bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and Dynamical Analysis of Multi-Area Network with a Third-Order Chaotic Power System
Authors: Yang Lixin , Gao Jie , Ma Jie
Published: October 2021

The synchronization of states is important to sustain the energy of consumers at any given time for power networks. This paper focuses on the multi-area power network model and then analyzes the cluster synchronization of this kind of network comprised of a third-order chaotic power system. Specifically, we investigate the rich dynamic properties of the single third-order power system. Furthermore, the multi-area network model with the chaotic power system is proposed and the adaptive controller is designed to achieve cluster synchronization. Combining analytical considerations with numerical simulations on a small-scale network, we address the cluster synchronous performance in the multi-area power network. Therefore, our results can provide a basic physical picture for power system dynamics and enable us to further understand the complex dynamical behavior in the multi-area power network.
Enhanced Differential Evolution Algorithm with Local Search Based on Hadamard Matrix
Authors: Deng Changshou , Dong Xiaogang , Tan Yucheng , Peng Hu
Published: October 2021

Differential evolution (DE) is a robust algorithm of global optimization which has been used for solving many of the real‐world applications since it was proposed. However, binomial crossover does not allow for a sufficiently effective search in local space. DE’s local search performance is therefore relatively poor. In particular, DE is applied to solve the complex optimization problem. In this case, inefficiency in local research seriously limits its overall performance. To overcome this disadvantage, this paper introduces a new local search scheme based on Hadamard matrix (HLS). The HLS improves the probability of finding the optimal solution through producing multiple offspring in the local space built by the target individual and its descendants. The HLS has been implemented in four classical DE algorithms and jDE, a variant of DE. The experiments are carried out on a set of widely used benchmark functions. For 20 benchmark problems, the four DE schemes using HLS have better results than the corresponding DE schemes, accounting for 80%, 75%, 65%, and 65% respectively. Also, the performance of jDE with HLS is better than that of jDE on 50% test problems. The experimental results and statistical analysis have revealed that HLS could effectively improve the overall performance of DE and jDE.
Biomass-Derived Adsorbents for Dye and Heavy Metal Removal from Wastewater
Authors: Ali Kashir , Javaid Muhammad Ussama , Ali Zaman , Zaghum Muhammad Junaid
Published: October 2021

Wastewater has a high concentration of dyes and heavy metals, which are the two most significant contaminants. Due to their high toxicity and vulnerability, they possess a potential threat to human health as well as the ecosystem. There are many ways to eliminate these pollutants from water but adsorption has attained much interest because of its low cost, easy application, and no secondary pollutants. Biomass is considered an ecological burden and a reason for the reduction in the earth’s carrying capacity. These materials may be used as cost-effective adsorbents to remove dyes and heavy metals from wastewater. This paper highlights recent advances made in dye and heavy metal adsorption in the last 10 years. The prime focus of this review paper is on the direct application of these biomasses without any chemical or physical alteration. The removal efficiencies and adsorption capabilities of different biomass-derived adsorbents for the removal of dyes and heavy metals from wastewater are summarised in this study. Additionally, the adsorption mechanisms underlying the removal of dyes and heavy metals using biomass-derived adsorbents have been discussed, with a focus on two kinetic models: pseudofirst-order and pseudosecond-order. Furthermore, the Langmuir and Freundlich isotherms were utilised to verify the experimental findings and to quantify the amount and degree of adsorption favorability. Based on what has been covered in the literature, the conclusion has been drawn. The future research needs are proposed in the area of biomass-derived adsorbent development, their modification for improved efficiencies, and application on large-scale wastewater treatment plants.
Metformin Use and Survival in Patients with Advanced Extrahepatic Cholangiocarcinoma: A Single-Center Cohort Study in Fuyang, China
Authors: Wu Jinqing , Zhou Yabo , Wang Guizhou
Published: October 2021

Aims. Metformin is an oral antidiabetic agent that has been widely prescribed for the treatment of type II diabetes. In recent years, anticancer properties of metformin have been revealed for numerous human malignancies. However, there are few indications available regarding the feasibility and safety of these studies in an advanced extrahepatic cholangiocarcinoma (EHCC) population. This study is aimed at evaluating the feasibility, safety, and value of metformin use and survival in patients with advanced EHCC. Methods. All patients with advanced EHCC observed at Fuyang People’s Hospital between January 2015 and November 2020 were included in the study. Case data, clinical information, and imaging results were abstracted from the self-administered questionnaire and electronic medical record. All patients were divided into study subjects and control subjects, and the study subjects were given metformin, 0.5 g, three times a day, while control subjects were without metformin. The metformin use and survival time of the subjects were asked by telephone, out-patient, or door-to-door visit, after they left the hospital. Results. One hundred and thirty-three study cases and 589 controls were included in the analysis. This study showed that metformin use cannot improve the overall survival rate of patients with advanced EHCC ([95% CI]: -17.05-0.375,

t
=
−
1.889

,

P

value = 0.061), but the survival time of patients with drainage treatment from control group (

n
=
496

) was significantly shorter than that of patients with drainage treatment from the study group (

n
=
113

), and the difference was statistically significant (

z
=
−
2.230

,

P

value = 0.026). There were significant differences between metformin used before or after the diagnosis of advanced EHCC (OR[95% CI], 3.432[2.617-4.502];

