bluuebunny/crossref_metadata_2025 huggingface dataset:
Job Scheduling in Cloud Computing Using a Modified Harris Hawks Optimization and Simulated Annealing Algorithm
Authors: Attiya Ibrahim , Abd Elaziz Mohamed , Xiong Shengwu
Published: March 2020

In recent years, cloud computing technology has attracted extensive attention from both academia and industry. The popularity of cloud computing was originated from its ability to deliver global IT services such as core infrastructure, platforms, and applications to cloud customers over the web. Furthermore, it promises on-demand services with new forms of the pricing package. However, cloud job scheduling is still NP-complete and became more complicated due to some factors such as resource dynamicity and on-demand consumer application requirements. To fill this gap, this paper presents a modified Harris hawks optimization (HHO) algorithm based on the simulated annealing (SA) for scheduling jobs in the cloud environment. In the proposed HHOSA approach, SA is employed as a local search algorithm to improve the rate of convergence and quality of solution generated by the standard HHO algorithm. The performance of the HHOSA method is compared with that of state-of-the-art job scheduling algorithms, by having them all implemented on the CloudSim toolkit. Both standard and synthetic workloads are employed to analyze the performance of the proposed HHOSA algorithm. The obtained results demonstrate that HHOSA can achieve significant reductions in makespan of the job scheduling problem as compared to the standard HHO and other existing scheduling algorithms. Moreover, it converges faster when the search space becomes larger which makes it appropriate for large-scale scheduling problems.
Assessment of the Effect of Replacing Normal Aggregate by Porcelinite on the Behaviour of Layered Steel Fibrous Self-Compacting Reinforced Concrete Slabs under Uniform Load
Authors: AL-Ridha Ahmed S. D. , Abbood Ali A. , Atshan Ali F.
Published: March 2020

In this research, an attempt has been made to study the effect of replacing all normal-weight aggregate “NWA” by lightweight aggregate “LWA” (having a volume equal to 60% of the volume of normal-weight aggregate) on the behaviour of layered steel fibrous self-compacting reinforced concrete slabs with various volume fractions of steel fiber under uniform area load using fine sand technique. The experimental work consists of two groups “NWA” and “LWA,” each group consists of three slab specimens (having an aspect ratio equal to the golden ratio, i.e., 1.618), the thickness of each slab is divided into two equal layers, the top layer is free from steel fibers, while the steel fibers exist only in the bottom layer with three volume fractions (0%, 0.4%, and 0.8%). Ultimate uniform load of the slabs decreases with the increase in steel fiber content, while the percentage of decrease in the bulk density remains rather constant. It was also found that the ultimate uniform load of the slabs in each group is significantly improved with increasing steel fiber content, and the percentage of this improvement is higher in lightweight concrete “LWC” than in normal-weight concrete “NWC” Finally, it was noticed that when steel fiber increased, the flexural strength of slabs increased higher than shear strength; therefore, the mode of failure has been changed from bending to shear mode for slabs of both groups “NWC” and “LWC.”
Arsenic Trioxide Treatment during Pregnancy for Acute Promyelocytic Leukemia in a 22-Year-Old Woman
Authors: Cochet Claire , Simonet Marion , Cattin Julie , Metz Jean-Patrick , Berceanu Ana , Deconinck Eric , Daguindau Etienne , Schillinger Françoise , Fenaux Pierre , Mottet Nicolas , Desbrosses Yohan
Published: March 2020

Acute leukemia during pregnancy is rare (1 for 100000 pregnancies). The association of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is known as the best therapy in standard-risk acute promyelocytic leukemia (APL). We describe the first case of a pregnancy with ATRA and ATO reported in the literature. In March 2018 at the University Hospital of Besançon, a 22-year-old woman was diagnosed with APL at 14 weeks of gestation (WG). She received a total of 2160 mg of ATRA and 930 mg of ATO between 14 and 35 WG. The mother’s cytological remission was very fast. No maternal or fetal complications occurred during pregnancy. The pediatrics outcomes were good. Many case reports about ATRA exposure during the second and third trimesters report no serious adverse effect for pregnancy. ATO is teratogenic, genotoxic, and carcinogenic and passes through the placenta. Fetal exposure seems to be associated with bad pregnancy outcomes (preterm delivery, decreased birth weight, and fetal loss) and with lung diseases in young adults. No clinical trial is obviously possible, and the only data available are environmental exposure or animal studies. This case report may help medical teams to make hard decision for a treatment of APL during pregnancy.
Delay Testing Method for Off-Site Asynchronous LTE Networks Based on Singular Value Removal
Authors: Ni Shuangshuang , Cui Ke , Zhang Kai , Zheng Guoxin
Published: March 2020

