bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Important Molecular Pathways and Candidate Diagnostic Biomarkers of Noninvasive to Invasive Stages in Gastric Cancer by In Silico Analysis
Authors: Tutunchi Sara , Akhavan Saeedeh , Bereimipour Ahmad , Hossein Ghaderian Sayyed Mohammad
Published: May 2021

Gastric cancer affects millions of people each year; it is the fifth deadliest cancer globally. Due to failure to perform routine tests such as endoscopy, it is usually diagnosed in the invasive stages. Therefore, finding diagnostic biomarkers in blood can help to speed up the initial diagnosis of cancer. This study aimed to find appropriate diagnostic biomarkers in the extracellular matrix of noninvasive to invasive stages of gastric cancer patients, using bioinformatics analysis. First, we selected the appropriate datasets from the GEO database. We evaluated the genes’ signaling pathways, biological processes, and molecular functions. More accurately, we assessed the genes, in which their protein products are released into the extracellular matrix; we evaluated their protein network. Then, we validated the candidate proteins in the GEPIA and TCGA databases. The extracellular matrix, tyrosine kinase receptors, and immune response pathways are effective factors, which are related to the highly expressed genes and metabolism; cell cycle pathways are also impressive on low-expression genes. 69 highly expressed proteins are released into the extracellular matrix. After drawing the protein network, 5 proteins were selected as more suitable candidates for further studies. These proteins’ expression significantly increases in the human samples, and the survival chart showed up to about 80% mortality in the individuals over time. With integrated bioinformatics analysis, BGN, LOX, MMP-9, SERPINE1, and TGFB1 proteins have been selected as suitable diagnostic biomarkers for noninvasive to invasive stages of gastric cancer. Further studies are needed to evaluate more precise mechanisms between these proteins.
MyOcrTool: Visualization System for Generating Associative Images of Chinese Characters in Smart Devices
Authors: Rai Laxmisha , Li Hong
Published: May 2021

Majority of Chinese characters are pictographic characters with strong associative ability and when a character appears for Chinese readers, they usually associate with the objects, or actions related to the character immediately. Having this background, we propose a system to visualize the simplified Chinese characters, so that developing any skills of either reading or writing Chinese characters is not necessary. Considering the extensive use and application of mobile devices, automatic identification of Chinese characters and display of associative images are made possible in smart devices to facilitate quick overview of a Chinese text. This work is of practical significance considering the research and development of real‐time Chinese text recognition, display of associative images and for such users who would like to visualize the text with only images. The proposed Chinese character recognition system and visualization tool is named as MyOcrTool and developed for Android platform. The application recognizes the Chinese characters through OCR engine, and uses the internal voice playback interface to realize the audio functions and display the visual images of Chinese characters in real‐time.
Management of Acute Wilsonian Hepatitis with Severe Hemolysis: A Successful Combination of Chelation and MARS Dialysis
Authors: Hassoun Jeremy , Hammer Nathalie , Magini Giulia , Ponte Belen , Ongaro Marie , Rougemont Anne-Laure , Goossens Nicolas , Frossard Jean-Louis , Spahr Laurent
Published: May 2021

Wilson’s disease is a rare hereditary disorder of copper metabolism leading to progressive accumulation of copper in several organs including the brain and the liver. Acute liver failure is a relatively rare hepatic manifestation of WD which may require urgent liver transplantation if medical treatment fails. We report here the case of a young woman who presented with classic acute Wilsonian hepatitis complicated by liver and renal failure and a severe hemolysis related to massive nonceruloplasmin bound copper accumulation requiring repeated blood transfusions. The early initiation of a combined treatment including conventional chelation therapy and repeated MARS dialysis sessions allowed a rapid control of hemolysis, a progressive decrease of free copper overload, and clinical recompensation without liver transplantation.
Intelligent Construction, Operation, and Maintenance of a Large Wastewater‐Treatment Plant Based on BIM
Authors: Li Jiu-Lin , Chen Li-Min , Xu Hao
Published: May 2021

Building information modeling (BIM) is a data‐based tool for engineering, design, and building management, which is used to parameterize and model various types of information. This information may then be shared and introduced throughout the building life‐cycle phases (planning, design, construction and operation, and maintenance (O&M)). Therefore, BIM allows engineers to correctly understand and efficiently respond to varying types of building information as well as serves as a foundation for cooperation between the design and construction teams. Hence, BIM plays an important role in increasing productivity, minimizing costs, and shortening construction times. In this article, we present a case example where BIM was used for intelligent construction of a large wastewater‐treatment plant (WTP). The process involved intelligent design and simulation techniques, management and simulation of construction works, digital delivery solutions, BIM‐based Internet of things O&M, and environmental monitoring. BIM was used to digitalize the construction, delivery, and O&M processes of the WTP. According to this case example, we also offer suggestions on how deep learning and intelligent control techniques can be used to enhance intelligent O&M in WTPs.
Aerodynamic Fields inside S-Shaped Baffled-Channel Air-Heat Exchangers
Authors: Menni Younes , Lorenzini Giulio , Kumar Ravinder , Mosavati Babak , Nekoonam Saeed
Published: May 2021

