bluuebunny/crossref_metadata_2025 huggingface dataset:
Interfering with the Expression of Ubiquitin-Like with PHD and Ring Finger Domains 1 Can Inhibit the Invasion of Human Renal Cell Carcinoma
Authors: Wu Susu , Pan Xiao , Cai Yanqun , Li Caiqin
Published: May 2022

Objective. The ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is a protein coding gene which is associated with colorectal cancer and other diseases. Therefore, the present study was aimed at investigating the effect and mechanism of UHRF1 protein on invasion and metastasis in human renal carcinoma cells. Methods. After UHRF1 was interfered with or overexpressed in renal carcinoma cell lines A498 and 769-P, the relative mRNA and protein level of UHRF1 was detected by RT-qPCR and immunofluorescence. The colony formation assay and MTT were performed to observe the proliferation and cell viability in each group. In addition, the invasion and metastasis of the cells in each group were detected by Transwell and wound healing assay. Finally, Western blot was utilized to measure protein expression of MMP-2 and MMP-9 and the level of protein in the Wnt/β-catenin signaling pathway. Results. The cell ability, proliferation, invasion, and metastasis in A498 and 769-P cells were inhibited after interfering with UHRF1. In addition, the expression of MMP-2, MMP-9, c-myc, and β-catenin was significantly decreased, while the expression of GSK-3β was significantly increased. However, contrasting results were demonstrated when UHRF1 was overexpressed. Conclusions. Interference with the expression of UHRF1 was able to inhibit the invasion and metastasis of human renal carcinoma cell lines A498 and 769-P, which may be related to mediating the Wnt/β-catenin signaling pathway and regulating the expression of MMP-2 and MMP-9.
Methods on the Determination of the Circuit Parameters in an Underwater Spark Discharge
Authors: Han Zhen , Zhang Xiaobing , Yan Bing , Qiao Liang , Li Zhihua
Published: May 2022

We constructed an underwater discharge system to conduct a number of experiments. Considering the constant resistance of the plasma channel, we got an analytic expression for the current containing unknown parameters on the basis of the Kirchhoff voltage law. Therefore, we are required to determine the total circuit resistance

R

with the measured current data in hand. Three methods are employed to get this job done, namely, nonlinear least squares with three variables (NLS-TV), nonlinear least squares with a single variable (NLS-SV), and waveform calculation method (WCM). The Levenberg–Marquardt (L-M) algorithm and particle swarm optimization (PSO) algorithm are employed in NLS-TV and NLS-SV, and the root mean square error (RMSE), as well as an improved cosine similarity (ICS), was selected to evaluate the performance of algorithms. The results show that NLS-TV gives an optimal solution with the combination of the PSO algorithm and L-M algorithm. Then, by calculation, R = 1.3195

Ω

, C = 0.56865 μF, and L = 17.172 μH. RMSE and ICS between fitted current data and measured one are 43.9689 and 0.9947, respectively. NLS-SV gives a satisfying solution either by PSO or by L-M, yet it needs information of angular frequency from the measured current waveform and the total inductance

C

. In this case, we get R = 1.3115

Ω

, L = 16.969 μH, RMSE = 48.0883, and ICS = 0.9967. As for WCM, it is completely dependent on the measured current waveform and the total inductance

C

. The corresponding values of

R

and

L

are 1.2463

Ω

and 16.993 μH. Also, we get RMSE = 52.1902 and ICS = 0.9728. For NLS-SV and WCM, the needed total capacitance during calculation is determined using the computed capacitance by NLS-TV. If the energy storage capacitance is used as the total capacitance, the obtained solution is frustrating. Therefore, independent use of NLS-SV or WCM demands a precise capacitance of the total circuit measured by an RLC meter. We also draw a conclusion that ignoring the capacitance of other parts of the circuit is incorrect and will lead to an enormous error during calculation.
Study on Temperature Field Evolution and Frozen Wall Closure Judgment Criteria of Inclined Shaft under Inclined Holes Freezing Condition
Authors: Zhang Chi , Zhang Yu , Yang Weihao , Li Haipeng , Lu Quan
Published: May 2022

A similarity experiment study is conducted to investigate the evolution characteristics of temperature field and frozen wall closure judgment criteria for the inclined shaft, under inclined holes freezing condition using an adjustable-angle freeze sinking analogous instrument. The changes of temperature and frozen wall thickness with the freezing time in the inclined shaft section, are recorded in real time, and the water pressure of axial and radial hydrological holes are measured. The results demonstrate that the soil temperature change can be divided into three stages under the conditions of salt-water temperature of -32°C and flow rate of 3.18 m/s: rapid cooling before reaching the freezing point, slow cooling in the process of freezing latent heat release, and accelerated cooling and stabilization after freezing latent heat release. The distance from the freezing pipe is the main factor affecting the freezing wall temperature. Affected by the arched arrangement of frozen pipes, the freezing speed in the position of arch crown and arch baseline is slower than the position of wall corner and base plate. A new judgment criterion of frozen wall closure based on the water pressure of the axial hydrological pipe is recommended. In all, this paper has an enlightenment significance for understanding the evolution of the soil temperature field, and predicting the frozen wall closure time in applications of the inclined holes freezing method for the inclined shaft.
Effects of Yellow Light on Airborne Microbial Composition and on the Transcriptome of Typical Marker Strain in Ward
Authors: Zhao Xuanqi , Wei Jing , Chen Wenjie , Xu Xuan , Zhu Ruizhe , Tian Puyuan , Chen Tingtao
Published: May 2022

