bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism
Authors: Tao Shuang , Bai Zhengyang , Liu Yaobang , Gao Yali , Zhou Jia , Zhang Yangyang , Li Jinping
Published: June 2022

Background. Chemoresistance poses a great hindrance in the treatment of breast cancer (BC). Interestingly, exosome (Exo)-mediated transfer of long noncoding RNAs (lncRNAs) has been reported to regulate chemoresistance in diverse diseases. We herein investigate the potential role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) transferred by BC cell-derived Exo in chemoresistance of BC cells. Methods. BC-related lncRNAs were identified. Exosomes were isolated and verified from BC cells. The expression patterns of MALAT1 were then examined in the adriamycin (ADR)-sensitive and resistant cells and the isolated Exo, followed by the analysis of the downstream microRNA (miRNA) of MALAT1. The role and mechanism of MALAT1 transmitted by BC cell-derived Exo in BC cell metastasis and chemoresistance were assessed. Results. MALAT1 was highly expressed in BC cells and their Exo. In addition, MALAT1 delivered by BC cell-derived Exo augmented the malignant properties and chemoresistance of BC cells. Mechanistically, MALAT1 bound to miR-1-3p and limited the miR-1-3p expression, which sequentially targeted the vasodilator-stimulated phosphoprotein (VASP) protein. Moreover, silencing of VASP inhibited the activation of the RAP1 member of RAS oncogene family (Rap1) signaling pathway, which led to the attenuation of BC cell malignant properties and chemoresistance. In vivo assay further validated the tumor-promoting effect of Exo-MALAT1 via regulation of the miR-1-3p/VASP/Rap1 axis. Conclusion. Collectively, MALAT1 loaded by BC cell-derived Exo can accelerate BC cell metastasis and chemoresistance via disruption of miR-1-3p-mediated inhibition of the VASP/Rap1 signaling axis.
High-Resolution Direction of Arrival Estimation of Underwater Multitargets Using Swarming Intelligence of Flower Pollination Heuristics
Authors: Ahmed Nauman , Wang Huigang , Tu Shanshan , Alsaif Norah A.M. , Zahoor Raja Muhammad Asif , Kashif Muhammad , Armghan Ammar , Abdalla Yasser S. , Ali Wasiq , Ali Farman
Published: June 2022

Developing the parameter estimation, particularly direction of arrival (DOA), utilizing the swarming intelligence-based flower pollination algorithm (FPA) is considered an optimistic solution. Therefore, in this paper, the features of FPA are applied for viable DOA in the case of several robust underwater scenarios. Moreover, acoustic waves impinging from the far-field multitarget are evaluated using the different number of hydrophones of uniform linear array (ULA). The measuring parameters like robustness against noise and element quantity, estimation accuracy, computation complexity, various numbers of hydrophones, variability analysis, frequency distribution and cumulative distribution function of root mean square error (RMSE), and resolution ability are applied for analyzing the performance of the proposed model with additive white Gaussian noise (AWGN). For this purpose, particle swarm optimization (PSO), minimum variance distortion-less response (MVDR), multiple signal classification (MUSIC), and estimation of signal parameter via rotational invariance technique (ESPRIT) standard counterparts are employed along with Crammer–Rao bound (CRB) to improve the worth of the proposed setup further. The proposed scheme for estimating the DOA generates efficient outcomes compared to the state-of-the-art algorithms over the Monte Carlo simulations.
Nanomaterials: A Potential Hope for Life Sciences from Bench to Bedside
Authors: Shinde Mahesh Uttamrao , Patwekar Mohsina , Patwekar Faheem , Bajaber Majed A. , Medikeri Anuradha , Mohammad Firdous Sayeed , Mukim Mohammad , Soni Sanjay , Mallick Jewel , Jawaid Talha
Published: June 2022