P

value = 0.001) in survival time. And there was significant difference between the duration of metformin use and survival prognosis (OR[95% CI], 2.967[1.383-6.368];

P
=
0.005

). Conclusion. Metformin can improve the survival of advanced EHCC patients who underwent drainage treatment, especially for metformin use after diagnosis of advanced EHCC and long duration of metformin.
Parameter Measurement of Live Animals Based on the Mirror of Multiview Point Cloud
Authors: Zhang Jinsong , Qin Yue , Wang Li
Published: October 2021

Scale and standardization are essential to the prosperity of the breeding industry. During large‐scale, standardized breeding, the selective breeding of good livestock breeds hinges on the accurate measurement of body parameters for live animals. However, the complex shooting environment brings several urgent problems, such as the missing of many local data in the point cloud and the difficulty in the automatic acquisition of body data. To solve these problems, this paper proposes a method for parameter measurement of live animals based on the mirror of multiview point cloud. Firstly, the acquisition and stitching principles were given for the multiview point cloud data on body parameters of live animals. Next, the authors presented a way to make up for the data missing areas in the point cloud. Finally, this paper acquires the body mirror data of live animals and scientifically calculates the body parameters. The proposed measurement method was proved effective through experiments.
Results from Phase I Extension Study Assessing Pexidartinib Treatment in Six Cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT
Authors: Tap William D. , Singh Arun S. , Anthony Stephen Patrick , Sterba Mike , Zhang Chao , Healey John H. , Chmielowski Bartosz , Cohn Allen Lee , Shapiro Geoffrey I. , Keedy Vicki L. , Wainberg Zev A. , Puzanov Igor , Cote Gregory M. , Wagner Andrew J. , Braiteh Fadi , Sherman Eric , Hsu Henry H. , Peterfy Charles , Gelhorn Heather L. , Ye Xin , Severson Paul , West Brian L. , Lin Paul S. , Tong-Starksen Sandra
Published: October 2021

Purpose:

To assess the response to pexidartinib treatment in six cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity.

Patients and Methods:

From this two-part phase I, multicenter study, pexidartinib, a small-molecule tyrosine kinase inhibitor that targets CSF1R, KIT, and FMS-like tyrosine kinase 3 (FLT3), was evaluated in six adult patient cohorts (part 2, extension) with advanced solid tumors associated with dysregulated CSF1R. Adverse events, pharmacokinetics, and tumor responses were assessed for all patients; patients with tenosynovial giant cell tumor (TGCT) were also evaluated for tumor volume score (TVS) and patient-reported outcomes (PRO). CSF1 transcripts and gene expression were explored in TGCT biopsies.

Results:

Ninety-one patients were treated: TGCT patients (n = 39) had a median treatment duration of 511 days, while other solid tumor patients (n = 52) had a median treatment duration of 56 days. TGCT patients had response rates of 62% (RECIST 1.1) and 56% (TVS) for the full analysis set. PRO assessments for pain showed improvement in patient symptoms, and 76% (19/25) of TGCT tissue biopsy specimens showed evidence of abnormal CSF1 transcripts. Pexidartinib treatment of TGCT resulted in tumor regression and symptomatic benefit in most patients. Pexidartinib toxicity was manageable over the entire study.

Conclusions:

These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile.
Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas
Authors: O'Sullivan Coyne Geraldine , Kummar Shivaani , Hu James , Ganjoo Kristen , Chow Warren A. , Do Khanh T. , Zlott Jennifer , Bruns Ashley , Rubinstein Lawrence , Foster Jared C. , Juwara Lamin , Meehan Robert , Piekarz Richard , Streicher Howard , Sharon Elad , Takebe Naoko , Voth Andrea Regier , Bottaro Donald , Costello Rene , Wright John J. , Doroshow James H. , Chen Alice P.
Published: October 2021

Purpose:

Soft-tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated vascular endothelial growth factor (VEGF) levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population.

Patients and Methods:

We performed an open-label, multi-institution, single-arm phase II trial of single-agent cabozantinib in adult patients with advanced STS and progressive disease after at least 1 standard line of systemic therapy. Patients received 60 mg oral cabozantinib once daily in 28-day cycles, and dual primary endpoints of overall response rate and 6-month progression-free survival (PFS) were assessed. Changes in several circulating biomarkers were assessed as secondary endpoints.

Results:

Six (11.1%; 95% CI, 4.2%–22.6%) of the 54 evaluable patients enrolled experienced objective responses (all partial responses). Six-month PFS was 49.3% (95% CI, 36.2%–67.3%), with a median time on study of 4 cycles (range, 1–99). The most common grade 3/4 adverse events were hypertension (7.4%) and neutropenia (16.7%). Patients' levels of circulating hepatocyte growth factor (HGF), soluble MET, and VEGF-A generally increased after a cycle of therapy, while soluble VEGFR2 levels decreased, regardless of clinical outcome.

