bluuebunny/crossref_metadata_2025 huggingface dataset:
FGFR2Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma
Authors: Cleary James M. , Raghavan Srivatsan , Wu Qibiao , Li Yvonne Y. , Spurr Liam F. , Gupta Hersh V. , Rubinson Douglas A. , Fetter Isobel J. , Hornick Jason L. , Nowak Jonathan A. , Siravegna Giulia , Goyal Lipika , Shi Lei , Brais Lauren K. , Loftus Maureen , Shinagare Atul B. , Abrams Thomas A. , Clancy Thomas E. , Wang Jiping , Patel Anuj K. , Brichory Franck , Vaslin Chessex Anne , Sullivan Ryan J. , Keller Rachel B. , Denning Sarah , Hill Emma R. , Shapiro Geoffrey I. , Pokorska-Bocci Anna , Zanna Claudio , Ng Kimmie , Schrag Deborah , Jänne Pasi A. , Hahn William C. , Cherniack Andrew D. , Corcoran Ryan B. , Meyerson Matthew , Daina Antoine , Zoete Vincent , Bardeesy Nabeel , Wolpin Brian M.
Published: April 2021

We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent FGFR2 fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified FGFR2 extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with FGFR2 p.H167_N173del. Expression of this FGFR2 EID in NIH3T3 cells resulted in constitutive FGFR2 activation, oncogenic transformation, and sensitivity to FGFR inhibitors. Three patients with FGFR2 EIDs were treated with Debio 1347, an oral FGFR1/2/3 inhibitor, and all showed partial responses. One patient developed an acquired L618F FGFR2 kinase domain mutation at disease progression and experienced a further partial response for 17 months to an irreversible FGFR2 inhibitor, futibatinib. Together, these findings reveal FGFR2 EIDs as an alternative mechanism of FGFR2 activation in IHCC that predicts sensitivity to FGFR inhibitors in the clinic.

Significance:

FGFR2 EIDs are transforming genomic alterations that occur predominantly in patients with IHCC. These FGFR2 EIDs are sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic.

This article is highlighted in the In This Issue feature, p. 2355
The Impact of the SARS-CoV-2 (COVID-19) Pandemic on Gastroenterology Training
Authors: Pisani Anthea , Cremers Isabelle , Ellul Pierre
Published: April 2021

Introduction: The SARS-CoV-2 (COVID-19) pandemic has brought about a radical change in our working patterns. These changes can affect the training that gastroenterology trainees undergo, especially endoscopy since these are aerosol-generating procedures. The aim of this survey was to assess the effect of the COVID-19 pandemic on gastroenterology training across the European countries. Methodology: A questionnaire was set up whereby the different elements of training were analysed. The questionnaire (online) was distributed among trainees through the National Representatives of the European Board of Gastroenterology and Hepatology. Results: In total, 86 trainees (females: 55%; mean age: 32.5 years [SD ±4.57 years]; mean training duration of 2.68 years [SD ±1.63]) from 22 different countries were recruited. From the cohort, 10.5% were considered as vulnerable for acquiring COVID-19. During their job, 4.7% acquired the infection and 26.7% were placed in quarantine. Most trainees noted that their various aspects of gastroenterology training were moderately or severely affected during the initial height of the pandemic: clinical gastroenterology training (67.4%), outpatients (75.5%), didactic teaching (88.3%), multidisciplinary team meetings (65.2%) and endoscopy training (75.6%). Later, when the number of COVID-19-related infections decreased across Europe, the above modalities returned to normal for <50% of the trainees. Conclusion: This European-wide survey has demonstrated that gastroenterology training has been severely impacted during both the initial height of the pandemic and afterwards. Furthermore, the psychological impact on trainees, in terms of training quality, duration and exposure to COVID-19, is unknown. A re-assessment of each centre training programme should be done as to ensure that a high standard of training is still being delivered.
Cystamine Treatment Fails to Prevent the Development of Pulmonary Hypertension in Chronic Hypoxic Rats
Authors: Markvardsen Lars K. , Sønderskov Lene D. , Wandall-Frostholm Christine , Pinilla Estéfano , Prat-Duran Judit , Aalling Mathilde , Mogensen Susie , Andersen Charlotte U. , Simonsen Ulf
Published: April 2021