Airborne diseases are transmitted by pathogens in the air. The complex microbial environment in wards is usually considered a major cause of nosocomial infection of various diseases which greatly influences the health of patients with chronic diseases, whereas the illuminant of wards impacts on the microbe especially the disease marker strain is seldom studied. In the present study, high-throughput sequencing was used to study the effect of yellow light on airborne microbial composition, and changes of transcriptome of marker strains Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which were isolated from wards, were further studied after the irradiation by yellow light. High-throughput sequencing results indicated that yellow light significantly decreased α-diversity. The relative abundance of Firmicutes at the phylum level, and Clostridium sensu stricto 1, Paraclostridium at the genus level were significantly reduced. RNA sequencing results declared that yellow light significantly downregulated the genes associated with flagella, heme transport system and carbohydrate, amino acid metabolism in E. coli, and the genes related to arginine biosynthesis and the biosynthesis of isoleucine, leucine, and valine in S. aureus. Meanwhile, yellow light significantly upregulated the genes relating to porphyrin metabolism in P. aeruginosa. In conclusion, our work reveals the impacts of yellow light on the microbe in wards, pointing out the application value of yellow light in the prevention of infectious diseases in clinical practice.
The Application of 5G and Artificial Intelligence Technology in the Innovation and Reform of College English Education
Authors: Zang Guangya , Liu Ming , Yu Baoying
Published: May 2022

Artificial intelligence and Fifth-Generation (5G) communication networks are examples of new information technologies that have aided and facilitated educational reform and progress. Built on the convincing requirements of college English education, with the advantage of artificial intelligence technology, we can enhance the teaching mode effectiveness, cultivate students' critical thinking ability, implement personalized wisdom and interactive learning, and thus realize artificial intelligence, and the effective use of 5G in English education is becoming a research hotspot area to be addressed. It is necessary to create a teaching aid system that uses a high-speed network and new type of technology. The specific techniques and measures for introducing 5G technology and artificial intelligence into higher education and English learning are discussed in this study. Students in higher education can benefit from the proposed technique by obtaining a better understanding of the subject and promoting their critical thinking skills. Finally, an experiment is performed to see how operative this technique is at teaching English when compared to traditional methods. The results are analyzed to determine that using this method is effective and boosts students' interest in learning as well as their hands-on abilities.
Identification and Validation of a GPX4-Related Immune Prognostic Signature for Lung Adenocarcinoma
Authors: Feng Zhenxing , Li Bo , Chen Qingliang , Zhang Hong , Guo Zhigang , Qin Jianwen
Published: May 2022

Lung adenocarcinoma (LUAD) is a commonly occurring histological subtype of lung cancer. Glutathione peroxidase 4 (GPX4) is an important regulatory factor of ferroptosis and is involved in the development of many cancers, but its prognostic significance has not been systematically described in LUAD. In this study, we focused on developing a robust GPX4-related prognostic signature (GPS) for LUAD. Data for the training cohort was extracted from The Cancer Genome Atlas, and that for the validation cohort was sourced from the GSE72094 dataset including 863 LUAD patients. GPX4-related genes were screened out by weighted gene coexpression network analysis and Spearman’s correlation analysis. Then, Cox regression and least absolute shrinkage and selection operator regression analyses were employed to construct a GPS. The ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and GSEA were utilized to evaluate the relationship between GPS and the tumor microenvironment (TME). We constructed and validated a GPS premised on four GPX4-related genes (KIF14, LATS2, PRKCE, and TM6SF1), which could classify LUAD patients into low- and high-score cohorts. The high-risk cohort presented noticeably poorer overall survival (OS) as opposed to the low-risk cohort, meaning that the GPS may be utilized as an independent predictor of the OS of LUAD. The GPS was also adversely correlated with multiple tumor-infiltrating immune cells and immune-related processes and pathways in TME. Furthermore, greater sensitivity to erlotinib and lapatinib were identified in the low-risk cohort based on the GDSC database. Our findings suggest that the GPS can effectively forecast the prognosis of LUAD patients and may possibly regulate the TME of LUAD.
Bilateral Scapular Fractures Occurring as a Result of a First-Time Seizure
Authors: Betten David P. , Batson Ian S. , Babiarz Leah N. , Owen Kristen N.
Published: May 2022

The violent nature of generalized tonic-clonic seizures puts individuals at risk of a large number of potential injuries. These can occur due both to the profound muscular contractions that accompany these episodes as well as falls and other traumatic events that occur due to the period of loss of consciousness that occurs during generalized seizures. While injuries such as soft tissue contusions, tongue biting, dental injuries, and facial lacerations resulting from falls from standing predominate, bony injuries are not uncommon. We present a case of bilateral scapular fractures that occurred in an otherwise healthy 32-year male who presented with shoulder and back pain and inability to perform any significant movement of his upper arms secondary to pain after experiencing an apparent first-time generalized tonic-clonic seizure. The presence of unilateral and bilateral scapular fractures, while uncommonly described, should be considered as an additional potential orthopedic injury that may occur secondary to a generalized tonic-clonic seizure. In the absence of observed significant forceful traumatic injury, this injury is unusual, and its presence noted in a patient experiencing sudden loss of consciousness should raise heightened concern of seizures as the potential etiology.
Prediction of Bronchopneumonia Inpatients’ Total Hospitalization Expenses Based on BP Neural Network and Support Vector Machine Models
Authors: Wu Cuiyun , Zha Dahui , Gao Hong
Published: May 2022

