bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Application of Deep Belief Network Based on Stochastic Adaptive Particle Swarm Optimization
Authors: Yang Jianjian , Chang Boshen , Wang Xiaolin , Zhang Qiang , Wang Chao , Wang Fan , Wu Miao
Published: August 2020

Due to the problem of poor recognition of data with deep fault attribute in the case of traditional superficial network under semisupervised and weak labeling, a deep belief network (DBN) was proposed for deep fault detection. Due to the problems of deep belief network (DBN) network structure and training parameter selection, a stochastic adaptive particle swarm optimization (RSAPSO) algorithm was proposed in this study to optimize the DBN. A stochastic criterion was proposed in this method to make the particles jump out of the original position search with a certain probability and reduce the probability of falling into the local optimum. The RSAPSO-DBN method used sample data to train the DBN and used the final diagnostic error rate to construct the fitness value function of the particle swarm algorithm. By comparing the minimum fitness value of each particle to determine the advantages and disadvantages of the model, the corresponding minimum fitness value was selected. Using the number of network nodes, learning rate, and momentum parameters, the optimal DBN classifier was generated for fault diagnosis. Finally, the validity of the method was verified by bearing data from Case Western Reserve University in the United States and data collected in the laboratory. Comparing BP (BP neural network), support vector machine, and heterogeneous particle swarm optimization DBN methods, the proposed method demonstrated the highest recognition rates of 87.75% and 93.75%. This proves that the proposed method possesses universality in fault diagnosis and provides new ideas for data identification with different fault depth attributes.
Visual Impairment among Primary School Children in Gondar Town, Northwest Ethiopia
Authors: Ferede Ayanaw Tsega , Alemu Destaye Shiferaw , Gudeta Alemayehu Desalegn , Alemu Haile Woretaw , Melese Mulusew Asferaw
Published: August 2020

Background. An impairment of the visual system at or shortly after birth adversely affects educational performance of children which typically occurs through vision. Limited evidence on the magnitude and causes of visual impairment is one of the reasons for the low priority given to eye care in low-income countries. Objectives. To estimate the prevalence and determine the causes of visual impairment in primary school children in Gondar town, Northwest Ethiopia. Materials and Methods. A descriptive cross-sectional study was conducted among 1289 children aged 5–15 years who were randomly selected in 9 primary schools (government and private) from May to June 2016. Visual acuity was measured at 6 m using Snellen’s chart, and children with an acuity of less than 6/18 in the better eye underwent refraction and a detailed eye examination. A cause of their impairment was determined. Data were recorded using pretested tools. . Statistical Package for Social Sciences version 16 was used to enter and analyze the data using 95% confidence intervals. Results. The prevalence of visual impairment was 1.8%. Refractive errors (nearly 70%) followed by strabismus and cataract, each contributing 4.3%, were the most frequent causes of visual impairment in the study population. Majority (87%) of the children had moderate degree of vision impairment, and 10–15-year age groups are the more affected ones. Children of age fifteen and above showed statistically significant association with visual impairment (p=0.005). Conclusion. The magnitude of visual impairment in primary school children in the study area is significant. School screening programme is recommended to minimize the burden of visual impairment in the study area.
A Noncommunicative Memory-Pushing Fuzzy Control Strategy for Sensorless Multirobot Systems
Authors: Zhang Lin , Zheng Xianhua , Feng Shang , Su Lingling
Published: August 2020

Considering the characteristics of equipment on underground fully mechanized coal mining face, a multirobot system, which takes heavy-duty mobile support robot (HMSR) as the pushing robot and middle trough (MT) as the manipulated object, is established. To overcome the problem of unstable communication and potential pressure loss, a memory-pushing fuzzy control strategy is proposed to achieve better practical performance without human-guided operations. The pushing dynamics without communication is derived to proof the convergence of the dynamic system, and the time-based memory-pushing fuzzy model is built for compensating the potential pressure loss. Finally, the proposed control strategy is simulated in virtual environment, which integrates our pushing dynamics, and an industrial experiment is demonstrated as well. Both the simulation and industrial experiments show the efficiency and feasibility of the proposed method.
Proliferation of Vascular Smooth Muscle Cells under ox‐LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR‐17∼92a Cluster Activation
Authors: Shen Julian , Wei Wei , Wang Xialei , Yang Jingda , Lu Lu , Lv Xinru , Xue Xiehua
Published: August 2020

