bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training improves adipose tissue metabolism and vasculature regardless of baseline glucose tolerance and sex
Authors: Honkala Sanna Maria , Motiani Piryanka , Kivelä Riikka , Hemanthakumar Karthik Amudhala , Tolvanen Erik , Motiani Kumail Kumar , Eskelinen Jari-Joonas , Virtanen Kirsi A , Kemppainen Jukka , Heiskanen Marja Anneli , Löyttyniemi Eliisa , Nuutila Pirjo , Kalliokoski Kari K , Hannukainen Jarna Christina
Published: August 2020

Introduction

We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex.

Research design and methods

26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4–6×30 s at maximum effort) and MICT (40–60 min at 60% of maximal aerobic capacity (VO2peak)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation.

Results

Training increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO2peakand VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT.

Conclusions

Short-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants.
Novel subgroups of type 2 diabetes and their association with microvascular outcomes in an Asian Indian population: a data-driven cluster analysis: the INSPIRED study
Authors: Anjana Ranjit Mohan , Baskar Viswanathan , Nair Anand Thakarakkattil Narayanan , Jebarani Saravanan , Siddiqui Moneeza Kalhan , Pradeepa Rajendra , Unnikrishnan Ranjit , Palmer Colin , Pearson Ewan , Mohan Viswanathan
Published: August 2020

Introduction

Type 2 diabetes is characterized by considerable heterogeneity in its etiopathogenesis and clinical presentation. We aimed to identify clusters of type 2 diabetes in Asian Indians and to look at the clinical implications and outcomes of this clustering.

Research design and methods

From a network of 50 diabetes centers across nine states of India, we selected 19 084 individuals with type 2 diabetes (aged 10–97 years) with diabetes duration of less than 5 years at the time of first clinic visit and performed k-means clustering using the following variables: age at diagnosis, body mass index, waist circumference, glycated hemoglobin, serum triglycerides, serum high-density lipoprotein cholesterol and C peptide (fasting and stimulated). This was then validated in a national epidemiological data set of representative individuals from 15 states across India.

Results

We identified four clusters of patients, differing in phenotypic characteristics as well as disease outcomes: cluster 1 (Severe Insulin Deficient Diabetes, SIDD), cluster 2 (Insulin Resistant Obese Diabetes, IROD), cluster 3 (Combined Insulin Resistant and Deficient Diabetes, CIRDD) and cluster 4 (Mild Age-Related Diabetes, MARD). While SIDD and MARD are similar to clusters reported in other populations, IROD and CIRDD are novel clusters. Cox proportional hazards showed that SIDD had the highest hazards for developing retinopathy, followed by CIRDD, while CIRDD had the highest hazards for kidney disease.

Conclusions

Compared with previously reported clustering, we show two novel subgroups of type 2 diabetes in the Asian Indian population with important implications for prognosis and management. The coexistence of insulin deficiency and insulin resistance seems to be peculiar to the Asian Indian population and is associated with an increased risk of microvascular complications.
Rift valley fever: diagnostic challenges and investment needs for vaccine development
Authors: Petrova Velislava , Kristiansen Paul , Norheim Gunnstein , Yimer Solomon A
Published: August 2020

Rift valley fever virus (RVFV) is a causative agent of a viral zoonosis that constitutes a major clinical burden in wild and domestic ruminants. The virus causes major outbreaks in livestock (sheep, goats, cattle and camels) and can be transmitted to humans by contaminated animal products or via arthropod vectors. Human-to-human transmission has not been reported to date, but spill-over events from animals have led to outbreaks in humans in Africa and the Arabian Peninsula. Currently, there is no licensed human vaccine against RVFV and the virus is listed as a priority pathogen by the World Health Organisation (WHO) due to the high epidemic potential and the lack of effective countermeasures. Multiple large RVFV outbreaks have been reported since the virus was discovered. During the last two decades, over 4000 cases and ~1000 deaths have been reported. The lack of systematic surveillance to estimate the true burden and incidence of human RVF disease is a challenge for planning future vaccine efficacy evaluation. This creates a need for robust diagnostic methodologies that can be deployed in remote regions to aid case confirmation, assessment of seroprevalence as well as pathogen surveillance required for the different stages of vaccine evaluation. Here, we perform comprehensive landscaping of the available diagnostic solutions for detection of RVFV in humans. Based on the identified gaps in the currently available in-house and commercially available methods, we highlight the specific investment needs for diagnostics that are critical for accelerating the development of effective vaccines against RVFV.
Lifestyle medicine for type 2 diabetes: practice-based evidence for long-term efficacy of a multicomponent lifestyle intervention (Reverse Diabetes2 Now)
Authors: Pot Gerda K , Battjes-Fries Marieke CE , Patijn Olga N , van der Zijl Nynke , Pijl Hanno , Voshol Peter
Published: August 2020

Introduction

A wealth of evidence supports short-term efficacy of lifestyle interventions in type 2 diabetes (T2D). However, little is known about long-term effects of lifestyle interventions in real-life settings.

Methods

This observational, single-arm study evaluated long-term impact of ‘Voeding Leeft: Reverse-Diabetes2-Now’, a 6-month multicomponent lifestyle programme, on glycaemic control and glucose-lowering medication (GLmed) use, other T2D parameters and quality of life in 438 T2D participants at 6, 12, 18 and 24 months using paired sample t-tests, χ2and generalised linear models.