This paper presents an experimental campaign of transmission delay measurements under asynchronous condition for the communication-based train control (CBTC) systems. A three-stage asynchronous clock correction method is proposed. Before and after the working stage, the clock difference between transmitter and the receiver is calculated, moreover the relative offset and relative skew between two terminals of the working stage are derived, and it further leads towards the experimental verification of the transmission delay. In order to improve the measurement accuracy, the singular values are distinguished and eliminated in the test. Using this method, the transmission delay of the Long-Term Evolution for Metro (LTE-M) communication between the train and the signalling room in Shanghai Zhangjiang Metro Training Line is measured successfully, which demonstrates the effectiveness of the proposed one-way transmission delay test.
Enhancing the Phytoremediation of Hydrocarbon-Contaminated Soils in the Sudd Wetlands, South Sudan, Using Organic Manure
Authors: Ruley J. A. , Amoding A. , Tumuhairwe J. B. , Basamba T. A. , Opolot E. , Oryem-Origa H.
Published: March 2020

Phytoremediation of hydrocarbon-contaminated soils is a challenging process. In an effort to enhance phytoremediation, soil was artificially contaminated with known concentration of light crude oil containing Total petroleum hydrocarbon (TPH) at a concentration of 75 gkg−1 soil. The contaminated soil was subjected to phytoremediation trial using four plant species (Oryza longistaminata, Sorghum arundinaceum, Tithonia diversifolia, and Hyparrhenia rufa) plus no plant used as control for natural attenuation. These phytoremediators were amended with concentrations (0, 5 and 10 gkg−1 soil) of organic manure (cow dung). Results at 120 days after planting, showed that application of manure at concentrations of 5 and 10 gkg−1 soil combined with an efficient phytoremediator can significantly enhance reduction of TPH compared to natural attenuation or use of either manure or a phytoremediator alone (p<0.05). The study also showed that a treatment combination of manure 5 gkg−1 soil, with a phytoremediator gives a similar mean percentage reduction of TPH as manure 10 gkg−1 soil (p>0.05). Therefore, the study concludes that use of phytoremediators and manure 5 gkg−1 soil could promote the restoration of TPH contaminated-soils in the Sudd region of South Sudan.
User’s Attitude under the Perspective of Mental Energy Flow
Authors: Yang Jing , Zhao Qingchao , Zhao Xin , Wu Di , Li Ming , Zhang Wei
Published: March 2020

The analysis of the attitudes of online users plays an important role in real life and the future society, which can help us to analyze and predict the behavior of the users. The researchers also carried out a lot of related work. However, most of the previous classic methods searched the rules of the structure of the graph or the propagation path and did not consider the internal psychological dynamic mechanism of the user. In the context of big data, identifying online behavioral motivations of users through online information should be a future development trend. In this paper, we delve into the users’ internal psychological energy based on the Elaboration Likelihood Model and divide the user’s behavioral drive into the central route and the peripheral route. The degree of user’s processing of the known information and elaboration determines which route is more effective. The central route is mainly the user’s behavioral habits studied through user role theory. In the peripheral route, it calculates the influence of other users through a kind of hydromechanics algorithm—FluidRating. The final model we called ELMFluid which can express the flow of psychological energy through thermodynamics and hydromechanics. The experiments are performed using two real datasets in the end. The results show that the new model is superior to other algorithms.
Endovascular Treatment of Venous Bypass Graft Pseudoaneurysm with the New Solaris Self-Expanding Covered Stent
Authors: San Norberto Enrique M. , Fidalgo-Domingos Liliana A. , Cenizo Noelia , Revilla Álvaro , Taylor James H. , Vaquero Carlos
Published: March 2020

Nonanastomotic pseudoaneurysm formation after vascular reconstruction is a rarely encountered problem. Covered stent graft constitutes a minimal approach. To our knowledge, the present study constitutes the first case of implantation of Solaris stent graft in Europe. A 69-year-old man with severe cardiac dysfunction presented a pseudoaneurysm of a popliteal to popliteal artery reversed saphenous vein bypass graft. The patient was successfully treated by the percutaneous placement of a Solaris self-expanding covered stent. The postimplantation arteriogram demonstrated exclusion of the pseudoaneurysm, complete apposition of the stent, and adequate runoff. No complications occurred, and the patient was discharged from the hospital one day later receiving 75 mg of clopidogrel. Endovascular exclusion by covered stent deployment offers a safe, rapid, and minimally invasive alternative to open surgical resection in patients with lower limb venous graft pseudoaneurysm. The Solaris covered stent provides a new catheter-based device with adequate navigability and exceptional accurate delivery system.
Influence of Karst Caves at Pile Side on the Bearing Capacity of Super-Long Pile Foundation
Authors: Wang Peisen , Ding Hongyan , Zhang Puyang
Published: March 2020