In this review we hope to explain regarding nanoparticles (NPs), Nanoparticles are very small materials that range from 1 to 100 nm size. And the subclasses of nanoparticles are mentioned. Nanomaterials are formulated by nanoparticles. Research on nanomaterials is used to improve in material technology and synthesis gained the support. Nanomaterials are gradually becoming popularized and starting to arise as commodities. Nanotechnology refers to a set of scientific disciplines and designing where peculiarities that occur at aspects in the nanometre scale are used in the plan, characterization, formulation and use of materials, structures gadgets and system. Here application of nanomaterial and nanotechnology is explained. The use of nanomaterials in the production of biosensors for detection of pathogens, formulation of nanomaterial‐based biosensors for detection of antibiotics, Nanomedicines and the application of nanotechnology in food business Etc were discussed. Hazards and risk of nanomaterials are studied under nanotoxicology. Nanotechnology is ab arising science as would be considered normal to have quick areas of strength for improvements. It is anticipated to contribute altogether to financial development and occupation creation in the next few decades.
Sunitinib Reduced the Migration of Ectopic Endometrial Cells via p-VEGFR-PI3K-AKT-YBX1-Snail Signaling Pathway
Authors: Fan Xiaodan , Tong Yanyan , Chen Yiting , Chen Yichen
Published: June 2022

Endometriosis (EMs) is one of the most common gynecological diseases, lacking effective treatment. EMs are currently being treated with small molecule targeted therapy, which has resulted in a significant reduction in patient suffering. Our previous studies have shown that sunitinib plays an obvious role in migration. Consequently, the purpose of this study is to explore the molecular mechanism by which sunitinib suppressed the ectopic endometrial migration. The ectopic endometrial cells from patients were divided into two groups: the control group and the sunitinib group. Co-IP and protein spectrum assay were employed to filtrate differential proteins between two groups, and then, our study discovered a signaling pathway, p-VEGFR-PI3K-AKT-YBX1-Snail, in the cell of EMs. To confirm this signaling pathway, VEGF165 was added to the sunitinib group to upregulate the expression of VEGFR. Next, the expression of p-VEGFR, PI3K, AKT, YBX1, and snail was measured in the control group and sunitinib group (compared with the control group: p-VEGFR, PI3K, AKT, YBX1, and snail,

∗
∗
∗
∗
P
<
0.0001

) and the VEGFR+sunitinib group (compared with the sunitinib group: p-VEGFR, PI3K, AKT, and snail,

∗
∗
∗
∗
P
<
0.0001

; YBX1,

∗
∗
∗
P
<
0.001

); finally, the outcome was as expected. In addition to in vitro experiments, we also conducted in vivo experiments in mice. In the EMs mouse model, we found sunitinib reduced the number of heterotopic foci (

t
=
11.16

,

∗
∗
∗
∗
P
<
0.0001

) and inhibited the expression of p-VEGFR, YBX1, and snail by immunofluorescence. To sum up, sunitinib exactly reduced the migration of ectopic endometrial cells with the involvement of the p-VEGFR-PI3K-AKT-YBX1-Snail signaling pathway in both in vitro and in vivo experiments. This study suggests that sunitinib presents a potential targeted drug for EMs therapy.
The Effects of Temperature and Impact Velocity on the Shock Wave Response of Pore-Embedded Metallic Glasses
Authors: Patra Indrajit , Abdulhadi Ahmed M. , Fahim Fatima Safaa , Bashar Bashar S. , Alawsi Taif , Salmani Mohammad
Published: June 2022

In this work, the shock wave response of a pore-embedded CuZr metallic glass (PEMG) under different impact velocities (0.5–1.5 km/s) and initial temperatures (300–600 K) was evaluated through the molecular dynamics (MD) simulation. The results indicated that the nucleation and growth of nanoscale shear events around the pore were the dominant mechanisms for plastic deformation under the shock wave. It was also found that the increase in the impact velocity led to the filling of pore, which was due to the structural softening and the local temperature increment in the vicinity of pore. Moreover, the spall event originated from the formation and coalescence of tension transformation zones, leading to the formation of nanovoids in the system. At higher velocities, the spallation was accompanied with the formation of more nanovoids with smaller sizes, inducing the brittle failure in the system. The MD outcomes also showed that the increase in initial temperature decreased the shock pressure and flow shear stress and led to the smoother spallation in the PEMG.
Understanding the Impact of Rural Returnees’ Hometown Identity on Their Successful Entrepreneurship with the Operations Research Framework
Authors: Sun Feihan , Miao Xumei , Feng Xiaoyan , Ye Chongliang
Published: June 2022

