bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Glucosides of Peony Protect Cardiomyocytes against Oxidative Stress and Inflammation by Reversing Mitochondrial Dynamics and Bioenergetics
Authors: Wang Mengmeng , Li Qiang , Zhang Ying , Liu Hao
Published: December 2020

Total glucosides of peony (TGP) are used to treat rheumatoid arthritis and systemic lupus erythematosus. We explored the protective effects of TGP on cardiomyocyte oxidative stress and inflammation in the presence of hydrogen peroxide by focusing on mitochondrial dynamics and bioenergetics. Our study demonstrated that hydrogen peroxide significantly repressed cardiomyocyte viability and promoted cell apoptosis through induction of the mitochondrial death pathway. TGP treatment sustained cardiomyocyte viability, reduced cardiomyocyte apoptosis, and decreased inflammation and oxidative stress. Molecular investigation indicated that hydrogen peroxide caused mitochondrial dynamics disruption and bioenergetics reduction in cardiomyocytes, but this alteration could be normalized by TGP. We found that disruption of mitochondrial dynamics abolished the regulatory effects of TGP on mitochondrial bioenergetics; TGP modulated mitochondrial dynamics through the AMP-activated protein kinase (AMPK) pathway; and inhibition of AMPK alleviated the protective effects of TGP on mitochondria. Our results showed that TGP treatment reduces cardiomyocyte oxidative stress and inflammation in the presence of hydrogen peroxide by correcting mitochondrial dynamics and enhancing mitochondrial bioenergetics. Additionally, the regulatory effects of TGP on mitochondrial function seem to be mediated through the AMPK pathway. These findings are promising for myocardial injury in patients with rheumatoid arthritis and systemic lupus erythematosus.
Composite Learning Sliding Mode Control of Nonlinear Systems Subject to Actuator Failures
Authors: Hou Xianmin , Wang Songyu
Published: December 2020

This article focuses on controlling single-input-single-output (SISO) nonlinear systems with actuator failures via sliding mode control (SMC) and composite learning SMC (CLSMC). In the design of the SMC, an integer-order sliding surface is proposed, and an adaptive law is constructed to update the parameter evaluation in the actuator failure. The SMC method can achieve the tracking error approaching zero if a strict permanent excitation (PE) condition is satisfied. To mitigate this requirement, by using all data recorded while the controller works, we construct prediction errors that are utilized to produce a composite learning adaptive law. Then, the proposed CLSMC method not only drives the tracking error to zero but also realizes the accurate evaluation of the unmatched unknown parameter in the actuator failure. In addition, in the proposed CLSMC method, we only need to satisfy an interval excitation (IE) condition. Simulation results are presented to indicate the validity of our methods.
MQHD: Dynamic Load Balancing Method for Energy-Aware Storage Systems
Authors: Xie Xiaoling
Published: December 2020

Aiming at the problem that some disks of energy-aware storage systems are easily overloaded, a dynamic load balancing method based on multiqueue and heat degree (MQHD) is proposed. According to data popularity, MQHD divides data into multiple least recently used (LRU) queues by data access frequency and access temporal locality and uses heat degree to measure the load pressure brought by each data unit to a disk. When a disk is overloaded, MQHD calculates the load pressure ratio (LPR) according to the disk overload degree and then selects some appropriate data to migrate according to the LPR. The experimental results show that, compared with the popular data concentration method (PDC), the workload-adaptive management method (WAM), and the energy model-based file migration strategy (EM-FMS), MQHD is the most effective. Under given experimental conditions, the request change ratio (RCR) value of MQHD is 0.371, EM-FMS is 0.2872, and WAM is 0.0114. Compared with EM-FMS, MQHD has better rapidity and less overhead.
Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta‐Analysis
Authors: Wang Shu , Liu Mingyue , Lian Siheng , Liu Naiming , Zhang Guibin , Zhao Qingchun , Zhang Yingshi , Jian Lingyan
Published: December 2020

Objective. The phosphatidylinositol 3‐kinase (PI3K) signaling pathway is a promising treatment target for patients with breast cancer (BC). Our study aimed to evaluate the most effective and safe PI3K inhibitor for patients with BC, especially in PIK3CA mutation. Methods. Electronics databases were systematically searched from their inception to June 2020 for published randomized controlled trials (RCTs) comparing PI3K inhibitor therapy versus non‐PI3K inhibitor therapy in patients with BC that mentioned or reported data of PIK3CA‐mutated patient subgroups. Eligible RCTs had to report at least one of the following clinical outcomes: objective response rate (ORR), progression‐free survival (PFS), or adverse events (AE). Results. Nine eligible RCTs involving 3872 BC patients and four PI3K inhibitor therapy arms (i.e., alpelisib, buparlisib, pictilisib, and taselisib) were included. In evaluating ORR, beneficial significant results of PI3K inhibitors could be found in the PIK3CA mutated group (1.952, 1.012 to 3.766); analogous results could also be found in 6m‐PFS (1.519, 1.144 to 2.018) and PFS from HR data (‐0.346, ‐0.525 to ‐0.168). From pairwise and network meta‐analyses, buparlisib showed the most favorable ORR, as it was significantly different from fulvestrant in the PIK3CA‐mutated patient group (2.80, 1.56 to 5.03). Alpelisib ranked first in the assessment of 6m‐PFS and was significantly different from fulvestrant in the PIK3CA‐mutated group (2.33, 1.45 to 3.44). The above PI3K inhibitors had good safety with few serious AEs. PROSPERO registration CRD42020193932. Conclusion. The PI3K inhibitors alpelisib and buparlisib appear to have superior efficacy and safety therapeutic choices for patients with BC, especially in PIK3CA‐mutated patients.
A Lightweight Internet Sharing Scheme for Sectional Medical Images according to Existing Hospital Network Facilities and Basic Information Security Rules
Authors: Qiao Liang , Wu Hao , Wu Yi , Wu Wenjing , Yang Jingyi , Nian Yongjian , Chen Mingsheng , Bai Sen , Huang Hao , Qiu Mingguo
Published: December 2020