Introduction: Pulmonary hypertension is characterized by vasoconstriction and remodeling of pulmonary arteries, leading to right ventricular hypertrophy and failure. We have previously found upregulation of transglutaminase 2 (TG2) in the right ventricle of chronic hypoxic rats. The hypothesis of the present study was that treatment with the transglutaminase inhibitor, cystamine, would inhibit the development of pulmonary arterial remodeling, pulmonary hypertension, and right ventricular hypertrophy. Methods: Effect of cystamine on transamidase activity was investigated in tissue homogenates. Wistar rats were exposed to chronic hypoxia and treated with vehicle, cystamine (40 mg/kg/day in mini-osmotic pumps), sildenafil (25 mg/kg/day), or the combination for 2 weeks. Results: Cystamine concentration-dependently inhibited TG2 transamidase activity in liver and lung homogenates. In contrast to cystamine, sildenafil reduced right ventricular systolic pressure and hypertrophy and decreased pulmonary vascular resistance and muscularization in chronic hypoxic rats. Fibrosis in the lung tissue decreased in chronic hypoxic rats treated with cystamine. TG2 expression was similar in the right ventricle and lung tissue of drug and vehicle-treated hypoxic rats. Discussion/Conclusions: Cystamine inhibited TG2 transamidase activity, but cystamine failed to prevent pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial muscularization in the chronic hypoxic rat.
Neocortical Anatomy in the South American Plains Vizcacha, Lagostomus maximus, Reveals Different Strategies in Encephalic Development among Hystricomorpha and Myomorpha Rodents
Authors: Schmidt Alejandro Raúl , Gariboldi María Constanza , Cortasa Santiago Andrés , Proietto Sofía , Corso María Clara , Inserra Pablo Ignacio Felipe , Jaime Vanina Soledad , Halperin Julia , Vitullo Alfredo Daniel , Dorfman Verónica Berta
Published: April 2021

Depending on the presence or absence of sulci and convolutions, the brains of mammals are classified as gyrencephalic or lissencephalic. We analyzed the encephalic anatomy of the hystricomorph rodent Lagostomus maximus in comparison with other evolutionarily related species. The encephalization quotient (EQ), gyrencephaly index (GI), and minimum cortical thickness (MCT) were calculated for the plains vizcacha as well as for other myomorph and hystricomorph rodents. The vizcacha showed a gyrencephalic brain with a sagittal longitudinal fissure that divides both hemispheres, and 3 pairs of sulci with bilateral symmetry; that is, lateral-rostral, intraparietal, and transverse sulci. The EQ had one of the lowest values among Hystricomorpha, while GI was one of the highest. Besides, the MCT was close to the mean value for the suborder. The comparison of EQ, GI, and MCT values between hystricomorph and myomorph species allowed the detection of significant variations. Both EQ and GI showed a significant increase in Hystricomorpha compared to Myomorpha, whereas a Pearson’s analysis between EQ and GI depicted an inverse correlation pattern for Hystricomorpha. Furthermore, the ratio between MCT and GI also showed a negative correlation for Hystricomorpha and Myomorpha. Our phylogenetic analyses showed that Hystricomorpha and Myomorpha do not differ in their allometric patterning between the brain and body mass, GI and brain mass, and MCT and GI. In conclusion, gyrencephalic neuroanatomy in the vizcacha could have developed from the balance between the brain size, the presence of invaginations, and the cortical thickness, which resulted in a mixed encephalization strategy for the species. Gyrencephaly in the vizcacha, as well as in other Hystricomorpha, advocates in favor of the proposal that in the more recently evolved Myomorpha lissencephaly would have arisen from a phenotype reversal process.
Stroke in Sri Lanka: How Can We Minimise the Burden?
Authors: Ranawaka Udaya K. , Venketasubramanian Narayanaswamy
Published: April 2021

The burden of stroke in Sri Lanka is high and steadily increasing. Accurate estimation of the burden is hampered by a paucity of epidemiological data. More neurologists, stroke units, facilities for modern treatments and multi-disciplinary rehabilitation services are urgently needed. Essential drugs for risk factor control and secondary prevention are available in many hospitals. Aggressive preventive strategies and promoting stroke awareness are the best ways to minimise the stroke burden in Sri Lanka.
Association Between Malnutrition and Sarcopenia During Hospitalisation in Older People: A Challenge in Rehabilitation
Authors: Papadopoulou Sousana
Published: April 2021

Very little is known about the effect of malnutrition on short-term changes of body composition, particularly muscle, among older hospitalized patients. We sought to investigate the association of malnutrition as assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria with changes of thigh muscle mass and muscle strength among older patients during hospitalization. Forty-one patients (age range 66–97 years, 73% female) participated in this prospective longitudinal observational study. Nutritional status was evaluated using the GLIM criteria on admission and at discharge. Functional status and mid-thigh magnetic resonance imaging (MRI) measurements of cross-sectional area (CSA) were conducted on admission and before discharge. In all, 17% were malnourished and 83% had no malnutrition. Mean mid-thigh muscle CSA declined by 7.0 cm2 (−9%) in malnourished patients during hospitalization (p = 0.008) and remained unchanged among non-malnourished patients (−1%, p = 0.390). Mean mid-thigh CSA of subcutaneous and intermuscular fat did not change significantly during hospitalization in both groups. Malnourished subjects lost 10% of handgrip strength (−1.8 kg) and 12% of knee extension strength (−1.5 kg) during hospitalization. However, the magnitude of both changes did not differ between groups. In a stepwise multiple regression analysis, malnutrition and changes in body weight during hospitalization were the major independent risk factors for the reduction of muscle CSA. Malnutrition according to the GLIM criteria was significantly and independently associated with acute muscle wasting in frail older patients during 2-week hospitalization.
Prenatal Bisphenol A Exposure and Early Childhood Behavior and Cognitive Function: A Chinese Birth Cohort Study
Authors: Huang Zhaohui , Fu Weinan , Dou Lianjie , Bao Huihui , Wu Wanke , Su Puyu , Huang Kun , Zhu Peng , Sheng Jie , Xu Yuanyuan , Tao Fangbiao , Hao Jiahu
Published: April 2021

