impact of Coexpression Modules Constructed by WGCNA for Diffuse Large B‐Cell Lymphoma
Authors: Xiao Jianjun , Wang Xuemei , Bai Haitao
Published: June 2020

Objective. Diffuse large B‐cell lymphoma (DLBCL) is a highly aggressive malignant tumor, accounting for 30‐40% of non‐Hodgkin’s lymphoma. Our aim was to construct novel prognostic models of candidate genes based on clinical features. Methods. RNA‐seq and clinical data of DLBCL were retrieved from TCGA database. Coexpression modules were constructed by WGCNA. Then, we investigated the interactions between modules and clinical features. By overall survival analysis, prognostic candidate genes from modules of interest were identified. A coexpression network of prognostic candidate genes was then constructed through WGCNA. GEPIA was used to analyze the expression of a candidate gene between DLBCL and normal samples. Results. 19 coexpression modules were constructed by 12813 genes from 52 DLBCL samples. The number of genes in modules ranged from 34 to 5457. We found that the purple module was significantly related with histological type (p value = 1e‐04). Overall survival analysis revealed that MAFA‐AS1, hsa‐mir‐338, and hsa‐mir‐891a were related with prognosis of DLBCL (p value = 0.027, 0.039, and 0.022, respectively). A coexpression network was constructed for the three prognostic genes. MAFA‐AS1 was interacted with 36 genes, hsa‐mir‐891a was interacted with 11 genes, while no gene showed interaction with hsa‐mir‐338. Using GEPIA, we found that MAFA‐AS1 showed low expression in DLBCL samples (p < 0.01). Conclusion. We constructed a coexpression module related with histological type and identified three candidate genes (MAFA‐AS1, hsa‐mir‐338, and hsa‐mir‐891a) that possessed potential value as prognostic biomarkers and therapeutic targets of DLBCL.
Relation Extraction Based on Fusion Dependency Parsing from Chinese EMRs
Authors: Zhai Pengjun , Huang Xin , Zhang Beibei , Fang Yu
Published: June 2020

The Electronic Medical Record (EMR) contains a great deal of medical knowledge related to patients, which has been widely used in the construction of medical knowledge graphs. Previous studies mainly focus on the features based on surface semantics of EMRs for relation extraction, such as contextual feature, but the features of sentence structure in Chinese EMRs have been neglected. In this paper, a fusion dependency parsing-based relation extraction method is proposed. Specifically, this paper extends basic features with medical record feature and indicator feature that are applicable to Chinese EMRs. Furthermore, dependency syntactic features are introduced to analyse the dependency structure of sentences. Finally, the F1 value of relation extraction based on extended features is 4.87% higher than that of relation extraction based on basic features. And compared with the former, the F1 value of relation extraction based on fusion dependency parsing is increased by 4.39%. The results of experiments performed on a Chinese EMR data set show that the extended features and dependency parsing all contribute to the relation extraction.
Generalized Weighted Statistical Convergence for Double Sequences of Fuzzy Numbers and Associated Korovkin-Type Approximation Theorem
Authors: Alotaibi Abdullah
Published: June 2020

We define the notions of weightedλ,μ-statistical convergence of orderγ1,γ2and strongly weightedλ,μ-summability ofγ1,γ2for fuzzy double sequences, where0<γ1,γ2≤1. We establish an inclusion result and a theorem presenting a connection between these concepts. Moreover, we apply our new concept of weightedλ,μ-statistical convergence of orderγ1,γ2to prove Korovkin-type approximation theorem for functions of two variables in a fuzzy sense. Finally, an illustrative example is provided with the help ofq-analogue of fuzzy Bernstein operators for bivariate functions which shows the significance of our approximation theorem.
Using Improved Prospect Theory to Develop a Partner Selection Method for Virtual Enterprises with Unknown Weight
Authors: Su Nina , Zhu Xianqi , Xin Yunsheng
Published: June 2020

A “virtual enterprise” is an effective organization formed by enterprises and partners under market opportunity which can flexibly adapt to the dynamic market demand and improve the competitiveness of enterprises. To select virtual enterprise partners objectively and scientifically, this study proposes the evaluation model of the innovation resource capability of the alternative enterprises under the unknown weight. In the multigranularity hesitation fuzzy language environment, the unknown weight is solved by using fuzzy entropy theory. The risk attitude of decision-making enterprises is introduced by using the improved prospect theory and the selection of partners is comprehensively considered. Finally, a case study is presented to demonstrate the effectiveness of the proposed approach. The research intends to enable the virtual enterprise to choose the partners swiftly such that they can compensate for the shortcomings and optimize the allocation of innovation resources.
Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand-binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer
Authors: Kyriakopoulos Christos E. , Eickhoff Jens C. , Ferrari Anna C. , Schweizer Michael T. , Wargowski Ellen , Olson Brian M. , McNeel Douglas G.
Published: June 2020

Purpose:

Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase I trial.