Results

At 24 months, 234 participants provided information on GLmed and HbA1c (‘responders’). 67% of the responders used less GLmed, and 28% ceased all GLmed. Notably, 71% of insulin users at baseline (n=47 of 66 insulin users) were off insulin at 24 months. Mean HbA1c levels were similar at 24 months compared with baseline (55.6±12.8 vs. 56.3±10.5 mmol/mol, p=0.43), but more responders had HbA1c levels ≤53 mmol/mol at 24 months (53% vs 45% at baseline). Furthermore, triglyceride levels (−0.34±1.02 mmol/L, p=0.004), body weight (−7.0±6.8 kg, p<0.001), waist circumference (−7.9±8.2 cm, p<0.001), body mass index (−2.4±2.3 kg/m2, p<0.001) and total cholesterol/high-density lipoprotein (HDL) ratio (−0.22±1.24, p=0.044) were lower, while HDL (+0.17 ± 0.53 mmol/L, p<0.001) and low-density lipoprotein-cholesterol levels (+0.18 ± 1.06 mmol/L, p=0.040) were slightly higher. No differences were observed in fasting glucose or total cholesterol levels. Quality of life and self-reported health significantly improved.

Conclusion

This study indicates robust, durable real-life benefits of this lifestyle group programme after up to 24 months of follow-up, particularly in terms of medication use, body weight and quality of life in T2D patients.
Cardiorespiratory fitness on a treadmill in an adult cystic fibrosis population
Authors: Torvanger Ole , Os Audun , Skjonsberg Ole Henning , Edvardsen Elisabeth
Published: August 2020

Objectives

(1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO2peak) and forced expiratory volume in 1 s (FEV1).

Methods

A total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO2peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured.

A low CRF was defined as a VO2peak <80% of predicted, ventilatory limitation was defined as a breathing reserve <15%, exercise hypoxaemia was defined as an oxygen saturation <88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV1and VO2peak were calculated using linear regression.

Results

The VO2peak was 40.6±11.5 and 35.2±8.9 mL kg−1min−1, which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO2peak was moderately affected by age, for men (r=−0.36, p<0.001) and women (r=−0.53, p<0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO2peak and FEV1was r=0.64 (p<0.001). In participants with a low CRF, FEV1ranged from 20% to 112% of predicted.

Conclusions

The correlation between VO2peak and FEV1was moderate. The majority of the tests resulted in a VO2peak within normal limits. Interestingly, 44% of the tests with a low VO2peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients.
Alien species of Mediterranean origin in the Baltic Sea Region: current state and risk assessment
Authors: Dobrzycka-Krahel Aldona , Medina-Villar Silvia
Published: August 2020

Due to globalization and climate warming, the introduction and establishment of alien species has increased in recent years. The Mediterranean Sea Region (MSR) has not been explored as a common donor of alien species to the Baltic Sea Region (BSR); however, in the context of global warming, the BSR could be more suitable for alien species from the MSR. We evaluated the alien species of Mediterranean origin present in the BSR, with emphasis on aggressive, aquatic and terrestrial species spread in at least two countries of the BSR. Introduction pathways and the year of first record in the BSR were assessed for Mediterranean species. Using an analytical hierarchy process, we also performed a risk assessment for aggressive Mediterranean species in the BSR. In total, 6145 alien species were recorded in the BSR, but only 3033 species were verified. For 292 of these species, there is evidence of impact in the BSR, 10 of these (3.4%) are native to the MSR (six animals (Alphitophagus bifasciatus, Chrysolina americana, Tenebrio molitor, Limax maximus, Oxychilus draparnaudi, and Limacus flavus) and four plants (Linaria repens, Veronica filiformis, Prunus cerasifera, and Viola odorata)). Based on the risk assessment, eight of them represent moderate risk (L. flavus, L. maximus, O. draparnaudi, T. molitor, L. repens, V. filiformis, V. odorata, and P. cerasifera). In total, 715 freshwater and terrestrial species are spread in at least two countries of the BSR: 131 of them (18.3%) are of Mediterranean origin, all of them are terrestrial species (123 plants and eight animals). In general, Mediterranean plants were recorded earlier than animals in the BSR, as most of the plants were recorded in the years 1651–1750 and 1801–1900. Seven of the eight Mediterranean animals were introduced as contaminants of food, plants, or nursery material. Most of the Mediterranean plants in the BSR escaped from agriculture or horticulture (46.1%) or were transported as contaminants on animals or as seed contaminants (33.6%). This study is a first evaluation of the flux of species from the MSR to the BSR and will help the stakeholders to make decisions to prevent and control alien species in the BSR.
Statistical methods applied to the search of sterile neutrinos
Authors: Agostini Matteo , Neumair Birgit
Published: August 2020