Introduction: Biomonitoring of bisphenol A (BPA) in human blood is still scarce, although already noticeable. We aimed to examine the associations between prenatal serum BPA concentrations and behavior and cognitive function in preschool children. Methods: A total of 1,782 mother-child pairs with complete demographic information, blood samples, and psychological measurements were included from the China-Anhui Birth Cohort (C-ABCS). We detected serum BPA concentrations and assessed children’s neurodevelopment using a set of psychometric scales. Results: The median prenatal maternal serum BPA concentration was 0.23 (P25, P75: 0.07, 0.52) ng/mL, with a detection frequency of 85.19%. Compared with the girls with the lowest concentrations, those with highest BPA concentrations had increased risks of inhibitory self-control impairment [relative risk (RR) = 3.66, 95% confidence interval (CI): 1.53, 7.58], emergent metacognition impairment (RR = 1.70, 95% CI: 1.07, 2.78), conduct problem (RR = 1.68, 95% CI: 1.12, 2.39), peer relationship problem (RR = 2.57, 95% CI: 1.33, 4.47), higher total difficulties score (RR = 1.76, 95% CI: 1.12, 2.67), and higher impact factor score (RR = 1.52, 95% CI: 1.11, 2.05), while the boys with the highest prenatal BPA concentrations had an increased risk of conduct problem compared with those with the lowest concentrations (RR = 1.59, 95% CI: 1.09, 2.24) (P-interaction = 0.011). After stratification by age, high prenatal BPA concentrations were associated with increased ADHD (RR = 4.44, 95% CI: 1.54, 10.85) among children aged 3 years, not among children aged 4 years. Conclusion: Our study revealed the sex-specific and age-specific impacts of prenatal BPA exposure on preschool children’s cognitive and behavioral development.
Assessment of voltage stability based on power transfer stability index using computational intelligence models
Authors: Ghadban Ahmed Majeed , Salman Ghassan Abdullah , Hussein Husham Idan
Published: April 2021

In this paper, the importance of voltage stability is explained, which is a great problem in the EPS. The estimation of VS is made a priority so as to make the power system stable and prevent it from reaching voltage collapse. The power transfer stability index (PTSI) is used as a predictor utilized in a PSN to detect the instability of voltages on weakened buses. A PSI is used to obtain a voltage assessment of the PSNs. Two hybrid algorithms are developed. The (CA-NN) and the (PSO-NN). After developing algorithms, they are compared with the actual values of PTSI NR method. The algorithms installed on the 24 bus Iraqi PS. The actual values of PTSI are the targets needed. They are obtained from the NR algorithm when the input data is Vi, δi, Pd, Qd for the algorithm. The results indicate that a weak bus that approaches voltage collapse and all results were approximately the same. There is a slight difference with the actual results and demonstrated classical methods are slower and less accurate than the hybrid algorithms. It also demonstrates the validation and effectiveness of algorithms (CA-NN, and PSO-NN) for assessing voltage-prioritizing algorithms (CA-NN). The MATLAB utilized to obtain most of the results.
Adaptive hysteresis band current control of grid connected PV inverter
Authors: Sankar R. S. Ravi , Venkatesh A. , Kollipara Deepika
Published: April 2021

In this paper, adaptive hysteresis band current controller is implemented to control the current injected into the grid. Initially it was implemented by B.K Bose for control of the machine drive. Now it is implemented for the grid connected PV inverter, to control the current injected into Grid. It is well suitable for the distribution generation. The adaptive hysteresis band controller changes the bandwidth based on the modulating frequency, supply voltage, input DC voltage and slope of the reference current. Consequently, the controller generates pulses to the inverter. It is advantageous over the conventional hysteresis controller, as the switching frequency is maintained almost constant. Thereby quality of grid current is also improved. It is verified in time domain analysis of simulation using MATLAB.
Implementation of SHE-PWM technique for single-phase inverter based on Arduino
Authors: Mohammed Laith A. , Husain Taha A. , T. Ibraheem Ahmed M.
Published: April 2021

This paper presents design and practical implementation of single-phase inverter based on selective harmonic elimination-pulse width modulation (SHE-PWM) technique. Microcontroller mega type Arduino used as a controller for producing the gate pulses. The optimized switching angles determination results in wide range of output voltage. Depending on number of switching angles, the lower order harmonics (LOHs) can be eliminated to improve the output voltage waveform. A comparison study using MATLAB/Simulink for sinusoidal-PWM and SHE-PWM techniques, which shows for the same LOH in the output voltage waveform, the SHE-PWM has less number of pulses per half cycle than sinusoidal-PWM strategy. The reduction in number of pulses results less switching losses. The simulation done using ten switching angles to drive R-L load. A prototype of SHE-PWM inverter with R-L load is used to validate the simulation results.
Finite control set model predictive direct current control strategy with constraints applying to drive three-phase induction motor
Authors: Ali Anmar Kh. , Omar Riyadh G.
Published: April 2021