The differences in development and situation of karst caves lead to two kinds of karst caves, and the karst cave may be on the pile side or at the pile bottom, which has a different influence on the bearing capacity of pile foundation. The paper presents a numerical analysis of the influence of karst caves at pile side on the bearing capacity of super-long pile foundation in karst areas. According to the size of pile foundation of a real bridge project, this paper modelized karst caves and investigated the karst cave from the effect of length, height, and thickness of roof on horizontal and vertical bearing capacity of pile foundation. The main conclusions can be drawn as: when the horizontal displacement at the top of pile foundation is greater than 0.05 m, the horizontal load is correlated positively with the length of karst cave; when the vertical displacement is greater than 0.07 m, the vertical load is correlated negatively with the thickness of the roof of karst cave. However, the height of karst cave has little effect on the bearing capacity; also the existence of karst cave has little influence on the dynamic response of pile foundation. The results of this study can be important with reference to the design and construction of pile foundations in karst areas.
One Lung Soldier: A Ventilation Conundrum in a Postpneumonectomy Syndrome Complicated by Acute Respiratory Syndrome
Authors: Purewal Jaskaran K. , Sakul N. F. N. , Balabbigari Nikhita R. , Nenninger Alberto , Kotecha Nisha
Published: March 2020

Postpneumonectomy syndrome involves mediastinal shift causing dynamic airway obstruction via compression of the main bronchus and distal trachea. A few case reports describe the development of ARDS in patients with postpneumonectomy syndrome. Reeb et al. (2017) describe the mortality of postpneumonectomy ARDS anywhere from 33% to 88%. One may encounter difficulty in intubation and ventilation as parameters based on ideal body weight may not apply. Prone positioning ventilation and ECMO have been successfully used in isolated cases. We present such a case and highlight challenges in management. A 70-year-old male Vietnam veteran with remote history of right pneumonectomy thirty years prior presented with fever, cough, and dyspnea. Physical exam was significant for T 36.3°C, BP 162/73, heart rate 145 BPM, RR 22 breaths/minute, ht. 1.72 m, and wt. 78 kg, with transmitted right lung sounds and rhonchi on the left. Labs showed WBC 23.92/nL and procalcitonin 0.84 ng/mL. CXR showed left infiltrate and opacification of right hemithorax with right mediastinal shift. EKG showed atrial fibrillation. He was started on broad spectrum antibiotics for pneumonia, but deteriorated, and was intubated for respiratory distress from ARDS. Vasopressors were initiated for shock. Given the history of pneumonectomy, he was initially ventilated with lower tidal volumes (320 mL). However, incremental changes were made to tidal volumes, and ETT was repositioned several times for hypoxia. Epoprostenol and cisatracurium were also initiated. Positional changes would lead to sudden desaturation; hence, prone positioning ventilation was not done. He was not considered for ECMO due to his pneumonectomy status. Unfortunately, his condition worsened progressively and he expired. The guidelines for ARDS are well established. However, postpneumonectomy patients are unique as seen in our patient. It is unclear whether an endobronchial tube advanced into the left bronchus could have helped difficult airway management resulting from suspected postpneumonectomy syndrome as suggested by CXR. Higher tidal volumes were also unsuccessful in alleviating hypoxia and led to persistently elevated plateau pressures and driving pressures as high as 23, which was inconsistent with our goal of lung protective ventilation. Few case reports describe the successful use of prone positioning ventilation or ECMO in postpneumonectomy patients with ARDS. Although not well studied, low tidal volumes supported with ECMO may have been a favorable strategy for our patient.
Antioxidant Activities of Streptomyces sp. strain MUSC 14 from Mangrove Forest Soil in Malaysia
Authors: Kemung Hefa Mangzira , Tan Loh Teng-Hern , Chan Kok-Gan , Ser Hooi-Leng , Law Jodi Woan-Fei , Lee Learn-Han , Goh Bey-Hing
Published: March 2020

The mangrove ecosystem of Malaysia remains yet to be fully explored for potential microbes that produce biologically active metabolites. In the present study, a mangrove‐derived Streptomyces sp. strain MUSC 14 previously isolated from the state of Pahang, Malaysia Peninsula, was studied for its potential in producing antioxidant metabolites. The identity of Streptomyces sp. strain MUSC14 was consistent with the genotypic and phenotypic characteristics of the Streptomyces genus. The antioxidant potential of Streptomyces sp. strain MUSC 14 was determined through screening of its methanolic extract against sets of antioxidant assays. The results were indicative of Streptomyces sp. strain MUSC 14 displaying strong antioxidant activity against ABTS, DPPH free radicals and metal chelating activity of 62.71 ± 3.30%, 24.71 ± 2.22%, and 55.82 ± 2.35%, respectively. The result of ferric reducing activity measured in terms of dose was equivalent to 2.35–2.45 μg of positive control ascorbic acid. Furthermore, there was a high correlation between the total phenolic content and the antioxidant activities with r = 0.979, r = 0.858, and r = 0.983 representing ABTS, DPPH, and metal chelation, respectively. Overall, the present study suggests that Streptomyces sp. strain MUSC 14 from mangrove forest soil has potential to produce antioxidant metabolites that can be further exploited for therapeutic application.
Antimicrobial Effect of a Peptide Containing Novel Oral Spray on Streptococcus mutans
Authors: Xiong Kaixin , Chen Xuan , Hu Hantao , Hou Huihui , Gao Peng , Zou Ling
Published: March 2020