Context: Alismatis rhizome decoction (AD) exhibits antiatherosclerotic activities. The activity of AD against vascular smooth muscle cell (VSMC) proliferation remains unclear. Objective. The mechanisms and effects of AD on oxidized low‐density lipoprotein (ox‐LDL)‐induced VSMC proliferation were explored. Materials and methods. The male SD rats were fed with AD (2.56 g/mL) or 0.9% NaCl by oral gavage 4 mL twice daily for 7 d. Then, AD‐containing serum (ADcs) was collected. MTS assay was applied to measure the VSMC viability. The proliferation of VSMCs was detected by 5‐bromodeoxyuridine (BrdU) immunocytochemistry. The microRNA (miRNA) profiling was performed, and the target genes of miRNAs were searched from the TargetScan 7.2 database. The expressions of matrix metalloproteinases‐2/9 (MMP‐2/9), cyclin D1/E, cyclin‐dependent kinase inhibitor 1B (p27), extracellular regulated protein kinases 1/2 (ERK1/2), and ERK1/2 phosphorylation were examined by western blotting or quantitative reverse transcription PCR. Results. The ox‐LDL‐induced miR‐17‐92a expression promoted VSMC proliferation. AD and the ERK1/2 inhibitor U0126 (10 μmol/L) inhibited VSMC proliferation and reduced the overexpression of miR‐17∼92a. AD was found to inhibit phosphorylation of ERK1/2 and reduced the expression of MMP‐2/9 in VSMCs. The expression of cyclin D1/E was suppressed, and p27 was elevated following treatment with AD as well as ERK1/2 inhibitor. According to the TargetScan 7.2 database, the target genes of miR‐17∼92a act on tissue inhibitors of metalloproteinases (TIMPs)‐MMPs, p27/21 cyclins, and peroxisome‐proliferator‐activated receptor α (PPARα) ATP‐binding cassette transporter (ABC) A1/G1, which are involved in the process of atherosclerosis. Conclusions. AD inhibits ox‐LDL‐induced VSMC proliferation via inhibiting ERK1/2 and miR‐17∼92a activation. The results provide the multitarget mechanisms for application of AD in the treatment of atherosclerosis. It would be helpful to the treatment of cardiovascular and cerebral diseases.
Sutureless Approach for Gastroschisis Patients in Palestine
Authors: Abuzneid Yousef S. , Abukhalaf Sadi A. , Rabi Duha , Rabee Abdelrahman , Mashhour Safwan , Abukarsh Radwan
Published: August 2020

Gastroschisis is a ventral abdominal wall congenital defect with bowel herniation outside the abdominal cavity. Gastroschisis traditional management is the primary operative closure surgery (POCS), but the sutureless silo approach (SSA), a novel alternative, gains wide acceptance in the developed countries and across nations. This study describes the first-ever gastroschisis patient managed with the sutureless silo approach in Palestine. In addition, we shall use this case as the very first nucleus for the upcoming gastroschisis management in our referral hospital because the SSA yields a reduced hospital stay which is fundamental to our institution due to the limited number of beds and lower management costs to the hospital and families.
Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential
Authors: Zhao Ashley G. , Shah Kiran , Cromer Brett , Sumer Huseyin
Published: August 2020

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied bothin vitroandin vivoin many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.
Experimental Study on Noncoaxial Characteristics of Saturated Remolded Loess
Authors: Jiang Xuemeng , Niu Haoshuang , Huang Wenpeng , Shang Xuwen , Wang Deng
Published: August 2020

In practical engineering, if the influence of noncoaxial stress and strain is not considered, part of soil deformation will be ignored, resulting in the structural design which is not safe enough. A series of undrained tests was performed on remolded loess specimens using a hollow cylinder apparatus to examine the coupling between principal stress magnitude and direction in these specimens. First, the elastic parameters of remolded loess were obtained, and these parameters were used as the basis for investigating the noncoaxiality of the soil body under principal stress axis rotation (PSAR). The effects of elastic strain, intermediate principal stress coefficient, and magnitude of the deviatoric stress on the noncoaxiality of remolded loess were also investigated. The results of these experiments show that remolded loess exhibits significant noncoaxial behavior during PSAR. The noncoaxiality angle of remolded loess cyclically fluctuates with increases in the principal stress angle. It was also observed that the noncoaxiality angle will be overestimated if the effects of elastic strain are overlooked. Reversals in the direction of PSAR cause dramatic changes in the noncoaxiality angle. Increases in the intermediate principal stress coefficient are accompanied by increases in the noncoaxiality angle, up to a certain degree; however, these changes do not affect the development of the noncoaxiality angle. In coupled rotational tests with a range of deviatoric stress amplitudes, it was observed that changes in the deviatoric stress amplitude will affect the development of the noncoaxiality angle; increases in the deviatoric stress amplitude cause the noncoaxiality angle versus principle stress angle plot to shift to the left gradually, thus accelerating the trends of the noncoaxiality angle. Increases in the cycle number also increase the noncoaxiality of remolded loess.
A Visual Tracking Method Based on an Adaptive Overlapping Correlation Filter for Robotic Real-Time Cognitive Imaging
Authors: Lan Yihua , Ma Pianpian , Xu Anfeng , Liu Jinjiang
Published: August 2020