In this, work the finite control set (FCS) model predictive direct current control strategy with constraints, is applied to drive three-phase induction motor (IM) using the well-known field-oriented control. As a modern algorithm approach of control, this kind of algorithm decides the suitable switching combination that brings the error between the desired command currents and the predicated currents, as low as possible, according to the process of optimization. The suggested algorithm simulates the constraints of maximum allowable current and the accepted deviation, between the desired command and actual currents. The new constraints produce an improvement in system performance, with the predefined error threshold. This can be applied by avoiding the switching combination that exceeds the limited values. The additional constraints are more suitable for loads that require minimum distortion in harmonic and offer protection from maximum allowable currents. This approach is valuable especially in electrical vehicle (EV) applications since its result offers more reliable system performance with low total harmonics distortion (THD), low motor torque ripple, and better speed tracking.
Image encryption under spatial domain based on modify 2D LSCM chaotic map via dynamic substitution-permutation network
Authors: Mohammed Rana Saad , Jabbar Khalid Kadhim , Hilal Hussien Abid
Published: April 2021

Image encryption has become an important application aspect of information security. Most attempts are focused on increasing the security aspect, the quality of the resulting image, and the time consumed. On the other hand, dealing with the color image under the spatial domain in this filed is considered as another challenge added to the proposed method that make it sensitivity and difficulty. The proposed method aims to encode a color image by dealing with the main color components of the red (R), green (G), and blue (B) components of a color image to strengthen the dependence of each component by modifying a two dimensional logistic- sine coupling map (2D- LSCM). This is to satisfy the statistical features and reduce time-consumption, and benefit from a mixing step of the second of advanced encryption standard (AES) candidates (serpent block cipher) and modified it to achieve in addition of confusion and diffusion processes. The experimental results showed that our proposed method had the ability to resist against statistical attacks and differential attacks. It also had a uniform histogram, a large key space, complex and faster, closer Shannon entropy to 8, and low correlation values between two adjacent pixels compared with other methods.
Detecting spam e-mails using stop word TF-IDF and stemming algorithm with Naïve Bayes classifier on the multicore GPU
Authors: Jaiswal Manjit , Das Sukriti , Khushboo Khushboo
Published: April 2021

A spam filter is a program which is used to identify unwanted emails and prevents those messages from getting into a user's mail. The study was focused on how the algorithms can be applied on a number of e-mails consisting of both ham and spam e-mails. First, the working principle and steps which are followed for implementation of stop words, TF-IDF and stemming algorithm on NVIDIA’s Tesla P100 GPU are discussed and to verify the findings by executing of Naïve Bayes algorithm. After complete training and testing of the spam e-mails dataset taken from Kaggle by using the proposed method, we got a high training accuracy of 99.67% and got a testing accuracy of about 99.03% on the multicore GPU that boosted the speed of execution of training time period and testing time period which is improved of training and testing accuracy around 0.22% and 0.18% respectively when compared to that after applying only Naïve Bayes i.e. conventional method to the same dataset where we found training and testing accuracy to be 99.45% and 98.85% respectively. Also, we found that training time taken on GPU is 1.361 seconds which was about 1.49X faster than that taken on CPU which is 2.029 seconds. And the testing time taken on GPU is 1.978 seconds which was about 1.15X faster than that taken on CPU which is 2.280 seconds.
The effects of using variable lengths for degraded signal acquisition in GPS receivers
Authors: Hussain Arif , Magsi Hina , Ahmed Arslan , Hussain Hadi , Khand Zahid Hussain , Akhtar Faheem
Published: April 2021

The signal acquisition in GPS receivers is the first and very crucial process that may affect the overall performance of a navigation receiver. Acquisition program initiates a searching operation on received navigation signals to detect and identify the visible satellites. However, signal acquisition becomes a very challenging task in a degraded environment (i.e, dense urban) and the receiver may not be able to detect the satellites present in radio-vicinity, thus cannot estimate an accurate position solution. In such environments, satellite signals are attenuated and fluctuated due to fading introduced by Multipath and NLOS reception. To perform signal acquisition in such degraded environments, larger data accumulation can be effective in enhancing SNR, which tradeoff huge computational load, prolonged acquisition time and high cost of receiver. This paper highlights the effects of fading on satellite signal acquisition in GPS receiver through variable data lengths and SNR comparison, and then develops a statistical relationship between satellite visibility and SNR. Furthermore it also analyzes/investigates the tradeoff between computation load and signal data length.
IoT based on secure personal healthcare using RFID technology and steganography
Authors: Khan Haider Ali , Abdulla Raed , Selvaperumal Sathish Kumar , Bathich Ammar
Published: April 2021

Internet of things (IoT) makes it attainable for connecting different various smart objects together with the internet. The evolutionary medical model towards medicine can be boosted by IoT with involving sensors such as environmental sensors inside the internal environment of a small room with a specific purpose of monitoring of person's health with a kind of assistance which can be remotely controlled. RF identification (RFID) technology is smart enough to provide personal healthcare providing part of the IoT physical layer through low-cost sensors. Recently researchers have shown more IoT applications in the health service department using RFID technology which also increases real-time data collection. IoT platform which is used in the following research is Blynk and RFID technology for the user's better health analyses and security purposes by developing a two-level secured platform to store the acquired data in the database using RFID and Steganography. Steganography technique is used to make the user data more secure than ever. There were certain privacy concerns which are resolved using this technique. Smart healthcare medical box is designed using SolidWorks health measuring sensors that have been used in the prototype to analyze real-time data.
A fully integrated violence detection system using CNN and LSTM
Authors: Sharma Sarthak , Sudharsan B. , Naraharisetti Saamaja , Trehan Vimarsh , Jayavel Kayalvizhi
Published: April 2021