The frequentist statistical methods applied to search for short-baseline neutrino oscillations induced by a sterile neutrino with mass at the eV scale are reviewed and compared. The comparison is performed under limit setting and signal discovery scenarios, considering both when an oscillation would enhance the neutrino interaction rate in the detector and when it would reduce it. The sensitivity of the experiments and the confidence regions extracted for specific data sets change considerably according to which test statistic is used and the assumptions on its probability distribution. A standardized analysis approach based on the most general kind of hypothesis test is proposed.
THE ENERGY–POLLUTION–HEALTH NEXUS: A PANEL DATA ANALYSIS OF LOW- AND MIDDLE-INCOME ASIAN COUNTRIES
Authors: TAGHIZADEH-HESARY FARHAD , RASOULINEZHAD EHSAN , YOSHINO NAOYUKI , CHANG YOUNGHO , TAGHIZADEH-HESARY FARZAD , MORGAN PETER J.
Published: August 2020

Increased consumption of nonrenewable energy sources may lead to more air pollution, resulting in negative health impacts in a society. The main purpose of this study is to investigate the relationship between fossil fuel energy consumption and health issues using generalized method of moments estimation technique for data from 18 Asian countries (both low- and middle-income) over the period 1991–2018. The findings demonstrate that fossil fuel energy consumption increases the risk of lung and respiratory diseases. In addition, the results demonstrate the significant effect of CO2 emissions and fossil fuel consumption on undernourishment and death rates. Furthermore, we find that increases in the gross domestic product per capita and healthcare expenditure may help reduce undernourishment and death ratio. The conclusion recommends that diversification of energy in low- and middle-income countries from too much reliance on fossil fuels to more renewable energy sources can improve energy insecurity, at the same time reduce greenhouse gas emissions and minimize the negative impacts on human health.
VIETNAM’s INCOMPLETE EXCHANGE RATE PASS-THROUGH
Authors: XUAN PHAM THI THANH
Published: August 2020

We measure exchange rate pass-through (ERPT) for Vietnam and find that Vietnam’s ERPT is low, incomplete, and time varying. Our results also indicate that during appreciation periods ERPT is modest, but that during downturns ERPT effects are much larger. Moreover, our results indicate that the flexible exchange rate regime has successfully anchored the ERPT.
Visible-light photocatalytic activity of Fe@TiO2 core–shell composite synthesized by sol–gel method
Authors: Yeh Min Yen , Yang Tzu Yuan , Wu Tsung Chi , Lee Shiow Yueh , Chang Shun Hsyung
Published: August 2020

Core–shell structure [Formula: see text] was synthesized by sol–gel method. The photocatalytic degradation of methylene blue over the [Formula: see text] reached 98% under UV light irradiation within 5 h. The band gap of the core–shell [Formula: see text] was found to have a redshift through a sintering treatment. The redshifted [Formula: see text] had a good performance of methylene-blue degradation (reaching 85%) under visible light irradiation for 5 h.
Simulation in design air spindle with orifice and distribution grooves
Authors: Thang Vu Toan , Duc Truong Minh , Dat Nguyen Trong , Trung Nguyen Thanh , Tung Vu Thanh
Published: August 2020

This paper presents some results of simulation using ANSYS CFX software in design air spindle which has the structure in the form of orifice and grooves to ensure uniform pressure distribution and avoiding air hammer; it is also easy to manufacture and reduces costs. The results of simulation are good in investigating operation of air-spindle which is changed some parameters to find the optimal working mode for the air spindle with speed in the range of 5000–20,000 rpm.
A study on heating and determining the temperature generation on the sheet metal before the deep drawing process
Authors: Luyen The-Thanh , Mac Thi-Bich , Banh Tien-Long , Nguyen Duc-Toan
Published: August 2020

Thermal-assisted machining (TAM) is an effective processing solution to improve productivity and product quality made from materials with high strength and hardness. This method is widely used in nonchip machining such as forging, stamping, deep drawing, etc. For the method of heating on the molds, it is possible to control local heat or uniform heat on the workpiece. However, the calculation of heat capacity, heat transfer as well as the heating time to achieve the temperature on the workpiece is necessary to design suitable molds and heating system. This study focuses on a heating system that uses single-sided thermostatic heating rods to heat the molds, verify the effect of the heating time on the temperature of the workpieces and then control the temperature on the workpieces at various heat levels through a heating control system. Thereby, this study proposes to build a mathematical model between temperature and heating time on the workpiece.
The Floral Microbiome: Plant, Pollinator, and Microbial Perspectives
Authors: Vannette Rachel L.
Published: August 2020

Flowers at times host abundant and specialized communities of bacteria and fungi that influence floral phenotypes and interactions with pollinators. Ecological processes drive variation in microbial abundance and composition at multiple scales, including among plant species, among flower tissues, and among flowers on the same plant. Variation in microbial effects on floral phenotype suggests that microbial metabolites could cue the presence or quality of rewards for pollinators, but most plants are unlikely to rely on microbes for pollinator attraction or reproduction. From a microbial perspective, flowers offer opportunities to disperse between habitats, but microbial species differ in requirements for and benefits received from such dispersal. The extent to which floral microbes shape the evolution of floral traits, influence fitness of floral visitors, and respond to anthropogenic change is unclear. A deeper understanding of these phenomena could illuminate the ecological and evolutionary importance of floral microbiomes and their role in the conservation of plant–pollinator interactions.
Synthesis and Electrochemical Performance of a Homogenously Dispersed LiaMn2-x-y- ZFexCoyNizO4-dCld Lithium Ion Battery Cathode Material
Authors: Limpert Matthew , Atwater Terrill B. , Ruth Ashley L.
Published: August 2020