Computer vision is a very important research direction in the cognitive computing field. Robots encounter various target-tracking problems with computer vision systems. Robust scale estimation is an important issue in tracking algorithms. Most of the available methods have difficulty addressing even reasonable changes of scale in complex videos. In this paper, we propose a visual tracking method based on robust scale estimation, which uses a discriminant correlation filter based on a time-dependent scale-space filter and an adaptive cross-correlation filter. The tracker uses separate essential filters for sample migration and scale estimation. Furthermore, the built-in scale estimation method can be introduced into other tracking algorithms. We validate the proposed method on the UAV123 dataset. The results of comparison experiments with the traditional correlation filter tracking method demonstrate that the proposed method improves the success rate and tracking accuracy while controlling the computational complexity; its success rate measured by the area under the curve is 0.638, while at a location error precision of 20%, it is 0.649.
The Passing Fads and Emergent Trends of Project Culture in Construction Industry
Authors: He Qinghua , Li Jin , Wan Jingyuan , Zhang Zhenyu , Chen Zhen
Published: August 2020

Project culture in construction industry is unique, distinguishing one project from others, and plays a role in the processing of construction projects. The aim of this paper is to conduct a holistic review of the extant literature and identify the future trends of project culture. The method of a systematic literature review was conducted to overview the extant articles on project culture in construction industry until 2019. After searching in ISI Web of Science, Scopus, and Google Scholar, we obtained a total number of 31 papers and refinement was made by content analysis. Four aspects were analyzed: the nature of project culture, the diagnosis of project culture, factors influencing project culture, and research focus. It provides a map of project culture from philosophy paradigms. And findings show that research on project culture was mainly from the function paradigm (the integration position) in which culture can be manipulated for better project performance. A few from nonfunction paradigm (the fragment position) stressed sense making of project culture. This study proposes a framework consisting of a hybrid function/nonfunction paradigms and diagnoses project culture from explicit and implicit aspects. These findings make a firm foundation for the exploration of project culture from multiperspectives in theory and practice.
Long-Term Glucocorticoid Use and Cancer Risk: A Population-Based Cohort Study in South Korea
Authors: Oh Tak Kyu , Song In-Ae
Published: August 2020

Long-term glucocorticoid (GC) exposure causes immunosuppression; therefore, the risk of cancer may be increased in long-term GC users. We investigated whether long-term GC use is associated with a higher risk of cancer in the population without cancer. A population-based cohort study using data from the National Health Insurance Service was conducted among the South Korean adult population in 2010. Long-term GC users were defined as those who were prescribed a continuous supply of oral GC for ≥30 days. The primary endpoint was a new cancer diagnosis from January 1, 2011, to December 31, 2015. Among 770,880 individuals included in the analysis, 1,602 (0.2%) were long-term GC users and 36,157 (4.7%) were newly diagnosed with cancer from January 2011 to December 2015. In the multivariable Cox regression analysis, the risk of cancer among long-term GC users was 1.23-fold higher than that of the unexposed individuals [95% confidence interval (CI), 1.06–1.43; P = 0.007]. In the competing risk analyses, the risks of liver cancer and lung cancer were 1.46-fold (95% CI, 1.03–2.07; P = 0.034) and 1.52-fold (95% CI, 1.04–2.21; P = 0.029) higher in the long-term GC users than that of the unexposed individuals, respectively. We found that long-term GC exposure might be associated with a higher risk of overall cancer, and this association was more evident for lung and liver cancer risk. However, because there might be unmeasured and potential confounders in this study, the results should be interpreted carefully, and future studies should be performed to confirm these findings.

Impact:

Long-term glucocorticoid therapy might be associated with a higher cancer risk. This association was more evident for lung and liver cancer risk. Our findings suggest that long-term prescriptions of glucocorticoids should be administered carefully considering the risk of cancer.
Immune Checkpoint Inhibition is Safe and Effective for Liver Cancer Prevention in a Mouse Model of Hepatocellular Carcinoma
Authors: Chung Andrew S. , Mettlen Marcel , Ganguly Debolina , Lu Tianshi , Wang Tao , Brekken Rolf A. , Hsiehchen David , Zhu Hao
Published: August 2020

Cirrhosis is a high-risk state for hepatocellular carcinoma (HCC) development and represents an opportunity to prevent cancer. In the precancerous state of cirrhosis, there is an accumulation of neoantigens that may be specifically targetable through immunotherapy. We asked whether immune checkpoint inhibition could prevent tumorigenesis in a mouse model of diethylnitrosamine and carbon tetrachloride–induced HCC. We found that initiation of anti-PD-1 therapy prior to tumorigenesis could prevent up to 46% of liver tumors. This significant reduction in tumor burden was accompanied by infiltration of CD4+ Th cells and CD8+ cytotoxic T cells into the liver parenchyma. Importantly, anti-PD-1 therapy did not exacerbate liver dysfunction or worsen overall health in this liver disease model. Given the safety and preservation of quality of life observed with long-term immunotherapy use, an immunotherapy chemoprevention strategy is likely associated with a low risk-to-benefit ratio and high value care in select patients. These results encourage a prevention trial in cirrhotic patients with the highest risk of developing HCC.