Background. With the outbreak of COVID-19, large-scale telemedicine applications can play an important role in the epidemic areas or less developed areas. However, the transmission of hundreds of megabytes of Sectional Medical Images (SMIs) from hospital’s Intranet to the Internet has the problems of efficiency, cost, and security. This article proposes a novel lightweight sharing scheme for permitting Internet users to quickly and safely access the SMIs from a hospital using an Internet computer anywhere but without relying on a virtual private network or another complex deployment. Methods. A four-level endpoint network penetration scheme based on the existing hospital network facilities and information security rules was proposed to realize the secure and lightweight sharing of SMIs over the Internet. A “Master-Slave” interaction to the interactive characteristics of multiplanar reconstruction and maximum/minimum/average intensity projection was designed to enhance the user experience. Finally, a prototype system was established. Results. When accessing SMIs with a data size ranging from 251.6 to 307.04 MB with 200 kBps client bandwidth (extreme test), the network response time to each interactive request remained at approximately 1 s, the original SMIs were kept in the hospital, and the deployment did not require a complex process; the imaging quality and interactive experience were recognized by radiologists. Conclusions. This solution could serve Internet medicine at a low cost and may promote the diversified development of mobile medical technology. Under the current COVID-19 epidemic situation, we expect that it could play a low-cost and high-efficiency role in remote emergency support.
Experimental Study on the Characteristics of Granular Materials’ Flows and Fractures under Uniaxial Compression
Authors: Zhao Futian , Liu Jun , Xiao Zhimin , Liu Mingqing , Wang Yue , Ou Chen , Zhen Mengyang
Published: December 2020

The mechanical behaviors of granular materials have high complexity. Since the mechanical behaviors of granular materials are difficult to describe theoretically, in this paper, the flow and fracture characteristics of granular materials were discussed by the experimental method. An experimental method was firstly proposed to identify the mechanical behaviors of granular materials under extra loading. An experimental device, which can be used to monitor force and displacement between particles, was invented. The uniaxial compression experiments of granular particles with different materials and grades were carried out, and the overall and local force between particles was obtained and investigated. Due to the flow of particles, the overall force rises in a fluctuating manner and the local force is not distributed evenly. Then, the particle fragments were sieved layer by layer. It was confirmed that the particles and loading strength have great influences on fractures of granular materials.
What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence
Authors: Nogueira Bárbara Cristina Félix , Campos Artur Kanadani , Alves Raul Santos , Sarandy Mariáurea Matias , Novaes Rômulo Dias , Esposito Debora , Gonçalves Reggiani Vilela
Published: December 2020

Cytokines and growth factors are known to play an important role in the skin wound closure process; however, in knockout organisms, the levels of these molecules can undergo changes that result in the delay or acceleration of this process. Therefore, we systematically reviewed evidence from preclinical studies about the main immunoregulatory molecules involved in skin repair through the analysis of the main mechanisms involved in the depletion of immunoregulatory genes, and we carried out a critical analysis of the methodological quality of these studies. We searched biomedical databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to those which used knockout animals and excision or incision wound models without intervention. A total of 27 studies were selected; data for animal models, gene depletion, wound characteristics, and immunoregulatory molecules were evaluated and compared whenever possible. Methodological quality assessments were examined using the ARRIVE and SYRCLE’s bias of risk tool. In our review, the extracellular molecules act more negatively in the wound healing process when silenced and the metabolic pathway most affected involved in these processes was TGF-β/Smad, and emphasis was given to the importance of the participation of macrophages in TGF-β signaling. Besides that, proinflammatory molecules were more evaluated than anti-inflammatory ones, and the main molecules evaluated were, respectively, TGF-β1, followed by VEGF, IL-6, TNF-α, and IL-1β. Overall, most gene depletions delayed wound healing, negatively influenced the concentrations of proinflammatory cytokines, and consequently promoted a decrease of inflammatory cell infiltration, angiogenesis, and collagen deposition, compromising the formation of granulation tissue. The studies presented heterogeneous data and exhibited methodological limitations; therefore, mechanistic and highly controlled studies are required to improve the quality of the evidence.
Influence of Decoupled Charge Structure and Filler on the Blasting Effect
Authors: Zhang Yiping , Luo Yi , Wan Sipeng , Tian Yingxiang , Ding Huanchao , Zhang Xiaoxiao , Fang Chengcheng , Zhang Yuyao
Published: December 2020