Lithium manganese oxide spinels are attractive materials for lithium-ion battery cathodes due to their capability for high voltage application paired with a three-dimensional conductive pathway that can allow for improved lithium insertion and deinsertion kinetics. However, this material suffers from limited cyclability as a result of the energy barriers for removing lithium from the octahedral sites and capacity fading as a result of manganese dissociation. This work incorporates a multiple doping strategy for selecting capacity distribution across various voltage regimes. The resulting electrochemical cells are able to produce useful capacity at 5.2 V, 4.7 V, 4.1 V, and 2.75 V. Additionally, materials synthesized in a laboratory setting and via large scale production via licensing with no cobalt content has resulted in capacities exceeding 200 mAh/g. These materials achieve 75% capacity retention at 3C vs. C/10 discharge down to 2.75 V.
High-Normal Preconception TSH Levels Have No Adverse Effects on Reproductive Outcomes in Infertile Women Undergoing the First Single Fresh D5 Blastocyst Transfer
Authors: Zhang Yuchao , Wu Wenbin , Liu Yanli , Guan Yichun , Wang Xingling , Jia Liting
Published: August 2020

Purpose. To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first single fresh D5 blastocyst transfer. Methods. This was a retrospective study. Euthyroid patients undergoing the first single fresh D5 blastocyst transfer from January 2018 to May 2019 were initially included. The patients were divided into a low TSH (0.27–2.5 mIU/L) group and a high-normal TSH (2.5–4.2 mIU/L) group. The reproductive outcomes were compared between the groups. Results. A total of 824 women were ultimately included, 460 of whom had serum TSH levels less than 2.5 mIU/L and 364 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.84, 0.65, 0.61, and P=0.234, 0.145, 0.083). No significant differences were observed in terms of gestational age, single live birth rates, birth weight, or birth length. Conclusion. High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first single fresh D5 blastocyst transfer. Further studies are needed to test whether the results might be applicable to a wider population.
Convergence Analysis of an Improved BFGS Method and Its Application in the Muskingum Model
Authors: Yang Tianshan , Li Pengyuan , Wang Xiaoliang
Published: August 2020

The BFGS method is one of the most effective quasi-Newton algorithms for minimization-optimization problems. In this paper, an improved BFGS method with a modified weak Wolfe–Powell line search technique is used to solve convex minimization problems and its convergence analysis is established. Seventy-four academic test problems and the Muskingum model are implemented in the numerical experiment. The numerical results show that our algorithm is comparable to the usual BFGS algorithm in terms of the number of iterations and the time consumed, which indicates our algorithm is effective and reliable.
Synthesis of Zeolite from Electrolytic Manganese Residue: Investigation on the Variation of the Propert of Zeolite during the Conversion Process
Authors: Li Changxin , Yu Yuan , Zhang Qingwu , Zhong Hong , Wang Shuai
Published: August 2020

In this study, the cation exchange capacity (CEC); phosphate immobilization capacity (PIC); and chemical, mineralogical, and morphological characteristics of the synthesized electrolytic manganese residue (EMR) based zeolite (EMRZ) were systematically investigated during the synthesis process. By varying synthesis conditions, different zeolites with different purity were generated, and it was proven that a lower Si/Al ratio, relatively higher temperature, and relatively longer time favored the synthesis of zeolite. Besides, the decrease in Si/Al ratio and variation within a narrow range contributed to the forming of Al rich zeolite. Meanwhile, the discrepancy of CEC and PIC of EMRZ contributed to the case in which various elements in EMRZ do have an impact on CEC (Na2O element and type of zeolite) and PIC (calcium and iron components). Moreover, the synthesis conditions were optimized and evaluated in terms of their CEC, specific surface area (SSA), and crystallinity. According to the analyses using XRD, FE-SEM, and XRF and the SSA analysis, the EMRZ (mainly zeolite A, LTA) synthesized under the optimum conditions (initial Si/Al ratio of 1.5, at 100°C, for 1.5 h) was found to be mainly composed of highly ordered cubic zeolites A crystals with a Si/Al ratio of 1.02 and a CEC of 3.45 meq/g.
Numerical Simulation of Strength, Deformation, and Failure Characteristics of Rock with Fissure Hole Defect
Authors: Chen Shaojie , Xia Zhiguo , Feng Fan
Published: August 2020