A numerical study of an especial heat exchanger (HE) equipped with complicated geometry baffles was performed in this research study. This shell-and-tube HE could be applied in various engineering applications like solar collectors. It can be acknowledged that generating longitudinal vortices in the flow results in enhancing the turbulent convective heat transfer. In order to generate these vortices, S-shaped baffles can be applied. It should be noted that computational analysis of shell-and-tube HEs is considered a challenging task due to these vortices. So, in this study, a commercial CFD software has been used for solving the problem and important equation and numerical approach used in the simulation have been explained. The aerodynamic aspect with respect to stream function, mean, axial, and transverse velocities, dynamic pressure, turbulent dissipation rate, turbulence kinetic energy, turbulent viscosity, and turbulence intensity fields was included in this research. This study reports many physical phenomena, such as the turbulence, instability, flow separation, and the appearance of reverse secondary currents. The average speed changed in different areas, where it is low next to the baffles. Velocity amounts are paramount around the upper channel’s wall, starting from the upper left side of the last baffle to the exit. This increase in velocity can be justified by a reduction in flow area and pressure augmentation.
In Situ g‐C3N4@Zno Nanocomposite: One‐Pot Hydrothermal Synthesis and Photocatalytic Performance under Visible Light Irradiation
Authors: Luu Thi Lan Anh , Neto Mateus Manuel , Van Thang Pham , Nguyen Ngoc Trung , Nguyen Thi Tuyet Mai , Nguyen Xuan Sang , Nguyen Cong Tu
Published: May 2021

In situ g‐C3N4@ZnO nanocomposites (with 0, 1, 3, 5, and 7 wt.% of g‐C3N4 in nanocomposite) were synthesized via a one‐pot hydrothermal method using precursors of urea, zinc nitrate hexahydrate, and hexamethylenetetramine. The g‐C3N4@ZnO nanocomposites were characterized by X‐ray diffraction, scanning electron microscope, diffuse reflectance spectroscopy, and photoluminescence spectroscopy. The photocatalyst activity of g‐C3N4@ZnO nanocomposites was evaluated via methylene blue degradation experiment under visible light irradiation. The g‐C3N4@ZnO nanocomposites showed an enhancement in photocatalytic activity in comparison to pure ZnO which increased with the g‐C3N4 content (1, 3, 5, and 7 wt.%) in nanocomposites. The photocatalytic activity reached the highest efficiency of 96.8% when the content of g‐C3N4 was 7.0 wt.%. Nanocomposite having 7.0 wt.% of g‐C3N4 also showed good recyclability with degradation efficiency higher than 90% even in the 4th use. The improvement of photocatalytic activity could be attributed to the adsorption ability and effective separation of electron‐hole pairs between g‐C3N4 and ZnO. This work implies a simple method to in situ prepare the nanocomposite material of g‐C3N4 and semiconductors oxide for photocatalyst applications with high efficiency and good recyclability.
Small‐Scale 5G Testbeds for Network Slicing Deployment: A Systematic Review
Authors: Esmaeily Ali , Kralevska Katina
Published: May 2021

Developing specialized cloud‐based and open‐source testbeds is a practical approach to investigate network slicing functionalities in the fifth‐generation (5G) mobile networks. This paper provides a comprehensive review of most of the existing cost‐efficient and small‐scale testbeds that partially or fully deploy network slicing. First, we present relevant software packages for the three main functional blocks of the ETSI NFV MANO framework and for emulating the access and core network domains. Second, we define primary and secondary design criteria for deploying network slicing testbeds. These design criteria are later used for comparison between the testbeds. Third, we present the state‐of‐the‐art testbeds, including their design objectives, key technologies, network slicing deployment, and experiments. Next, we evaluate the testbeds according to the defined design criteria and present an in‐depth summary table. This assessment concludes with the superiority of some of them over the rest and the most dominant software packages satisfying the ETSI NFV MANO framework. Finally, challenges, potential solutions, and future works of network slicing testbeds are discussed.
An Animated Functional Data Analysis Interface to Cluster Rapid Lung Function Decline and Enhance Center-Level Care in Cystic Fibrosis
Authors: Pratt Jesse , Su Weiji , Hayes Don , Clancy John P. , Szczesniak Rhonda D.
Published: May 2021