Patients and Methods:

Patients with metastatic castration-sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-PFS (PPFS).

Results:

Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month time point. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared with patients without immunity (HR = 0.01; 95% CI, 0.0–0.21; P = 0.003).

Conclusions:

pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials.

See related commentary by Shenderov and Antonarakis, p. 5056
Overcoming Barriers
Authors: Gustafson Dakota , Raju Sneha , Wu Ruilin , Ching Crizza , Veitch Shawn , Rathnakumar Kumaragurubaran , Boudreau Emilie , Howe Kathryn L. , Fish Jason E.
Published: June 2020

Objective:

Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to ACE2 (angiotensin-converting enzyme 2). While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about COVID-19 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis.

Approach and Results:

Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of COVID-19 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 expression, such as diabetes mellitus, hypertension, and cardiovascular disease.

Conclusions:

Rapidly emerging data on COVID-19, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.
Genotype-Guided Dosing of Warfarin in Chinese Adults
Authors: Guo Chengxian , Kuang Yun , Zhou Honghao , Yuan Hong , Pei Qi , Li Jingle , Jiang Weihong , Ng Chee M. , Chen Xiaoping , Huo Yong , Cui Yimin , Wang Xiaobin , Yu Jingjing , Sun Xue , Yu Wanying , Chen Peng , Miao Da , Liu Wenyu , Yu Zaixin , Ouyang Zewei , Shi Xiangjiang , Lv Chunmei , Peng Zijing , Xiong Guozuo , Zeng Gaofeng , Zeng Jianping , Dai Haiying , Peng Jianqiang , Zhang Yuming , Xu Fanghua , Wu Jie , Chen Xiaoliang , Gong Hao , Yang Zhiyuan , Wu Xianming , Fang Qiulian , Yang Liu , Li Haigang , Tan Hongyi , Huang Zhijun , Tang Xiaohong , Yang Qiong , Tu Shan , Wang Xiaoyan , Xiang Yuxia , Huang Jie , Wang Xiaomin , Cai Jingjing , Jiang Shanjie , Huang Lu , Peng Jinfu , Gong Liying , Zou Chan , Yang Guoping
Published: June 2020

Background:

Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients.

Methods:

We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy.

Results:

A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1–10.2];
P
=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1–24.4]). The incidence of adverse events was low in both groups.

Conclusions:

The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02211326.
Computed Tomography-Aortography Versus Color-Duplex Ultrasound for Surveillance of Endovascular Abdominal Aortic Aneurysm Repair
Authors: Jean-Baptiste Elixène , Feugier Patrick , Cruzel Coralie , Sarlon-Bartoli Gabrielle , Reix Thierry , Steinmetz Eric , Chaufour Xavier , Chavent Bertrand , Salomon du Mont Lucie , Ejargue Meghann , Maurel Blandine , Spear Rafaelle , Midy Dominique , Thaveau Fabien , Desgranges Pascal , Rosset Eugenio , Hassen-Khodja Réda , Bureau Pascale , Ravoux Mireille , Bozzetto Catherine , Sevestre-Pietri Marie-Antoinette , Terriat Béatrice , Favier Claire , Degeilh Maryse , Le Hello Claire , Favre Jean-Pierre , Rinckenbach Simon , Loppinet Anca , Goueffic Yann , Connault Jérôme , Alimi Yves , Barthélémy Pierre , Magne Jean-Luc , Seinturier Christophe , Choukroun Marie-Luce , Rouyer Olivier , Bitton Liliane , Becquemin Jean-Pierre
Published: June 2020

Background

Color-duplex ultrasonography (DUS) could be an alternative to computed tomography-aortography (CTA) in the lifelong surveillance of patients after endovascular aneurysm repair (EVAR), but there is currently no level 1 evidence. The aim of this study was to assess the diagnostic accuracy of DUS as an alternative to CTA for the follow-up of post-EVAR patients.

Methods

Between December 16, 2010, and June 12, 2015, we conducted a prospective, blinded, diagnostic-accuracy study, in 15 French university hospitals where EVAR was commonly performed. Participants were followed up using both DUS and CTA in a mutually blinded setup until the end of the study or until any major aneurysm-related morphological abnormality requiring reintervention or an amendment to the follow-up policy was revealed by CTA. Database was locked on October 2, 2017. Our main outcome measures were sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of DUS against reference standard CTA. CIs are binomial 95% CI.