Using discrete element software, namely, particle flow code as two‐dimensional program (PFC2D), two types of models were established: vertical fissure hole combination and horizontal fissure hole combination with ratios of major and minor axis of ellipse being 1, 1.2, 1.5, 2, and 3, which corresponded to a total of ten samples. The failure mode, mechanical behavior, and stress state before and after crack generation in elliptical hole crack combination models with different ratios of major and minor axis were analyzed. The crack development, stress field evolution, and acoustic emission characteristics of the vertical fissure model and horizontal fissure model were studied at the optimized ratio of major and minor axis of ellipse being 1.5. The results showed that elliptical hole fissure with different ratios of major and minor axis resulted in the decrease in the strength and elastic modulus of rock and increase in the peak strain of rock. The effect of the horizontal fissure model on the peak strength, peak strain, and elastic modulus of rock was found to be greater than that of the vertical fissure hole model. Ellipses with different ratios of major and minor axis in various models slightly influenced the rock failure modes, and their failure modes corresponded to tensile shear failure and tensile failure. Before crack formation, the tensile stress concentration areas of each model were, respectively, distributed at the upper and lower ends of the vertical fissure and the major axis of ellipse, and the compressive stress concentration areas were distributed at both ends of the major axis of ellipse and the fissure in the horizontal direction. After the model failed, the compressive stress concentration areas of the vertical fissure model and the horizontal fissure model transferred to the left upper part and the right upper part of the model along the left end of the hole and the right end of the fissure, respectively. When the ratio of major and minor axis of ellipse was 1.5, cracks in the vertical model and the horizontal model of fissure developed along the axial direction at the ends of cracks and holes, respectively, and then secondary cracks were generated at the ends of left and right sides. The maximum compressive stress in each stage of the vertical fissure model was greater than that of the horizontal fissure model, and when the model was damaged, its stress release was more.
miR‐30e‐3p Promotes Cardiomyocyte Autophagy and Inhibits Apoptosis via Regulating Egr‐1 during Ischemia/Hypoxia
Authors: Su Bo , Wang Xiantao , Sun Yuhan , Long Manyun , Zheng Jing , Wu Wenhao , Li Lang
Published: August 2020

Background. Microvascular obstruction (MVO) can result in coronary microcirculation embolism and myocardial microinfarction. Myocardial injury induced by MVO is characterized by continuous ischemia and hypoxia of cardiomyocytes. Autophagy and apoptosis are closely associated with various cardiovascular diseases. Based on our previous study, we observed a decrease in miR‐30e‐3p expression and an increase in Egr‐1 expression in a rat coronary microembolization model. However, the specific function of miR‐30e‐3p in regulating autophagy and apoptosis in an ischemia/hypoxia (IH) environment remains to be deciphered. We exposed cardiomyocytes to an IH environment and then determined whether miR‐30e‐3p was involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by regulating Egr‐1. Methods. Cardiomyocytes were isolated from rats for our in vitro study. miR‐30e‐3p was either overexpressed or inhibited by transfection with lentiviral vectors into cardiomyocytes. 3‐Methyladenine (3‐MA) was used to inhibit autophagy. RT‐qPCR and western blotting were used to determine the expression levels of miR‐30e‐3p, Egr‐1, and proteins related to the autophagy and apoptosis process. Autophagic vacuoles and autophagic flux were evaluated using transmission electron microscopy (TEM) and confocal microscopy, respectively. Cardiomyocyte viability was evaluated using the MTS assay. Cell injury was assessed by lactate dehydrogenase (LDH) leakage, and apoptosis was determined by flow cytometry. Results. Both miR‐30e‐3p expression and autophagy were significantly inhibited, and apoptosis was increased in cardiomyocytes after 9 hours of IH exposure. Overexpression of miR‐30e‐3p increased autophagy and inhibited apoptosis, as well as suppressed Egr‐1 expression and decreased cell injury. In addition, inhibition of miR‐30e‐3p reduced autophagy and increased apoptosis and cell injury. Conclusions. miR‐30e‐3p may be involved in promoting cardiomyocyte autophagy and inhibiting apoptosis by indirectly regulating Egr‐1 expression in an IH environment.
The Prognosis Analysis of Liver Cirrhosis with Acute Variceal Bleeding and Validation of Current Prognostic Models: A Large Scale Retrospective Cohort Study
Authors: Zhao Yan , Ren Mudan , Lu Guifang , Lu Xinlan , Yin Yan , Zhang Dan , Wang Xin , Ma Wenhui , Li Yarui , Cai Guohong , Lin Yiguang , He Shuixiang
Published: August 2020

Background. Acute variceal bleeding is a major cause of death in liver cirrhosis. This large scale retrospective cohort study aims to analyze the prognosis of patients with cirrhosis and acute variceal bleeding and to validate the current prognostic models. Methods. Patients with cirrhosis and acute variceal bleeding were enrolled from Jan 2019 to March 2020. The independent prognostic factors for in‐hospital death were identified by logistic regression analyses. Area under curves (AUCs) was compared among Child‐Pugh, cirrhosis acute gastrointestinal bleeding (CAGIB) score, and model for end‐stage liver disease (MELD) and neutrophil‐lymphocyte ratio (NLR) scores. Results. Overall, 379 patients with liver cirrhosis and acute variceal bleeding were consecutively evaluated. The majority of the patients were males (59.1%) and the mean age of all patients were 53.7 ± 1.3 years (range 14‐89). Hepatitis B virus (HBV) was the most common underlying cause of liver cirrhosis (54.1%). 72 (19%) patients had hepatocellular carcinoma. Multivariate logistic regression analyses showed that age, HCC, WBC, total serum bilirubin, serum creatinine, and ALT were independently associated with in‐hospital death. And the odds ratios (ORs) for in‐hospital death were 1.066 (95% CI 1.017‐1.118, P = 0.008), 7.19 (95% CI 2.077‐24.893, P = 0.001), 1.123 (95% CI 1.051‐1.201, P = 0.001), 1.014 (95% CI 1.005‐1.023, P = 0.003), 1.012 (95% CI 1.004‐1.021, P = 0.006), and 1.005 (95% CI 1.000‐1.009, P = 0.036), respectively. In the whole cohort with HCC patients, the AUCs of Child‐Pugh, CAGIB, MELD and NLR scores were 0.842 (95% CI 0.801‐0.878), 0.840 (95% CI 0.799‐0.876), 0.798 (95% CI 0.754‐0.838), and 0.688 (95% CI 0.639‐0.735), respectively. The differences were statistically significant between Child‐Pugh and NLR scores (P = 0.0118), and between CAGIB and NLR scores (P = 0.0354). Conclusion. Child‐Pugh and CAGIB scores showed better predictive performance for prognosis of patients with cirrhosis and acute variceal bleeding than NLR scores.
Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway
Authors: Chen Jincan , Wang Jie , Deng Yuanyuan , Wang Tao , Miao Tifang , Li Chengpeng , Cai Xianhong , Liu Ying , Henri Justin , Chen Lanmei
Published: August 2020