Objective. BP neural network (BPNN) model and support vector machine (SVM) model were used to predict the total hospitalization expenses of patients with bronchopneumonia. Methods. A total of 355 patients with bronchopneumonia from January 2018 to December 2020 were collected and sorted out. The data set was randomly divided into a training set (

n
=
249

) and a test set (

n
=
106

) according to 7 : 3. The BPNN model and SVM model were constructed to analyze the predictors of total hospitalization expenses. The effectiveness was compared between these two prediction models. Results. The top three influencing factors and their importance for predicting total hospitalization cost by the BPNN model were hospitalization days (0.477), age (0.154), and discharge department (0.083). The top 3 factors predicted by the SVM model were hospitalization days (0.215), age (0.196), and marital status (0.172). The area under the curve of these two models is 0.838 (95% CI: 0.755~0.921) and 0.889 (95% CI: 0.819~0.959), respectively. Conclusion. Both the BPNN model and SVM model can predict the total hospitalization expenses of patients with bronchopneumonia, but the prediction effect of the SVM model is better than the BPNN model.
Comparison between Dynamic Stabilization and Instrumented Fusion in the Treatment of Spinal Stenosis with Degenerative Lumbar Scoliosis
Authors: Luo Lei , Liu Liehua , Li Pei , Zhao Chen , Liang Lichuan , Luo Fei , Zhou Qiang , Chen Yanhong , Fang Lang
Published: May 2022

Objective. Posterior instrumented fusion is the most widely accepted surgical treatment for spinal stenosis with degenerative lumbar scoliosis (DLS). However, long fusion can affect daily activities due to lumbar stiffness. Dynamic stabilization has been introduced to overcome the drawbacks of fusion in recent years. This study aimed to compare the outcomes of dynamic stabilization (Dynesys system) with posterior instrumented fusion for the management of spinal stenosis with DLS. Methods. This study retrospectively reviewed 65 consecutive patients with spinal stenosis and DLS who were undergoing surgical treatment between January 2013 and December 2017. Among them, 34 patients (Dynesys group) had fenestration decompression and Dynesys stabilization, whereas 31 patients (fusion group) underwent posterior instrumented fusion. Clinical outcomes, radiographic data, and postoperative complications were compared between the two groups. Results. The mean number of fixed segments was 3.6 ± 0.9 in the Dynesys group and 4.2 ± 1.0 in the fusion group. Lower average values of operating time and blood loss were observed in the Dynesys group (

P
<
0.05

). At an average follow-up of 42 months, there were no significant differences in the visual analog scale for the leg pain (VASleg), the scoliosis Cobb’s angle, and the lumbar lordosis between the two groups (

P
>
0.05

). The visual analog scale for back pain (VASback), oswestry disability index (ODI), and lumbar stiffness disability index (LSDI) scores of the Dynesys group were lower compared with the fusion group (

P
<
0.05

). The range of motion (ROM) of implanted segments was significantly higher in the Dynesys group as compared to the fusion group (

P
<
0.05

). The overall complications were less in the Dynesys group, but the difference was not statistically significant (

P
>
0.05

). Conclusion. Both dynamic stabilization and instrumented fusion can improve the clinical outcomes of patients with spinal stenosis and mild DLS. Compared to instrumented fusion, dynamic stabilization has the advantages of less invasion and motion preservation.
An In Vitro Pilot Study on the Effects of Silver Diamine Fluoride on Periodontal Pathogens and Three-Dimensional Scaffolds of Human Fibroblasts and Epithelial Cells
Authors: Ho Yolanda , Gyurko Robert , Uzel Naciye Guzin , Steffensen Bjorn , Xenoudi Pinelopi , Loo Cheen , Zoukhri Driss
Published: May 2022

Objective. The aims of this study were to investigate the antibacterial and cytotoxic effects of silver diamine fluoride (SDF) on periodontal pathogens and human skin constructs, respectively. Background. SDF has been proven to have bactericidal effects on cariogenic bacteria. No studies to date evaluated the bactericidal effects of SDF on periodontal pathogens nor its effect on epithelium and fibroblasts. Methods. Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans were cultured in monospecies biofilms, exposed to increasing concentrations of SDF and inoculated on agar plates to assess viability. Human gingival fibroblasts in 2D cultures were exposed to 1 μL of 0.394% of SDF and viewed using real-time imaging. Finally, SDF was applied to human, 3D tissue scaffolds of fibroblasts and keratinocytes, and termed human skin equivalents (HSE). A clinical dose of 38% SDF was applied, and HSE were cultured for 12 hours, 1, 3, 5, and 10 days. The tissue was observed clinically and histologically with hematoxylin and eosin staining and TUNEL. Results. S. mutans and A. actinomycetemcomitans growth was completely inhibited using all dilutions of SDF, whereas P. gingivalis was still viable with 0.197% and 0.098% of SDF. Single-layer fibroblasts experienced immediate necrosis upon contact with SDF. Application of SDF to HSE showed maturation of a whitish lesion within 24 hours, followed by pigmented, crusted tissue after 3 days. Histological evaluation of treated tissues showed apoptotic cells in the epithelium and upper half of the connective tissue. Conclusion. Our data suggest that SDF has bactericidal properties against two periodontal pathogens: P. gingivalis and A. actinomycetemcomitans. SDF caused immediate necrosis of monolayer fibroblasts, but does not extend to the full extent of layered fibroblasts in HSE.
Comparative Study on the Crystallite Size and Bandgap of Perovskite by Diverse Methods
Authors: Ahmed Mohammad Tanvir , Islam Shariful , Ahmed Farid
Published: May 2022