Recently, the number of violence-related cases in places such as remote roads, pathways, shopping malls, elevators, sports stadiums, and liquor shops, has increased drastically which are unfortunately discovered only after it’s too late. The aim is to create a complete system that can perform real-time video analysis which will help recognize the presence of any violent activities and notify the same to the concerned authority, such as the police department of the corresponding area. Using the deep learning networks CNN and LSTM along with a well-defined system architecture, we have achieved an efficient solution that can be used for real-time analysis of video footage so that the concerned authority can monitor the situation through a mobile application that can notify about an occurrence of a violent event immediately.
Geomorphological description of the biome Pampa (Brazil) with support of digital elevation model and geographic information system
Authors: Robaina Luís Eduardo de Souza , Trentin Romario , Sccoti Anderson Augusto Volpato
Published: April 2021

In Brazil, the Pampa Biome is restricted to the far south in the state of Rio Grande do Sul, where it occupies an area of 176,496 km², which corresponds to 63% of the territory state and 2.07% of the Brazilian territory. The biome is characterized by the predominance of native fields with the presence of riparian forests, hillside forests, dwarf-palms fields, xerophyte bushes, wetlands, rocky outcrops, etc. Geomorphologically the landscape of the biome is very varied due to the lithological and structural conditions that interacted in the performance of surface processes. The landscapes consists of plains areas associated with Quaternary deposits; undulating reliefs associated with the sedimentary Basins, which consists of a volcano-sedimentary sequence by rocks formed in different depositional environments of the Paraná Basin and by rocks that represent a Plateau Volcanism and; a dissected plateau relief associated with the Precambrian crystalline basement. This paper describes quantitatively the relief through equations using Geographic Information Systems and the representation of the earth surface in the form of numerical digital models. Digital processing as well as the database were organized and managed by GIS, ArcGIS 10.3®, with spatial analysis and three-dimensional analysis tools. For each of the large geomorphological compartments that make up the Biome, a description of the landforms, and landforms elements were established and mapped. Relief shapes are described by the amplitude and slope of the terrain defined in flat areas, slightly undulations hills, undulating hills and large hills and buttes. For the determination of the relief elements the difference of topographic height, distance and the direction angle of the neighboring points in relation to the central cell (zenith and nadir angles) was used, through online application, available in the website << http://sil.uc.edu/geom/app >>. The relief elements determined are the flat, peak, ridge, shouder, spur, slope, hollow, footslope, valley, pit. The grouping of landforms and landform elements allowed the distinction of predominant morphological patterns for each geomorphological compartment in the Pampa Biome.
Proposta metodológica para elaboração de um indicador de fragilidade ambiental para fragmentos florestais
Authors: Takikawa Bruno Yuji , Silva Darllan Collins da Cunha e , Lourenço Roberto Wagner
Published: April 2021

A expansão das atividades antrópicas resultou na perda de quase 88% da cobertura florestal original da Mata Atlântica, impulsionando o processo de fragmentação e a perda de habitat, principais causas de extinção da fauna e flora. Diante disso, este artigo teve por objetivo desenvolver uma metodologia para identificação de fragmentos florestais prioritários para ações de proteção ambiental em uma bacia hidrográfica com forte ação antrópica. O indicador elaborado teve como escopo a avaliação dos parâmetros relacionados à forma, uso de entorno do fragmento e a qualidade da saúde da vegetação. Para tanto, foi gerado o Índice de Circularidade (IC), o Índice de Efeito de Borda (IEB) e o Índice de Qualidade Biofísica do Fragmento (IQBF). Foi aplicado o método de Análise Hierárquica de Processos (AHP) para atribuir pesos relacionados à importância de cada um dos índices resultando na elaboração de um indicador que pudesse demonstrar o estado de fragilidade das florestas da área de estudo, chamado de Indicador de Fragilidade Florestal (IFF). Os resultados mostraram que dos 27 fragmentos florestais estudados, apenas 01 fragmento foi considerado com baixa fragilidade, 22 com média fragilidade e 04 com alta fragilidade florestal. Pode-se afirmar que os resultados do IFF mostraram que o tipo de uso das terras adjacentes aos fragmentos florestais é o principal fator em relação aos demais. Finalmente, a modelagem utilizando dados espaciais e AHP se mostraram bastante úteis e ágeis na determinação de áreas prioritárias para gestão e conservação de remanescentes florestais, podendo ser replicada para outras bacias hidrográficas.
METTL3 Regulates Angiogenesis by Modulating let-7e-5p and miRNA-18a-5p Expression in Endothelial Cells
Authors: Chamorro-Jorganes Aránzazu , Sweaad Walid K. , Katare Rajesh , Besnier Marie , Anwar Maryam , Beazley-Long N. , Sala-Newby Graciela , Ruiz-Polo Iñigo , Chandrasekera Dhananjie , Ritchie Alison A. , Benest Andrew V. , Emanueli Costanza
Published: April 2021

Objective:

Postnatal angiogenesis is critical in vascular homeostasis and repair. m
6
A (N6-methyladenosine) RNA methylation is emerging as a new layer for fine-tuning gene expression. Although the contribution of the m
6
A-catalyzing enzyme, METTL3 (methyltransferase-like 3), in cancer biology has been described, its role in endothelial cell (EC) function, particularly during angiogenesis, remains unclear.