Conclusions:

Cabozantinib single-agent antitumor activity was observed in patients with selected STS histologic subtypes (alveolar soft-part sarcoma, undifferentiated pleomorphic sarcoma, extraskeletal myxoid chondrosarcoma, and leiomyosarcoma) highlighting the biomolecular diversity of STS.
Comparison of the Effect of Foot and Palm Reflexology Massage on Respiratory Distress Syndrome in Premature Infants under Noninvasive Ventilation
Authors: Miralizadeh Aysan , Peyman Akram , Jamali Soltani Neda , Ashktorab Tahereh
Published: October 2021

Introduction: Respiratory distress is one of the life-threatening conditions in preterm infants. Sensory deprivation in preterm infants hospitalized in the intensive care units affects their physiological and psychological development. Therefore, this study is an attempt to compare the effects of foot and palm reflexology on respiratory distress in infants subjected to noninvasive ventilation. Methods: In this clinical study, 150 infants hospitalized at Fatemieh Hospital in Hamadan were randomly assigned to 3 groups. In the intervention groups, the reflexology massage to foot and palm was performed for 10 min within 3 days in 6 rounds. In the control group, leg warming was performed. In each group, the personal information checklist, the respiratory distress score, oxygen saturation percentage, and respiratory rate before and after the daily intervention were examined. Data analysis was performed using the standard statistical tests in SPSS. Results: The results mirrored the statistically significant difference between the intervention and control groups 3 days into the intervention with regard to the average oxygen saturation percentage, respiratory rate, and the respiratory distress score (p < 0.05). When eliminating the effect of confounding variables, therapeutic intervention applied to palm compared to foot had a greater effect on reducing respiratory distress score in the studied infants. Conclusion: The reflexology massage method, especially palm reflexology massage, contributes to the mitigation of respiratory distress in preterm infants subjected to noninvasive ventilation. Hence, this low-cost and efficient intervention program can be recommended as a complementary method for preterm infants with respiratory distress.
The Myelic Limited Dorsal Malformation: Prenatal Ultrasonographic Characteristics of an Intermediate Form of Dysraphism
Authors: Vande Perre Saskia , Guilbaud Lucie , de Saint-Denis Timothée , Maurice Paul , Lallemant-Dudek Pauline , Maisonneuve Emeline , Dhombres Ferdinand , Blondiaux Eléonore , Ducou le Pointe Hubert , Zerah Michel , Jouannic Jean-Marie , Garel Catherine
Published: October 2021

Objectives: The aim of the study was to report a subtype of dysraphism designated as myelic limited dorsal malformation (MyeLDM) and to describe its characteristics at prenatal ultrasound (US). Methods: It was a retrospective study from 2014 to 2020 based on second-line US evaluation of patients referred to our institution for myelomeningocele (MMC). Magnetic resonance imaging and acetylcholine esterase evaluation in the amniotic fluid were also offered. Major and minor criteria for open and closed dysraphism were defined and recorded for each patient. Patients were included as MyeLDM when both criteria of closed and open dysraphism were observed in the same fetus. Correlations were obtained with the postpartum data. Results: Twenty patients fulfilled the inclusion criteria, some of them being very close to MMC, others very close to limited dorsal myeloschisis (LDM), and others lying in between. There were 13 live-born neonates and 7 terminations of pregnancy. Correlations between prenatal and postpartum data were overall very good. Conclusion: Our series describe the ultrasonographic characteristics of an intermediate type of dysraphism and suggest that there is a continuum between MMC and LDM with numerous possibilities of hybrid forms (MyeLDM) sharing characteristics of both open and closed dysraphisms.
Sodium Alginate versus Plasma Thrombin Cell Blocks in Diagnostic Cytopathology: A Comparative Analysis
Authors: Gupta Shruti , Gautam Upasana , Susheilia Shaily , Bansal Baneet , Uppal Radha , Srinivasan Radhika
Published: October 2021