Results

This study recruited prospectively 659 post-EVAR patients of whom 539 (82%) were eligible for further analysis. Following the baseline inclusion visit, 940 additional follow-up visits were performed in the 539 patients. Major aneurysm-related morphological abnormalities were revealed by CTA in 103 patients (17.2/100 person-years [95% CI, 13.9–20.5]). DUS accurately identified 40 patients where a major aneurysm-related morphological abnormality was present (sensitivity, 39% [95% CI, 29–48]) and 403 of 436 patients with negative CTA (specificity, 92% [95% CI, 90–95]). The negative predictive value and positive predictive value of DUS were 92% (95% CI, 90–95) and 39% (95% CI, 27–50), respectively. The positive likelihood ratio was 4.87 (95% CI, 2.9–9.6). DUS sensitivity reached 73% (95% CI, 51–96) in patients requiring an effective reintervention.

Conclusions

DUS had an overall low sensitivity in the follow-up of patients after EVAR, but its performance improved meaningfully when the subset of patients requiring effective reinterventions was considered.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01230203.
Diagnosis of Infective Endocarditis by Subtype Using
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F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Authors: Wang Tom Kai Ming , Sánchez-Nadales Alejandro , Igbinomwanhia Efehi , Cremer Paul , Griffin Brian , Xu Bo
Published: June 2020

Background

Infective endocarditis (IE) remains a difficult to diagnose condition associated with high mortality.
18
F-fluorodeoxyglucose positron emission tomography/computed tomography (
18
F-FDG PET/CT) has recently emerged as another IE imaging modality, although diagnostic accuracy varies across observational studies and types of IE. This meta-analysis assessed the diagnostic performance of
18
F-FDG PET/CT for IE and its subtypes.

Methods

We searched Pubmed, Cochrane, and Embase from January 1980 to September 2019 for studies reporting both sensitivity and specificity of
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F-FDG PET/CT for IE. Meta-Disc 1.4 was used to pool data for all cases of IE and its subgroups of native valve IE, prosthetic valve IE, and cardiac implantable electronic devices IE.

Results

We screened 2566 records from the search, assessed 52 full-text articles, and included 26 studies totaling 1358 patients (509 IE cases). Pooled sensitivity and specificity (95% CI, inconsistency I-square statistic) were 0.74 (0.70–0.77, 71.5%) and 0.88 (0.86–0.91, 78.5%) for all cases of endocarditis. Corresponding parameters for native valve IE were sensitivity 0.31 (0.21–0.41, 29.4%) and specificity 0.98 (0.95–0.99, 34.4%); for prosthetic valve IE: sensitivity 0.86 (0.81–0.89, 60.0%) and specificity 0.84 (0.79–0.88, 75.2%); and for cardiac implantable electronic devices IE: sensitivity 0.72 (0.61–0.81, 76.2%) and specificity 0.83 (0.75–0.89, 83.6%). Pooled sensitivities and specificities were higher for the 17 studies since 2015 than the 9 studies published before 2015.

Conclusions

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F-FDG PET/CT had high specificity for all IE subtypes; however, sensitivity was markedly lower for native valve IE than prosthetic valve IE and cardiac implantable electronic devices IE. It is, therefore, a useful adjunct modality for assessing endocarditis, especially in the challenging scenarios of prosthetic valve IE and cardiac implantable electronic devices IE, with improving performance over time, related to advances in
18
F-FDG PET/CT techniques.
Adverse Pregnancy Conditions Among Privately Insured Women With and Without Congenital Heart Defects
Authors: Downing Karrie F. , Tepper Naomi K. , Simeone Regina M. , Ailes Elizabeth C. , Gurvitz Michelle , Boulet Sheree L. , Honein Margaret A. , Howards Penelope P. , Valente Anne M. , Farr Sherry L.
Published: June 2020

Background

In women with congenital heart defects (CHD), changes in blood volume, heart rate, respiration, and edema during pregnancy may lead to increased risk of adverse outcomes and conditions. The American Heart Association recommends providers of pregnant women with CHD assess cardiac health and discuss risks and benefits of cardiac-related medications. We described receipt of American Heart Association–recommended cardiac evaluations, filled potentially teratogenic or fetotoxic (Food and Drug Administration pregnancy category D/X) cardiac-related prescriptions, and adverse conditions among pregnant women with CHD compared with those without CHD.