Objective. To investigate the antibacterial effect of a novel antimicrobial peptide containing oral spray GERM CLEAN on Streptococcus mutans (S. mutans) in vitro and further explore the related mechanisms at phenotypic and transcriptional levels. Methods. The disk diffusion method was used to preliminarily appraise the antimicrobial effect of GERM CLEAN. The minimal inhibitory concentration (MIC) of GREM CLEAN towards S. mutans was determined by the broth dilution method. S. mutans virulence‐related phenotypic assays including initial adhesive assay, pH drop, exopolysaccharides (EPS), and biofilm formation measurements and quantitative real‐time PCR (qRT‐PCR) were further applied to detect the inhibitory mechanisms of GREM CLEAN at 1/2MIC. Results. The diameter (10.18 ± 1.744 mm) of inhibition zones formed by GERM CLEAN preliminarily indicated its inhibitory effect on the major cariogenic bacteria S. mutans. The minimal inhibitory concentration of GERM CLEAN on S. mutans was 100% mass fraction (the stock solution). The study of the antibacterial mechanism showed that GERM CLEAN had a certain inhibitory effect on the initial adhesion, acid production, extracellular polysaccharides (EPS) production, and biofilm formation of S. mutans. GERM CLEAN disturbed S. mutans biofilm physiology mainly through destruction of biofilm architecture and suppression of bacterial growth. The results of qRT‐PCR further confirmed that the expression levels of EPS and lactic acid generation genes including gtfB, gtfC, gtfD, and ldh were significantly repressed by treating with GERM CLEAN, and this was consistent with our phenotypic results. Conclusion. The novel antimicrobial peptide containing oral spray GERM CLEAN has an anti‐Streptococcus mutans effect and the inhibitory property may be due to suppression of the virulence factors of S. mutans including adhesive, acidogenicity, EPS, and biofilm formation.
Linear Complexity of Generalized Cyclotomic Sequences of Order 4 over Fl
Authors: Sun Yuhua , Wang Qiuyan , Yan Yang , Yan Tongjiang , Li Hui
Published: March 2020

Generalized cyclotomic sequences of period pq have several desirable randomness properties if the two primes p and q are chosen properly. In particular, Ding deduced the exact formulas for the autocorrelation and the linear complexity of these sequences of order 2. In this paper, we consider the generalized sequences of order 4. Under certain conditions, the linear complexity of these sequences is developed over a finite field Fl. The results show that, in many cases, they have high linear complexity.
Spatiotemporal Approaches for Quality Control and Error Correction of Atmospheric Data through Machine Learning
Authors: Kim Hye-Jin , Park Sung Min , Choi Byung Jin , Moon Seung-Hyun , Kim Yong-Hyuk
Published: March 2020

We propose three quality control (QC) techniques using machine learning that depend on the type of input data used for training. These include QC based on time series of a single weather element, QC based on time series in conjunction with other weather elements, and QC using spatiotemporal characteristics. We performed machine learning-based QC on each weather element of atmospheric data, such as temperature, acquired from seven types of IoT sensors and applied machine learning algorithms, such as support vector regression, on data with errors to make meaningful estimates from them. By using the root mean squared error (RMSE), we evaluated the performance of the proposed techniques. As a result, the QC done in conjunction with other weather elements had 0.14% lower RMSE on average than QC conducted with only a single weather element. In the case of QC with spatiotemporal characteristic considerations, the QC done via training with AWS data showed performance with 17% lower RMSE than QC done with only raw data.
Diabetes, Fetal Demise, and Shoulder Dystocia: The Importance of Glucose Screening to Prevent Catastrophic Obstetric Outcomes
Authors: Hussain S. Ahmed , Smith Alisha M. , Cross Jennifer A.
Published: March 2020

Diabetes is associated with increased risk of stillbirth and shoulder dystocia. Compared with uncomplicated pregnancies, diabetic patients have a 4-6x risk of stillbirth and 2-3x risk of shoulder dystocia. A 34 yo G2P0010 presented with a 40+3 wga IUFD with nonstandard antenatal glucose screening. Admission labs included a hemoglobin A1c of 6.6. She had a vaginal delivery complicated by a 30-minute shoulder dystocia that was not relieved by McRoberts, suprapubic pressure, Rubin II, Wood’s Screw, or posterior arm delivery. Nitroglycerine was administered, after which Wood’s Screw was successful resulting in delivery of an infant weighing 4190 grams (85th percentile for gestational age). A 31 yo G1 presented with a 37+1 wga IUFD. Her 28 wga three-hour GTT was notable for an elevated value at one hour (216 mg/dL). Admission labs included a hemoglobin A1c of 6.6. She had a vaginal delivery complicated by a 30-minute shoulder dystocia that was relieved via posterior axillary sling after failure of McRoberts, suprapubic pressure, Rubin II, Wood’s Screw, and Gaskin’s, resulting in the delivery of an infant weighing 3590 g (92nd percentile for gestational age). We present two cases of severe shoulder dystocia in patients who both presented with term IUFD and diabetic-range hemoglobin A1c. There is minimal literature on diabetic patients with pregnancies affected by both stillbirth and shoulder dystocia. These cases underscore the importance of glucose screening and control to prevent catastrophic obstetric outcomes.
Detection of Moderate Traumatic Brain Injury from Resting-State Eye-Closed Electroencephalography
Authors: Lai Chi Qin , Ibrahim Haidi , Abd. Hamid Aini Ismafairus , Abdullah Mohd Zaid , Azman Azlinda , Abdullah Jafri Malin
Published: March 2020