This research demonstrates the fast synthesis of CH3NH3PbBr3 perovskite powder via antisolvent addition and further thin-film synthesis by one-step spin coating. The structural and optical properties are investigated via X-ray diffraction, Fourier-transform infrared spectroscopy, and UV–Vis spectroscopy. Crystallite sizes are compared by three different size estimation techniques, which range between 95.8 nm and 105 nm. The perovskite showed a higher absorption coefficient over 104 cm−1 and a refractive index from 3.4 to 2.3 in the visible spectrum. The bandgap was estimated via three district methods, which revealed a very slightly varied bandgap in the range of 2.29 eV–2.32 eV.
The Key Technologies of Marine Multiobjective Ship Monitoring and Tracking Based on Computer Vision
Authors: Li Qiang , Yang Li
Published: May 2022

In recent years, one of the key research contents of computer vision is to realize the online monitoring and information tracking of unknown targets by sea ships. For multitarget ships at sea, the most important thing is the information tracking direction. It is very appropriate to apply this computer vision technology to ship monitoring at sea. This paper uses the ship target detection algorithm (STDA) to study the tracking and detection of sea multitarget ships based on computer vision to be applied in practice and improve the protection and safety of sea navigation. Based on the background of ocean intelligent monitoring, the image processing algorithm of key target detection and tracking in the ship detection and tracking system is studied, and the ocean monitoring video image is obtained by installing the detection and tracking effect of the shipborne camera verification system. The ship object detection algorithm (STDA) of the sea antenna is compared with the traditional target detection algorithm. Experimental results show that the proposed algorithm can effectively eliminate the noise interference caused by the waves and the sky, with strong accuracy and real-time performance. The research results of this paper can effectively compensate for the shortcomings of the traditional TLD multitarget ship tracking algorithm and make its speed and real-time performance greatly meet the requirements of ship monitoring. At the same time, it improves the marine monitoring capability to provide reliable technical support for the development of intelligent ships.
The Impact of Artificial Intelligence and Digital Economy Consumer Online Shopping Behavior on Market Changes
Authors: Xiong Ying
Published: May 2022

The rapid development of online technology has facilitated the gradual growth and development of e‐commerce and online marketing, creating a new business model and new opportunities. This has had a major impact on the future development of the market economy and the international competitiveness of companies and countries. At the same time, its appearance has also subverted the traditional retail market, and the convenience, reliability, and security of payment have been quickly recognized by people. Technological innovations represented by artificial intelligence have driven the development of the digital economy for decades. In order to better strengthen the statistics of the online shopping market and promote the development of the real economy, this study discusses the analysis of consumer behavior in online shopping based on the market changes of artificial intelligence and digital economy. Through the questionnaire, it can be found that all age groups have been exposed to online shopping, most of them are young people, and the number of shopping per month is still concentrated between 4 and 11 times. The study also examined the size of China’s online retail market and found that there were 820 million Internet shoppers in China by December 2021, which is forecast to be 910 million by 2022. The report also found that the B2C market share will reach nearly 61% in 2021 due to the B2C model featuring higher quality goods and more guaranteed services.
Pyruvate Kinase M1 Suppresses Development and Progression of Prostate Adenocarcinoma
Authors: Davidson Shawn M. , Schmidt Daniel R. , Heyman Julia E. , O'Brien James P. , Liu Amy C. , Israelsen William J. , Dayton Talya L. , Sehgal Raghav , Bronson Roderick T. , Freinkman Elizaveta , Mak Howard H. , Fanelli Giuseppe Nicolò , Malstrom Scott , Bellinger Gary , Carracedo Arkaitz , Pandolfi Pier Paolo , Courtney Kevin D. , Jha Abhishek , DePinho Ronald A. , Horner James W. , Thomas Craig J. , Cantley Lewis C. , Loda Massimo , Vander Heiden Matthew G.
Published: May 2022

Altered metabolism helps sustain cancer cell proliferation and survival. Most cancers, including prostate cancers, express the M2 splice isoform of pyruvate kinase (PKM2), which can support anabolic metabolism to support cell proliferation. However, Pkm2 expression is dispensable for the formation and growth of many cancers in vivo. Expression of pyruvate kinase isoform M1 (Pkm1) is restricted to relatively few tissues and has been reported to promote growth of select tumors, but the role of PKM1 in cancer has been less studied than PKM2. To test how differential expression of pyruvate kinase isoforms affects cancer initiation and progression, we generated mice harboring a conditional allele of Pkm1 and crossed these mice, or those with a Pkm2 conditional allele, with a Pten loss-driven prostate cancer model. Pkm1 loss led to increased PKM2 expression and accelerated prostate cancer development, whereas Pkm2 deletion led to increased PKM1 expression and suppressed tumor progression. Metabolic profiling revealed altered nucleotide levels in tumors with high PKM1 expression, and failure of these tumors to progress was associated with DNA replication stress and senescence. Consistent with these data, a small molecule pyruvate kinase activator that mimics a high activity PKM1-like state suppressed progression of established prostate tumors. Analysis of human specimens showed PKM2 expression is retained in most human prostate cancers. Overall, this study uncovers a role for pyruvate kinase isoforms in prostate cancer initiation and progression, and argues that pharmacologic pyruvate kinase activation may be beneficial for treating prostate cancer.