In the past ten years, China’s rapid urbanization has hollowed out the rural population considerably. Although returnee entrepreneurship has become a catalyst for retaining people and revitalizing the countryside, most disenfranchised Chinese villages struggle to retain their returnees, owing to their lack of infrastructure and low quality of life. However, many e-commerce villages and live broadcast villages have emerged in the eastern coastal plains of China. Returnees, inspired with a strong hometown identity, have become the driving force in the development of these villages. This study investigates the relationship between the hometown identity of returnees and their entrepreneurial success with the operations research framework. We explored the mediating role of the agglomeration of knowledge to illustrate the mechanism between the hometown identity and entrepreneurial success, while testing the moderating effect and conditional indirect effects of the returnees’ creativity through moderated mediation analysis. Using the time lag research method, we collected field data from villages in the northern plains of Jiangsu Province. The research results showed a positive correlation between the hometown identity and entrepreneurial success, with agglomerated knowledge production as an important intermediary. Returnees with a stronger sense of a hometown identity and higher creativity are more likely to enjoy entrepreneurial success. This research has important reference significance for all levels of government concerned with rural development, and returnees who desire to start their own businesses.
Comparative Potential of Zinc Sulfate, L-Carnitine, Lycopene, and Coenzyme Q10 on Cadmium-Induced Male Infertility
Authors: Iftikhar Ayesha , Akhtar Muhammad Furqan , Saleem Ammara , Riaz Amjad , Zehravi Mehrukh , Rahman Md. Habibur , Md Ashraf Ghulam
Published: June 2022

The human exposure to toxic chemicals and heavy metals is one of the main predisposing factors contributing to male infertility. Acute exposure to cadmium chloride results in testicular damage and infertility. The purpose of the present study was to investigate and compare the curative effect of coenzyme Q10 (CoQ10), lycopene, L-carnitine (LC), and zinc sulfate against the cadmium-induced infertility in male Wistar rats. Cadmium chloride (0.4 mg/kg/day) was orally administered to rats for three consecutive days. Then, oral administration of different treatments (i.e., LC 100 mg/kg, CoQ10 20 mg/kg, lycopene 4 mg/kg, zinc sulfate 6 mg/kg, and a combination LC-CoQ10 at 500/50 mg/kg) was carried out for 30 days. The impact of different treatments on semen parameters, such as sperm count and motility, testicular antioxidants, and serum testosterone, was determined. Furthermore, the morphology of epididymis sperms and histopathology of rat testes were also assessed. Cadmium exposure decreased the sperm count, progressive sperm motility, testosterone, superoxide dismutase (SOD), and catalase and reduced glutathione (GSH). It also caused banana sperm tail, bent sperm head, vacuolization of seminiferous tubules, and oligospermia in rat testes. All treatments with nutraceuticals improved sperm count, sperm morphology, serum testosterone, vacuolization of seminiferous tubules, and oligospermia in diseased rats. Treatment with lycopene, LC, and LC-CoQ10 improved progressive sperm motility and other parameters and increased SOD, GSH, and CAT in the rat testes. CoQ10 also increased SOD activity in rat testes’ tissue homogenates. It is concluded from the current study that all nutraceuticals partially improved reproductive toxicity of cadmium. The administration of lycopene and a high-dose combination of LC-CoQ10 were more efficacious in treating cadmium-induced infertility than other treatments. Treatment of cadmium-exposed rats with lycopene, LC, CoQ10, and LC-CoQ10 improved sperm count and motility through reduction of testicular oxidative stress and improving serum testosterone.
H∞ Filter for Discrete‐Time Takagi–Sugeno Fuzzy Systems with Time‐Varying Delays via a Novel Wirtinger‐Based Inequality
Authors: Wang Wanru , Wen Yonggang , Sun Liankun , Ma Kaifan
Published: June 2022

This paper is devoted to the analysis and design of H∞ filtering for discrete‐time Takagi–Sugeno (TS) fuzzy systems with time‐varying delays. By using the delay‐partitioning method, more systematic information is introduced, which can reduce the conservatism of the conclusion. By constructing an appropriate Lyapunov functional and combining with a newly Wirtinger‐based summation inequality, the existence condition of the H∞ filter is obtained. Thus, utilizing the contract matrix transformation method, the H∞ filter design for discrete‐time TS fuzzy systems with time‐varying delay based on LMI is proposed. Finally, a few numerical analysis results are given to prove the eﬀectiveness of the method.
Gingiva-Derived Mesenchymal Stem Cells Attenuate Imiquimod- (IMQ-) Induced Murine Psoriasis-Like Skin Inflammation
Authors: Ye Ziyu , Liang Yanfang , Lin Bihua , Li Yanyun , Chai Xingxing , Lian Jiachun , Zhang Xueying , Che Zhengping , Zeng Jincheng
Published: June 2022