Traumatic brain injury (TBI) is one of the injuries that can bring serious consequences if medical attention has been delayed. Commonly, analysis of computed tomography (CT) or magnetic resonance imaging (MRI) is required to determine the severity of a moderate TBI patient. However, due to the rising number of TBI patients these days, employing the CT scan or MRI scan to every potential patient is not only expensive, but also time consuming. Therefore, in this paper, we investigate the possibility of using electroencephalography (EEG) with computational intelligence as an alternative approach to detect the severity of moderate TBI patients. EEG procedure is much cheaper than CT or MRI. Although EEG does not have high spatial resolutions as compared with CT and MRI, it has high temporal resolutions. The analysis and prediction of moderate TBI from EEG using conventional computational intelligence approaches are tedious as they normally involve complex preprocessing, feature extraction, or feature selection of the signal. Thus, we propose an approach that uses convolutional neural network (CNN) to automatically classify healthy subjects and moderate TBI patients. The input to this computational intelligence system is the resting-state eye-closed EEG, without undergoing preprocessing and feature selection. The EEG dataset used includes 15 healthy volunteers and 15 moderate TBI patients, which is acquired at the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. The performance of the proposed method has been compared with four other existing methods. With the average classification accuracy of 72.46%, the proposed method outperforms the other four methods. This result indicates that the proposed method has the potential to be used as a preliminary screening for moderate TBI, for selection of the patients for further diagnosis and treatment planning.
Adult Ectopic Cervical Thymic Tissue in relation to a Parathyroid Adenoma and a Papillary Thyroid Carcinoma: A Report of Two Cases
Authors: Nijhawan Vijay Shrawan , Sehrawat Roopali , Goyal Neeti , Gupta Manish
Published: March 2020

Ectopic cervical thymus is a rare congenital anomaly, which results because of the failure of complete descent of the thymus. They are incidental findings in the young and may disappear during the early years of life; however, they have rarely been described in adults. Some of them may undergo hyperplasia or neoplastic transformation and become visible or cause symptoms. We report two rare cases of incidentally detected cervical thymic tissue in adults. In one case, the thymic tissue was seen adjacent to a parathyroid adenoma of the left inferior parathyroid gland. In the other, it was seen adjacent to the left inferior parathyroid gland in a case of papillary thyroid carcinoma. In both these cases, the ectopic thymic tissue was diagnosed as a result of pathological examination, not clinically by macroscopic appearance during operation or radiological evaluation. The finding needs to be noted as these ectopic foci can occasionally give rise to hyperplasia and neoplasms of the thymus.
Centralized Maintenance Time Prediction Algorithm for Freight Train Wheels Based on Remaining Useful Life Prediction
Authors: Shi Hongmei , Yang Jinsong , Si Jin
Published: March 2020

Many freight trains for special lines have in common the characteristics of a fixed group. Centralized Condition-Based Maintenance (CCBM) of key components, on the same freight train, can reduce maintenance costs and enhance transportation efficiency. To this end, an optimization algorithm based on the nonlinear Wiener process is proposed, for the prediction of the train wheels Remaining Useful Life (RUL) and the centralized maintenance timing. First, Hodrick–Prescott (HP) filtering algorithm is employed to process the raw monitoring data of wheel tread wear, extracting its trend components. Then, a nonlinear Wiener process model is constructed. Model parameters are calculated with a maximum likelihood estimation and the general deterioration parameters of wheel tread wear are obtained. Then, the updating algorithm for the drift coefficient is deduced using Bayesian formula. The online updating of the model is realized, based on individual wheel monitoring data, while a probability density function of individual wheel RUL is obtained. A prediction method of RUL for centralized maintenance is proposed, based on two set thresholds: “maintenance limit” and “the ratio of limit-arriving.” Meanwhile, a CCBM timing prediction algorithm is proposed, based on the expectation distribution of individual wheel RUL. Finally, the model is validated using a 500-day online monitoring data on a fixed group, consisting of 54 freight train cars. The validation result shows that the model can predict the wheels RUL of the train for CCBM. The proposed method can be used to predict the maintenance timing when there is a large number of components under the same working conditions and following the same path of degradation.
Validity Prediction of Amplitude-Integrated EEG in Early Neuromotor Development Outcomes in High-Risk Neonates
Authors: Guo Jian , Wang Wentao , Zhou Qili
Published: March 2020