Two new Ru(II) complexes containing O, O-chelated ligands, Ru(dip)2(SA) (Ru-1) and Ru(dmp)2(SA) (Ru-2) (dip = 4,7-diphenyl-1,10-phenanthroline; dmp = 2,9-dimethyl-1,10-phenanthroline; SA = salicylate) were synthesized to evaluate their cytotoxicity in vitro. These complexes were found to exhibit moderate antitumor activity to different types of human cancers, including A549 (human lung carcinoma), MCF-7 (breast cancer), HeLa (human cervical cancer), and HepG2 (human hepatocellular carcinoma) cell lines, but displayed low toxicity to human normal cell lines BEAS-2B (immortalized human bronchial epithelial cells) when compared with that of cisplatin. Further studies revealed that these complexes could induce apoptosis in A549 cells, including activating caspase family proteins and poly (ADP-ribose) polymerase (PARP), reducing Bcl-2/Bax and Bcl-xl/Bad ratio, enhancing cellular reactive oxygen species (ROS) accumulation, triggering DNA damage, decreasing mitochondrial membrane potential (MMP), and leading cytochrome c release from mitochondria. Notably, complex Ru-1 showed low toxicity to developing zebrafish embryos. The obtained results suggest that these new synthetic complexes have the potential to be developed as low-toxicity agents for lung cancer treatment.
Retroperitoneal Ectopic Location of an Intrauterine Device Revealed by Renal Colic: An Exceptional Case
Authors: Ziani Idriss , Boualaoui Imad , Ibrahimi Ahmed , El Sayegh Hachem , Benslimane Lounis , Nouini Yassine
Published: August 2020

The intrauterine device (IUD) is one of the most effective contraceptive methods. Its Pearl Index is less than 1 per 100 women. It is the most used method around the world: about 100 million users. However, its insertion can cause certain complications, such as infection, expulsion, or perforation essentially when the rules of use are poorly applied. Perforation remains exceptional but one of the most serious complications. Indeed, after a perforation, the IUD could be located in different neighboring organs. We report a new case of IUD ectopic location in the peritoneal cavity, which was diagnosed 7 years after the insertion and as part of the renal colic assessment. The surgery was performed to remove the IUD which was embedded in the peritoneum and compresses the ureter and causes dilation upstream. To our knowledge, this is the first case reported in the literature of an ectopic location in the retroperitoneal space of an intrauterine device.
FPGA Implementation of A∗ Algorithm for Real-Time Path Planning
Authors: Zhou Yuzhi , Jin Xi , Wang Tianqi
Published: August 2020

The traditional A∗ algorithm is time-consuming due to a large number of iteration operations to calculate the evaluation function and sort the OPEN list. To achieve real-time path-planning performance, a hardware accelerator’s architecture called A∗ accelerator has been designed and implemented in field programmable gate array (FPGA). The specially designed 8-port cache and OPEN list array are introduced to tackle the calculation bottleneck. The system-on-a-chip (SOC) design is implemented in Xilinx Kintex-7 FPGA to evaluate A∗ accelerator. Experiments show that the hardware accelerator achieves 37–75 times performance enhancement relative to software implementation. It is suitable for real-time path-planning applications.
Smart Radio Resource Management for Content Delivery Services in 5G and Beyond Networks
Authors: Neznik Dominik , Dobos Lubomir , Papaj Jan
Published: August 2020

In 5G networks, the spectrum allocation techniques play a very important part of the quality of content delivery services. The processes of channelling and device selection are important in the 5G technology and beyond with many access devices in networks to improve the quality of services. In this paper, we propose a method based on Fuzzy Logic, Game Theory, and Smart Method (which is a combination of Fuzzy Logic and Game Theory). These methods are suitable to improve the speed and quality of links of data routing in networks. The paper shows that effective spectrum allocation to devices is not an option but a requirement in a huge data flow environment of the wireless communications, if one wants to ensure acceptable speed and quality of the connection and to provide adequate quality of the services. Each of the selected methods for radio resource management has some advantages and disadvantages in the evaluation of results. The paper describes the process of channel allocation with different methods for IEEE 802.11xx networks that are in the focus of our research in the sphere of wireless communication. Companies use cloud computing to provide services and to share information, but there needs to be some radio resource management to effectively use the services in the wireless mobile environment because the number of different types of devices being connected to the wireless networks to create smart homes and smart cities is growing.
Prevention of Diabetic Complications by Walnut Leaf Extract via Changing Aldose Reductase Activity: An Experiment in Diabetic Rat Tissue
Authors: Abbasi Zahra , Jelodar Gholamali , Geramizadeh Bita
Published: August 2020