Significance:

Differential expression of PKM1 and PKM2 impacts prostate tumorigenesis and suggests a potential therapeutic vulnerability in prostate cancer.
Drug-Tolerant Persister Cells in Cancer Therapy Resistance
Authors: Dhanyamraju Pavan Kumar , Schell Todd D. , Amin Shantu , Robertson Gavin P.
Published: May 2022

One of the current stumbling blocks in our fight against cancer is the development of acquired resistance to therapy, which is attributable to approximately 90% of cancer-related deaths. Undercutting this process during treatment could significantly improve cancer management. In many cases, drug resistance is mediated by a drug-tolerant persister (DTP) cell subpopulation present in tumors, often referred to as persister cells. This review provides a summary of currently known persister cell subpopulations and approaches to target them. A specific DTP cell subpopulation with elevated levels of aldehyde dehydrogenase (ALDH) activity has stem cell-like characteristics and a high level of plasticity, enabling them to switch rapidly between high and low ALDH activity. Further studies are required to fully elucidate the functions of ALDH-high DTP cells, how they withstand drug concentrations that kill other cells, and how they rapidly adapt under levels of high cellular stress and eventually lead to more aggressive, recurrent, and drug-resistant cancer. Furthermore, this review addresses the processes used by the ALDH-high persister cell subpopulation to enable cancer progression, the ALDH isoforms important in these processes, interactions of ALDH-high DTPs with the tumor microenvironment, and approaches to therapeutically modulate this subpopulation in order to more effectively manage cancer.
Transcriptional Repression by FoxM1 Suppresses Tumor Differentiation and Promotes Metastasis of Breast Cancer
Authors: Kopanja Dragana , Chand Vaibhav , O'Brien Eilidh , Mukhopadhyay Nishit K. , Zappia Maria P. , Islam Abul B.M.M.K. , Frolov Maxim V. , Merrill Bradley J. , Raychaudhuri Pradip
Published: May 2022

The transcription factor Forkhead box M1 (FoxM1) is overexpressed in breast cancers and correlates with poor prognosis. Mechanistically, FoxM1 associates with CBP to activate transcription and with Rb to repress transcription. Although the activating function of FoxM1 in breast cancer has been well documented, the significance of its repressive activity is poorly understood. Using CRISPR–Cas9 engineering, we generated a mouse model that expresses FoxM1-harboring point mutations that block binding to Rb while retaining its ability to bind CBP. Unlike FoxM1-null mice, mice harboring Rb-binding mutant FoxM1 did not exhibit significant developmental defects. The mutant mouse line developed PyMT-driven mammary tumors that were deficient in lung metastasis, which was tumor cell-intrinsic. Single-cell RNA-seq of the tumors revealed a deficiency in prometastatic tumor cells and an expansion of differentiated alveolar type tumor cells, and further investigation identified that loss of the FoxM1/Rb interaction caused enhancement of the mammary alveolar differentiation program. The FoxM1 mutant tumors also showed increased Pten expression, and FoxM1/Rb was found to activate Akt signaling by repressing Pten. In human breast cancers, expression of FoxM1 negatively correlated with Pten mRNA. Furthermore, the lack of tumor-infiltrating cells in FoxM1 mutant tumors appeared related to decreases in pro-metastatic tumor cells that express factors required for infiltration. These observations demonstrate that the FoxM1/Rb-regulated transcriptome is critical for the plasticity of breast cancer cells that drive metastasis, identifying a prometastatic role of Rb when bound to FoxM1.

Significance:

This work provides new insights into how the interaction between FoxM1 and Rb facilitates the evolution of metastatic breast cancer cells by altering the transcriptome.
RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System
Authors: De Mey Wout , Esprit Arthur , Thielemans Kris , Breckpot Karine , Franceschini Lorenzo
Published: May 2022

Recent advances in the manufacturing, modification, purification, and cellular delivery of ribonucleic acid (RNA) have enabled the development of RNA-based therapeutics for a broad array of applications. The approval of two SARS-CoV-2–targeting mRNA-based vaccines has highlighted the advances of this technology. Offering rapid and straightforward manufacturing, clinical safety, and versatility, this paves the way for RNA therapeutics to expand into cancer immunotherapy. Together with ongoing trials on RNA cancer vaccination and cellular therapy, RNA therapeutics could be introduced into clinical practice, possibly stewarding future personalized approaches. In the present review, we discuss recent advances in RNA-based immuno-oncology together with an update on ongoing clinical applications and their current challenges.
Interactome of Aiolos/Ikaros Reveals Combination Rationale of Cereblon Modulators with HDAC Inhibitors in DLBCL
Authors: Hagner Patrick R. , Chiu Hsiling , Chopra Vivek S. , Colombo Martino , Patel Nisha , Estevez Maria Ortiz , Waldman Michelle F. , Loos Remco , Towfic Fadi , Gandhi Anita K.
Published: May 2022

Purpose:

Cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex CRL4CRBN, is the target of the small molecules lenalidomide and avadomide. Upon binding of the drugs, Aiolos and Ikaros are recruited to the E3 ligase, ubiquitylated, and subsequently degraded. In diffuse large B-cell lymphoma (DLBCL) cells, Aiolos and Ikaros are direct transcriptional repressors of interferon-stimulated genes (ISG) and degradation of these substrates results in increased ISG protein levels resulting in decreased proliferation and apoptosis. Herein, we aimed to uncover the mechanism(s) Aiolos and Ikaros use to repress ISG transcription and provide a mechanistic rationale for a combination strategy to enhance cell autonomous activities of CRBN modulators (CELMoD).