See related Spotlight by Mohammed et al., p. 897
How Does Obesity Drive Human Carcinogenesis? Challenges in Dissecting the Mechanisms of Adipose–Epithelial Signaling
Authors: Colacino Justin , Djuric Zora , Brenner Dean E.
Published: August 2020

Obesity is the second leading environmental association with cancer risk; yet, the mechanisms by which obesity drives carcinogenesis are poorly understood. The paper published in this issue of Cancer Prevention Research by Holowatyj and colleagues explores the mechanisms of human visceral adipose–epithelial signaling using samples collected at surgery in patients with invasive colorectal cancer. They identify pathway intermediates potentially involved in the regulation of fibrosis, inflammation, glycosis, and epithelial–mesenchymal transition in neoplastic tissue. ‘Omics-based profiling of perioperative human biosamples has potential for inherent biases (preoperative and intraoperative drug therapies, hydration, dynamics, inflammatory response to surgical intervention) and appropriate control samples are difficult to identify and collect. Solutions to this dilemma may include strategies to identify patients undergoing similar surgical procedures but who are without neoplasms, for example, patients with gynecologic problems, abdominal exploration for suspected appendicitis, symptoms or resection of gall stone disease or undergoing bariatric surgery. As the field continues to grow, studies incorporating robust statistical analyses, validation of findings in diverse cohorts, and public data sharing will be essential to identify biological pathways linking obesity and carcinogenesis to be further interrogated using focused, hypothesis-driven approaches.

See related article by Holowatyj et al., p. 817
An Initial Cost-Effectiveness Analysis of Magnetic Resonance-Guided Laser Interstitial Thermal Therapy in Pediatric Epilepsy Surgery
Authors: Sacino Matthew , Huang Sean S. , Alexander Hepzibha , Fayed Islam , Keating Robert F. , Oluigbo Chima O.
Published: August 2020

Introduction: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new technology that provides a clinically efficacious and minimally invasive alternative to conventional microsurgical resection. However, little data exist on how costs compare to traditional open surgery. The goal of this paper is to investigate the cost-effectiveness of MRgLITT in the treatment of pediatric epilepsy. Methods: We retrospectively analyzed the medical records of pediatric patients who underwent MRgLITT via the Visualase® thermal therapy system (Medtronic, Inc., Minneapolis, MN, USA) between December 2013 and September 2017. Direct costs associated with preoperative, operative, and follow-up care were extracted. Benefit was calculated in quality-adjusted life years (QALYs), and the cost-effectiveness was derived from the discounted total direct costs over QALY. Sensitivity analysis on 4 variables was utilized to assess the validity of our results. Results: Twelve consecutive pediatric patients with medically refractory epilepsy underwent MRgLITT procedures. At the last postoperative follow-up, 8 patients were seizure free (Engel I, 66.7%), 2 demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). The average cumulative discounted QALY was 2.11 over the lifetime of a patient. Adjusting for inflation, MRgLITT procedures had a cost-effectiveness of USD 22,211 per QALY. Our sensitivity analysis of cost variables is robust and supports the procedure to be cost-­effective. Conclusion: Our data suggests that MRgLITT may be a cost-effective alternative to traditional surgical resection in pediatric epilepsy surgery.
Evaluation of Noise Reduction Interventions in a School
Authors: Taborda Renata Falótico , Gomes Raquel Fornaziero , Rocha Clayton Henrique , Samelli Alessandra Giannella
Published: August 2020

Introduction: Noise in the school environment has been a major concern in many countries around the world. Students need a favorable signal-to-noise ratio in the classroom to ensure adequate speech intelligibility, which is directly dependent on the acoustics of the classroom and favorable noise levels in these environments. Objective: To evaluate the effectiveness of physical, organizational, and educational interventions to achieve noise reduction in a school. Methods: Presentations on the effects of noise were made to school administrators, teachers, and students (educational activities), and also to the students’ families. Then, thermoacoustic treatment, changes in break times, equipment maintenance, and scheduling of students’ departure were applied. Sound pressure levels were measured before and after interventions for the unoccupied and occupied classroom conditions (n = 11 classrooms) and of the school’s outside areas (n = 4). Self-administered printed pre- and postintervention multiple-choice questionnaires were completed by the students in the classroom. Measures of the signal-to-noise ratio of the teachers’ voice before and after the interventions were also conducted (n = 3 classrooms). The interventions included installation of an acoustic ceiling, installation of air-conditioning, and replacement of the existing furniture with wood furniture. Results: Comparing the pre- and postintervention questionnaires, the Annoyance Index was reduced from 0.78 to 0.59. The tinnitus reported by the individuals increased significantly in the postintervention questionnaire (p < 0.001). Significant reductions in noise levels in both unoccupied and occupied classrooms were observed. There was also an improvement in the mean signal-to-noise ratio in the evaluated classrooms (n = 3) from +7.5 to +8.4 dB. Conclusion: Subjective measures and objective assessments demonstrated that both physical and educational interventions had a positive effect on short-term changes in habits and noise reduction in the school environment.
Severe Infections following Rituximab Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Authors: Li Zhi-Ying , Chen Min , Zhao Ming-Hui
Published: August 2020