Background: Cell blocks (CBs) are an essential adjunct in cytopathology practice. The aim of this study was to compare 2 techniques of CB preparation – plasma thrombin (PT) method with sodium alginate (SA) method for overall cellularity, morphological preservation, obscuring artefacts, immunocytochemistry (ICC), suitability for molecular analysis, and cost of preparation. Design: A total of 80 fine-needle aspirates from various sites and serous effusion samples were included. Of these cases, by random selection, 40 each were prepared by PT method and SA methods, respectively. The haematoxylin-eosin-stained sections from the formalin-fixed, paraffin-embedded CBs from both methods were evaluated in a blinded fashion by 2 cytopathologists and scored for cellularity, artefacts, and morphological preservation and analysed by χ2 test with Yates correction. We evaluated 6 cases from each method by ICC for a range of membrane, cytoplasmic and nuclear marker expression. DNA was extracted from four cases to evaluate their utility for molecular analysis. Results: CB sections from PT and SA techniques showed comparable cellularity and excellent cytomorphological preservation. Blue gel-like artefacts were common in the SA technique but did not interfere with morphological evaluation. ICC staining results were also similar. DNA yield and utility for PCR were also comparable. The SA-CB cost half that of PT-CB (USD 0.4 vs. USD 1). Conclusion: SA technique of CB preparation is an excellent low-cost alternative to PT method for CB preparation.
Expression of Oncogenic Molecules in Pediatric Ulcerative Colitis
Authors: Arai Nobuyasu , Kudo Takahiro , Tokita Kazuhide , Kyodo Reiko , Sato Masamichi , Miyata Eri , Hosoi Kenji , Ikuse Tamaki , Jimbo Keisuke , Ohtsuka Yoshikazu , Shimizu Toshiaki
Published: October 2021

Introduction: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. Methods: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. Results: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. Conclusions: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.
Epidemiological Review of Gastroesophageal Junction Adenocarcinoma in Asian Countries
Authors: Manabe Noriaki , Matsueda Kazuhiro , Haruma Ken
Published: October 2021

Background: Similar trends in the prevalence of gastroesophageal reflux disease (GERD), obesity, and Helicobacter pylori infection have been observed in Asian and Western countries despite their time differences. However, it is unclear whether the prevalence of gastroesophageal junction adenocarcinomas in Asian countries is increasing. In this review, we discuss the epidemiological trends of gastroesophageal junction adenocarcinoma in Asian countries. Summary: The prevalence of GERD is increasing in Asian countries, but most cases are considered mild. Obesity is a serious problem worldwide, but it is considered less serious in Asia than in Western countries. In Asian countries where gastric cancer is common, both cardiac and noncardiac cancers are associated with high rates of H. pylori infection, which is considered a carcinogenic risk factor for both sites of cancer. The widespread use of H. pylori eradication therapy for chronic gastritis in several Asian countries has not directly led to an increased prevalence of esophageal adenocarcinoma. One of the originating sites of junctional adenocarcinoma in most Asian countries is Barrett’s esophagus, with short-segment Barrett’s esophagus having much lower carcinogenicity than long-segment Barrett’s esophagus. Key Messages: Considering the future trends of several risk factors for gastroesophageal junction adenocarcinoma in Asian countries, it is likely that the incidence of gastroesophageal junction adenocarcinoma will gradually increase, but not at a rate that exceeds that of squamous cell carcinoma, as in Western countries.
Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care
Authors: Lier Heiko , Fries Dietmar
Published: October 2021

Uncontrolled and massive bleeding with derangement of coagulation is a major challenge in the management of both surgical and seriously injured patients. The underlying mechanism of trauma-induced or -associated coagulopathy is tissue injury in the presence of shock and acidosis provoking endothelial damage, activation of inflammation, and coagulation disbalancing. Furthermore, the combination of ongoing blood loss and consumption of blood components that are essential for effective coagulation worsens uncontrolled hemorrhage. Additionally, therapeutic actions, such as resuscitation with replacement fluids or allogeneic blood products, can further aggravate coagulopathy. Of the coagulation factors essential to the clotting process, fibrinogen is the first to be consumed to critical levels during acute bleeding and current evidence suggests that normalizing fibrinogen levels in bleeding patients improves clot formation and clot strength, thereby controlling hemorrhage. Three different therapeutic approaches are discussed controversially. Whole blood transfusion is used especially in the military scenario and is also becoming more and more popular in the civilian world, although it is accompanied by a strong lack of evidence and severe safety issues. Transfusion of allogeneic blood concentrates in fixed ratios without any targets has been investigated extensively with disappointing results. Individualized and target-controlled coagulation management based on point-of-care diagnostics with respect to the huge heterogeneity of massive bleeding situations is an alternative and advanced approach to managing coagulopathy associated with massive bleeding in the trauma as well as the perioperative setting.
Romper a superfície da imagem – reflexões de Brecht sobre o cinema e a fotografia
Authors: Gutierrez Maria Alzuguir
Published: October 2021

Este artigo pretende apresentar algumas das ideias de Brecht sobre o cinema e a fotografia, elaboradas em obras literárias, ensaios e notas escritos ao longo de sua trajetória. A proposta aqui é oferecer ao leitor de português acesso a uma importante faceta do pensamento brechtiano, ainda pouco conhecida no Brasil: suas reflexões sobre a imagem técnica.
Begriffe des Bildungswesens und ihre Deutsch ↔ Spanisch – Übersetzung
Authors: Gruhn Dorit Heike
Published: October 2021