Experimental Design:

We conducted paired RNA sequencing with histone modification and Aiolos/Ikaros chromatin immunoprecipitation sequencing to identify genes regulated by these transcription factors and to elucidate correlations to drug sensitivity. We confirmed Aiolos/Ikaros mediated transcriptional complex formation in DLBCL patient samples including those treated with avadomide.

Results:

In DLBCL, the repression of ISG transcription is accomplished in part through recruitment of large transcriptional complexes such as the nucleosome remodeling and deacetylase, which modify the chromatin landscape of these promoters. A rational combination approach of avadomide with a specific histone deacetylase inhibitor leads to a significant increase in ISG transcription compared with either single agent, and synergistic antiproliferative activity in DLBCL cell lines.

Conclusions:

Our results provide a novel role for lineage factors Aiolos and Ikaros in DLBCL as well as further insight into the mechanism(s) of Aiolos and Ikaros–mediated transcriptional repression and unique therapeutic combination strategies.
Multiphoton Phosphorescence Quenching Microscopy Reveals Kinetics of Tumor Oxygenation during Antiangiogenesis and Angiotensin Signaling Inhibition
Authors: Martin John D. , Lanning Ryan M. , Chauhan Vikash P. , Martin Margaret R. , Mousa Ahmed S. , Kamoun Walid S. , Han Hee-Sun , Lee Hang , Stylianopoulos Triantafyllos , Bawendi Moungi G. , Duda Dan G. , Brown Edward B. , Padera Timothy P. , Fukumura Dai , Jain Rakesh K.
Published: May 2022

Purpose:

The abnormal function of tumor blood vessels causes tissue hypoxia, promoting disease progression and treatment resistance. Although tumor microenvironment normalization strategies can alleviate hypoxia globally, how local oxygen levels change is not known because of the inability to longitudinally assess vascular and interstitial oxygen in tumors with sufficient resolution. Understanding the spatial and temporal heterogeneity should help improve the outcome of various normalization strategies.

Experimental Design:

We developed a multiphoton phosphorescence quenching microscopy system using a low-molecular-weight palladium porphyrin probe to measure perfused vessels, oxygen tension, and their spatial correlations in vivo in mouse skin, bone marrow, and four different tumor models. Further, we measured the temporal and spatial changes in oxygen and vessel perfusion in tumors in response to an anti-VEGFR2 antibody (DC101) and an angiotensin-receptor blocker (losartan).

Results:

We found that vessel function was highly dependent on tumor type. Although some tumors had vessels with greater oxygen-carrying ability than those of normal skin, most tumors had inefficient vessels. Further, intervessel heterogeneity in tumors is associated with heterogeneous response to DC101 and losartan. Using both vascular and stromal normalizing agents, we show that spatial heterogeneity in oxygen levels persists, even with reductions in mean extravascular hypoxia.

Conclusions:

High-resolution spatial and temporal responses of tumor vessels to two agents known to improve vascular perfusion globally reveal spatially heterogeneous changes in vessel structure and function. These dynamic vascular changes should be considered in optimizing the dose and schedule of vascular and stromal normalizing strategies to improve the therapeutic outcome.
Evaluation of Inference-Based Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder: A Multicenter Randomized Controlled Trial with Three Treatment Modalities
Authors: Aardema Frederick , Bouchard Stéphane , Koszycki Diana , Lavoie Marc E. , Audet Jean-Sebastien , O’Connor Kieron
Published: May 2022

Introduction: Inference-based cognitive-behavioral therapy (I-CBT) is a specialized psychological treatment for obsessive-compulsive disorder (OCD) without deliberate and prolonged exposure and response prevention (ERP) that focuses on strengthening reality-based reasoning and correcting the dysfunctional reasoning giving rise to erroneous obsessional doubts and ideas. Objective: The present study aimed to evaluate the effectiveness of I-CBT through a comparison with appraisal-based cognitive behavioral therapy (A-CBT) and an adapted mindfulness-based stress reduction (MBSR) intervention. Methods: This was a two-site, parallel-arm randomized controlled trial (RCT) comparing I-CBT with A-CBT. The MBSR intervention acted as a non-specific active control condition. Following formal evaluation, 111 participants diagnosed with OCD were randomly assigned. The principal outcome measure was the Yale-Brown Obsessive-Compulsive Scale. Results: All treatments significantly reduced general OCD severity and specific symptom dimensions without a significant difference between treatments. I-CBT was associated with significant reductions in all symptom dimensions at post-test. Also, I-CBT led to significantly greater improvement in overvalued ideation, as well as significantly higher rates of remission as compared to MBSR at mid-test. Conclusions: I-CBT and MBSR appear to be effective, alternative treatment options for those with OCD that yield similar outcomes as A-CBT. I-CBT may have an edge in terms of the rapidity by which patients reach remission, its generalizability across symptom dimension, its potentially higher level of acceptability, and effectiveness for overvalued ideation. Future research is needed to assess whether additional alternative treatments options can help to increase the number of people successfully treated.
Conditioned Medium from Human Uterine Cervical Stem Cells Regulates Oxidative Stress and Angiogenesis of Retinal Pigment Epithelial Cells
Authors: Eiro Noemi , Sendon-Lago Juan , Cid Sandra , Saa Jorge , de Pablo Nagore , Vega Belen , Bermudez Maria A. , Perez-Fernandez Roman , Vizoso Francisco J.
Published: May 2022