Approach and Results:

To characterize the relevance of METTL3 in angiogenesis regulation, we performed gain- and loss-of-function studies in vitro. We demonstrated that depletion of METTL3 in ECs reduced the level of m
6
A and impaired EC function, whereas adenovirus-mediated METTL3 overexpression increased angiogenesis. Mechanistically, we showed that METTL3 depletion in ECs decreased mature angiogenic microRNAs let-7e-5p and the miR-17-92 cluster, and increased the expression of their common target, Tsp1 (thrombospondin 1). Conversely,
Ad.METTL3
increased the expression of let-7e-5p and miR-17-92 cluster and reduced protein levels of Tsp1 in ECs. Moreover, overexpression of let-7e-5p and miR-18a-5p restored the angiogenic potential of METTL3-depleted ECs. We corroborated our data in vivo employing 3 mouse models. When tested in an in vivo Matrigel plug assay, METTL3-depleted ECs had diminished ability to vascularize the plug, whereas overexpression of METTL3 promoted angiogenesis. Local
Ad.METTL3
gene transfer increased postischemic neovascularization in mice with either unilateral limb ischemia or myocardial infarction.

Conclusions:

METTL3 regulates m
6
A RNA methylation in ECs. Endogenous METTL3 is essential for EC function and angiogenesis, potentially through influencing let-7e and miR-17-92 cluster processing. Thus, the therapeutic modulation of METTL3 should be considered as a new approach for controlling angiogenic responses in the clinical setting.
Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial
Authors: Pawade Tania A. , Doris Mhairi K. , Bing Rong , White Audrey C. , Forsyth Laura , Evans Emily , Graham Catriona , Williams Michelle C. , van Beek Edwin J.R. , Fletcher Alison , Adamson Philip D. , Andrews Jack P.M. , Cartlidge Timothy R.G. , Jenkins William S.A. , Syed Maaz , Fujisawa Takeshi , Lucatelli Christophe , Fraser William , Ralston Stuart H. , Boon Nicholas , Prendergast Bernard , Newby David E. , Dweck Marc R.
Published: April 2021

Background:

Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis.

Methods:

In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and
18
F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score.

Results:

A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93–3.82 m/s]; aortic valve calcium score, 1152 AU [655–2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18–0.33 µg/L] to 0.11 µg/L [0.08–0.17 µg/L]) and alendronic acid (0.20 [0.14–0.28 µg/L] to 0.09 µg/L [0.08–0.13 µg/L]) but was unchanged with placebo (0.23 [0.17–0.30 µg/L] to 0.26 µg/L [0.16–0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198–804 AU] versus 354 AU [76–675 AU]; P=0.41) or alendronic acid and placebo (326 [138–813 AU] versus 354 AU [76–675 AU];
P
=0.49). Similarly, there were no differences in change in peak aortic jet velocity or
18
F-sodium fluoride aortic valve uptake.

Conclusions:

Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02132026.
LINC01278 Sponges miR‐500b‐5p to Regulate the Expression of ACTG2 to Control Phenotypic Switching in Human Vascular Smooth Muscle Cells During Aortic Dissection
Authors: Wang Weitie , Liu Qing , Wang Yong , Piao Hulin , Zhu Zhicheng , Li Dan , Wang Tiance , Liu Kexiang
Published: April 2021

Background

Phenotypic switching in vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of aortic dissection (AD). This study aims to explore the potential mechanisms of linc01278 during VSMC phenotypic switching.

Methods and Results

Twelve samples (6 AD and 6 control) were used for lncRNA, microRNA, and mRNA microarray analysis. We integrated the mRNA microarray data set with
GSE52093
to determine the differentially expressed genes. Bioinformatic analysis, including Gene Expression Omnibus 2R, Venn diagram analysis, gene ontology, pathway enrichment, and protein–protein interaction networks were used to identify the target lncRNA, microRNA, and mRNA involved in AD. Subsequently, we validated the bioinformatics data using techniques in molecular biology in human tissues and VSMCs. Linc01278, microRNA‐500b‐5p, and ACTG2 played an important role in the vascular smooth muscle contraction pathway. Linc01278 and ACTG2 were downregulated and miR‐500b‐5p was upregulated in AD tissues. Molecular markers of VSMC phenotypic switching, including SM22α, SMA, calponin, and MYH11, were downregulated in AD tissues. Plasmid‐based overexpression and RNA interference‐mediated downregulation of linc01278 weakened and enhanced VSMC proliferation and phenotypic switching, respectively. Dual‐luciferase reporter assays confirmed that linc01278 regulated miR‐500b‐5p that directly targeted ACTG2 in HEK293T cells.