With the continuous advancement of medical technology, the survival rate of high-risk children is increasing year by year, but the developmental problems that have gradually become apparent in the later stages have a serious impact on the quality of life of children. Amplitude-integrated EEG is an EEG monitoring technology developed for clinical use in newborns in recent years. Therefore, to better detect neuromata development in high-risk children, this study explores the validity prediction of amplitude-integrated EEG in early neuromata development in high-risk children. For 100 high-risk children, amplitude-integrated EEG was used for monitoring, and the exercise scale and validity predictors in the Bailey Infant Development Scale were used to assess whether high-risk children had neurobehavioral abnormalities. The experimental results show that the application of amplitude-integrated EEG can make accurate and effective predictions of early neuromata development outcomes in high-risk children. Compared with traditional neurological examination methods, it has higher sensitivity, specificity, positive predictive value, and consistency in predicting the early neuromata development outcomes of high-risk children. It is suitable for application and promotion in China and has a good application value.
Rb and p53-Deficient Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma Require Skp2 for Survival
Authors: Li George Z. , Okada Tomoyo , Kim Young-Mi , Agaram Narasimhan P. , Sanchez-Vega Francisco , Shen Yawei , Tsubokawa Norifumi , Rios Jordan , Martin Axel S. , Dickson Mark A. , Qin Li-Xuan , Socci Nicholas D. , Singer Samuel
Published: March 2020

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS.

Significance:

Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies.

See related commentary by Lambert and Jones, p. 2437
Destruction of a Microtubule-Bound MYC Reservoir during Mitosis Contributes to Vincristine's Anticancer Activity
Authors: Becker Sabrina , Kiecke Christina , Schäfer Eva , Sinzig Ursula , Deuper Lena , Trigo-Mourino Pablo , Griesinger Christian , Koch Raphael , Rydzynska Zuzanna , Chapuy Bjoern , von Bonin Frederike , Kube Dieter , Venkataramani Vivek , Bohnenberger Hanibal , Leha Andreas , Flach Johanna , Dierks Sascha , Bastians Holger , Maruschak Brigitte , Bojarczuk Kamil , Taveira Mateus de Oliveira , Trümper Lorenz , Wulf Gerburg M. , Wulf Gerald G.
Published: March 2020

Tightly regulated activity of the transcription factor MYC is essential for orderly cell proliferation. Upon deregulation, MYC elicits and promotes cancer progression. Proteasomal degradation is an essential element of MYC regulation, initiated by phosphorylation at Serine62 (Ser62) of the MB1 region. Here, we found that Ser62 phosphorylation peaks in mitosis, but that a fraction of nonphosphorylated MYC binds to the microtubules of the mitotic spindle. Consequently, the microtubule-destabilizing drug vincristine decreases wild-type MYC stability, whereas phosphorylation-deficient MYC is more stable, contributing to vincristine resistance and induction of polyploidy. PI3K inhibition attenuates postmitotic MYC formation and augments the cytotoxic effect of vincristine.

Implications:

The spindle's function as a docking site for MYC during mitosis may constitute a window of specific vulnerability to be exploited for cancer treatment.
The Importance of Mid-Follicular Phase Luteinizing Hormone Rise in GnRH Antagonist-Based Ovarian Stimulation for IVF
Authors: Vanetik Sharon , Beck-Fruchter Ronit , Segal Linoy , Kol Shahar
Published: March 2020

Introduction: Previous publications examined the endocrinology of follicular stimulation, focusing on luteinizing hormone (LH) levels changes. In selected, good prognosis IVF patients, a sharp drop in LH serum level was demonstrated between cycle days 2 and 6. Objective: The purpose of this study was to examine if this finding holds true for unselected patients. Methods: We retrospectively included 165 consecutive patients treated with a GnRH antagonist-based ovarian stimulation protocol during the year 2015. Results and Conclusions: In 33% of the patients an increase in LH, rather than the expected decrease, was demonstrated after 5 stimulation days. There was no difference in pregnancy outcome. Our results suggest that an increase in LH levels during ovarian stimulation occurs mainly in “high responders”, or “low responders”. LH rise in mid follicular phase may result in a sharp LH drop once a GnRH antagonist is given, and the possible need for LH supplementation.
A Single Monoclonal Antibody against the Peanut Allergen Ara h 2 Protects against Systemic and Local Peanut Allergy
Authors: Storni Federico , Cabral-Miranda Gustavo , Roesti Elisa , Zha Lisha , Engeroff Paul , Zeltins Andris , Cragg Mark , Vogel Monique , Bachmann Martin F.
Published: March 2020