Der vorliegende Artikel gibt einen Überblick über die Deutsch ↔ Spanisch - Äquivalenz von Begriffen des Bildungswesens in Bezug auf die Urkundenübersetzung. Zunächst wird die Übersetzung dieser Textsorte aus dem Blickwinkel verschiedener Übersetzungstheorien betrachtet. Nachfolgend werden – aus funktionaler Perspektive – die Adressaten der Zieltexte und ihre Bedürfnisse umrissen. Es folgen Beispiele für Fachausdrücke in beiden Sprachen, die in eine dreiteilige Systematik (vollständige Äquivalenz, Teiläquivalenz, Nicht-Äquivalenz) eingeordnet werden. Dabei stechen vor allem die “falschen Freunde” als häufige Fehlerquelle hervor. Eingegangen wird auch auf übersetzerische Hilfsmittel und die wichtigsten Übersetzungsstrategien im Rahmen der Übersetzung solcher Begriffe. Bezugssysteme sind das deutsche und das mexikanische Bildungswesen.
Influence of
GAS5
/MicroRNA‐223‐3p/P2Y12 Axis on Clopidogrel Response in Coronary Artery Disease
Authors: Liu Yan‐Ling , Hu Xiao‐Lei , Song Pei‐Yuan , Li He , Li Mu‐Peng , Du Yin‐Xiao , Li Mo‐Yun , Ma Qi‐Lin , Peng Li‐Ming , Song Ming‐Yu , Chen Xiao‐Ping
Published: October 2021

Background

Dual antiplatelet therapy based on aspirin and P2Y12 receptor antagonists such as clopidogrel is currently the primary treatment for coronary artery disease (CAD). However, a percentage of patients exhibit clopidogrel resistance, in which genetic factors play vital roles. This study aimed to investigate the roles of GAS5 (growth arrest‐specific 5) and its rs55829688 polymorphism in clopidogrel response in patients with CAD.

Methods and Results

A total of 444 patients with CAD receiving dual antiplatelet therapy from 2017 to 2018 were enrolled to evaluate the effect of
GAS5
single nucleotide polymorphism rs55829688 on platelet reactivity index. Platelets from 37 patients of these patients were purified with microbeads to detect GAS5 and microRNA‐223‐3p (miR‐223‐3p) expression. Platelet‐rich plasma was isolated from another 17 healthy volunteers and 46 newly diagnosed patients with CAD to detect GAS5 and miR‐223‐3p expression. A dual‐luciferase reporter assay was performed to explore the interaction between miR‐223‐3p and
GAS5
or
P2Y12
3′‐UTR in (human embryonic kidney 293 cell line that expresses a mutant version of the SV40 large T antigen) HEK 293T and (megakaryoblastic cell line derived in 1983 from the bone marrow of a chronic myeloid leukemia patient with megakaryoblastic crisis) MEG‐01 cells. Loss‐of‐function and gain‐of‐function experiments were performed to reveal the regulation of GAS5 toward P2Y12 via miR‐223‐3p in MEG‐01 cells. We observed that rs55829688 CC homozygotes showed significantly decreased platelet reactivity index than TT homozygotes in
CYP2C19
poor metabolizers. Platelet GAS5 expression correlated positively with both platelet reactivity index and
P2Y12
mRNA expressions, whereas platelet miR‐223‐3p expression negatively correlated with platelet reactivity index. Meanwhile, a negative correlation between GAS5 and miR‐223‐3p expressions was observed in platelets. MiR‐223‐3p mimic reduced while the miR‐223‐3p inhibitor increased the expression of GAS5 and P2Y12 in MEG‐01 cells. Knockdown of GAS5 by siRNA increased miR‐223‐3p expression and decreased P2Y12 expression, which could be reversed by the miR‐223‐3p inhibitor. Meanwhile, overexpression of GAS5 reduced miR‐223‐3p expression and increased P2Y12 expression, which could be reversed by miR‐223‐3p mimic.

Conclusions

GAS5
rs55829688 polymorphism might affect clopidogrel response in patients with CAD with the
CYP2C19
poor metabolizer genotypes, and GAS5 regulates P2Y12 expression and clopidogrel response by acting as a competitive endogenous RNA for miR‐223‐3p.
Long‐Term Medication Adherence Trajectories to Direct Oral Anticoagulants and Clinical Outcomes in Patients With Atrial Fibrillation
Authors: An Jaejin , Bider Zoe , Luong Tiffany Q. , Cheetham T. Craig , Lang Daniel T. , Fischer Heidi , Reynolds Kristi
Published: October 2021

Background

Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long‐term adherence to DOACs and clinical outcomes in real‐world clinical practice is not well understood. This study evaluated long‐term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system.

Methods and Results

We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long‐term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group‐based trajectory models. Factors associated with long‐term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long‐term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA
2
DS
2
‐VASc (0–1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05–1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30–0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence.

Conclusions

Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.
The Protective Role of Yin‐Yang 1 in Cardiac Injury and Remodeling After Myocardial Infarction
Authors: Huang Yu , Li Liangpeng , Chen Hongmei , Liao Qiao , Yang Xiaoli , Yang Dezhong , Xia Xuewei , Wang Hongyong , Wang Wei Eric , Chen Lianglong , Zeng Chunyu
Published: October 2021

Background

Exploring potential therapeutic target is of great significance for myocardial infarction (MI) and post‐MI heart failure. Transcription factor Yin‐Yang 1 (YY1) is an essential regulator of apoptosis and angiogenesis, but its role in MI is unclear.