Identifying disease progression through enhanced decision support tools is key to chronic management in cystic fibrosis at both the patient and care center level. Rapid decline in lung function relative to patient level and center norms is an important predictor of outcomes. Our objectives were to construct and utilize center-level classification of rapid decliners to develop an animated dashboard for comparisons within patients over time, multiple patients within centers, or between centers. A functional data analysis technique known as functional principal components analysis was applied to lung function trajectories from 18,387 patients across 247 accredited centers followed through the United States Cystic Fibrosis Foundation Patient Registry, in order to cluster patients into rapid decline phenotypes. Smaller centers (<30 patients) had older patients with lower baseline lung function and less severe rates of decline and had maximal decline later, compared to medium (30–150 patients) or large (>150 patients) centers. Small centers also had the lowest prevalence of early rapid decliners (17.7%, versus 24% and 25.7% for medium and large centers, resp.). The animated functional data analysis dashboard illustrated clustering and center-specific summaries of the rapid decline phenotypes. Clinical scenarios and utility of the center-level functional principal components analysis (FPCA) approach are considered and discussed.
Orthogonal Experimental Study on Heat Transfer Optimization of Backfill Slurry with Ice Particles
Authors: Wang Mei , Liu Peng , Jia Yuhang , Zhao Yujiao , Zhang Bo
Published: May 2021

To reduce the risk of high‐temperature geothermal environment in deep mine exploitation, an innovative method for cooling stopes by backfill slurry with ice particles has been focused on. In this paper, aiming at the cooling effect of backfill slurry with ice particles, an experimental device including stope region and ice‐filled filling slurry region was established for temperature measurement experimental simulation study. The results showed the ice‐filled slurry had a significant cooling effect on the stope region. Orthogonal design experiment and range analysis methods were applied for studying the influencing regularities of four factors, including boundary heat flux, ice‐water ratio, sand‐cement ratio, and slurry concentration. The effective cooling heat coefficient which is defined by radiation heat flux and boundary heat flux of surrounding rock was applied as an evaluation index for scheme optimization. The influencing rank of the four factors is boundary heat flux >sand‐cement ratio >ice‐water ratio >slurry concentration. By comprehensive analysis, the optimization of mixture ratio was obtained: the boundary heat flux of the simulated surrounding rocks is 111 W/m2, the ratio of ice to water is 8 : 5, the ratio of sand to cement is 4 : 1, and the slurry concentration is 64%.
Plant Leaves Extract Irrigation on Wound Healing in Diabetic Foot Ulcers
Authors: Jayalakshmi Muthu Srinivasan , Thenmozhi P. , Vijayaraghavan R.
Published: May 2021

Purpose. We aimed to evaluate and compare the efficacy of neem leaves extract with normal saline irrigation practice in wound dressing on healing outcome and clinic-physiological parameters among individuals with diabetic foot ulcer (DFU). Methods. A quasiexperimental with repeated measures design was used on two study groups. One group received neem leaf extract wound irrigation and another group received normal saline wound irrigation. Study participants were randomly assigned to each group from 100 DFU individuals. Demographic and clinical data sheets were used to collect baseline information. Random blood sugar and HbA1C measurement was performed on the initial day of visit for all participants. We used the PUSH tool for wound assessment (wound surface area, exudate amount, and tissue type), and clinic physiological parameters (temperature, pulse rate, respiration, blood pressure, wound pain, wound infection, and local warmth) assessment was performed at baseline and then at the end of each week till four weeks were completed. Participants attended a foot clinic every 3rd or 4th day for wound care. Results. Reduction of wound healing score (PUSH score) and other wound variables improved significantly in the neem leaves extract group (

p
<
0.001

). There were no significant changes in the clinic-physiological parameters. Conclusion. Neem leaves extract irrigation for foot ulcers is considered to be very safe as it did not cause any complication systematically during the study. Neem leaf extract solution can be used as an alternative solution for normal saline. Managing DFU requires continuous foot care and early risk identification of ulcer.
High Expressions of Notch and Survivin in Elderly Patients with Glioma Contribute to an Unfavorable Prognosis
Authors: Liao Yuguo , Zhou Kangsheng , Li Haikun , Yang Lin
Published: May 2021

Gliomas account for 24% of all primary brain and central nervous system tumors. To date, elderly patients constitute 10-25% of patients with a diagnosis of glioblastoma multiforme, but limited attention has been put on their optimal treatment, largely due to a very poor expected survival (only 4-6 months). Unraveling the molecular mechanism of gliomas provides an opportunity to develop novel biomarkers and therapeutic targets. In this study, we collected fasting blood samples from elderly patients diagnosed with glioma and who received treatment in our hospital between May 2016 and May 2019 and determined the expression levels of Notch and Survivin proteins in different clinical stages and their relationship with patient survival. A total of 68 healthy volunteers in this hospital during the same period served as healthy controls. Compared with the healthy controls, the expressions of Notch 1, Notch 2, Notch 3, and Survivin protein in the serum of elderly glioma patients were remarkably increased (

P
<
0.05

), but the expression of caspase-3 protein declined (

P
<
0.05

). As the clinical stage of the patient advanced, the expressions of Notch 1, Notch 2, Notch 3, and Survivin increased, and this increase was statistically significant (