Methods and Results

Using 2007 to 2014 US healthcare claims data, we ascertained a retrospective cohort of women with and without CHD aged 15 to 44 years with private insurance covering prescriptions during pregnancy. CHD was defined as ≥1 inpatient code or ≥2 outpatient CHD diagnosis codes >30 days apart documented outside of pregnancy and categorized as severe or nonsevere. Log-linear regression, accounting for multiple pregnancies per woman, generated adjusted prevalence ratios (aPRs) for associations between the presence/severity of CHD and stillbirth, preterm birth, and adverse conditions from the last menstrual period to 90 days postpartum. We identified 2056 women with CHD (2334 pregnancies) and 1 374 982 women without (1 524 077 pregnancies). During the last menstrual period to 90 days postpartum, 56% of women with CHD had comprehensive echocardiograms and, during pregnancy, 4% filled potentially teratogenic or fetotoxic cardiac-related prescriptions. Women with CHD, compared with those without, experienced more adverse conditions overall (aPR, 1.9 [95% CI, 1.7–2.1]) and, specifically, obstetric (aPR, 1.3 [95% CI, 1.2–1.4]) and cardiac conditions (aPR, 10.2 [95% CI, 9.1–11.4]), stillbirth (aPR, 1.6 [95% CI, 1.1–2.4]), and preterm delivery (aPR, 1.6 [95% CI, 1.4–1.8]). More women with severe CHD, compared with nonsevere, experienced adverse conditions overall (aPR, 1.5 [95% CI, 1.2–1.9]).

Conclusions

Women with CHD have elevated prevalence of adverse cardiac and obstetric conditions during pregnancy; 4 in 100 used potentially teratogenic or fetotoxic medications, and only half received an American Heart Association–recommended comprehensive echocardiogram.
Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs
Authors: Baehr Andrea , Umansky Kfir Baruch , Bassat Elad , Jurisch Victoria , Klett Katharina , Bozoglu Tarik , Hornaschewitz Nadja , Solyanik Olga , Kain David , Ferraro Bartolo , Cohen-Rabi Renee , Krane Markus , Cyran Clemens , Soehnlein Oliver , Laugwitz Karl Ludwig , Hinkel Rabea , Kupatt Christian , Tzahor Eldad
Published: June 2020

Background:

Ischemic heart diseases are leading causes of death and reduced life quality worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a large number of patients with MI develop chronic heart failure over time. We previously reported that a fragment of the extracellular matrix protein agrin promotes cardiac regeneration after MI in adult mice.

Methods:

To test the therapeutic potential of agrin in a preclinical porcine model, we performed ischemia–reperfusion injuries using balloon occlusion for 60 minutes followed by a 3-, 7-, or 28-day reperfusion period.

Results:

We demonstrated that local (antegrade) delivery of recombinant human agrin to the infarcted pig heart can target the affected regions in an efficient and clinically relevant manner. A single dose of recombinant human agrin improved heart function, infarct size, fibrosis, and adverse remodeling parameters 28 days after MI. Short-term MI experiments along with complementary murine studies revealed myocardial protection, improved angiogenesis, inflammatory suppression, and cell cycle reentry as agrin’s mechanisms of action.

Conclusions:

A single dose of agrin is capable of reducing ischemia–reperfusion injury and improving heart function, demonstrating that agrin could serve as a therapy for patients with acute MI and potentially heart failure.
Prospect Theory, Cascade Effects, and Migration: Analyzing Emigration “Fevers” in the Historical Atlantic World
Authors: O’Reilly William , Boyd James
Published: June 2020

Alongside the long-term migration systems that developed between Europe and the Americas, Atlantic migration history is replete with anomalous events—migration “fevers” that lie outside well-described norms in migratory processes. Prospect theory finds risk-seeking behavior to have been a compelling pre-condition for two instances of such migration fever in the eighteenth and nineteenth centuries, as well as for their subsequent cascade effects, creating a social dynamic of “irrational” migration. Prospect theory provides a testable framework for understanding why and how short-lived migration episodes acquired so much force and intensity and points toward a broader relationship with accepted decision-making structures in migration studies.
The First Systematic Survey of Restaurant Hygiene in Paris, 1908
Authors: Bruegel Martin , Lecocq Sébastien
Published: June 2020

In 1908, an unpublished investigation by the French government discovered a number of commercial kitchens that violated the 1903 law regarding hygiene and security in the workplace. A linear-probability model shows that restaurants in tourist neighborhoods were 12 percentage points more likely to transgress sanitary regulations than those in non-tourist areas. Many of the kitchens in the expensive restaurants of central Paris were in basements where they lacked fresh air, sunlight, and efficient waste evacuation. Clientele also mattered as a determinant of insalubrity. Local repeat customers whose loyalty depended on constant restaurant standards tended to exert more pressure on sanitation than did tourists who based their choices on culinary reputation, such as recommendations in Baedeker’s travel guide.