bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chalcone Derivative B8HA as A Novel Histone Deacetylase and Tubulin Dual-targeting Inhibitors, Inhibits Triple-Negative Breast Cancer Cells Proliferation
Authors: li kangkang , zheng qiuling , qi shulei , xie yi , Chen Xuehong 
Published: June 2022

Abstract
Purpose
Designing and synthesizing dual- and multi-target drugs have raised considerable interests due to their advantages in improving potencies as antitumor agents. In previous studies, our group designed and synthesized a series of novel chalcone based tubulin and histone deacetylase (HDAC) dual-targeting inhibitors. Among them, compound B8HA exhibited promising potency for the treatment of triple-negative breast cancer. In this work, we highlighted its biological evaluations in MDA-MB-231 and 4T1 cells.
Methods
The in vitro antiproliferative efficacies of compound B8HA against MDA-MB-231, MDA-MB-468, MCF-7, 4T1, A549, HCT-116, HT-29 and K562 were evaluated with MTT assay. Moreover, the potencies of B8HA as inhibitors of HDAC and tubulin polymerase were also evaluated in vitro and vivo.
Results
Comparing to the classical HDACi SAHA, B8HA has higher potency to induce apoptosis and inhibits the migratory and invasive abilities of tumor cells under the same dose in vitro and vivo. B8HA as tubulin inhibition is also able to inhibit the formation of capillary-like structures as well as to disrupt existing tubules.
Conclusion
These results indicated that compound B8HA is a potent inhibitor of both HDAC and tubulin, leading to excellent in vitro and in vivo antiproliferative activities.
Sequential Fear Generalization and Network Connectivity in Trauma Exposed Humans With and Without Psychopathology
Authors: zhu Xi , Suarez-Jimenez Benjamin , Lazarov Amit , Such Sara , Marohasy Caroline , Small Scott , Wager Tor , Lindquist Martin , Kissek Shmuel , Neria Yuval 
Published: June 2022

Abstract
While impaired fear generalization is known to underlie a wide range of psychopathology, the extent to which exposure to trauma by itself is resulted in deficient fear generalization and its neural abnormalities is yet to be studied. Similarly, the neural function of intact fear generalization in people who endured trauma and did not develop significant psychopathology is yet to be characterized. Here, we utilized fMRI, a generalization task, and a network connectivity approach to clarify behavioral and neural markers of trauma and resilience. The generalization task enabled longitudinal assessments of threat discrimination learning. Trauma-exposed (TEs) participants, compared to healthy controls (HCs) showed lower activity reduction in salience network (SN) and right executive control network (RECN) across the two sequential generalization stages, and worse discrimination learning in SN measured by linear deviation scores (LDS). Comparison of resilient, trauma-exposed healthy participants (TEHCs), trauma exposed individuals presenting with psychopathology (TEPGs), and HCs, revealed a resilience signature of network connectivity differences in the RECN during generalization learning measured by LDS. These findings may indicate a trauma exposure phenotype that has the potential to advance the development of innovative treatments by targeting and engaging specific neural dysfunction among trauma-exposed individuals, across different psychopathologies.
Analysis of the Effect of Spaceflight on Drug Potency to Quantify the Risk of Medication Failure for Exploration Space Missions
Authors: Reichard John , Phelps shean , Lehnhardt Kris , Young Millennia , Easter Benjamin 
Published: June 2022

Abstract
Pharmaceuticals selected for exploration space missions must remain stable and effective throughout mission timeframes. Although there have been six spaceflight drug stability studies, there has not been an analysis of these data. We sought to quantify the rate of spaceflight drug degradation and the time-dependent probability of drug failure resulting from loss of active pharmaceutical ingredient (API). Additionally, a review of previous spaceflight drug stability studies was performed to identify strategic research gaps that should be addressed prior to exploration missions. Data were extracted from these six spaceflight studies and analyzed to quantify API loss for 36 drug products with long-duration exposure to the spaceflight environment. Medications stored for up to 2.4 years in low Earth orbit (LEO) exhibit a loss of potency that, for most drugs, is within 5% of terrestrial lot-matched controls. Models estimate that spaceflight is associated with a ~1.5-fold increase in degradation rate and a corresponding increase in the probability of failure. However, this extra risk of drug failure is a fraction of the baseline failure risk observed for matched controls. All existing studies of spaceflight drug stability have focused primarily on repackaged solid oral medications. It is established that non-protective repackaging exposes medications to atmospheric factors that facilitates loss of potency. Our analysis suggests that although spaceflight exposure is associated with a loss of drug potency, the effect is a fraction of the terrestrial baseline. We conclude that a primary factor contributing to API loss may be nonprotective drug repackaging. This analysis highlights a critical need to evaluate the effect of current drug repackaging practices on API degradation, and if necessary develop and validate operationally appropriate protective drug repackaging for use on exploration missions.
Co-design, implementation, and evaluation of plain language genomic test reports
Authors: Brett Gemma , Ward Aisha , Bouffler Sophie , Palmer Elizabeth , Boggs Kirsten , Lynch Fiona , Springer Amanda , Nisselle Amy , Stark Zornitza 
Published: June 2022