Introduction: Retinal homeostasis is essential to avoid retinal pigment epithelium (RPE) damage resulting in photoreceptor death and blindness. Mesenchymal stem cells-based cell therapy could contribute to the maintenance of the retinal homeostasis. We have explored the effect of human uterine cervical stem cells (hUCESCs)-conditioned medium (hUCESC-CM) on RPE cells under oxidative stress condition. Methods: ARPE-19 cells were treated with hydrogen peroxide (H2O2) in the presence or absence of hUCESC-CM. qRT-PCR and Western blot were used to evaluate the expression of oxidative stress-related (HO-1, GCLC, and HSPB1) and vasculogenesis-related (VEGFA, PDGFA, and PDGFB) factors. Also, we assessed in vitro effects of hUCESC-CM on endothelial-cell (HUVEC) tube formation. Results: mRNA expression of HO-1, GCLC, HSPB1, VEGFA, PDGFA, and PDGFB were significantly increased in ARPE-19 cells treated with H2O2 + hUCESC-CM compared to cells treated with H2O2 only. Regarding the tube formation assay, HUVEC treated with supernatant from ARPE-19 cells treated with H2O2 + hUCESC-CM showed a significant increase in average vessel length, number of capillary-like junctions, and average of vessels area compared with HUVEC treated with supernatant from ARPE-19 cells treated with H2O2 only. Conclusion: Our results show potential therapeutic effects of hUCESC-CM on RPE, such as protection from damage by oxidative stress, stimulation of detoxifying genes, and a better vascularization.
Sarcopenia as a Predictor of the Functional Outcome in Patients with Intracranial Aneurysms
Authors: Rodrigues Renan Salomão , Rabelo Nicollas Nunes , Telles João Paulo Mota , Solla Davi Jorge Fontoura , Coelho Antônio Carlos Samaia da Silva , Jacobsen Teixeira Manoel , Figueiredo Eberval Gadelha
Published: May 2022

Introduction: Radiological indicators in head computed tomography (CT) scan have emerged as tools to evaluate sarcopenia using the sectional area and thickness of the temporal muscle. They can be obtained by standardized measurements in preoperative image assessment of patients with brain aneurysms. We aimed to evaluate the association between functional outcomes after interventions for intracranial aneurysms (IAs) and temporal muscle thickness (TMT) and area (TMA), as surrogates of sarcopenia. Methods: This is a prospective observational cohort study in patients who underwent microsurgery or embolization for ruptured or unruptured IA between January 2018 and December 2019, with a 6-month follow-up. Preoperative CT scans were analyzed to measure TMT and TMA. The functional outcome was assessed by the modified Rankin Scale (mRS). The main outcome was the relationship between sarcopenia and the postoperative functional outcome. Results: A total of 361 patients were included, of whom 199 (55.1%) had ruptured and 162 (44.9%) had unruptured lesions. Larger TMA significantly predicted better functional outcomes at discharge. TMT was associated with functional outcomes at both discharge and 6 months, adjusted for rupture and hypertension. Maximizing the sum sensitivity-specificity, an optimal TMT cutoff of 6.25 mm can predict unfavorable outcomes. Maximizing the positive predictive value × negative predictive value of a product, the cutpoint was 3.55 mm. Conclusions: Sarcopenia, represented by TMT and TMA, is associated with poorer functional results at discharge and 6-month follow-up in IA surgery. TMT below 6.25 mm was associated with unfavorable functional outcomes. These easily obtainable measurements may improve the decision-making process for patients with IAs.
The Identification and Characterization of Immunoreactive Fungal Proteins Recognized by Sera from Zimbabweans Sensitized to Fungi
Authors: Pfavayi Lorraine Tsitsi , Burchmore Richard , Sibanda Elopy Nimele , Baker Stephen , Woolhouse Mark , Mduluza Takafira , Mutapi Francisca
Published: May 2022