This study compared models of specimens with different filler media and decoupled charge structures in terms of the blasting effect. The test system combined a high-speed camera and high-speed static strain test analyzer. A physical model of a concrete single-borehole decoupled charge structure was designed to study the geometric elements of the blasting funnel, flyrock launch velocity, peak strain values, and distribution of the gravel lumpiness. The experimental results showed that for the same decoupling coefficient, when expandable polystyrene foam (EPS) was used as the filling medium, the radius, depth, and volume of the blasting funnel of the model specimen were larger, the flyrock launch velocity was slower, the peak stress of the specimen was higher, and the distribution of gravel lumpiness was more even. The relationship between the experimental index and the decoupling coefficient follows the changing trend of first increasing and then decreasing or first decreasing and then increasing. With air and EPS as the filling media, the concrete model specimens could achieve optimal blasting effects at decoupling coefficients of 1.83 and 1.69, respectively. The results confirm the feasibility and practicability of using EPS as a filler and can provide guidance and an experimental basis for the selection of the decoupling coefficient and filling medium in blasting engineering.
Transcranial Direct Current Stimulation Enhances Episodic Memory in Healthy Older Adults by Modulating Retrieval-Specific Activation
Authors: Huo Lijuan , Zheng Zhiwei , Huang Jia , Li Rui , Li Jin , Li Juan
Published: December 2020

Memory decline has become an issue of major importance in the aging society. Anodal transcranial direct current stimulation (atDCS) is a viable tool to counteract age-associated episodic memory deterioration. However, the underlying neural mechanisms are unclear. In this single-blind, sham-controlled study, we combined atDCS and functional magnetic resonance imaging to assess the behavioral and neural consequences of multiple-session atDCS in older adults. Forty-nine healthy older adults received either 10 sessions of anodal or sham stimulation over the left dorsolateral prefrontal cortex. Before and after stimulation, participants performed a source memory task in the MRI scanner. Compared to sham stimulation, atDCS significantly improved item memory performance. Additionally, atDCS significantly increased regional brain activity around the stimulation area in the prefrontal cortex and extended to the bilateral anterior cingulate cortex. Neural changes in the prefrontal cortex correlated with memory gains. Our findings therefore indicate that multiple-session offline atDCS may improve memory in older adults by inducing neural alterations.
Outage Probability Analysis of Decode-and-Forward Two-Way Relaying System with Energy Harvesting Relay
Authors: Toan Hoang Van , Hoang Tran Manh , Dung Le The
Published: December 2020

In this paper, we evaluate a two-way relay system consisting of two terminals and an intermediate relay. In this model, two terminals do not have a direct link but exchange data with each other via the relay in three phases. The relay utilizes energy harvesting technology to collect energy from the received signals of two terminals in the first two phases and then uses the obtained energy for signal transmission in the third phase. Each node is equipped with a single antenna and operates under a half-duplex mode. All wireless channels are influenced by reversible independent flat Rayleigh fading. Using analytical methods, we provide the exact and approximate closed-form expressions of user outage probability and system outage probability. The approximate expressions of these outage probabilities are more explicit and straightforward, providing a better understanding of the influences of network parameters on the system quality. Monte-Carlo simulations are used to confirm the correctness of mathematical analyses.
E74-Like Factor 3 Is a Key Regulator of Epithelial Integrity and Immune Response Genes in Biliary Tract Cancer
Authors: Suzuki Masami , Saito-Adachi Mihoko , Arai Yasuhito , Fujiwara Yuko , Takai Erina , Shibata Shinsuke , Seki Masahide , Rokutan Hirofumi , Maeda Daichi , Horie Masafumi , Suzuki Yutaka , Shibata Tatsuhiro , Kiyono Tohru , Yachida Shinichi
Published: December 2020

The transcription factor E74-like factor 3 (ELF3) is inactivated in a range of cancers, including biliary tract cancer (BTC). Here, we investigated the tumor-suppressive role of ELF3 in bile duct cells by identifying several previously unknown direct target genes of ELF3 that appear to be implicated in biliary duct carcinogenesis. ELF3 directly repressed ZEB2, a key regulator of epithelial–mesenchymal transition, and upregulated the expression of CGN, an integral element in lumen formation. Loss of ELF3 led to decreased cell–cell junctions and enhanced cell motility. ALOX5 and CXCL16 were also identified as additional direct targets of ELF3; their corresponding proteins 5-lipoxygenase and CXCL16 play a role in the immune response. Conditioned medium from cells overexpressing ELF3 significantly enhanced the migration of natural killer cells and CD8+ T cells toward the conditioned medium. Gene expression profiling for BTC expressing high levels of ELF3 revealed significant enrichment of the ELF3-related genes. In a BTC xenograft model, activation of ELF3 increased expression of ELF3-related genes, enhanced the tubular structure of the tumors, and led to a loss of vimentin. Overall, our results indicate that ELF3 is a key regulator of both epithelial integrity and immune responses in BTC.