Abstract
Understanding and communicating genomic results can be challenging for families and health professionals without genetic specialty training. Unlike modifying existing laboratory reports, plain language genomic test reports provide opportunity for patient/family-centered approaches. However, emerging examples generally lack co-design and/or evaluation in real-world settings. Through co-design involving patient groups, plain language experts, educators, and genetic health professionals, plain language genomic test report templates were produced for common test outcomes in rare disease. These reports were implemented as part of a national pediatric ultra-rapid genomic testing program. Family and genetic health professional experiences with report layout, content, and use were explored using surveys. Eight plain language genomic test report templates were developed. Of 154 families and 107 genetic health professionals issued with reports, 51 families and 57 clinicians responded (RR = 33% and 53%, respectively). Most families (82%) found their report helpful in understanding the result. Reports were shared by 63% of families, predominantly with family members (72%), or health professionals (68%). Clinicians (15%) adapted the reports for other settings. Through co-design, plain language genomic test reports implemented in a real-world setting can facilitate patient/family and caregiver understanding and communication of genomic test purpose, outcome, and potential clinical implications.
The effect of adverse pregnancy outcomes on early vascular aging in young women:The Kailuan Study
Authors: liu yan , LIN LIMING , TAO BONI , DING XIONG , Chen Shuohua , Wang Guodong , Shi Jihong , Huang Zhe , YU JIAXIN , YANG NING , Wu Shouling , Li Yuming 
Published: June 2022

Abstract
Backgroud: Adverse pregnancy outcomes (APOs) are at increased future cardiovascular risk and require effective risk mitigation. However, data regarding appropriate postpartum screening for young women with APOs are lacking. We aimed to investigate the association between APOs and early vascular aging (EVA) in young women.Methods: Women who gave birth from 1990 to 2020 and underwent brachial-ankle pulse wave velocity (baPWV) assessments in the postpartum period were recruited. We excluded women with age≥50 years at the baPWV assessment or missing postpartum health examinations. The history of APOs including hypertensive disorders of pregnancy, gestational diabetes, preterm delivery and low birth weight were assessed by medical records. EVA was defined as baPWV above the 90th percentile for different age group. Multivariable Logistic regression was used to evaluate the association of APOs and EVA. Results: 3,193 participants were included in the analysis, including 912 (28.6%) individuals with APOs. The detection rates of EVA in the non-APO group and the APOs group were 7.19% (164) and 13.9% (127), respectively (P<0.05). Compared with non-APO group, the OR (95% CI) of APO-induced EVA was 1.67(1.29-2.16). The risks in the 20-29, 30-39, and 40-49 age groups were 2.51 (1.13-5.59), 1.83 (1.30-2.59), and 1.35 (0.82-2.21) (P for trend <0.05). Conclusions: APOs are risk factors of EVA for young women and the risk decreased with increasing age. EVA should be an important indicator for preventive cardiovascular risk management in young women with APOs.Clinical trial registrationregistration number ChiCTR-TNRC-11001489 http://www.chictr.org.cn/showproj.aspx?proj=8050
Do expectation-maximization algorithms have to make use of ‘background distribution’ for de novo motif search?
Authors: Vladimirovich Bannikov Artyom 
Published: June 2022

Abstract
Sequence motif search remains an important problem in molecular biology. Many current tools for motif search utilize the expectation –maximization algorithm. Commonly, the algorithm assumes that a sub-sequence is produced by either the background distribution or the motif distribution. Likelihoods of having been sampled from the two distributions are computed for a sub-sequence. The ratio of the likelihoods is the subsequence score. Is background really needed? Definition of motif does not require background. Thus, the existence of background is hypothetical information that can lead the search astray. This work shows that the expectation-maximization algorithm does not have to utilize the background distribution to be practical. The relation between the number of logL minima and the number of sequences is exponential. Nevertheless, the time to find the constant fraction of motifs depends on the number of sequences linearly. Thus, relatively large sequence sets can be analyzed by the EM without the introduction of background.
Frequency-dependent alterations in the default mode network during general anesthesia: a study in the rat
Authors: Guo Fengru , Li Yuqin , Jian Zhaoxin , Cui Yan , Gong Wenhui , Li Airui , Xu Peng , Chen Ke , Yao Dezhong , Guo Daqing , Xia Yang 
Published: June 2022