Background. Increased activity of aldose reductase (AR) is one of the mechanisms involved in the development of diabetic complications. Inhibiting AR can be a target to prevent diabetes complications. This study is aimed at evaluating the effect of cyclohexane (CH) and ethanol extracts (ET) of walnut leaves on AR activity in the lens and testis of diabetic rats. Methods. Fifty-six male rats classified into seven groups as control and treatment groups and treated for 30 days. The treatment groups were treated with different concentrations of ET and CH. The diabetic control (DC) group was exposed to streptozotocin. AR activity was measured in the lens and testis. The expression of AR in the testis was evaluated by the immunohistochemistry method. Results. Both extracts significantly reduced the AR activity (ng/mg of tissue protein) in the testis (0.034±0.004, 0.038±0.010, and 0.040±0.007 in the treatment groups vs. 0.075±0.007 in the DC group) and lens (1.66±0.09, 2.70±0.47, and 1.77±0.20 in the treatment groups vs. 6.29±0.48 in the DC group) of the treatment group compared to those of the DC group (P<0.05). AR expression in the testes of the treatment groups was decreased compared with that of the DC group (P<0.0001). Conclusion. Walnut leaf extracts can reduce the activity and localization of AR in the testes and its activity in the lens of diabetic rats.
Phase I Study of P-cadherin–targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors
Authors: Subbiah Vivek , Erwin William , Mawlawi Osama , McCoy Asa , Wages David , Wheeler Catherine , Gonzalez-Lepera Carlos , Liu Holly , Macapinlac Homer , Meric-Bernstam Funda , Hong David S. , Pant Shubham , Le Dao , Santos Elmer , Gonzalez Jose , Roszik Jason , Suzuki Takeaki , Subach Ruth Ann , Madden Timothy , Johansen Mary , Nomura Fumiko , Satoh Hirokazu , Matsuura Tadashi , Kajita Masamichi , Nakamura Eri , Funase Yuichi , Matsushima Satoshi , Ravizzini Gregory
Published: August 2020

Purpose:

90Y-FF-21101 is an Yttrium-90–conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors.

Patients and Methods:

The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5–25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months.

Results:

111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity.

Conclusions:

The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.
Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma
Authors: Middleton Mark R. , McAlpine Cheryl , Woodcock Victoria K. , Corrie Pippa , Infante Jeffrey R. , Steven Neil M. , Evans Thomas R. Jeffry , Anthoney Alan , Shoushtari Alexander N. , Hamid Omid , Gupta Avinash , Vardeu Antonella , Leach Emma , Naidoo Revashnee , Stanhope Sarah , Lewis Sion , Hurst Jacob , O’Kelly Ita , Sznol Mario
Published: August 2020

Purpose:

Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through a high affinity T-cell receptor (TCR) binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Here, we report a multicenter phase I/II trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism of action of tebentafusp.

Patients and Methods:

Eighty-four patients with advanced melanoma received tebentafusp. Treatment efficacy, treatment-related adverse events, and biomarker assessments were performed for blood-derived and tumor biopsy samples obtained at baseline and on-treatment.

Results:

Tebentafusp was generally well-tolerated and active in both patients with metastatic uveal melanoma and patients with metastatic cutaneous melanoma. A 1-year overall survival rate of 65% was achieved for both patient cohorts. On-treatment cytokine measurements were consistent with the induction of IFNγ pathway–related markers in the periphery and tumor. Notably, tebentafusp induced an increase in serum CXCL10 (a T-cell attractant) and a reduction in circulating CXCR3+ CD8+ T cells together with an increase in cytotoxic T cells in the tumor microenvironment. Furthermore, increased serum CXCL10 or the appearance of rash (likely due to cytotoxic T cells targeting gp100-expressing skin melanocytes) showed a positive association with patient survival.

Conclusions:

These data suggest that redirecting T cells using a gp100-targeting TCR/anti-CD3 bispecific fusion protein may provide benefit to patients with metastatic melanoma. Furthermore, the activity observed in these two molecularly disparate melanoma classes hints at the broad therapeutic potential of tebentafusp.
Autoimmun-Retinopathie im Zusammenhang mit monoklonaler Gammopathie unklarer Signifikanz: ein Fallbericht
Authors: Eton Emily A. , Abrams Gary , Kahn Naheed W. , Fahim Abigail T.
Published: August 2020