Significance:

Thease finding shows that ELF3 regulates epithelial integrity and host immune responses and functions as a tumor suppressor in biliary tract cancer.
Optimal Timing for Cancer Screening and Adaptive Surveillance Using Mathematical Modeling
Authors: Curtius Kit , Dewanji Anup , Hazelton William D. , Rubenstein Joel H. , Luebeck Georg E.
Published: December 2020

Cancer screening and early detection efforts have been partially successful in reducing incidence and mortality, but many improvements are needed. Although current medical practice is informed by epidemiologic studies and experts, the decisions for guidelines are ultimately ad hoc. We propose here that quantitative optimization of protocols can potentially increase screening success and reduce overdiagnosis. Mathematical modeling of the stochastic process of cancer evolution can be used to derive and optimize the timing of clinical screens so that the probability is maximal that a patient is screened within a certain “window of opportunity” for intervention when early cancer development may be observable. Alternative to a strictly empirical approach or microsimulations of a multitude of possible scenarios, biologically based mechanistic modeling can be used for predicting when best to screen and begin adaptive surveillance. We introduce a methodology for optimizing screening, assessing potential risks, and quantifying associated costs to healthcare using multiscale models. As a case study in Barrett's esophagus, these methods were applied for a model of esophageal adenocarcinoma that was previously calibrated to U.S. cancer registry data. Optimal screening ages for patients with symptomatic gastroesophageal reflux disease were older (58 for men and 64 for women) than what is currently recommended (age > 50 years). These ages are in a cost-effective range to start screening and were independently validated by data used in current guidelines. Collectively, our framework captures critical aspects of cancer evolution within patients with Barrett's esophagus for a more personalized screening design.

Significance:

This study demonstrates how mathematical modeling of cancer evolution can be used to optimize screening regimes, with the added potential to improve surveillance regimes.
Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse in HPV-Positive Women with Normal Cytology and Five-Year Type Concordance: A Randomized Comparison
Authors: Inturrisi Federica , Bogaards Johannes A. , Heideman Daniëlle A.M. , Meijer Chris J.L.M. , Berkhof Johannes
Published: December 2020

Background:

In human papillomavirus (HPV)-based cervical screening programs, management of HPV-positive women with normal cytology is debated. Longitudinal information on HPV type persistence may be employed for risk stratification.

Methods:

We assessed the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after repeatedly testing positive for the same HPV type(s) in the randomized population-based screening study Amsterdam (POBASCAM). We compared 18-month CIN3+ risks in HPV-positive women (intervention, n = 1,066) to those in HPV-positive/cytology-negative women who tested HPV-positive in the next screening round (control, n = 111) five years later, stratified for HPV type concordance.

Results:

The 18-month CIN3+ risk was 15% in HPV-positive women in the intervention group, 40% in the control group after two-round type concordance (relative risk 2.6, 95% confidence interval 1.9–3.4), and 20% in the control group after a type switch (1.3, 0.5–3.2). The relative increase in CIN3+ risk after two-round type concordance was similar in <35-year-old (3.0, 2.0–4.4) and older women (2.2, 1.4–3.5), and was high in high-risk HPV-positive women who were HPV16/18/31/33/45-negative in both rounds (9.9, 4.4–21.9).

Conclusions:

Five-year HPV type concordance signals high CIN3+ risk and warrants referral for colposcopy without additional cytology triage.

Impact:

HPV screening programs become highly efficient when HPV-positive women with negative triage testing at baseline are offered repeat HPV genotyping after five years.
Genomic Characterization of de novo Metastatic Breast Cancer
Authors: Garrido-Castro Ana C. , Spurr Liam F. , Hughes Melissa E. , Li Yvonne Y. , Cherniack Andrew D. , Kumari Priti , Lloyd Maxwell R. , Bychkovsky Brittany , Barroso-Sousa Romualdo , Di Lascio Simona , Jain Esha , Files Janet , Mohammed-Abreu Ayesha , Krevalin Max , MacKichan Colin , Barry William T. , Guo Hao , Xia Daniel , Cerami Ethan , Rollins Barrett J. , MacConaill Laura E. , Lindeman Neal I. , Krop Ian E. , Johnson Bruce E. , Wagle Nikhil , Winer Eric P. , Dillon Deborah A. , Lin Nancy U.
Published: December 2020

Purpose:

In contrast to recurrence after initial diagnosis of stage I–III breast cancer [recurrent metastatic breast cancer (rMBC)], de novo metastatic breast cancer (dnMBC) represents a unique setting to elucidate metastatic drivers in the absence of treatment selection. We present the genomic landscape of dnMBC and association with overall survival (OS).

Experimental Design:

Targeted DNA sequencing (OncoPanel) was prospectively performed on either primary or metastatic tumors from 926 patients (212 dnMBC and 714 rMBC). Single-nucleotide variants, copy-number variations, and tumor mutational burden (TMB) in treatment-naïve dnMBC primary tumors were compared with primary tumors in patients who ultimately developed rMBC, and correlated with OS across all dnMBC.

Results:

When comparing primary tumors by subtype, MYB amplification was enriched in triple-negative dnMBC versus rMBC (21.1% vs. 0%, P = 0.0005, q = 0.111). Mutations in KMTD2, SETD2, and PIK3CA were more prevalent, and TP53 and BRCA1 less prevalent, in primary HR+/HER2− tumors of dnMBC versus rMBC, though not significant after multiple comparison adjustment. Alterations associated with shorter OS in dnMBC included TP53 (wild-type: 79.7 months; altered: 44.2 months; P = 0.008, q = 0.107), MYC (79.7 vs. 23.3 months; P = 0.0003, q = 0.011), and cell-cycle (122.7 vs. 54.9 months; P = 0.034, q = 0.245) pathway genes. High TMB correlated with better OS in triple-negative dnMBC (P = 0.041).