Abstract
The anesthetic states induced by general anesthesia are accompanied by changes in functional and effective connectivity in brain networks. Considering the perturbations in oscillations produced by anesthesia, we postulated that the capability of information transmission in brain networks has distinct manifestations in different frequency bands. Therefore, we implanted electrodes in brain regions of the rat default mode network (DMN) that are related to anesthetic states to acquire local field potentials. Data were computed with power spectral density, graphic theory analysis, fuzzy entropy, and directed phase transfer entropy. Our results illustrated that the transition patterns of DMN activity are frequency dependent. Collectively, the sedative and general anesthetic states derive from inharmonious information processing ໿instantiated by contrasting lower/higher-frequency changes in DMN activity. These results impart insights into the neural network mechanisms underlying anesthesia and suggest the potential of monitoring depth of anesthesia based on lower/higher frequency synergy at the network level.
Sensorless Control of Permanent Magnet Synchronous Motor Based on Adaptive Back-EMF Observer
Authors: Ye Yu , Cao Xiangang , Duan Yun , Wu Yuze , Yang Xin 
Published: June 2022

Abstract
Aiming at the problem that the change of motor parameters in actual operation will significantly reduce the control accuracy of the motor, this paper proposes a sensorless control method of permanent magnet synchronous motor based on an adaptive back-EMF observer. In the sensorless vector control algorithm, the mathematical model of the permanent magnet synchronous motor based on the coordinate axis transformation is established, the flux linkage of the permanent magnet synchronous motor is identified online, and the motor model is updated with the specified parameters, to realize the analysis of the rotor position and the permanent magnet synchronous motor. Accurate control of rotational speed. The back-EMF observer and the adaptive back-EMF observer are verified in the simulation environment. The simulation results show that the adaptive back-EMF observer can quickly converge to the actual value and track the motor parameters well. Enabling highly accurate rotor speed and position estimation. Finally, the permanent magnet synchronous motor control platform is built in the laboratory. Under the condition of the parameter change of the permanent magnet synchronous motor, the online identification of the parameters and the accurate control of the speed of the permanent magnet synchronous motor can be realized.
Comparative Performance of Ensemble Machine Learning for Arabic Cyberbullying and Offensive Language Detection
Authors: Khairy Marwa , Mahmoud Tarek M. , Omar Ahmed , El-Hafeez Tarek Abd 
Published: June 2022

Abstract

In recent years, research on abusive language and cyberbullying detection have gained a great deal of interest since it affects both individual victims and societies. Hateful communications, bullying, sexism, racism, aggressive content, harassment, toxic comments, and other forms of abuse have all increased dramatically due to the ease of access to social media platforms such as Facebook, Instagram, Twitter, and others. As a result, there is a significant need to identify, manage, and restrict the spread of offensive content on social networking sites, prompting us to perform this study to automate the detection of offensive language or cyberbullying. Having a balanced data set for a model would generate higher accuracy models, thus we build a new Arabic balanced data set to be used in the process of offensive detection. Lately, Ensemble Machine Learning has been used to enhance the performance of single classifiers. The aim of this study is to compare the performance of different single and ensemble machine learning algorithms in detecting Arabic text containing cyberbullying and offensive language. For this purpose, we have chosen three machine learning classifiers and three ensemble models and apply them to three Arabic datasets two of them are offensive datasets that are publicly available, and the third one which we constructed. The results showed that the ensemble machine learning methodology outperforms the single learner machine learning approach. Voting performs is the best among the trained ensemble machine learning classifiers, with accuracy scores of (71.1%, 76.7%, and 98.5%) for the three used datasets respectively, exceeding the score obtained by the best single learner classifier (65.1%, 76.2%, and 98%) for the same datasets. Finally we use hyperparameters tunning on the Arabic cyberbylluing data set to optize the performance of the voting technique.
A prediction system using AI techniques to predict Students’ learning difficulties using LMS for sustainable development at KFU
Authors: Koshiry Amr Mohamed El , El-Hafeez Tarek Abd , Omar Ahmed , Eliwa Entesar Hamed Ibraheem 
Published: June 2022

Abstract
With the emergence of the covid 19 pandemic, E-learning usage was the only way to solve the problem of study interruption in educational institutions and universities. Therefore, this field reserved significant attention in current times. In this paper, we used ten Machine Learning (ML) algorithms: Decision Tree(DT), Random Forest(RF), Logistic Regression(LR), SGD Classifier, Multinomial NB, K- Nearest Neighbors Classifier(KNN), Ridge Classifier, Nearest Centroid, Complement NB and Bernoulli NB) to build a prediction system based on artificial intelligence techniques to predict the difficulties students face in using the e-learning management system, to support related decision-making. Which, in turn, contributes supporting the sustainable development of technology at the university. From the results obtained, we detect the important factors that affect the use of
E-learning to solve students' learning difficulties using LMS by building a prediction system based on AI techniques.
Impact of institutional interventions on the rate of paclitaxel hypersensitivity reactions
Authors: Jao Mark E , Indorf Amy L , Segal Eve M , Miske Abby F , Eaton Keith D , Marsolini Trisha L , Ghuman Simran K 
Published: June 2022