Background: Exposure to fungal allergens poses a serious threat to human health, especially to mould-allergic individuals. The prevalence of fungal allergic disease is increasing globally but is poorly studied in Africa. Here, we aimed to identify and characterize fungal proteins that were immunoreactive against serum samples from fungal-sensitized Zimbabweans from Shamva district to inform the development of diagnostics and therapeutics. Methods: Crude protein extracts of the Ascomycota Aspergillus fumigatus, Alternaria alternata, Cladosporium herbarum, Epicoccum nigrum, Penicillium chrysogenum, and Saccharomyces cerevisiae as well as mucoromycota Rhizopus nigricans were individually separated by one-dimensional gel electrophoresis for protein staining and immunoblotting. A pool of eight sera from fungi-sensitive Zimbabwean children aged 3–5 years was used to screen the crude extracts to determine their immunoreactivity. Protein bands recognized by the sera were subjected to mass spectrometry to identify the individual proteins reactive with the sera. Results: The pooled serum sample reacted with 20 bands, which resolved to 34 distinct proteins, most of which were novel immunogens. The pool was most reactive to A. alternata. The proteins identified included peptidases (8/34), hydrolases (6/34), oxidoreductases (5/34), and glucosidases (4/34), while 11/34 were unknown. Eight of the proteins were predicted to be allergens using the Structural Database of Allergenic Proteins (SDAP). Conclusions: We identified novel immunogens from fungi expanding the number of known fungal allergens. These form a potential basis for diagnostics specific for the Zimbabwean population. Validation assays will now need to be carried out to further evaluate the cross-reactivity of the identified allergen candidates as well as investigate their potential recognition in a larger cohort of patients. Furthermore, there is now a need to conduct studies relating sensitization to these immunogens and clinical diseases in the population.
Distribution Changes of Neural Precursor Cells in the Brain Stem of Tg(SOD1*G93A)1Gur Mice
Authors: Shen Xiaoping , Tang Chunyan , Kang Qin , Zhu Yu , Xu Shengyuan , Jiang Jianxiang , Xu Renshi
Published: May 2022

Objectives: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation, and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice was studied in this study. The aims of this study were to investigate the change features of proliferation, differentiation, and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS. Methods: The proliferation, differentiation, and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60–70 days), onset (90–100 days), and progression (120–130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. Results: VCCs were mainly distributed in the around (peripheral) central canal (CC) and the nuclei of brain stem in adult WT mice. VCCs proliferated and differentiated into astrocytes and directionally migrated from the around CC to the nuclei of brain stem, and then to the ventral part of damaged regions in brain stem at the pre-onset, onset, and progression stages of TG mice. Conclusions: The data suggest that NPCs widely distributed in the brain stem of adult TG mice can differentiate into astrocytes and migrate into damaged brain regions. This response might be a potential mechanism to repair degenerated motor neurons and restore dysfunctional neural circuitry in ALS.
Which Electronic Health Record System Should We Use? A Systematic Review
Authors: Al Ani Mohammed , Garas George , Hollingshead James , Cheetham Drostan , Athanasiou Thanos , Patel Vanash
Published: May 2022

The UK government had intended to introduce a comprehensive Electronic Health Record (EHR) system in England by 2020. These EHRs would run across primary, secondary, and social care, linking data in a single digital platform. The objectives of this systematic review were to identify studies that compare EHR in terms of direct comparison between systems and to evaluate them using System and Software Quality Requirements and Evaluation (SQuaRE) ISO/IEC 25010. A systematic review was performed by searching Embase and Ovid MEDLINE databases between 1974 and April 2021. All original studies that appraised EHR systems and their providers were included. The main outcome measures were EHR system comparison and the eight characteristics of SQuaRE: functional suitability, performance efficiency, compatibility, usability, reliability, security, maintainability, and portability. A total of 724 studies were identified using the search criteria. After a review of titles and abstracts, this was filtered down to 40 studies as per the exclusion and inclusion criteria set out in our study. Seven studies compared more than one EHR. The following number of studies looked at the various aspects of the SQuaRE, respectively – 19 studies: functional suitability, performance efficiency: 18 studies, compatibility: 12 studies, usability: 25 studies, reliability: 6 studies, security: 2 studies, maintainability: 16 studies, portability: 13 studies. Epic was the most studied EHR system and one of the most implemented systems in the US market and one of the top ten in the UK. It is difficult to assess which is the most advantageous EHR system when they are assessed by SQuaRE’s 8 characteristics for software evaluation.
About decentralized swarms of asynchronous distributed cellular automata using inter-planetary file system’s publish-subscribe experimental implementation
Authors: Manuceau Vincent
Published: May 2022

This research describes the simple implementation of asynchronous distributed cellular automata and decentralized swarms of asynchronous distributed cellular automata built on top of inter-planetary file system’s publish-subscribe (IPFS PubSub) experimentation. Various publish-subscribe(PubSub) models are described. As an illustration, two distributed versions and a decentralized swarm version of a 2D elementary cellular automaton are thoroughly detailed to highlight the simplicity of implementation with IPFS and the inner workings of these kinds of cellular automata (CA). Both algorithms were implemented, and experiments were conducted throughout five datacenters of Grid’5000 testbed in France to obtain preliminary performance results in terms of network bandwidth usage. This work is prior to implementing a large-scale decentralized epidemic propagation modeling and prediction system based upon asynchronous distributed cellular automata with application to the current pandemic of SARS-CoV-2 coronavirus disease 2019 (COVID-19).
Correcting optical character recognition result via a novel approach
Authors: Maarouf Otman , El Ayachi Rachid , Biniz Mohamed
Published: May 2022

Optical character recognition (OCR) is a recognition system used to recognize the substance of a checked picture. This system gives erroneous results, which necessitates a post-treatment, for the sentence correction. In this paper, we proposed a new method for syntactic and semantic correction of sentences it is based on the frequency of two correct words in the sentence and a recursive technique. This approach starts with the frequency calculation of each two words successive in the corpora, the words that have the greatest frequency build a correction center. We found 98% using our approach when we used the noisy channel. Further, we obtained 96% using the same corpus in the same conditions.