Conclusions:

Genomic differences between treatment-naïve dnMBC and primary tumors of patients who developed rMBC may provide insight into mechanisms underlying metastatic potential and differential therapeutic sensitivity in dnMBC. Alterations associated with poor OS in dnMBC highlight the need for novel approaches to overcome potential intrinsic resistance to current treatments.
Oleanolic Acid Improves the Symptom of Renal Ischemia Reperfusion Injury via the PI3K/AKT Pathway
Authors: Yang JinRan , Li Xinchang , Yang Hua , Long Chenmei
Published: December 2020

Purpose: The aim of this study was to investigate the therapeutic effect of oleanolic acid (OA) on the renal ischemia reperfusion injury (RIRI) and the possible mechanism. Methods: The RIRI model was successfully established in rats. OA, LY294002 (a PI3K inhibitor), and OA combined with LY294002 were dosed to rats in 3 therapeutic groups, respectively. The blood was collected to detect the concentration of Cr and BUN by ELISA. The kidney of each rat was collected to detect the concentration of renal injury factor (Kim-1) and the HE staining was performed. Western blot was used to detect the expression level of PI3K, p-AKT, AKT, PDK1, Skp2, and p27 in the renal tissue homogenate. Results: The symptom of vacuolar degeneration and interstitial edema was greatly improved in the rat kidney from the 3 therapeutic groups, compared with that from the RIRI model group. No significant difference was observed among the 3 therapeutic groups. The concentration of Cr in the 3 therapeutic groups was greatly lower than that in the RIRI model group. The expression level of p-AKT/AKT, PI3K, PDK1, Skp2, and p27 in OA group, LY294002 group, and OA combined with LY294002 group was significantly lower than that in the RIRI model group, respectively. Conclusion: OA could improve the symptom of RIRI, possibly by inhibiting PI3K/AKT signal pathway.
Relationship between Soluble ST2 and Left Ventricular Geometry in Maintenance Hemodialysis Patients
Authors: Zhang Zhen , Xie Yeqing , Shen Bo , Nie Yuxin , Cao Xuesen , Xiang Fangfang , Zou Jianzhou
Published: December 2020

Introduction: Left ventricular hypertrophy (LVH) is a highly prevalent presentation of cardiac structural abnormality and a strong predictor of adverse outcomes in maintenance hemodialysis (MHD) patients. Different left ventricular geometry may provide additional clinical information. Soluble ST2 is a novel cardiac prognostic biomarker in MHD patients and is closely related to cardiac remodeling. Objective: This study sought to evaluate the association of sST2 and left ventricular structure in a cohort of MHD patients. Methods: Two hundred eighty-seven patients were enrolled. Left ventricular structure was assessed via transthoracic echocardiography. Left ventricular geometric patterns were defined according to left ventricular mass index and relative wall thickness (RWT). Serum sST2 levels were measured. Results: Prevalence of LVH was 44.9% in the study population. In univariate analysis, sST2 levels were correlated with interventricular septal wall thickness, posterior wall thickness, and RWT. After multivariate adjustment, sST2 was independently correlated with only RWT (p = 0.028). Comparing sST2 concentrations across different LV geometric patterns, we found sST2 levels were significantly increased in patients with concentric cardiac remodeling and concentric LVH. Conclusions: The present study found that sST2 were significantly increased in patients with concentric remodeling and concentric LVH. ST2/interleukin (IL)-33 signaling might participate in the process of cardiac remodeling via its pro-fibrotic action. Future studies on the mechanism of ST2/IL-33 pathway are needed.
Feedback-Related Brain Potentials Indicate the Influence of Craving on Decision-Making in Patients with Alcohol Use Disorder: An Experimental Study
Authors: Sehrig Sarah , Odenwald Michael , Rockstroh Brigitte
Published: December 2020

Introduction: Alcohol craving is a key symptom of alcohol use disorder (AUD) and a significant cause of poor treatment outcome and frequent relapse. Craving is supposed to impair executive functions by modulating reward salience and decision-making. Objective: The present study sought to clarify this modulation by scrutinizing reward feedback processing in an experimental decision-making task, which was accomplished by AUD patients in 2 conditions, in the context of induced alcohol craving and in neutral context. Methods: AUD inpatients (N = 40) accomplished the Balloon Analog Risk Task, while their EEG was monitored; counterbalanced across conditions, the tasks were preceded either by craving induction by means of imagery and olfactory alcohol cues, or by neutral cues. Decision choice and variability, and event-related potentials (ERPs) prior to (stimulus-preceding negativity [SPN]) and following (P2a) reward feedback upon decisions, and the outcome-related feedback-related negativity (FRN) were compared between conditions and between patients, who experienced high craving upon alcohol cues (N = 18) and those who did not (N = 22). Results: Upon craving induction (vs. neutral condition), high-craving AUD patients showed less adjustment of decision choice to preceding reward experience and more variable decisions than low-craving AUD patients, together with accentuated reward-associated ERP (SPN and P2a), while outcome-related FRN was not modified by craving. Conclusions: Results support orientation to reward in AUD patients, particularly amplified upon experienced craving, which may interfere with (feedback-guided) decision-making even in alcohol-unrelated context. Craving-accentuated ERP indices suggest neuroadaptive changes of cognitive-motivational states upon chronic alcohol abuse. Together with altered reward-related expectancies, this has to be considered in intervention and relapse prevention.
Mastering the Grammar of Past Tense Counterfactual Sentences: A Pilot Study of Adolescents Attending Low-Income Schools
Authors: Nippold Marilyn A. , Shinham Kristin , LaFavre Scott
Published: December 2020