Background: Peanut allergy is the most prevalent and dangerous food allergy. Peanuts consist of a large number of different allergens and peanut-allergic patients are frequently sensitized to multiple allergens. Hence, conventional desensitization approaches aim at targeting as many allergens as possible. Methods: The monoclonal anti-Ara h 2 antibody (mAb) was produced by hybridoma cells derived from WT BALB/c mice after immunization with a vaccine based on virus-like particles coupled to Ara h 2. BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum and mAbs were applied i.v. Challenge was performed the next day with the whole peanut extract intravenously and via skin prick test. Results: Here we show in peanut-allergic mice that a single high-affinity mAb specific for Ara h 2 is able to block systemic and local allergic reactions induced by the complex peanut extract. We confirm in vitro binding of the mAb to the inhibitory low-affinity FcγRIIb receptor using a sensitive biosensor and demonstrate in vivo that protection was dependent on FcγRIIb. Conclusion: A single mAb specific for Ara h 2 is able to improve local and systemic allergic symptoms induced by the whole allergen mixture.
Semaphorin-3A-Related Reduction of Thymocyte Migration in Chemically Induced Diabetic Mice
Authors: Francelin Carolina , Geniseli Ieda , Nagib Patrícia , Gameiro Jacy , Savino Wilson , Verinaud Liana
Published: March 2020

Background: Previous work revealed the existence of a severe thymic atrophy with massive loss of immature CD4+CD8+ thymocytes in animals developing insulin-dependent diabetes, chemically induced by alloxan. Furthermore, the intrathymic expression of chemokines, such as CXCL12, is changed in these animals, suggesting that cell migration-related patterns may be altered. One molecular interaction involved in normal thymocyte migration is that mediated by soluble semaphorin-3A and its cognate receptor neuropilin-1. Objectives: We investigated herein the expression and role of semaphorin-3A in the migratory responses of thymocytes from alloxan-induced diabetic mice. We characterized semaphorin-3A and its receptor, neuropilin-1, in thymuses from control and diabetic mice as well as semaphorin-3A-dependent migration of developing thymocytes in both control and diabetic animals. Methods: Diabetes was chemically induced after a single injection of alloxan in young adult BALB/c mice. Thymocytes were excised from control and diabetic individuals and subjected to cytofluorometry for simultaneous detection of semaphorin-3A or neuropilin-1 in CD4/CD8-defined subsets. Cell migration in response to semaphorin-3A was performed using cell migration transwell chambers. Results: Confirming previous data, we observed a severe decrease in the total numbers of thymocytes in diabetic mice, which comprised alterations in both immature (double-negative subpopulations) and mature CD4/CD8-defined thymocyte subsets. These were accompanied by a decrease in the absolute numbers of semaphorin-3A-bearing thymocytes, comprising CD4–CD8–, CD4+CD8+, and CD4–CD8+ cells. Additionally, immature CD4–CD8– and CD4+CD8+ developing T cells exhibited a decrease in the membrane density of semaphorin-3A. The relative and absolute numbers of neuropilin-1-positive thymocytes were also decreased in diabetic mouse thymocytes compared to controls, as seen in CD4–CD8–, CD4+CD8+, and CD4–CD8+ cell subpopulations. Functionally, we observed a decrease in the chemorepulsive role of semaphorin-3A, as revealed by transwell migration chambers. Such an effect was seen in all immature and mature thymocyte subsets. Conclusions: Taken together, our data clearly unravel a disruption in the normal cell migration pattern of developing thymocytes following chemically induced insulin-dependent diabetes, as ascertained by the altered migratory response to sempahorin-3A. In conceptual terms, it is plausible to think that such disturbances in the migration pattern of thymocytes from these diabetic animals may exert an impact in the cell-mediated immune response of these mice.
Monotonous Broom Hairs: A Feature of Trichoteiromania
Authors: João Ana Luísa , Cunha Nélia , Pessoa e Costa Tomás , Lencastre André
Published: March 2020

Trichoteiromania is a self-inflicted traumatic hair injury, with breaking of the hair shafts resulting from repetitive rubbing of the scalp. We describe a patient with trichoteiromania presenting with one lichenified pruriginous plaque on the scalp, associated with fracture and loss of hair shafts giving the conspicuous appearance of monotonous clusters of broom hairs under trichoscopy, which pointed to the diagnosis. As trichoteiromania can be considered a psychodermatological condition, patient education and a behavioral approach are of paramount importance in the management and prognosis of this disorder.
Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected – Narrative Review Article
Authors: AlTakarli Nourah S.
Published: March 2020

Background: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. Methods: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. Results: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.
Elevated Plasma X-Linked Neuroligin 4 Expression Is Associated with Autism Spectrum Disorder
Authors: Al-Ayadhi Laila Y. , Qasem Hanan Y. , Alghamdi Hend Ali M. , Elamin Nadra E.
Published: March 2020

Objectives: In this study, we compared plasma levels of neuroligin 4 (NLGN4) in children with autism versus matched healthy controls to examine a possible correlation between plasma NLGN4 and degree of autism severity as well as social impairment in autistic patients. Subjects and Methods: 88 autistic patients aged 3–12 years and 33 age- and sex-matched controls aged 3–9 years were recruited. Plasma levels of NLGN4 were determined using a commercial enzyme-linked immunoassay (ELISA). The Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS) were used to assess cognitive dysfunction and social impairment in autistic patients. Results: Plasma levels of NLGN4 were significantly higher (p = 0.001) in autistic children than in healthy controls. Despite alterations in the levels of NLGN4 in the subgroups of the autistic children, no correlation between plasma concentration of NLGN4 and cognitive problems or social impairment was observed (p> 0.05). Conclusion: Increased plasma concentrations of NLGN4 may play a role in the pathogenesis of autism, and it could be a valuable biomarker for autism. Further studies with larger sample sizes are warranted to validate this finding and also to explore the potential links between NLGN4 and the features of autism.
Role of Inflammation in Retinal Microcirculation in Diabetic Eyes: Correlation between Aqueous Flare and Microvascular Findings
Authors: Celik Buyuktepe Tuna , Özmert Emin , Demirel Sibel , Batıoğlu Figen
Published: March 2020