Methods and Results

The expression of YY1 was assessed in the C57BL/6J mouse heart following MI. Overexpression or silencing of YY1 in the mouse heart was achieved by adeno‐associated virus 9 injection. The survival, cardiac function, and scar size, as well as the apoptosis, angiogenesis, cardiac fibrosis, T helper 2 lymphocyte cytokine production, and macrophage polarization were assessed. The effects of YY1 on Akt phosphorylation and vascular endothelial growth factor production were also investigated. The expression of YY1 in heart was significantly stimulated by MI. The survival rate, cardiac function, scar size, and left ventricular volume of mice were improved by YY1 overexpression but worsened by YY1 silencing. YY1 alleviated cardiac apoptosis and fibrosis, promoted angiogenesis, T helper 2 cytokine production, and M2 macrophage polarization in the post‐MI heart, it also enhanced the tube formation and migration ability of endothelial cells. Enhanced Akt phosphorylation, along with the increased vascular endothelial growth factor levels were observed in presence of YY1 overexpression.

Conclusions

YY1 ameliorates cardiac injury and remodeling after MI by repressing cardiomyocyte apoptosis and boosting angiogenesis, which might be ascribed to the enhancement of Akt phosphorylation and the subsequent vascular endothelial growth factor up‐regulation. Increased T helper 2 cytokine production and M2 macrophage polarization may also be involved in YY1’s cardioprotective effects. These findings supported YY1 as a potential target for therapeutic investigation of MI.
Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
Authors: Paranjpe Ishan , Tsao Noah L. , De Freitas Jessica K. , Judy Renae , Chaudhary Kumardeep , Forrest Iain S. , Jaladanki Suraj K. , Paranjpe Manish , Sharma Pranav ,   CBIPM Genomics Team,   Regeneron Genetics Center, Glicksberg Benjamin S. , Narula Jagat , Do Ron , Damrauer Scott M. , Nadkarni Girish N.
Published: October 2021

Background

Despite advances in cardiovascular disease and risk factor management, mortality from ischemic heart failure (HF) in patients with coronary artery disease (CAD) remains high. Given the partial role of genetics in HF and lack of reliable risk stratification tools, we developed and validated a polygenic risk score for HF in patients with CAD, which we term HF‐PRS.

Methods and Results

Using summary statistics from a recent genome‐wide association study for HF, we developed candidate PRSs in the Mount Sinai Bio
Me
CAD patient cohort (N=6274) by using the pruning and thresholding method and LDPred. We validated the best score in the Penn Medicine BioBank (N=7250) and performed a subgroup analysis in a high‐risk cohort who had undergone coronary catheterization. We observed a significant association between HF‐PRS score and ischemic HF even after adjusting for evidence of obstructive CAD in patients of European ancestry in both Bio
Me
(odds ratio [OR], 1.14 per SD; 95% CI, 1.05–1.24;
P
=0.003) and Penn Medicine BioBank (OR, 1.07 per SD; 95% CI, 1.01–1.13;
P
=0.016). In European patients with CAD in Penn Medicine BioBank who had undergone coronary catheterization, individuals in the top 10th percentile of PRS had a 2‐fold increased odds of ischemic HF (OR, 2.0; 95% CI, 1.1–3.7;
P
=0.02) compared with the bottom 10th percentile.

Conclusions

A PRS for HF enables risk stratification in patients with CAD. Future prospective studies aimed at demonstrating clinical utility are warranted for adoption in the patient setting.
Genesis 1–3 and the Formation of Subjectivity in the Hodayot and the Two Spirits Teaching
Authors: Newsom Carol A.
Published: October 2021

Although the lived experience of subjectivity for persons in antiquity cannot be known directly, one can study certain texts as tools for the formation of subjects. Among the Dead Sea Scrolls two compositions are particularly instructive, the Hodayot found in 1QHa 2–9, 18–28 (the Hodayot of the Maskil, also known as Hodayot of the Community) and the Two Spirits Teaching (1QS 3:13–4:26). Each develops an understanding of subjectivity based on subtle interpretations of creation traditions, developed through sophisticated intertextual readings. The Hodayot privilege Gen 2–3; the Two Spirits Teaching emphasizes Gen 1. Although mutually contradictory on the surface, the two accounts actually develop subjectivities that share many similarities. By analyzing these converging patterns one may get some sense of the lived subjectivity that was created by the various texts and practices of the Yahad community.
The Eschatological Key
Authors: Douglass Rachel
Published: October 2021