P
<
0.05

). It was observed that high expressions of serum Notch 1, Notch 2, Notch 3, and Survivin were associated with poor overall survival of elderly patients with glioma. We used γ-secretase inhibitor MRK-003 and specific ligand Jagged1 to alter the Notch pathway in U251 cells. It was revealed that MRK-003 incubation effectively suppressed the mRNA expression of Survivin in U251 cells, but Jagged1 stimulation significantly promoted the mRNA expression of Survivin in U251 cells. Results of MTT and transwell migration assays revealed reduced U251 cell viability and migration following MRK-003 treatment and enhanced cell viability and migration following Jagged1 stimulation. In conclusion, the finding obtained from these results supports that Notch and Survivin proteins contribute to the development of glioma in elderly patients and could serve as prognostic factors.
Shaking Table Test on the Seismic Responses of a Slope Reinforced by Prestressed Anchor Cables and Double‐Row Antisliding Piles
Authors: Wu Zuo-ju , Wang Zhi-jia , Bi Jun-wei , Fu Xiao , Yao Yong
Published: May 2021

The combined retaining structure has gradually received considerable attention in the slope engineering, due to its good reinforcement effects. However, most of the published research studies were focused on the seismic responses of the single‐formal supporting structure only. The investigations of dynamic responses of the combined retaining structures are scarce, and the current seismic design is conducted mainly based on experiences. In this work, a series of large‐scale shaking table tests were conducted to investigate the seismic responses of the combined retaining structures (i.e., prestressed anchor cables and double‐row antisliding piles) and the reinforced slope under seismic excitations, including amplification effect of internal and surface acceleration of the reinforced slope, distribution and change of prestress of the anchor cable, dynamic response of soil pressure behind the antislide pile, and horizontal displacement of the reinforced slope surface. Test results show that, supported by the reinforcement of composite support system, the slope with the multilayer weak sliding surface can experience strong ground motion of 0.9 g. The load of the antisliding pile has reached 80% of its bearing capacity, and the load of the anchor cable has reached 75.0% of its bearing capacity. When the seismic intensity reaches 0.5 g, the slope surface has an obvious downward trend, which will make the corresponding soil pressure suddenly increase after the antislide pile. At the potential sliding zone, the axial force of the anchor cable will increase suddenly under the action of earthquake; after the earthquake, the initial prestress of the anchor cable will be lost, with the loss range of 17.0%∼23.0%. These test results would provide an important reference for the further study of the seismic performance of such composite support structure.
Applying System Dynamics of Discrete Supported Track to Analyze the Rail Corrugation Causation on Curved Urban Railway Tracks
Authors: Yin Xianxian , Wei Xiukun , Zheng Haichao
Published: May 2021

Urban rail corrugation on curved tracks with small radii causes strong howling during operation, which has been bothering subway operating companies for many years. Therefore, revealing its causes and growth is important for the comfort and safety of subway operation. Current studies believe that the occurrence of rail corrugation is largely due to the resonant vibration of the wheel-rail system. However, little attention has been paid to the key causes of the track resonance and the practical prediction of the occurrence probability of rail corrugation on the certain track. This paper intends to solve these above issues. Firstly, the practical model of predicting the rail corrugation growth is proposed based on the wheel-rail coupling interaction, the key causes of corrugation are investigated, and the sensitivity analysis is carried out, while the corrugation superposition model is introduced to the analyze the corrugation evolution as well as to validate the corrugation growth from the aspect of material friction and wear. Secondly, the impact of the key causes on the initiation and development of the rail corrugation is investigated based on the cosimulation. Finally, case studies validate the proposed theory model and method. The results show that the practical prediction model for the rail corrugation growth proposed in this paper is able to estimate the occurrence possibility of rail corrugation on a specific track, and the superharmonic resonance of the track directly excited by passing vehicles eventually leads to rail corrugation. It is also found that shortwave corrugation develops more rapidly, and adjusting the support stiffness or sleeper spacing leads to fluctuations in the corrugation wavelength and its wear rate.
Photocatalytic Degradation of Trifluralin in Aqueous Solutions by UV/S2O82− and UV/ZnO Processes: A Comparison of Removal Efficiency and Cost Estimation
Authors: Sadeghi Fatemeh , Fadaei Abdolmajid , Mohammadi-Moghadam Fazel , Hemati Sara , Mardani Gashtasb
Published: May 2021

Trifluralin is one of the most widely used herbicides, being accounted as the cause of cancer in human. In the present research, the UV/S2O82− and ZnO/UV processes’ efficiency in the removal of trifluralin was investigated. A lab scale equipped with a UV lamp was applied. The parameters were studied, including initial trifluralin concentration (0.4–1.2 mg/L), contact time (20–60 min), S2O82− concentration (20–60 μM), and ZnO concentration (50–150 mg/L). The remained trifluralin concentration was measured by HPLC. This study proved the trifluralin removal of 92.90 ± 1.6% and 87.91 ± 19.22% for UV/S2O82− and UV/ZnO processes in the best operation conditions (contact time of 60 min, the persulfate concentration of 40 μM, and the ZnO concentration of 100 mg/L). The optimal trifluraline concentrations were 1.2 mg/L and 0.6 mg/L for UV/S2O82− and UV/ZnO processes, respectively. In both processes, the removal efficiency of trifluralin increased significantly with increasing contact time. The findings exhibited that both processes UV/S2O82− and UV/ZnO followed the zero-order kinetic. The electrical energy consumed of UV/S2O82 and UV/ZnO was about 43.95 and 20.41 Kwh/kg, respectively. The results show that UV/S2O82− and ZnO/UV processes were appropriate as the effective treatment method for trifluralin removal. Therefore, it is proposed to study the performance of these processes as an environmentally friendly practice in full scale with real wastewater.
The Comparative Study on the Damage Zones of Cylindrical and Spherical Charges in Rock and Soil
Authors: Xu Qian , Wang Zhong-Qi
Published: May 2021