Introduction: Severe infections were not rare in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients treated with rituximab. The current study aimed to evaluate severe infections in AAV patients received rituximab administration in a single Chinese center. Methods: Twenty-seven patients were retrospectively included in this study. Their demographic and clinical data were analyzed. Severe infections were classified as grade ≥3 as proposed by the Common Terminology Criteria for Adverse Events V.4.0. Results: Patients were followed up for 23.6 ± 14.0 months from the time of rituximab initiation (mean rituximab dose 1,270.4 mg). Ten severe infection events were recorded in 10 (37.0%) patients, corresponding to an event rate of 20.9 per 100 person-years. Pulmonary infections were the leading infectious complications (90%). Eight of the 10 infections occurred during the first 12 months of follow-up. In multivariable analysis, severe infection in the first year was independently associated with age (HR: 1.121, 95% CI: 1.011–1.243, p = 0.031) and serum creatinine level (increased by per 88.4 μmol/L; HR: 1.493, 95% CI: 1.017–2.191, p = 0.041). Conclusion: In AAV patients receiving ri­tuximab, severe infections were common even with the low-dose regimen. Pulmonary infections were the leading cause, and most infections occurred during the first 12 months of follow-up. Older age and renal dysfunction were the risk factors for infection.
Influence of COVID-19 Pandemic on Endoscopic Procedures in Two European Large-Capacity Endoscopy Units: “Keep Calm, Keep Safe and Scope on?”
Authors: Zorniak Michal , Sirtl Simon , Mahajan Ujjwal Mukund , Stubbe Hans-Christian , Chapula Mateusz , Wosiewicz Piotr , Hartleb Marek , Mayerle Julia , Schulz Christian
Published: August 2020

Background: The COVID-19-pandemic poses challenges to the medical system and especially to endoscopic staff and patients. National, European and International societies provided recommendations on how to safely perform endoscopic procedures during the current pandemic. Until now, the effect of the current pandemic on tertiary endoscopy centers has not been reported. Objective: The aim of this was to analyze the influence of the early SARS-CoV2-pandemic on endoscopic care and work flow in 2 European tertiary endoscopy units. Methods: Data from 2 tertiary endoscopy units (Katowice and Munich) were retrospectively collected during the early pandemic and compared to an equivalent pre-pandemic period. Data include procedures, complications, benchmarks, and influence on endoscopy training. Results: During the early pandemic, we noted a highly significant decrease (49.1%) in the overall number of all endoscopies with a significant increase in therapeutic procedures. Besides, there were no significant differences in the number of urgent endoscopic retrograde cholangiopancreatography or interventional endoscopic ultrasound procedures. The exceptional situation reduced endoscopic procedures performed by trainees significantly. Conclusions: The SARS-CoV2-pandemic halved the endoscopy service of 2 tertiary centers while maintaining an urgent therapeutic service. Recommended personal safety measures in endoscopy proved to be efficient and safe in preventing SARS-CoV2 infection of staff or spreading. Unnecessarily, the SARS-CoV2 pandemic prevented routine endoscopy training.
Association of VEGF Gene Family Variants with Central Macular Thickness and Visual Acuity after Aflibercept Short-Term Treatment in Diabetic Patients: A Pilot Study
Authors: Abdelghany Ahmed A. , Toraih Eman A. , Mohamed Ahmed A. , Lashine Rehab M. , Mohammad Mai H.S. , Nafie Mohamed S. , Fawzy Manal S.
Published: August 2020