Background/Aim: This pilot study was designed to determine if adolescents had mastered the grammar of past tense counterfactual (PTCF) sentences (e.g., “If Julie had done all of the track workouts, she might have won the state meet”). Of interest was their ability to use the modal, auxiliary, and past participle verbs correctly in the main clause of a PTCF sentence. Prior research had indicated that PTCF sentences were challenging to older children. Hence, we wished to determine if PTCF sentences would continue to challenge adolescents. Methods: The participants were two groups of adolescents, who were aged 13 and 16 years, and a control group of young adults having a mean age of 22 years (n = 40 per group). Each participant read a set of four fables and completed a PTCF sentence based on the story. Each incomplete sentence contained a subordinate clause that employed the past perfect verb form (e.g., “If the fox had been able to jump higher…”). The participant’s task was to complete the sentence in writing, generating a grammatically correct main clause that contained the present perfect verb form (e.g., “he would have been able to reach the delicious grapes.”). Results: On the PTCF sentences task, the 16-year-olds earned a higher mean raw score than the 13-year-olds, but the two groups did not show a statistically significant difference. However, the 22-year-olds performed significantly better than the 13-year-olds. It was also found that using the correct form of the past participle verb was the most difficult aspect of the task for all three groups, and that mastering the grammar of PTCF sentences continued into adulthood. Discussion/Conclusion: The PTCF sentence is a late linguistic attainment, perhaps due to its infrequent occurrence in spoken language. The study offers implications for the concept of grammatical mastery and for the distinction between prescriptive and descriptive grammar.
Understanding of Inheritance and Genetic Variation Assessed through the Use of an Engaging Real-Life Survey
Authors: Ephrem Elshaddai , Gleason Erica , Maurer Kelly , Sullivan Kathleen E.
Published: December 2020

Aims: This study was undertaken to examine how a layperson is likely to interpret genetic information delivered in a clinical setting. Methods: A novel survey was designed to engage the reader in a simulated discussion of heritability as it might relate to human disease. The survey took approximately 5 min to administer. 307 individuals of different backgrounds completed the survey in the outpatient waiting room on their cell phone. Results: Overall, basic knowledge of inheritance and the concepts of heredity scored very well in the study cohort. Both knowledge and interpretation questions were answered correctly more often than not. There was generally no association between the scores on survey and gender or age. Conclusions: People recognize the basic concepts of heritability but struggle with real-life interpretations and more nuanced concepts of heredity.
Comparison of European Clinical Guidelines on the Management of Alcohol Use Disorders
Authors: Drummond Colin , Hillyard Miriam , Leonhardt Marja , Wurst Frieder , Dom Geert , Mann Karl , Bramness Jørgen G.
Published: December 2020

Background: Alcohol is a leading cause of morbidity and mortality in the European region, and tackling the harmful use of alcohol is a public health priority. Most countries in the region have national strategies for treating alcohol use disorders (AUD), but there is significant between-country variation. Objectives: This study aimed to compare clinical guidelines for the management of AUD from countries of the European region and to determine whether countries’ relative wealth or quality of their health systems had affected the guidelines. Methods: A survey was conducted of 24 countries. The survey encompassed how AUD clinical guidelines were researched, the range and expertise of contributors, which topics of AUD treatment were included, the definition of a “standard drink” used, and the publishing, funding, endorsement, and dissemination of the guideline. Results: Twenty-one of the 24 countries surveyed had a clinical guideline for AUD. All guidelines were underpinned by a literature review, and psychiatrists were the professional group most commonly involved in producing them. Most of the guidelines covered typical cornerstones of AUD care such as treatment of alcohol dependence, pharmacotherapy for relapse prevention, and detoxification. Definitions of a “standard drink” ranged from 8 to 20 grams of ethanol. Governments or governmental bodies were the main publishers and funders of guidelines, and the vast majority of guidelines were freely available online. There were no statistically significant effects of GDP, GDP per capita, or World Health Organization’s World Health Report rankings on whether countries were more likely to have an AUD clinical guideline, to have performed a systematic literature review, or to have involved service users in producing their guideline. Conclusions: The results of this survey reflect widespread good practice in producing AUD clinical guidelines across European countries. Regional research collaborations could offer significant time and cost savings in producing the evidence base from which guidelines are then written.
Can Diet Influence the COVID-19 Mortality Rate?
Authors: Avery Amanda
Published: December 2020

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.
Chronisch-thromboembolische pulmonale Hypertonie: Strukturiertes körperliches Training nach pulmonaler Endarteriektomie
Authors: Schmidt Magdalena , Spielmanns Marc
Published: December 2020