To compare the damage zones of spherical and cylindrical charges in rock and soil, a quasistatic spherical model was established to predict the characteristic dimension of the cavity. The results indicated that the damage zones of cylindrical charges were larger than those of spherical charges. Furthermore, the cavity development of two charges with different shapes was obtained by numerical simulation, and a comparison of the prediction results between the quasistatic model and numerical simulation was made. The comparison showed that the model could predict the damage zones exactly and faster than numerical simulation. Ultimately, the influence of explosions and soil media was discussed by the quasistatic model. It was observed that larger damage zones were generated by smaller values of the product of pressure and exponential expansion. However, the influence of soil media was complex, and larger damage zones were usually generated by the harder soil media.
Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations
Authors: Zhang Jian-hui , Ruan Dan-dan , Hu Ya-nan , Ruan Xing-lin , Zhu Yao-bin , Yang Xiao , Wu Jia-bin , Lin Xin-fu , Luo Jie-wei , Tang Fa-qiang
Published: May 2021

Gitelman syndrome (GS) is an autosomal recessive inherited salt‐losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide‐sensitive Na‐Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto’s thyroiditis were analyzed for genetic‐phenotypic association. Sanger sequencing revealed that two probands carried SLC12A3 compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto’s Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto’s thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low‐density electron‐dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long‐term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.
An Empirical Study on Big Data Model and Visualization of Internet+ Teaching
Authors: Zhang Hua , Tsai Sang-Bing
Published: May 2021

In this paper, we conduct an in-depth study and analysis of “Internet+ Business English” teaching through teaching big data model and visualization and elaborate on the change of educational objectives in the context of Internet education. From the perspective of individual value coordinates, the goal of education is to adhere to the people-oriented, personalized, and comprehensive free development of human beings; from the perspective of social value coordinates, the goal of education is to cultivate innovative talents for social innovation and development; through the multiple perspectives of the curriculum in the context of Internet education, we analyze the goal orientation and value reshaping of the curriculum in the context of educational change. The curriculum of the future will develop toward an intelligent curriculum and introduces the curriculum design and the form of curriculum organization in the context of Internet education. A comparison of the constructed regression and classification of a total of 27 data models reveals that the model constructed based on all data in the integrated education system is the most effective. The multiple linear regression model explained up to 66.5% of the variance in student academic performance; the explanatory power of the social and demographic characteristics dimension variables ranged from approximately 13% to 18%, the personal characteristics dimension variables ranged from 7% to 20%, and the student input dimension variables ranged from 10% to 17%. The highest correct prediction rate of the binary logistic regression model was 69%.
Recurrence Factors and Characteristic Trends of Papillary Thyroid Cancer over Three Decades
Authors: Chatchomchuan Waralee , Thewjitcharoen Yotsapon , Karndumri Krittadhee , Porramatikul Sriurai , Krittiyawong Sirinate , Wanothayaroj Ekgaluck , Vongterapak Somboon , Butadej Siriwan , Veerasomboonsin Veekij , Kanchanapitak Auchai , Rajatanavin Rajata , Himathongkam Thep
Published: May 2021

Background. The prevalence of thyroid cancer is rising worldwide. Although thyroid cancer has a favorable prognosis, up to 20% of patients experienced recurrent disease during the follow-up period. The present study aimed to examine the trend of incidence and factors associated with recurrence and outcomes of papillary thyroid cancer (PTC) in Thai patients over the last 30 years. Methods. We reviewed the clinical data of all patients with PTC who were treated between 1987 and 2019 at Theptarin Hospital. Clinical characteristics, epidemic trend, factors associated with the persistence/recurrence of the disease, overall disease-specific survival rate, and overall disease-free survival rate were analysed. Results. A total of 235 patients with PTC who were registered between 1987 and 2019 were reviewed. The mean age was 42.5 ± 14.3 years, with a mean follow-up of 9.5 years. Papillary thyroid microcarcinoma (PTMC) was consistently increased and accounted for 21.4% (50/235) of total cases. The American Thyroid Association (ATA) risk stratification was high in 24% of all PTMCs in the last decade, and 16.0% of these patients experienced local recurrence during the follow-up period. Coexistence with Hashimoto’s thyroiditis (HT) was found in one-fifth of the patients with PTC and was correlated with a low recurrence rate (HR: 0.16,