Introduction: Diabetic retinopathy (DR) is one of the major vision-threatening causes worldwide. Searching for an individualized therapeutic strategy to prevent its progress is challenging. Objective: This work aimed to investigate the association of angiogenesis-inducer vascular endothelial growth factor (VEGF) gene family and related receptor variants (rs833069, rs12366035, rs7664413, rs7993418, and rs2305948) with susceptibility of DR and the response to 1 dose of aflibercept treatment in type 2 diabetes mellitus (T2DM). Methods: Consecutive eligible patients with T2DM (n = 125) and 110 unrelated controls were enrolled in this preliminary prospective case-controlled study. Genotyping was identified using TaqMan real-time PCR. Adjusted odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association with the clinical/ophthalmological characteristics and early response to intravitreal aflibercept treatment in terms of improved visual acuity (BCVA) and central macular thickness (CMT). Results: We found that both VEGFB rs12366035 and VEGFC rs7664413 conferred higher risk for DR progression under allelic (OR [95% CI]: 1.71 [1.07–2.74]), homozygote comparison (3.55 [1.32–9.57]), and recessive (3.77 [1.43–9.93]) models for the former and under allelic (2.09 [1.25–3.490, homozygote comparison (2.76 [1.02–7.45]), and recessive (2.62 [0.98–6.98] models for the latter. In contrast, VEGFR1 rs7993418 conferred protection against DR under heterozygote comparison and dominant models. The rs12366035*T/T genotype showed the worst pretreatment BCVA score (0.35 ± 0.24) compared to other corresponding genotypes (0.66 ± 0.26 in C/T and 0.54 ± 0.25 in C/C carriers) (p = 0.008). Meanwhile, patients with rs7993418*G/G of VEGFR1 exhibited a significant reduction in CMT after aflibercept injection (12.26 ± 35.43 µ in G/G vs. 3.57 ± 8.74 µ in A/A) (p = 0.037). Conclusions: Polymorphisms of the studied VEGF/receptors could be considered as genetic risk factors of DM/DR development and could play an important role in aflibercept early response for DR patients in the study population.
Zonas de cisalhamento normais no SW do Cráton Amazônico: análise microestrutural das rochas miloníticas do Granito Indiavaí
Authors: Silva Danielle Cristine da , Silva Carlos Humberto da , Costa Ana Cláudia Dantas da
Published: August 2020

Zonas de cisalhamento dúcteis de cinemática normal em orógenos continentais previamente espessados por eventos orogênicos compressivos têm suscitado grande interesse na comunidade científica. Na porção sudoeste do Cráton Amazônico, na região de Indiavaí, porção centro-oeste do Brasil, ocorrem as zonas de cisalhamento Água Rica e Cristo Rei, que afetam as rochas do Granito Indiavaí. Análise das estruturas em escala mesoscópica revela progressiva transformação de um protólito granítico com foliação fraca, passando a rochas com textura protomilonítica, milonítica até ultramilonítica. Análise microestrutural demonstra gradual diminuição do tamanho dos grãos ocasionando o aumento da matriz. As rochas com foliação incipiente não apresentam matriz. Observam-se quartzo recristalizado, extinção ondulante nos feldspatos, intensos processos de sericitização no plagioclásio e ortoclásio com pertitas em chamas. Nos protomilonitos, a matriz perfaz de 20 a 30% da rocha e é composta de quartzo e biotita. São observados porfiroclastos de feldspato potássico, com fraturas, falhas e extinção ondulante. Nos milonitos, a matriz perfaz de 60 a 75% da rocha e é composta de quartzo, biotita e muscovita. Ocorrem porfiroclastos de quartzo comumente na forma de fitas, que apresentam recristalização por migração de limite de grão. Feldspato potássico e plagioclásio exibem extinção ondulante e recristalização por protuberância. Nos ultramilonitos predomina a matriz, que é basicamente composta de quartzo, muscovita e biotita de granulação média. Estima-se que os processos que atuaram no desenvolvimento da foliação milonítica ocorreram em temperaturas entre 400 e 600°C. Análise dos indicadores cinemáticos revela que o movimento tectônico foi normal. Interpreta-se que as zonas de cisalhamento Cristo Rei e Água Limpa são parte de um sistema de cisalhamento extensional desenvolvido em crosta intermediária durante período Toniano.
Challenges and Potential Improvements to Patient Access to Pharmaceuticals
Authors: Psotka Mitchell A. , Fiuzat Mona , Solomon Scott D. , Chauhan Cynthia , Felker G. Michael , Butler Javed , Teerlink John R. , Sinha Shashank S. , O’Connor Christopher M. , Konstam Marvin A.
Published: August 2020

Patient access to a drug after US regulatory approval is controlled by complex interactions between governmental and third-party payers, pharmacy benefit managers, distributers, manufacturers, health systems, and pharmacies that together mediate the receipt of goods by patients after prescription by clinicians. Recent medication approvals highlight why and how the distribution of clinically beneficial novel therapies is controlled. Although imposed limitations on availability may be rational considering the fiduciary responsibilities of payers and escalating spending on health care and pharmaceuticals, transparency and communication are lacking, and some utilization management may disproportionately affect vulnerable populations. Analysis of the current health insurance landscape suggests mechanisms by which patient access to appropriate medications can be improved and patient and clinician frustration reduced while acknowledging the financial realities of the pharmaceutical marketplace. We propose creation of a shared, standardized, and transparent process for coverage decisions that minimizes administrative barriers and is defensible on the basis of clinical and cost-effectiveness evidence. These reforms would benefit patients and improve the efficiency of the pharmaceutical system.
Microdissection of the Human Renal Nervous System
Authors: García-Touchard Arturo , Maranillo Eva , Mompeo Blanca , Sañudo José Ramón
Published: August 2020