Conclusions

These data demonstrate that linc01278 regulates ACTG2 to control the phenotypic switch in VSMCs by sponging miR‐500b‐5p. This linc01278‐miR‐500b‐5p‐ACTG2 axis has a potential role in developing diagnostic markers and therapeutic targets for AD.
Watching the Brain as It (Un)Binds: Beta Synchronization Relates to Distractor–Response Binding
Authors: Pastötter Bernhard , Moeller Birte , Frings Christian
Published: April 2021

Human action control relies on event files, that is, short-term stimulus–response bindings that result from the integration of perception and action. The present EEG study examined oscillatory brain activities related to the integration and disintegration of event files in the distractor–response binding (DRB) task, which relies on a sequential prime–probe structure with orthogonal variation of distractor and response relations between prime and probe. Behavioral results indicated a DRB effect in RTs, which was moderated by the duration of the response-stimulus interval (RSI) between prime response and probe stimulus onset. Indeed, a DRB effect was observed for a short RSI of 500 msec but not for a longer RSI of 2000 msec, indicating disintegration of event files over time. EEG results revealed a positive correlation between individual DRB in the RSI-2000 condition and postmovement beta synchronization after both prime and probe responses. Beamformer analysis localized this correlation effect to the middle occipital gyrus, which also showed highest coherency with precentral and inferior parietal brain regions. Together, these findings suggest that postmovement beta synchronization is a marker of event file disintegration, with the left middle occipital gyrus being a hub region for stimulus–response bindings in the visual DRB task.
Menopausal osteoporosis: screening, prevention and treatment
Authors: Yong EL , Logan S
Published: April 2021

Screening for osteoporosis in women can be based on age and weight, using the Osteoporosis Screening Tool for Asians and assessment for other risk factors such as early menopause, Chinese ethnicity and other secondary factors. Based on the resulting risk profile, women can be triaged to dual-energy X-ray absorptiometry (DEXA) scanning for definite diagnosis of osteoporosis. Treatment should be considered in women with previous fragility fractures, DEXA-diagnosed osteoporosis and high risk of fracture. Exercise improves muscle function, can help prevent falls and has moderate effects on improvements in bone mass. Women should ensure adequate calcium intake and vitamin D. Menopausal hormone therapy (MHT) effectively prevents osteoporosis and fractures, and should be encouraged in those aged < 50 years. For women aged < 60 years, MHT or tibolone can be considered, especially if they have vasomotor or genitourinary symptoms. Risedronate or bisphosphonates may then be reserved for those aged over 60 years.
The Challenge of Forging Consent to UN Mediation in Internationalized Civil Wars: The Case of Syria
Authors: Hellmüller Sara
Published: April 2021

This article analyzes how the internationalization of civil wars influences conflict parties’ consent to UN mediation processes. Illustrated by the UN mediation in Syria, I argue that internationalization influences consent directly by obstructing the advent of a costly stalemate and the parties’ perception of mediation as a ‘way out,’ and indirectly by reducing mediators’ leverage and perceived impartiality thereby limiting their tools to foster consent. The article makes three contributions. First, it presents a novel conceptual framework to understand the impact of internationalization on conflict parties’ consent. Second, it provides a long-term analysis of UN mediation in Syria from 2012–2020. Third, it contributes to a broader discussion about how civil wars end. This is of particular relevance as the prioritization of a political over a military end to civil wars, which was dominant in the early post-Cold War period, is no longer unquestioned.
Littérature Orale et Société. La Chanson ‘Attention Au Sida’ et la Vie Sociale en rd Congo
Authors: Mbwangi Julien Mbwangi
Published: April 2021

La littérature est bel et bien un essai de construction d’un monde idéal. Ainsi, tout texte littéraire, quelle que soit sa nature est en miniature une construction mentale dans laquelle le réel est perçu comme palimpseste de l’imaginaire. Dans ce sens, les écrivains, les artistes, les musiciens ont une responsabilité face aux événements qui affectent leur environnement. Par leur esprit de projection, ils ont le pouvoir d’orienter le cours des événements. Luambo Makiadi Franco dont nous avons analysé le texte est un exemple d’un auteur sensible qui, par son art, a donné une orientation objective devant un problème social. La littérature de ce point de vue constitue une loupe pour bien voir la société et l‘orienter.
A Theology of Psalm 88
Authors: Thornhill A. Chadwick
Published: April 2021

Psalm 88 is a hopeless exception among the laments in which the psalmist does not end with a confident turn to the ‘Thou,’ but rather lingers in his solitude and anguish. As such, the psalm stands as a unique entry in the Psalter for its lack of theological or existential resolution. This essay suggests that the unresolved and unanswered suffering found in the psalm provides an important model of a faithful sufferer who continues to cry to God though he feels abandoned by him.
On the Fall of Angels and the Fallenness of Nature: An Evangelical Hypothesis Regarding Natural Evil
Authors: Ortlund Gavin
Published: April 2021