In the first volume of his systemic series, German theologian Jürgen Moltmann begins his systematics with a musical metaphor; “The eschatological is not one element of Christianity, but it is the medium of Christian faith as such, the key in which everything is set …” Moltmann then goes on to propose that the eschaton is a temporal event, which breaks the logic of his initial metaphor of the key signature. This essay will explore the differences between understanding the eschaton explicated as the key that Christian hope is set as opposed to a temporal alternative, such as the time signature. Jeremy Begbie is brought into the conversation to explicate how “harmony” can guide our conversation of music theory, and Miguel De La Torre illuminates how Moltmann’s claim, which while revolutionary in many aspects, continues to rely on Eurocentric understanding of salvation history, just as music theory tends towards Eurocentrism. We also examine what we lose out on when we leave this uninterrogated. To conclude, we explore how Moltmann’s proposal about Christian hope becomes more coherent within the metaphor of key signature and right relationship instead of time signature and temporality.
Sand, Water, and Stars: Chinese Mapping of the Gobi and Taklamakan Deserts
Authors: Papelitzky Elke
Published: October 2021

Many Chinese maps from the mid-sixteenth century onwards mark the Gobi Desert as a prominent strip visually separating China from what lies beyond. Even before that time, the Gobi, as well as the Taklamakan Desert appeared on maps. Influenced by statements from the early classic “Yugong,” Chinese scholars and Han literati during late imperial China’s history had perceived the deserts as some kind of boundary, while with the integration of these regions into Qing territory, the imperial Manchu view shifted away from the desert being a boundary. The terms for the desert as well as the graphical depiction on maps link the desert to water and to some extent also to celestial phenomena. This article explores the history and cultural significance of the desert from the Song to the mid-Qing period based on maps in relation with relevant texts and draws connections to the origins and changes of these depictions.
The “Spirit of Yhwh” and Samson’s Martial Rage: A Leitmotif of the Biblical Warrior Tradition
Authors: Johnson Dylan
Published: October 2021

In Judg 14–15, the source of Samson’s strength is not his uncut hair, but the רוח־יהוה. A Leitmotif of the biblical warrior tradition, the רוח־יהוה is a corporealized metaphor of fiery anger that envelops Samson and grants him great power. This motif was adapted from early biblical poetry, in which Yhwh’s wrath erupted as a fiery breath (רוח) against his cosmic foes. This study explores how the historical context of Judg 14–15 informs the use of this motif, comparing the רוח־יהוה with similar concepts of martial anger in Near Eastern and Greek warrior traditions. Like Mesopotamian melammu and Greek μηνις, the רוח־יהוה was part of a corporeal code that enabled ancient minds to think about the relations between mortals and divine beings in the context of battle.
Mercy and Monarchy
Authors: Krauter Stefan
Published: October 2021

This article compares De clementia, a somewhat neglected minor work of the Roman Stoic philosopher L. Annaeus Seneca, and Paul’s Letter to the Romans. First, Seneca’s ideas about rule as a god-given task of moral improvement of the subjects and the role of mercy (clementia) within it are analysed. Then, Seneca’s argument is compared with Paul’s thoughts concerning salvation by grace in his Letter to the Romans. Seneca’s short political treatise De clementia shows a considerable number of interesting and specific agreements with Paul’s reasoning in the Letter to the Romans, even more than his other writings, which have been in the focus of scholarly investigation. Finally, some suggestions are made about the possible source(s) of the convergences and how they could be interpreted.
Did a Little Birdie Really Tell Odin? Applying Theory of Mind to Old Norse Religion
Authors: Taggart Declan
Published: October 2021

Theory of mind, the theory that humans attribute mental states to others, has become increasingly influential in the Cognitive Science of Religion in recent years, due to several papers which posit that supernatural agents, like gods, demons, and the dead, are accredited greater than normal knowledge and awareness. Using Old Norse mythology and literary accounts of Old Norse religion, supported by archaeological evidence, I examine the extent to which this modern perspective on religious theory of mind is reflected in religious traditions from the Viking Age. I focus especially on the extent to which superperception and superknowledge were attributed to Old Norse supernatural agents and the impact of this on expressions of religion; how the attribution of theory of mind varied with circumstances and the agents to which it was being attributed; and the extent to which features of religious theory of mind common in other societies were present in the historical North. On this basis, I also evaluate the usefulness of Old Norse historiography to Cognitive Science of Religion and vice versa.
The Counterintuitiveness of Supernatural Dreams and Religiosity
Authors: Nordin Andreas , Bjälkebring Pär
Published: October 2021

One challenge for cognitive, evolutionary and anthropological studies of religion is to offer descriptions and explanatory models of the morphology and functions of supernatural dreaming, and of the religiosity, use of experience, and cultural transmission that are associated with these representations. The anthropological and religious studies literature demonstrates that dreaming, dream experience and narrative are connected with religious ideas and practices in traditional societies. Scholars have even proposed that dreaming is a primary source of religious beliefs and practice (here labelled DPSR theory). Using Barrett’s coding system, we measured a high frequency of minimally counterintuitive dream content among Hindu Nepalese, and we aim to quantify (1) the relation between counterintuitive imagery and reported likelihood to communicate dreams in general and to religious experts, (2) the relation between counterintuitive imagery and reported religiosity, and (3) the proclivity to communicate SA dreams among those who are more or less religious. These aims will then be related to the broader topic of (4) possible explanatory value of DPSR theory, or versions thereof, by framing the issue at the level of cultural transmission, religiosity and credibility of religious dream representations in relation to MCI theory. The article mainly draws upon data from ethnographic research among Hindu Nepalese.
Do You Approach Positive Events or Do They Approach You? Linking Event Valence and Time Representations in a Dutch Sample
Authors: Loermans Annemijn C. , de Koning Bjorn B. , Krabbendam Lydia
Published: October 2021