Despite the use of renal denervation to treat hypertension, the anatomy of the renal nervous system remains poorly understood. We performed a detailed quantitative analysis of the human renal nervous system anatomy with the goal of optimizing renal denervation procedural safety and efficacy. Sixty kidneys from 30 human cadavers were systematically microdissected to quantify anatomic variations in renal nerve patterns. Contrary to current clinical perception, not all renal innervation followed the main renal artery. A significant portion of the renal nerves (late arriving nerves) frequently reached the kidney (73% of the right kidney and 53% of the left kidney) bypassing the main renal artery. The ratio of the main renal artery length/aorta-renal hilar distance proved to be a useful variable to identify the presence/absence of these late arriving nerves (odds ratio, 0.001 (95% CI, 0.00002–0.0692;
P
: 0.001) with a cutoff of 0.75 (sensitivity: 0.68, specificity: 0.83, area under ROC curve at threshold: 0.76). When present, polar arteries were also highly associated with the presence of late arriving nerve. Finally, the perivascular space around the proximal main renal artery was frequently occupied by fused ganglia from the solar plexus (right kidney: 53%, left kidney: 83%) and/or by the lumbar sympathetic chain (right kidney: 63%, left kidney: 60%). Both carried innervation to the kidneys but importantly also to other abdominal and pelvic organs, which can be accidentally denervated if the proximal renal artery is targeted for ablation. These novel anatomic insights may help guide future procedural treatment recommendations to increase the likelihood of safely reaching and destroying targeted nerves during renal denervation procedures.
Uncovered Contribution of Kv7 Channels to Pulmonary Vascular Tone in Pulmonary Arterial Hypertension
Authors: Mondéjar-Parreño Gema , Barreira Bianca , Callejo María , Morales-Cano Daniel , Barrese Vincenzo , Esquivel-Ruiz Sergio , Olivencia Miguel A. , Macías Miguel , Moreno Laura , Greenwood Iain A. , Perez-Vizcaino Francisco , Cogolludo Angel
Published: August 2020

K
+
channels play a fundamental role regulating membrane potential of pulmonary artery (PA) smooth muscle cells and their impairment is a common feature in pulmonary arterial hypertension (PAH). K
+
voltage-gated channel subfamily Q (
KCNQ1-5
) or Kv7 channels and their regulatory subunits subfamily E (KCNE) regulatory subunits are known to regulate vascular tone, but whether Kv7 channel function is impaired in PAH and how this can affect the rationale for targeting Kv7 channels in PAH remains unknown. Here, we have studied the role of Kv7/KCNE subunits in rat PA and their possible alteration in PAH. Using the patch-clamp technique, we found that the total K
+
current is reduced in PA smooth muscle cells from pulmonary hypertension animals (SU5416 plus hypoxia) and Kv7 currents made a higher contribution to the net K
+
current. Likewise, enhanced vascular responses to Kv7 channel modulators were found in pulmonary hypertension rats. Accordingly, KCNE4 subunit was highly upregulated in lungs from pulmonary hypertension animals and patients. Additionally, Kv7 channel activity was enhanced in the presence of Kv1.5 and TASK-1 channel inhibitors and this was associated with an increased KCNE4 membrane abundance. Compared with systemic arteries, PA showed a poor response to Kv7 channel modulators which was associated with reduced expression and membrane abundance of Kv7.4 and KCNE4. Our data indicate that Kv7 channel function is preserved and KCNE4 is upregulated in PAH. Therefore, compared with other downregulated channels, the contribution of Kv7 channels is increased in PAH resulting in an enhanced sensitivity to Kv7 channel modulators. This study provides insight into the potential usefulness of targeting Kv7 channels in PAH.
Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in >29 000 Families
Authors: Tegegne Balewgizie S. , Man Tengfei , van Roon Arie M. , Asefa Nigus G. , Riese Harriëtte , Nolte Ilja , Snieder Harold
Published: August 2020

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all
P
<0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (−0.20/−0.16) and with diastolic BP (−0.15/−0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, −0.08 to −0.23) and diastolic BP (range, −0.20 to −0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap.
Heart Failure in Women With Hypertensive Disorders of Pregnancy
Authors: Honigberg Michael C. , Riise Hilde Kristin Refvik , Daltveit Anne Kjersti , Tell Grethe S. , Sulo Gerhard , Igland Jannicke , Klungsøyr Kari , Scott Nandita S. , Wood Malissa J. , Natarajan Pradeep , Rich-Edwards Janet W.
Published: August 2020

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84–2.35],
P
=0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50–2.68,
P
<0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (
P
interaction
=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.
Gentle
Authors: Kwak Young Joon , Richmond Christopher
Published: August 2020

Gentle explores the slow, subtle doom of everyday trans-femme ennui in traditional domestic space. It engages with confinement at “home,” constricting body shapers, and absent intimacy through a dance of desire and antagonism with the phantom gaze of the viewer. “Ordinary” spaces and rituals reveal an inherent queerness. ©2020 Young Joon Kwak. To view supplemental materials related to this article, please view http://www.mitpressjournals.org/doi/suppl/10.1162/DRAM_a_00937 .
The Return of the Dybbuk: Between Ritual Healing and Stage Performance
Authors: Bilu Yoram
Published: August 2020