P
=
0.013

). Only age ≥55 years associated with the persistence/recurrence of the disease. The overall disease-free survival and disease-specific survival rates were 77.4% and 98.3%, respectively. Conclusions. The prognosis of PTC is generally considered favorable. However, approximately one-fourth of patients with PTMC demonstrated more aggressive clinical behavior, particularly in the last decade of the study. Coexistence of HT contributed to a better prognosis.
Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer
Authors: Li Yue , Wang Meng , Yang Muwen , Xiao Yunyun , Jian Yunting , Shi Dongni , Chen Xiangfu , Ouyang Ying , Kong Lingzhi , Huang Xinjian , Bai Jiewen , Hu Yameng , Lin Chuyong , Song Libing
Published: May 2021

Balancing mRNA nuclear export kinetics with its nuclear decay is critical for mRNA homeostasis control. How this equilibrium is aberrantly disrupted in esophageal cancer to acquire cancer stem cell properties remains unclear. Here we find that the RNA-binding protein interleukin enhancer binding factor 2 (ILF2) is robustly upregulated by nicotine, a major chemical component of tobacco smoke, via activation of JAK2/STAT3 signaling and significantly correlates with poor prognosis in heavy-smoking patients with esophageal cancer. ILF2 bound the THO complex protein THOC4 as a regulatory cofactor to induce selective interactions with pluripotency transcription factor mRNAs to promote their assembly into export-competent messenger ribonucleoprotein complexes. ILF2 facilitated nuclear mRNA export and inhibited hMTR4-mediated exosomal degradation to promote stabilization and expression of SOX2, NANOG, and SALL4, resulting in enhanced stemness and tumor-initiating capacity of esophageal cancer cells. Importantly, inducible depletion of ILF2 significantly increased the therapeutic efficiency of cisplatin and abrogated nicotine-induced chemoresistance in vitro and in vivo. These findings reveal a novel role of ILF2 in nuclear mRNA export and maintenance of cancer stem cells and open new avenues to overcome smoking-mediated chemoresistance in esophageal cancer.

Significance:

This study defines a previously uncharacterized role of nicotine-regulated ILF2 in facilitating nuclear mRNA export to promote cancer stemness, suggesting a potential therapeutic strategy against nicotine-induced chemoresistance in esophageal cancer.
Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer
Authors: Kim Seung Tae , Smith Simon A. , Mortimer Peter , Loembé Arsene-Bienvenu , Cho Heejin , Kim Kyoung-Mee , Smith Claire , Willis Sophie , Irurzun-Arana Itziar , Berges Alienor , Hong Jung Yong , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Kozarewa Iwanka , Pierce Andrew J. , Dean Emma , Lee Jeeyun
Published: May 2021

Purpose:

Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.

Patients and Methods:

Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m2 on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.

Results:

The RP2D was established as ceralasertib 240 mg BD days 1–14 plus paclitaxel 80 mg/m2 on D1, D8, D15 every 28 days. The most common toxicities were neutropenia (n = 39, 68%), anemia (n = 25, 44%), and thrombocytopenia (n = 21, 37%). In the full analysis set of 57 patients, the overall response rate (ORR) was 22.6% (95% CI, 12.5–35.3). In 33 patients with melanoma, resistant to prior anti-PD1 therapy, the ORR was 33.3% (95% CI, 18.0–51.8). In the melanoma subset, the mPFS was 3.6 months (95% CI, 2.0–5.8), the median duration of response was 9.9 months (95% CI, 3.7–23.2), and the mOS was 7.4 months (95% CI, 5.7–11.9).

Conclusions:

Ceralasertib in combination with paclitaxel was well tolerated in patients with advanced malignancies and showed evidence of antitumor activity. Durable responses were observed in patients with advanced cutaneous, acral, and mucosal melanoma resistant to anti-PD1/L1 treatment.

See related commentary by Ashworth, p. 4667
PML/RARα Destabilization by Hyperthermia: A New Model for Oncogenic Fusion Protein Degradation?
Authors: Wu Hsin Chieh , Rérolle Domitille , de Thé Hugues
Published: May 2021

Summary: In this issue, Maimaitiyiming and colleagues demonstrate thermic stress–induced PML/RARα oncogenic fusion protein destabilization driven by corepressor aggregation. Hyperthermia synergizes with PML/RARα degradation by arsenic trioxide (ATO) and may circumvent ATO-resistance in historic acute promyelocytic leukemia patients. This novel approach could be extended to other corepressor-associated oncogenic fusion proteins.