Background: Data on exercise training in chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA) as well as data on clinical and haemodynamic changes shortly after PEA are lacking. Objective: The objective of this prospective study was to analyse the safety, feasibility, and the effectiveness of combined supervised inpatient rehabilitation in patients with CTEPH directly after PEA. Methods: CTEPH patients started a 19-week rehabilitation program (3 weeks as inpatients and continued at home for another 16 weeks) with supervised exercise training as follow-up treatment shortly after PEA. Haemodynamics were assessed by right heart catheterisation before PEA and 22 weeks after PEA. Non-invasive assessments as transthoracic echocardiography and 6-min walking distance (6MWD) were performed before PEA and after 3 (that is, beginning of rehabilitation), 6, and 22 weeks following PEA. Adverse events were recorded throughout the study. Results: Forty-five CTEPH patients were included (49% female, 57.6 ± 12.4 years old, 60% WHO functional class III). Rehabilitation was started 3.3 ± 0.9 weeks after PEA. Exercise training was well tolerated in all patients without severe side effects. Haemodynamics measured by right heart catheterisation significantly improved from pre-PEA to 22 weeks post-PEA in cardiac output (+1.2 ± 1.5 L/min, 33.4%, p = 0.001) and mean pulmonary arterial pressure (-19 ± 13 mm Hg, –39.6%, p < 0.0001). Right heart size measured by echocardiography, 6MWD, quality of life, and oxygen saturation significantly improved not only within the first 3 weeks after PEA but also during the following 19 weeks of exercise training. Conclusions: Supervised exercise training was feasible as early follow-up treatment after PEA. Further controlled studies are needed to discriminate the effects of PEA and early follow-up rehabilitation. Trial Registration: The study was registered at clinicaltrials.gov (NCT01393327) on July 13, 2011. The study start date was January 2010, and completion date was December 2013.
Facetas do direito administrativo chinês: a reforma de 2014 da lei do processo administrativo ― a justiça administrativa de segurança pública ― o sistema de cartas e visitas
Authors: Frota Hidemberg Alves da
Published: December 2020

Com esteio no exame da legislação da RPC, combinado com a análise da literatura especializada de língua inglesa (constituída, em sua maioria, por artigos científicos de juristas de nacionalidade ou ascendência chinesa), o presente artigo científico visa a familiarizar a comunidade jurídica de língua portuguesa com facetas peculiares ao Direito Administrativo chinês, concernentes (1) às fontes normativas que influenciam a modelação da legislação administrativista, (2) a aspectos relevantes da reforma de 2014 da Lei do Processo Administrativo (LPA), (3) à Justiça Administrativa e às prisões administrativas, a título de longa manus do Sistema de Segurança Pública e do Direito Administrativo Sancionador, e (4) ao sistema de cartas e visitas (xinfang zhidu), como não apenas serviço formal de ouvidoria governamental e partidária, mas também instância informal de reforma de decisões administrativas e judiciais.
Análise comparada das leis gerais de processo administrativo da Espanha e do Brasil à luz da sustentabilidade
Authors: Souza Alisson de Bom de
Published: December 2020

Este artigo analisa comparativamente as leis gerais de processo administrativo da Espanha e do Brasil utilizando como marco teórico o paradigma da sustentabilidade. Nesse aspecto, em um primeiro momento, verifica-se a relevância da atividade administrativa estatal processualizada e, por conseguinte, a capacidade organizatória sob o cenário jurídico-político das iniciativas legislativas nos Estados espanhol e brasileiro. Posteriormente, apresenta-se o marco teórico da sustentabilidade e seu(s) ponto(s) de interseção com o processo administrativo, especialmente o normatizado na Espanha e no Brasil.
Títulos de Desenvolvimento Social: utilizando a lógica do mercado de capitais para financiar políticas públicas no Brasil
Authors: Schiefler Gustavo Henrique Carvalho , Adib Luccas Augusto Nogueira
Published: December 2020

Este artigo analisa os Títulos de Desenvolvimento Social, instrumento jurídico destinado ao investimento e financiamento de políticas públicas por meio do qual o Estado ressarci e remunera investidores em razão do atingimento de resultados em projetos de impacto social. Além de apresentar as linhas básicas deste instituto, este artigo também identifica as experiências internacionais existentes e oferece uma proposta de estruturação jurídica para a sua implementação no Brasil.
Caso Simelane: o controle judicial dos atos de nomeação expedidos pelo chefe do Poder Executivo à luz do critério das considerações relevantes e do princípio da racionalidade
Authors: Frota Hidemberg Alves da
Published: December 2020

Este artigo pretende difundir subsídios teóricos hauridos do julgamento do processo judicial Democratic Alliance v. President of South Africa and Others (caso Simelane). Analisam-se as peculiaridades desse caso concreto, os principais argumentos esposados pela Suprema Corte de Apelação e pela Corte Constitucional da África do Sul, o posicionamento da doutrina sul-africana, o contexto subjacente do Direito Administrativo e do Direito Constitucional sul-africanos contem­porâneos e o seu diálogo com o Direito Administrativo Comparado e com a história do Direito sul-africano. Ao fim, inspira-se em tal julgado para propor a adoção do princípio da racionalidade e do critério das considerações relevantes como balizas para o controle, pelo Poder Judiciário brasileiro, de nomeações que consubstanciam atos de natureza político-governamental ou análoga.
Análise Jurídica da Gestão de Terras Devolutas Localizadas na Faixa de Fronteira
Authors: Caramês Brenda Rocha , Olivio Karoline Araujo , Fischer Luly Rodrigues da Cunha
Published: December 2020