Hintergrund: Monoklonale Gammopathie unklarer Signifikanz (MGUS) ist eine Plasmazelldyskrasie und Vorstufe des Multiplen Myeloms. Okuläre Manifestationen sind bekannt, bislang wurde jedoch noch kein Zusammenhang mit einer Autoimmun-Retinopathie nachgewiesen. Fallvorstellung: Eine 57-jährige Frau stellte sich mit seit einem Jahr bestehendem progressiven, beidseitigen, peripheren Verlust des Sehvermögens, Photopsien und Nachtblindheit vor. Die Augenhintergrunduntersuchung und umfassende ergänzende Tests legten den Verdacht einer hereditären oder einer Autoimmun-Retinopathie nahe. Man stellte bei der Patientin antiretinale Antikörper gegen Carboanhydrase II- und Enolase-Proteine bei einem negativen Gen-Panel für Netzhautdystrophie fest. Die Untersuchung auf Malignität war negativ, aber bei der Patientin wurde MGUS, eine prämaligne Erkrankung, diagnostiziert. Die Patientin wurde mit Immunsuppressiva behandelt, wobei sie im Hinblick auf ihre Symptomatik und die augenmedizinischen Untersuchungen am deutlichsten auf Rituximab ansprach. Schlussfolgerung: MGUS sollte bei Patienten ohne andere autoimmune oder maligne Krankheitsprozesse als potenziell ätiologisch für eine Autoimmun-Retinopathie in Betracht gezogen werden. Eine Behandlung mit Immunsuppressiva kann bei der Begrenzung der Krankheitsprogression von Nutzen sein, und Rituximab erweist sich bei Patienten mit Retinopathie, die auf andere Wirkstoffe nicht ansprechen, als wirksam.
Psicanálise e Semiótica: situação em 2020
Authors: Beividas Waldir
Published: August 2020

Descrevo neste texto como se apresenta atualmente, a meu ver, a situação de interface entre a psicanálise de S. Freud e de J. Lacan e a semiótica europeia de A. J. Greimas. Centro a atenção em como a interface teve inícios, nos anos 1960, em decorrência da abertura da psicanálise, por Lacan, para o campo estruturalista da linguística de F. de Saussure, nos anos 1950. Registro alguns tópicos desenvolvidos na interface: (i) a questão do conceito de significante, por Lacan, com o intento de mais bem ajustá-lo frente ao sentido, significado, significação, efeitos de sentido; (ii) a questão do conceito de pulsão, na tentativa de melhor arranjo dos seus desdobramentos em patologias e nas paixões humanas, a desenhar um percurso gerativo da subjetividade inconsciente; (iii) o conceito freudiano de transferência, enfatizado por Lacan como sujeito-suposto-saber, e minha leitura dele, para ampliação de suas incidências, com o recurso da teoria semiótica das modalizações sintáxicas do discurso. A finalidade geral do texto não é outra senão evitar que a interface esmoreça, pois que imperativa, quando o que está em jogo é o desafio do melhor conhecimento possível sobre os difíceis meandros por onde flui a subjetividade humana.
Psicanálise e Semiótica Tensiva: elementos para uma abordagem semiótica dos afetos
Authors: Ravanello Tiago
Published: August 2020

O presente estudo tem por objetivo apresentar bases para uma abordagem dos afetos, conceito muito caro ao campo da clínica e da pesquisa freudiana, por uma via discursiva. O intuito principal é o de evitar, portanto, os recursos de redução biológica comuns às leituras do projeto psicanalítico que acabam por delimitar os fenômenos afetivos como o resultado de ações que se dariam no plano de um referente orgânico, imprimindo uma leitura de estilo realista ao projeto epistemológico freudiano. Para tanto, este artigo utiliza como recurso a discussão com a semiótica tensiva e o resgate de conceitos próprios aos trabalhos de Saussure, Hjelmslev e Greimas. Como resultado, é apresentado um modelo embasado na concepção de tensividade para reconstrução do modelo econômico freudiano.
L’ être humain est l’enjeu fondamental de toute démarche sémiotique
Authors: Tomasella Saverio
Published: August 2020

Dans cet article, l’auteur invite à un croisement entre psychanalyse et sémiotique. Selon son expérience, ce métissage serait fécond pour les deux disciplines. Il propose de créer une métasémiotique, qui soit une sémiotique psychanalytique à l’écoute de l’inconscient. S’appuyant sur les méthodes déjà existantes, comme la sémanalyse de Julia Kristeva et la déconstruction anasémique de Nicolas Abraham et Maria Torok, proche de la philosophie de Jacques Derrida, la démarche sémiotique tient compte des cinq polarités principales de l’inconscient, que sont le réel, l’imaginaire, le symbolique, le nécessaire et le sensible. Elle s’intéresse aux processus dynamiques de production de sens, dans et hors langage. La mise en œuvre concrète de la métasémiotique, notamment par l’étude de certaines mythologies contemporaines, a permis de repérer différentes formes de fantasmes, selon qu’ils sont créés par le sujet lui-même ou imposés par son environnement. Cette découverte est confirmée au quotidien par la pratique clinique de la psychanalyse. Elle souligne l’importance de l’écoute des spécificités individuelles et groupales, sans chercher à les écraser ou à les remplacer en imposant de l’extérieur les concepts des doctrines en vogue. En effet, les recherches métasémiotiques confirment le fondement éthique de toute démarche herméneutique, par le respect de l’être humain, de sa subjectivité singulière irréductible et de sa dignité inaliénable.