See related article by Maimaitiyiming et al., p. 388.
Fat Embolism Syndrome, a Diagnostic Dilemma: Case Report and Review of the Literature
Authors: Salah Rhita , El Alami Réda , Chalouah Badr , Benchakroun Mohammed , Jaafar Abdeloihab , Bouabid Salim
Published: May 2021

Fat embolism syndrome (FES) remains a diagnostic dilemma on a world scale. It has a variable degree of presentation, which makes the diagnostic confirmation hard to obtain. FES is a life-threatening condition which is usually associated with orthopedic trauma, particularly long bones fractures whose early fixation helps in preventing it. It requires supportive care, and no specific treatment is needed. Here, we report the case of a FES in a 20 year-old male patient with right femoral shaft fracture following a motorbike accident, which is diagnosed by Gurd’s criteria and confirmed after exclusion of other diagnosis with similar clinical presentation.
Identification of the TTC26 Splice Variant in a Novel Complex Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Authors: Alfadhel Majid , Umair Muhammad , Almuzzaini Bader , Asiri Abdulaziz , Al Tuwaijri Abeer , Alhamoudi Khaloud , Alyafee Yusra , Al-Owain Mohammed
Published: May 2021

Ciliopathies constitute heterogeneous disorders that result from mutations in ciliary proteins. These proteins play an important role in the development of organs, physiology, and signaling pathways, and sequence variations in the genes encoding these proteins are associated with multisystem disorders. In this study, we describe a severe ciliopathy disorder that segregates in an autosomal recessive manner in a nonconsanguineous Saudi family. The proband exhibited features such as cholestasis, cystic dilatation of intrahepatic biliary ducts, diabetes insipidus, dysmorphic facial features, optic atrophy, pituitary hypoplasia, hydrocephalus, aqueductal stenosis, hyperextensible knee joints, bilateral knee dislocation, polydactyly, and syndactyly. Whole-genome sequencing and Sanger sequencing revealed a homozygous splice site variant (c.4–1G>C; NM_024926.3) in the tetratricopeptide repeat domain 26 (TTC26) gene located in chromosome 7q34, which cosegregated perfectly with the disease phenotype. qRT-PCR revealed a substantial decrease in the expression of the TTC26 gene as compared to the normal control, suggesting the pathogenicity of the identified variant. This report further strengthens the evidence that homozygous variants in the TTC26 gene cause severe ciliopathies with diverse phenotypes. We named this newly characterized condition as BRENS syndrome, which stands for biliary, renal, neurological, and skeletal features.
CHA2DS2-VASc Score as a Predictor of Cardiovascular and All-Cause Mortality in Chronic Kidney Disease Patients
Authors: Vodošek Hojs Nina , Ekart Robert , Bevc Sebastjan , Piko Nejc , Hojs Radovan
Published: May 2021

Introduction: Chronic kidney disease (CKD) is a risk factor for cardiovascular and all-cause mortality. Recognition of high-risk patients is important and could lead to a different approach and better treatment. The CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF), but it is also a useful predictor of outcome in other cardiovascular conditions, independent of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in predicting cardiovascular and all-cause mortality in CKD patients. Methods: Stable nondialysis CKD patients were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed till the same end date, until kidney transplantation or until their death. Results: Eighty-seven CKD patients were included (60.3 ± 12.8 years, 66% male). Mean follow-up time was 1,696.5 ± 564.6 days. During the follow-up, 21 patients died and 11 because of cardiovascular reasons. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular and all-cause mortality. In multivariate Cox regression analysis, in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, hemoglobin, high-sensitivity C-reactive protein, and intact parathyroid hormone were included, CHA2DS2-VASc score was an independent predictor of cardiovascular (HR: 2.04, CI: 1.20–3.45, p = 0.008) and all-cause mortality (HR: 2.06, CI: 1.43–2.97, p = 0.001). The same was true after adding total cholesterol, triglycerides, and smoking status to both the analyses. Conclusion: The CHA2DS2-VASc score is a simple, practical, and quick way to identify the risk for cardiovascular and all-cause mortality in CKD patients.
A Phenomenological Exploration of the Voices Reported by Borderline Personality and Schizophrenia Patients
Authors: Barrera Alvaro , Bajorek Tomasz , Dekker Romanie , Hothi Gurjiven , Lewis Alexandra , Pearce Steve
Published: May 2021

Introduction: Over time, there have been different views regarding the verbal auditory hallucinations (VAHs) reported by borderline personality disorder (BPD) and schizophrenia patients. More recently, their similarity has been emphasized, a view that undoubtedly has significant implications in terms of differential diagnosis and management. To explore this important issue, we undertook a detailed phenomenological assessment of persistent VAH reported by BPD and schizophrenia DSM-IV participants. Methods: The Psychotic Symptoms Rating Scale (PSYRATS), the Revised Beliefs About Voices Questionnaire (BAVQ-R), the Multidimensional Scale for Hallucinations (MSH), and a detailed clinical interview were administered to 11 BPD and 10 schizophrenia DSM-IV participants. Results: The VAHs of both groups were similar regarding intensity, reported as located inside or outside the head, and frequency in which they were described as a third-person phenomenon. However, the patients’ stance towards their VAH was clearly different. Whilst BPD patients identified them in a clear way in terms of gender and age and disliked them, schizophrenia patients identified them more vaguely, reported them both as more disruptive but at the same time engaged with them more positively; schizophrenia patients also integrated their VAH more into delusions. Discussion: Whilst reporting similar intensity of their VAH, the 2 groups’ stance towards them were strikingly different in that BPD participants regarded them as identifiable and unequivocally unpleasant whilst schizophrenia participants regarded them in a rather vague and ambiguous manner. Methodologically, this preliminary study suggests that in-depth phenomenological assessment can help to elucidate the differential diagnosis of VAH in these, possibly other, clinical groups. Further research is warranted to establish whether these preliminary findings are replicated on a bigger clinical sample.
Luz da diferença: responsabilidade, alteridade e a “lógica do cuidado”
Authors: Dias Diego Madi
Published: May 2021