The two performative genres of the dybbuk constitute a reciprocal system—as a Jewish possession illness and as a canonical play. Tracking the two highlights the dialectical relationship between the dybbuk-as-illness and the Dybbuk-as-play. Dybbuk possession cases reemerged in Israel at the end of the 20th century; one new and highly publicized case in particular kindled opposing moral crusades.
Different Enhancement of the East Asian Summer Monsoon under Global Warming and Interglacial Epochs Simulated by CMIP6 Models: Role of the Subtropical High
Authors: He Chao , Zhou Wen
Published: August 2020

Southerly wind in the lower troposphere is an essential feature of East Asian summer monsoon (EASM) circulation, which is reported to be enhanced under global warming scenarios and interglacial epochs. Based on an analysis of an ensemble of CMIP6 models, this study shows that the magnitude of intensification of the EASM circulation is much smaller under global warming scenarios than during interglacial epochs. Distinct changes in the western North Pacific subtropical high (WNPSH) are responsible for the different responses of the EASM circulation. The WNPSH is substantially enhanced during interglacial epochs, which acts to strengthen the southerly wind associated with the EASM on the western flank of the WNPSH. However, the change in the WNPSH is insignificant and cannot strengthen the EASM under global warming scenarios, and the weakly enhanced EASM circulation may be a direct response to intensified heating over the Tibetan Plateau. The land–ocean thermal contrast explains the different responses of the WNPSH. During interglacial epochs, the summertime surface warming over the subtropical North Pacific is much weaker than over Eurasia due to the large thermal inertia of the ocean to increased insolation, and the WNPSH is intensified as a response to the suppressed latent heating over the subtropical North Pacific. The fast response of the WNPSH to abrupt quadrupling of CO2 without sufficient ocean warming is an analog to the interglacial epochs, but it is offset by the effect of slow oceanic warming, resulting in an insignificant change of the WNPSH under global warming scenarios.
Influence of Madden–Julian Oscillation on the Intraseasonal Variability of Summer and Winter Monsoon Rainfall in the Philippines
Authors: Bagtasa Gerry
Published: August 2020

The present study investigates the influence of the Madden–Julian oscillation (MJO) on the intraseasonal variability of summer and winter monsoon rainfall in the Philippines. The monsoon wind–terrain interaction that gives rise to rainfall in the Philippines leads to a sharp contrast between west and east coast rainfall patterns during summer and winter monsoon seasons, respectively. During the summer monsoon season, the eastward-propagating MJO modulates tropical cyclone (TC) activity in the western North Pacific (WNP) on MJO phases 5–7. TC rainfall and remote TC precipitation due to Rossby wave response to TC heating induces strong southwesterly flow that enhances moisture transport and brings anomalous rainfall to the western region of the Philippines. On the other hand, during the winter season, an induced Matsuno–Gill-type pattern to the southeast of the Philippines influences the strength of the Asian winter monsoon. Active (inactive) convection in the tropical Maritime Continent and western Pacific during MJO phases 4–6 produces the anomalous Philippine Sea cyclonic (anticyclonic) circulation. The cyclonic (anticyclonic) anomaly leads to an enhanced (weakened) northeast monsoon flow and wet (dry) rainfall anomaly along the eastern Philippines.
Refraction and Straining of Near-Inertial Waves by Barotropic Eddies
Authors: Asselin Olivier , Thomas Leif N. , Young William R. , Rainville Luc
Published: August 2020

Fast-moving synoptic-scale atmospheric disturbances produce large-scale near-inertial waves in the ocean mixed layer. In this paper, we analyze the distortion of such waves by smaller-scale barotropic eddies, with a focus on the evolution of the horizontal wavevector k under the effects of straining and refraction. The model is initialized with a horizontally uniform (k = 0) surface-confined near-inertial wave, which then evolves according to the phase-averaged model of Young and Ben Jelloul. A steady barotropic vortex dipole is first considered. Shear bands appear in the jet region as wave energy propagates downward and toward the anticyclone. When measured at a fixed location, both horizontal and vertical wavenumbers grow linearly with the time t elapsed since generation such that their ratio, the slope of wave bands, is time independent. Analogy with passive scalar dynamics suggests that straining should result in the exponential growth of |k|. Here instead, straining is ineffective, not only at the jet center, but also in its confluent and diffluent regions. Low modes rapidly escape below the anticyclonic core such that weakly dispersive high modes dominate in the surface layer. In the weakly dispersive limit, k = −t∇ζ(x, y, t)/2 provided that (i) the eddy vertical vorticity ζ evolves according to the barotropic quasigeostrophic equation and (ii) k = 0 initially. In steady flows, straining is ineffective because k is always perpendicular to the flow. In unsteady flows, straining modifies the vorticity gradient and hence k, and may account for significant wave–eddy energy transfers.