Purpose: To investigate the correlation between aqueous flare and macular microvascular status assessed by optic coherence tomography angiography (OCTA) in diabetes mellitus. Methods: A cross-sectional study was conducted on 52 diabetic patients with nonproliferative retinopathy, 44 diabetic patients without retinopathy, and 20 nondiabetic age-matched controls. Spectral domain OCT, OCTA, and laser flare-cell meter were performed. Results: Compared to eyes without retinopathy, eyes with retinopathy had higher flare intensity (p = 0.024), enlarged capillary nonperfusion area (p < 0.001), and enlarged foveal avascular zone (p < 0.001). There was a significant correlation between flare intensity and capillary nonperfusion areas (p < 0.001, r = 0.511) and superficial capillary density (p = 0.005, r = –0.388) in diabetic eyes with retinopathy. Conclusion: The results demonstrated a positive correlation between aqueous flare levels, an indicator of intraocular inflammation, and microvascular damage demonstrated by OCTA in the early stages of diabetic retinopathy (DR). This finding supports the role of inflammation in the pathogenesis of DR.
Physician and Hospital Utilization of P2Y12 Inhibitors in ST-Segment–Elevation Myocardial Infarction in the United States
Authors: Faridi Kamil F. , Garratt Kirk N. , Kennedy Kevin F. , Maddox Thomas M. , Secemsky Eric A. , Butala Neel M. , Yeh Robert W
Published: March 2020

Background:

Ticagrelor and prasugrel are potent P2Y12 inhibitors with superior efficacy compared with clopidogrel among patients with ST-segment–elevation myocardial infarction (STEMI), though use in recent practice is not well described. In this retrospective study, we assessed trends, predictors, and variation in use of P2Y12 inhibitors in patients with STEMI in the United States.

Methods and Results:

We identified 169 505 STEMI patients in the Chest Pain-Myocardial Infarction Registry from October 2013 through March 2017. We determined national utilization rates of P2Y12 inhibitors at discharge, patient predictors for each medication, and variation in use between hospitals. In a subset of 9655 Medicare patients ≥65 years old, we compared 1-year adjusted risks of death, myocardial infarction, stroke, and bleeding based on hospital quartile of potent P2Y12 inhibitor use. Rates of ticagrelor use increased from 18.0% to 44.0%, while rates of prasugrel and clopidogrel use decreased from 24.6% to 13.5% and 57.4% to 42.6%, respectively. Prior percutaneous coronary intervention was the strongest clinical predictor for use of ticagrelor (adjusted odds ratio, 1.13 [95% CI, 1.09–1.18]) and prasugrel (adjusted odds ratio, 1.27 [95% CI, 1.21–1.34]) compared with clopidogrel. Predictors of clopidogrel use included no insurance, insurance with Medicare or Medicaid, and features associated with higher bleeding risk. The median hospital usage rate for newer P2Y12 inhibitors was 51.3% (interquartile range, 35.0%–65.9%), with substantial variation between hospitals (adjusted median odds ratio, 2.92 [95% CI, 2.77–3.10]). Among patients ≥65 years old, there were no differences in adjusted 1-year risks of adverse outcomes across hospital quartiles of potent P2Y12 inhibitor use.

Conclusions:

Almost one-half of STEMI patients by 2017 were discharged on ticagrelor while far fewer received prasugrel. Patient characteristics are associated with P2Y12 inhibitor selection, though substantial hospital variation exists. Identifying barriers to use of more potent P2Y12 inhibitors may improve patient-centered decision-making for STEMI patients.
Antihypertensive and Renal Mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors
Authors: Wilcox Christopher S.
Published: March 2020

Empaglifolzin, canagliflozin, and dapagliflozin are SGLT2 (sodium-glucose linked transporter type 2) inhibitors for treatment of type 2 diabetes mellitus that also reduce blood pressure, mortality, and cardiovascular disease and slow the loss of glomerular filtration rate. SGLT2 inhibitors inhibit the coupled reabsorption of sodium and glucose from the proximal tubules, thereby increasing renal glucose and sodium excretion, but they have more widespread renal effects, including inhibition of the sodium:proton exchanger. They increase the delivery of sodium to the loop of Henle and can thereby activate the tubuloglomerular feedback response to correct glomerular hyperfiltration. There are multiple potential mechanisms whereby these drugs lower blood pressure and preserve kidney function that are the focus of this review.