In order to think and talk about time, people often use the ego- or time-moving representation. In the ego-moving representation, the self travels through a temporal landscape, leaving past events behind and approaching future events; in the time-moving representation, the self is stationary and temporal events pass by. Several studies contest to the psychological ramifications of these two representations by, inter alia, demonstrating a link between them and event valence. These studies have, however, been limited to English speakers, even though language has been found to affect time representation. The present study therefore replicated Margolies and Crawford’s (2008) experiment on event valence and time representation amongst speakers of Dutch. Unlike Margolies and Crawford (2008), we do not find that positive valence leads to the endorsement of an ego-moving statement. Future studies will need to determine the ways through which language might moderate the relation between event valence and time representation.
A revised phylogeny of Alpine newts unravels the evolutionary distinctiveness of the Bosnian alpine newt – Ichthyosaura alpestris reiseri (Werner, 1902)
Authors: Šunje Emina , Stroil Belma Kalamujić , Raffaëlli Jean , Zimić Adnan , Marquis Olivier
Published: October 2021

The Bosnian alpine newt (Ichthyosaura alpestris reiseri) is endemic to Prokoško Lake (Mt. Vranica, Bosnia & Herzegovina); its evolutionary history is partially clarified and its taxonomic position remains unclear. Due to severe anthropogenic pressures on Mt. Vranica (fish introduction in Prokoško Lake, pollution), it has been assumed that this form of Alpine newt is extinct from the Lake. Nevertheless, some specimens originating from Prokoško Lake are still maintained in captivity in two European zoos and by several private keepers. The main goals of the present study are: (1) to investigate the presence of Alpine newts in the Prokoško Lake and the wider area of Mt. Vranica, (2) to conduct phylogenetic analysis on found specimens of Alpine newts in relation to other Balkan populations. Newts were not registered inside Prokoško Lake but several individuals were found in water bodies surrounding the Lake. Genetic analysis shows that these individuals carry the same haplotype as Alpine newts from a captive population originating from Prokoško Lake. All the Alpine newts originating from mt. Vranica are monophyletic on mtDNA markers, hence form an Evolutionary Significant Unit within I. alpestris that is of specific conservation importance. Results corroborate previous findings concerning the complex pattern of genetic diversity of Alpine newt populations in the Balkans that is poorly understood.
Response of soybean genotypes from Northeast China to Heterodera glycines races 4 and 5, and characterisation of rhg1 and Rhg4 genes for soybean resistance
Authors: Huang Minghui , Qin Ruifeng , Li Chunjie , Wang Mingze , Jiang Ye , Yu Jinyao , Chang Doudou , Tian Zhongyan , Chen Qingshan , Guo Xiaoli , Jiao Yongqing , Wang Congli
Published: October 2021

Soybean cyst nematode (SCN, Heterodera glycines) is a devastating plant-parasitic nematode worldwide. Two SCN races, race 4 (HG Type 1.2.3.5.6.7) and race 5 (HG Type 2.5.7), with increased virulence were previously identified in Northeast China. To obtain new resistance sources to these SCN populations, the response of 62 genotypes, including 51 local varieties and breeding lines, and 11 indicator lines for SCN race and HG Type identification, were evaluated. Four new primers in the regions of two loci of GmSHMT08 (Rhg4) and GmSNAP18 (rhg1) were designed for PCR amplification and subsequent sequencing to characterise haplotypes instead of genome resequencing. Results indicated three haplotypes among 51 local genotypes; there were 26 lines in Haplotype I carrying both the rhg1-a and Rhg4-a resistant loci as in ‘Peking’, 13 lines in Haplotype II containing only the resistant rhg1-a locus but Rhg4-b susceptible loci, and 12 lines in Haplotype III with rhg1-c and Rhg4-b susceptible loci. Interestingly, there was no ‘PI 88788’-type resistance identified in Northeast China, although it accounts for 90% of sources in the USA. Two local breeding lines in Haplotype I displayed resistance to both SCN races. The resistance lines carried higher copy number (>1) of the tandem duplication at the rhg1 locus compared with susceptible lines (⩽1). The combination of the two microsatellite markers, Sat_162 on Chr 8 and 590 on Chr 18, distinguished the three haplotypes and predicted the resistance/susceptibility for SCN race 5. The knowledge of the phenotypes and molecular characteristics of 51 local breeding lines in Northeast China will accelerate the utilisation of sources for broad-based SCN resistance and marker-assisted selection.