This article considers the fall of angels as a possible explanation for the problem of natural evil. First, it situates this explanation in relation to other contemporary responses to the problem of natural evil. Second, it charts out the historical development of this view, giving special attention to its articulation in the writings of several prominent 20th-century theologians and Christian thinkers. Finally, it raises several theological principles that commend this view for further evaluation.
Apathy or Passion? The New Testament View of God the Father at the Cross
Authors: Root Terry
Published: April 2021

The classic theistic doctrine of an immutable God, unaffected by anything outside of God and apathetically incapable of suffering, underpins many atonement theories which project only the suffering of Jesus at the cross. That view is heavily dependent upon the continuing acceptance of the theological paradox of the immutable divine Father and the suffering divine Son. This essay argues that this view is too narrowly christological, lacking in theological context and unsupported by the New Testament witness to the unique relationship and unity of purpose in action of the Father and the Son. It further argues that when that narrow christology is contextualised by the theology of the New Testament witness a picture emerges of God the Father united in suffering love with God the Son at the cross to redeem creation from the effects of sin. Additionally it demonstrates that divine action in Christ’s resurrection and exaltation, as explicitly described within the New Testament witness, strengthens the hypothesis that both the Father and the Son willingly undertook the sacrificial suffering necessary to achieve their unity of purpose.
Paul’s Use of the Psalms in Romans: A Critical Analysis
Authors: Norden Christopher G.
Published: April 2021

Paul’s quotations from the Psalms in Romans are examined to help determine how Paul understands and uses the Psalms and what this says about Paul’s general use of the OT. The approach taken is to analyse the quotations in order to draw conclusions about the texts Paul uses, how he interacts with them, and the extent to which he adapts them. The contexts of the quotations are then analysed. These analyses are used to critique the contrasting views of Richard Hays and Christopher Stanley. It is concluded that Paul is a careful user of the LXX text, and that his understanding of David’s authorship and the Davidic-Messianic link are important to him.
Quid Pro Quo Satisfaction? An Analysis and Response to Garry Williams on Penal Substitutionary Atonement and Definite Atonement
Authors: Lynch Michael
Published: April 2021

Advocates of definite atonement have often argued that penal substitutionary atonement entails the doctrine that Christ satisfied for the sins of the elect alone. Recently, Garry Williams published two essays in a book entitled From Heaven He Came and Sought Her defending the thesis that logical consistency demands that if one affirms penal substitution, classically understood, then one must affirm definite atonement. This paper responds to Williams’s two essays and his main thesis by noting several historical considerations that significantly undermine Williams’s exposition of what he deems to be the ‘classic’ doctrine of penal substitutionary atonement. Further it is shown that the various theological problems proffered by Reformed theologians against Williams’s pecuniary version of penal substitution—such as R. L. Dabney’s response to John Owen’s double-payment argument—are inadequately addressed.
How do Conceptions of Allah’s Being in Islam Compare with those of God’s Being in Christianity?
Authors: Dodds Adam
Published: April 2021

How do conceptions of Allah’s being in Islam in relate to conceptions of God’s being in Christianity? Two Qur’anic passages that describe Allah’s being, Surah 112 and Surah 24:35, lead to the claims Allah is unity and Allah is the light. Drawing on Islamic theology and a breadth of tafsir (commentary) literature, I study these two claims pertaining to Allah’s being (tawhid). Then I examine a Christian understanding of God’s unity, and the meaning of ‘God is light’ in 1 John 1:5, drawing on trinitarian theologians and biblical commentaries. Next the implications of these studies for Islamic and Christian doctrines of creation will also be analysed. The conclusion addresses whether the Islamic and Christian conceptions of the divine being studied are comparable, compatible, contrasting, or contradictory. The goal is to contribute toward the wider discussion of the inter-relation between the Islamic Allah and Biblical God.
Spatiotemporal Analysis of Extreme Precipitation in the Missouri River Basin from 1950 – 2019
Authors: Flanagan Paul , Mahmood Rezaul
Published: April 2021

Extreme precipitation events are challenging to local and regional stakeholders across the United States. The Missouri River Basin (MoRB), covering an area over 1.29 million km2, is prone to extreme precipitation events. These events are exacerbated by the complex terrain in the west and the numerous weather and climate features which impact the region on a seasonal/annual basis (low-level jets, mesoscale convective systems, extreme cold air intrusions, etc.). Without an in-depth analysis of extreme precipitation in the MoRB, the evolving nature of extreme precipitation is not known. This warrants an analysis of extreme precipitation, especially relating to sub-annual variations when extreme precipitation is more impactful. To this end, data from 131 United States Historical Climatology Network (USHCN) stations were used to determine the nature of extreme precipitation from 1950 – 2019. Annual 99th percentile and annual station maximum precipitation events occur more frequently in the eastern MoRB than in the western MoRB, in line with the annual precipitation climatology. Results show that 99th percentile events and annual station maximum precipitation events are becoming more frequent across the MoRB. Through analysis of 3-month extreme precipitation trends, areas in the eastern and southern MoRB are shown to have an increasing event frequency and intensity. Frequency shifts in the 99th percentile events, however, have occurred across the entire region. The increasing frequency of extreme events in the western MoRB represent a significant change for the hydroclimate of the region. Overall, the results from this work show that MORB extreme precipitation has increased in frequency and intensity during the 1950 – 2019 period.