Neste ensaio, proponho uma reflexão sobre os limites da justiça a partir do conceito de “diferença”, considerando a perspectiva dos povos indígenas. Argumento que esses povos não estão no passado, mas oferecem futuros possíveis por meio de um repertório ético ainda amplamente ignorado de atitudes de responsabilidade e cuidado frente ao que é outro. Analiso alguns elementos do sistema alimentar entre os indígenas guaranis, cuja incompreensão por parte de uma abordagem da alimentação baseada em nutrientes permite elucidar dois modos articulados de operação da colonialidade, conforme ensinou Denise Ferreira da Silva: exclusão e oclusão. Concluo com a defesa de uma pactuação descolonizante pela participação de profissionais indígenas e negros(as) nos processos de decisão e gestão em saúde como meio de efetivar a universalidade no acesso ao cuidado e à proteção do Estado.
O mal e o niilismo no romance “Os demônios”, de Dostoiévski
Authors: Golin Luana Martins
Published: May 2021

Os temas do mal e do niilismo são recorrentes na obra dostoievskiana. Contudo, em Os demônios (1871), o próprio título e a epígrafe da obra já sugerem, de maneira mais explícita, o caráter do demoníaco nas ações das personagens. O suicídio, o assassinato, a violação, a morte, o caos, a censura, a falta de liberdade e a destruição são elementos presentes e atuantes na narrativa. Esse artigo buscou aproximar o olhar sobre as forças e o movimento do mal, cujo fim é a falta de sentido, o nada.
Conatus interruptus
Authors: Bensussan Gerard
Published: May 2021

--
Dostoiévski em Nietzsche: considerações crítico-genealógicas
Authors: Cabral Alexandre
Published: May 2021

O presente artigo pretende assinalar dois modos de Nietzsche se apropriar da obra de Dostoiévski com o propósito de fortalecer seu projeto genealógico. Nesse sentido, Dostoiévski fornece um excelente material psicológico e fisiológico, que possibilitará a Nietzsche distinguir os diversos modos de concretização do ressentimento, além da idiotia como elemento central na caracterização do tipo do Redentor, tal como se encontra presente na obra O anticristo.
Apresentação
Authors: Cabral Jimmy Sudario , Bensussan Gérard
Published: May 2021

Apresentação dossiê
Characterizing Diaschisis-Related Thalamic Perfusion and Diffusion After Middle Cerebral Artery Infarction
Authors: Xia Cong , Zhou Jiaying , Lu Chunqiang , Wang Yuancheng , Tang Tianyu , Cai Yu , Ju Shenghong
Published: May 2021

Background and Purpose:

Ipsilateral thalamic diaschisis (ITD) initially describes functional depression of the thalamus ipsilateral to a supratentorial lesion, but accumulating evidence has shown morphological changes also occur. Therefore, we aimed to characterize thalamic perfusion and diffusion related to ITD over time and their inter-relationships after middle cerebral artery infarction.

Methods:

Eighty-five patients with middle cerebral artery infarction who underwent diffusion kurtosis imaging and arterial spin labeling were retrospectively included. ITD was diagnosed as ipsilateral thalamic hypoperfusion present on ≥2 cerebral blood flow maps. The thalamic asymmetrical index was calculated as (ipsilateral value−contralateral value)/contralateral value×100%. Finally, the inter-relationships of thalamic perfusion and diffusion were analyzed.

Results:

ITD was present in 56/85 patients (65.9%, ITD+). In ITD+ patients, larger abnormal perfusion volume, higher perfusion-infarct mismatch and lower rates of focal hyperperfusion were observed than ITD− patients. Infarction affecting the corona radiata were more frequent among ITD+ patients. Mean kurtosis were slightly but significantly increased within the ipsilateral thalamus compared with the contralateral one in ITD+ patients of subacute and chronic groups, while fractional anisotropy was significantly increased in subacute group but decreased in chronic group for both ITD+ and ITD− patients. Mean diffusivity was significantly increased in ITD+ patients of chronic group. Furthermore, the AI
CBF
was negatively and significantly correlated with AI
MK
and AI
FA
in ITD+ patients in subacute group, and AI
MD
, even after adjustment for abnormal perfusion volume and days from symptoms onset, in chronic group. ITD+ patients had significantly higher National Institutes of Health Stroke Scale and modified Rankin Scale scores at admission and discharge and also showed a trend to independent association with clinical outcome at discharge.

Conclusions:

The combination of arterial spin labeling and diffusion kurtosis imaging can reveal early, time-specific thalamic perfusion and diffusion changes after middle cerebral artery infarction. ITD-related hypoperfusion was significantly correlated with underlying microstructural alterations.