Human gingiva-derived mesenchymal stem cells (GMSCs) are isolated from the gingival propria with promising regenerative, immunomodulatory, and anti-inflammatory properties. Recently, several studies, including ours, have found that GMSCs have the therapeutic potentials of nerve regeneration and skin disorders in various types such as the cell itself, cell-free conditioned medium, or extracellular vesicles (EVs). However, the mechanobiological behavior of GMSCs is closely related to the culture conditions. Therefore, the purpose of this study was to evaluate the function of human GMSCs on imiquimod- (IMQ-) induced murine psoriasis-like skin inflammation in two-dimensional (2D) and three-dimensional (3D) culture conditions. Here, we isolated and characterized GMSCs in 2D and 3D culture conditions and found that GMSCs in 2D and 3D infusion can significantly ameliorate the IMQ-induced murine psoriasis-like skin inflammation, reduce the levels of Th1- and Th17-related cytokines IFN-γ, TNF-α, IL-6, IL-17A, IL-17F, IL-21, and IL-22, and upregulate the percentage of spleen CD25+CD3+ T cells while downregulate the percentage of spleen IL-17+CD3+ T cells. In summary, our novel findings reveal that GMSCs in 2D and 3D infusion may possess therapeutic effects in the treatment of psoriasis.
Rule-Based Engine for Automatic Allocation of Smallholder Dairy Producers in Preidentified Production Clusters
Authors: Mavura Fatuma , Pandhare Sanket M. , Mkoba Elizabeth , Nyambo Devotha G.
Published: June 2022

Smallholder dairy producers account for around half of all African livestock ventures; nevertheless, they face challenges in producing more milk due to an insufficient framework and infrastructure to maximize their output. Smallholder dairy producers in this scenario use a variety of tactics to boost milk output. However, the attempts need multiple heuristics, time, and financial investment. Furthermore, because of a lack of extension officers, smallholder dairy producers become trapped in failure cycles, unsuccessful attempts, and a diminished motivation to continue farming. Therefore, the interventions were more straightforward as smallholder dairy producers with comparable characteristics grouped. This research aimed to create a rule-based engine that automatically assigns smallholder dairy producers to predefined clusters. About 78 stakeholders were interviewed, including 69 smallholder dairy producers and 9 extension officers from Meru-Arusha, Tanzania. The 10 production features and 6 predefined clusters were adopted from the previous study. Therefore, a rule-based engine used the selected 10 production features. As a result, the rule-based engine automatically assigns the smallholder dairy producers to their respective clusters. Therefore, smallholder dairy producers share their farming skills and experience to increase milk output through these clusters. Furthermore, extension officers in the system provide timely assistance to smallholder dairy producers with farming concerns.
Green Synthesis of Silver Nanoparticles Using Thespesia populnea Bark Extract for Efficient Removal of Methylene Blue (MB) Degradation via Photocatalysis with Antimicrobial Activity and for Anticancer Activity
Authors: Yahya Tahir Muhammad , Ahmad Awais , A. Alothman Asma , Mushab Mohammed Sheikh Saleh , Ali Shafaqat
Published: June 2022

The green synthesis method was used to effectively fabricate Ag‐NPs by using Thespesia populnea bark extract. The structural, morphological, elemental composition, and optical properties of as‐synthesized Ag‐NPs were characterized by powder X‐ray diffraction (P‐XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDAX), transmission electron microscopy (TEM), and UV‐Vis spectroscopy. Their photocatalytic efficiency as a photocatalyst was examined by degradation of methylene blue (MB) dye under direct sunlight irradiation. After 120 minutes of sunlight irradiation, Ag‐NPs show photocatalytic degradation efficiency (DE percent) of 92%. The hydroxyl and superoxide radicals were found to be responsible for biodegradation. To the best of our acquaintance, this is the first research to use Ag‐NPs as a photocatalyst for the efficient degradation of MB dye and its antimicrobial activity by using Thespesia populnea bark extract. The cytotoxic viability against SK‐MEL cell line with a median inhibitory concentration (IC50) of 45 μL/mg proved its potent anticancer property. Based on the findings, the study revealed the significance of as‐synthesized green Ag‐NPs over other physically/chemically prepared Ag‐NPs.
Bibliometric Review on Corporate Social Responsibility of the Food Industry
Authors: He Mingli , Yu Weiping , Han Xiaoyun
Published: June 2022