O presente artigo apresenta os resultados da pesquisa sobre o instituto das Terras Devolutas, com foco naquelas situadas em faixa de fronteira, por meio da análise doutrinária, assim como através dos acórdãos publicados pelo Superior Tribunal de Justiça (STJ) e referentes ao tema. Busca-se compreender o entendimento desta Corte em relação aos seguintes questionamentos: os imóveis localizados na faixa de fronteira, apenas por estarem localizados nesta faixa, são necessariamente classificados como bens da União? E ainda, é possível a ocorrência de usucapião na faixa de fronteira?
Das Demokratieprinzip
Authors: Schmidt-Aßmann Eberhard
Published: December 2020

Este artigo demonstra a precariedade do tratamento do princípio democrático nas obras gerais de direito administrativo alemão da atualidade e propõe uma sistemática para o tratamento do princípio no campo doutrinário.
A ineficiência do atual modelo de responsabilização civil do Estado no Brasil e a necessidade de prevenção de danos
Authors: Faria Luzardo
Published: December 2020

O objetivo deste trabalho é analisar o atual modelo de responsabilização civil do Estado adotado pelo ordenamento jurídico brasileiro, salientando, inicialmente, três aspectos que demonstram sua ineficiência: (i) as limitações financeiras do Estado e o argumento da reserva do possível, que pode servir como fato excludente da responsabilidade; (ii) o regime de precatórios, que inviabiliza a adequada satisfação dos créditos judiciais reconhecidos aos cidadãos em face da Fazenda Pública; (iii) a dificuldade de indenizar danos extrapatrimoniais causados a direitos fundamentais. Embora a doutrina tradicional sempre tenha considerado o dano como elemento essencial do instituto da responsabilidade civil do Estado, defende-se que, seguindo o que já foi feito no âmbito do Direito Civil e do Direito Ambiental, essa matéria deve passar por uma revisão nesse ponto. Por fim, entende-se pela necessidade de aplicação, ao Direito Administrativo brasileiro, das tutelas contra o ilícito (tutela inibitória e tutela de remoção do ilícito), previstas, inovadoramente, no art. 497, parágrafo único, do CPC.
A Administração Pública patrocinadora: o contrato de patrocínio como instrumento de concretização do interesse público.
Authors: Alves Diego Prandino
Published: December 2020

O presente artigo investiga o contrato de patrocínio celebrado pela Administração Pública com particulares, visando ao incentivo de iniciativas privadas de interesse público. Inicialmente, traça uma breve definição e caracterização do patrocínio, bem como pontua algumas as diretrizes da atividade publicitária no âmbito da Administração Pública. A partir desses conceitos, caracteriza o patrocínio ativo da Administração Pública como instrumento de consecução do interesse público a ser satisfeito no caso concreto, podendo ser utilizando com finalidades de marketing comercial, de fomento social ou de legitimação da atividade administrativa. Em conclusão, ressalta que a atuação patrocinadora da Administração constitui meio legítimo e relevante de concretização da atividade administrativa e do interesse público.
O papel das organizações da sociedade civil (OSC) na contemporaneidade
Authors: Gomes Camila Paula de Barros
Published: December 2020

O artigo trata da relação entre o Poder Público e o Terceiro Setor, a partir da análise da Lei 13.019/14, conhecida como Marco do Terceiro Setor. Analisa a importância da aproximação entre sociedade civil e Estado e a relevância do fomento às atividades privadas de utilidade pública. Detalhamse os mecanismos que possibilitam a formação de vínculos entre Administração Pública e entidades sem fins lucrativos, bem como destaca-se a importância do controle sobre as referidas entidades. Por fim, verifica-se a manutenção das qualificações de organização social e organização da sociedade civil de interesse público no contexto do Marco do Terceiro Setor.
A Administração Pública consensual: novo paradigma de participação dos cidadãos na formação das decisões estatais
Authors: Faleiros Júnior José Luiz de Moura
Published: December 2020

O trabalho investiga os novos rumos do Direito Administrativo brasileiro, especialmente no que tange ao controle da Administração Pública na formação do consenso para a tomada de decisões, com os olhares voltados à importância de se compreender a passagem de uma viciosa relação de supremacia a uma valorosa relação de ponderação, que marca o atual estágio evolutivo da interação entre a sociedade e o Estado para a implementação do fundamento constitucional da cidadania a partir do acolhimento do princípio da soberania popular. Após um breve escorço histórico sobre as recentes reformas do Estado, analisar-se-á o tema discutido a partir da propositura de um modelo de Administração Pública que se ajuste às exigências da sociedade moderna hipercomplexa, fomentando a discussão sobre o arquétipo capaz de propiciar uma gestão eficiente, baseada em mecanismos de governança e de tomada de decisões com participação democrática, a partir da lógica do consenso.
Duração de convênios administrativos: aspectos gerais e o caso dos convênios de regulação de serviços de saneamento básico por consórcio público
Authors: Marrara Thiago
Published: December 2020

O artigo cuida da figura dos convênios administrativos no Brasil, apresenta seus elementos de identificação e examina seu prazo de duração. Conclui-se que os prazos restritivos de duração de contratos de prestação de serviços da Lei Geral de Licitações não se aplicam aos ajustes cooperativos. Em seguida, trata-se do convênio firmado com consórcios públicos para fins de regulação de saneamento básico e mostra-se que existe discricionariedade do administrador público para definir seu prazo de duração, não havendo que se estender as restrições dos contratos administrativos instrumentais aos convênios do gênero.