Abstract
Purpose Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution, intravenous dexamethasone, oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization.Methods Patients who received paclitaxel from April 20, 2018 to December 8, 2020 having a HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of paclitaxel infusion. Incidence of all HSR prior to and post standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed.Results There were 3581 infusions in the pre-standardization group and 1179 infusions in the post- standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p=0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% in the post-standardization group (p=0.55). Conclusions This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA is a safe premedication regimen for paclitaxel. No change in severity of reactions was seen. Overall, better adherence to premedication administration was seen post standardization.
Cdon suppresses Vascular Smooth Muscle Calcification via Repression of Wnt/Runx2 axis
Authors: Kang Jong-Sun , Ahn Byeong-Yun , Kim Su Woo , Jeong Yideul , Leem Young-Eun 
Published: June 2022

Abstract
Osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) is a risk factor associated with vascular diseases. Wnt signaling is one of the major mechanisms implicated in osteogenic conversion of VSMCs. Since Cdon plays a negative role in Wnt signaling in distinct cellular processes, we sought to investigate the role of Cdon in vascular calcification. The expression of Cdon is significantly downregulated in VSMCs of aortas of patients with atherosclerosis and aortic stenosis. Consistently, calcification models including vitamin D3 (VD3)-injected mice and VSMCs cultured with calcifying media exhibited reduced Cdon expression. Cdon ablation mice (cKO) exhibited exacerbated aortic stiffness and calcification in response to VD3, compared to the control. Cdon depletion induced the osteogenic conversion of VSMCs accompanied by cellular senescence. The Cdon-deficient aortas showed a significant alteration in gene expression related to cell proliferation and differentiation together with Wnt signaling regulators. Consistently, Cdon depletion or overexpression in VSMC elevated or attenuated Wnt-reporter activities, respectively. The deletion mutant of second immunoglobulin domain (Ig2) in Cdon ectodomain failed to suppress Wnt signaling and osteogenic conversion of VSMCs. Furthermore, the treatment of purified the recombinant proteins of entire ectodomain or Ig2 domain of Cdon displayed suppressive effects on Wnt signaling and VSMC calcification. Our results demonstrate a protective role of Cdon in VSMC calcification via suppressing Wnt signaling. The Ig2 domain of Cdon has a potential as a therapeutic tool to prevent vascular calcification.
A Neural-Related Gene Risk Score for Head and Neck Squamous Cell Carcinoma
Authors: TAO Zhuo-ying , Yang Wei-fa , Zhu Wang-yong , Wang Lei-lei , Li Kar Yan , Guan Xin-yuan , Su Yu-xiong 
Published: June 2022

Abstract
ObjectivesThis study was aimed to establish a neural-related gene risk score (NRGRS) for the prediction of head and neck squamous cell carcinoma (HNSCC) prognosis, and explore its prognostic value on the benefit of immune checkpoint inhibitor (ICI) therapy.Materials and MethodsBased on the transcriptome data of HNSCC patients (n = 546) from The Cancer Genome Atlas (TCGA), 37 neural-related hub genes were identified by weighted gene co-expression network analysis. Four genes (ITGA5, PYGM, GNG7 and ATP2A3) were identified to construct NRGRS using Lasso-Cox regression method based on the TCGA cohort and validated in the Gene Expression Omnibus (GEO) cohort (n = 109). The survival analysis and Cox regression were performed to validate the prognostic value of NRGRS. Afterward, the molecular and immune characteristics in NRGRS-defined subgroups were analyzed and the prediction value of NRGRS on the benefit of ICI therapy was compared with other biomarkers.ResultsNRGRS-high patients had a worse overall survival than NRGRS-low patients. A low NRGRS was correlated with DNA repair-related and immune response-related pathways, while a high NRGRS was associated with Wnt-beta-catenin signaling, neurotrophic signaling and metabolism-related pathways. Tumors with high NRGRS were more likely to have high TP53, CDKN2A, FAT1 and NOTCH1 mutation rates and have high infiltration of naive CD4 + T cells, resting NK cells, M0, M2 macrophages and resting mast cells, which illustrated suppressive immunity and less benefit from ICI therapy.ConclusionIn conclusion, NRGRS is a promising prognostic biomarker to predict the survival, the molecular and immune characteristics, and also immunotherapy benefit for HNSCC patients.Clinical RelevanceThis study provides evidence for the potential correlation between neural-related transcriptome alteration and immune activity in HNSCC.