Corporate social responsibility (CSR) in the food industry has received increasing attention in recent years. Many scholars have paid attention to case studies and other empirical analyses in this field, but there is no systematic or scientific literature review. The purpose of this study is to quantitatively evaluate the knowledge structure, research hotspots, and development history in CSR in the food industry. After searching, screening, and commenting, 498 articles were left for citation analysis, co-citation analysis, and co-word analysis. The main findings of the research are as follows: (1) The overall development status of the research in the field. The analysis of the three fields that constitute the knowledge structure. (2) Research in this field has become a hot spot, but the research is rather scattered, and the scholars and experts do not have a special research core. (3) The keywords’ cluster results in 9 clustering tags, which are further grouped into 7 groups. The research of the scholars focuses on the food supply chain, consumer perception, and social media communication. (4) The research topics in this field focus on environmental responsibility, nutrition and health, and food safety. The research results show that future research should be more in-depth and reflect the new characteristics of the Internet, digitalization, and big data.
Application of Dynamic 18F-FDG PET/CT for Distinguishing Intrapulmonary Metastases from Synchronous Multiple Primary Lung Cancer
Authors: Lv Weize , Yang Min , Zhong Hongcheng , Wang Xiaojin , Yang Shuai , Bi Lei , Xian Jianzhong , Pei Xiaofeng , He Xinghua , Wang Ying , Lin Zhong , Cao Qingdong , Jin Hongjun , Shan Hong
Published: June 2022

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted [Formula: see text] value based on dynamic scanning, and corresponding maximum diameter ([Formula: see text]) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of [Formula: see text] and [Formula: see text] ([Formula: see text]; [Formula: see text]) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between [Formula: see text] and [Formula: see text] from all groups was determined. There was no significant difference for [Formula: see text] between the IPM and sMPLC groups, while the IPM group had a significantly higher [Formula: see text] than the sMPLC group. The AUC of [Formula: see text] for differentiating sMPLC from IPM was 0.80 (cut-off value of [Formula: see text], sensitivity 79%, specificity 75%, [Formula: see text]). There was a good correlation (Pearson [Formula: see text], 95% CI: 0.79-0.96, [Formula: see text]) between [Formula: see text] and [Formula: see text] in the IPM group but not in the sMPLC group (Pearson [Formula: see text], [Formula: see text]). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. [Formula: see text] calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules.
RLMD‐PA: A Reinforcement Learning‐Based Myocarditis Diagnosis Combined with a Population‐Based Algorithm for Pretraining Weights
Authors: Moravvej Seyed Vahid , Alizadehsani Roohallah , Khanam Sadia , Sobhaninia Zahra , Shoeibi Afshin , Khozeimeh Fahime , Sani Zahra Alizadeh , Tan Ru-San , Khosravi Abbas , Nahavandi Saeid , Kadri Nahrizul Adib , Azizan Muhammad Mokhzaini , Arunkumar N. , Acharya U.Rajendra
Published: June 2022

Myocarditis is heart muscle inflammation that is becoming more prevalent these days, especially with the prevalence of COVID‐19. Noninvasive imaging cardiac magnetic resonance (CMR) can be used to diagnose myocarditis, but the interpretation is time‐consuming and requires expert physicians. Computer‐aided diagnostic systems can facilitate the automatic screening of CMR images for triage. This paper presents an automatic model for myocarditis classification based on a deep reinforcement learning approach called as reinforcement learning‐based myocarditis diagnosis combined with population‐based algorithm (RLMD‐PA) that we evaluated using the Z‐Alizadeh Sani myocarditis dataset of CMR images prospectively acquired at Omid Hospital, Tehran. This model addresses the imbalanced classification problem inherent to the CMR dataset and formulates the classification problem as a sequential decision‐making process. The policy of architecture is based on convolutional neural network (CNN). To implement this model, we first apply the artificial bee colony (ABC) algorithm to obtain initial values for RLMD‐PA weights. Next, the agent receives a sample at each step and classifies it. For each classification act, the agent gets a reward from the environment in which the reward of the minority class is greater than the reward of the majority class. Eventually, the agent finds an optimal policy under the guidance of a particular reward function and a helpful learning environment. Experimental results based on standard performance metrics show that RLMD‐PA has achieved high accuracy for myocarditis classification, indicating that the proposed model is suitable for myocarditis diagnosis.
On Classification of Semigroup N by Green’s Theorem
Authors: Wazzan Suha , Ozalan Nurten Urlu
Published: June 2022

In previous papers, it has been recently defined a new class of semigroups based on both Rees matrix and completely 0‐simple semigroups. For this new structure, it has been introduced with certain basic properties and finiteness conditions. The main goal of the paper is to prove Green’s Theorem for by indicating the existence of Green’s lemma. We also study generalized Green’s relation over and present some new findings. In particular, we classify our semigroup associated with generalized Green’s relation by constructing good homomorphism.
Information Visualization Design of Web under the Background of Big Data
Authors: Deng Ran , Ni Taile
Published: June 2022

With the rapid development of the Internet, the information on the Internet presents an explosive growth. Cloud computing and big data analysis technology based on Internet information rise accordingly. However, all web pages contain not only important information but also the noise information irrelevant to the subject information. They seriously affect the accuracy of information extraction, so the research of web page information extraction technology arises at the historic moment and becomes the research hotspot. The quality of web page text information will directly affect the accuracy of later information processing and decision-making. If we can accurately evaluate the information of the web pages captured from the Internet and classify the extracted web pages according to the corresponding characteristics, we can not only improve the efficiency of information processing, but also improve the practical value of the information decision-making system. From the practical application requirements and user-friendly operation point of view, the information visualization of web design based on big data is studied in this paper. Specifically, the system designed in this paper improves the traditional template-based web information extraction method, establishes a web information extraction rule scheme combined with templates, and achieves the goal of web information extraction rule selection and template generation in the visual environment. Finally, the visualization algorithm based on T-SNE verifies the effectiveness of the web page information visualization algorithm designed in this paper.
Desafíos de la educación en enfermería en pandemia: percepción y experiencia de los estudiantes de enfermería sobre la incorporación de la simulación virtual
Authors: Soto Paula , Muñoz Serrano Mónica , González Montero Daniela , Vergara Arias Karen
Published: June 2022

Introducción: en el contexto de la pandemia mundial por COVID-19 se incorporan nuevas metodologías de enseñanza-aprendizaje para contribuir al logro de los objetivos de aprendizaje frente al cierre de las universidades y de los campos clínicos. Esta investigación evalúa la percepción y la experiencia de los estudiantes de tercer y cuarto año de pregrado de enfermería, frente al uso de escenarios de simulación virtual como complemento de la práctica clínica. Materiales y métodos: un total de 68 estudiantes (26%) respondieron la encuesta de percepción sobre su experiencia del uso de la simulación virtual a través del software vSim for Nursing™. Se realizó un análisis cuantitativo y cualitativo de los datos. Resultados:  un 89,7% de los estudiantes consideraron que la simulación virtual es útil para el aprendizaje y que contribuye principalmente para la comprensión de los contenidos y desarrollo de las habilidades de valoración clínica.
Discusión: la experiencia en la simulación virtual es realista y útil tanto para aprender nuevos conocimientos, para reforzar los saberes previos y así también como una buena preparación para la práctica clínica. Se visualiza su incorporación desde el inicio al término de la carrera. Sin embargo, para áreas como salud mental otras metodologías podrían ser más adecuadas para mejorar las habilidades de comunicación.
Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS–MAPK Pathway Inhibition in Pancreatic Cancer
Authors: Ravichandran Mirunalini , Hu Jingjie , Cai Charles , Ward Nathan P. , Venida Anthony , Foakes Callum , Kuljanin Miljan , Yang Annan , Hennessey Connor J. , Yang Yang , Desousa Brandon R. , Rademaker Gilles , Staes Annelot A.L. , Cakir Zeynep , Jain Isha H. , Aguirre Andrew J. , Mancias Joseph D. , Shen Yin , DeNicola Gina M. , Perera Rushika M.
Published: June 2022

The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS–MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the selective degradation of the iron storage complex ferritin, in MEKi-treated cells. Ferritinophagy promotes mitochondrial iron–sulfur cluster protein synthesis and enhanced mitochondrial respiration. Accordingly, suppressing iron utilization sensitizes PDA cells to MEKi, highlighting a critical and targetable reliance on lysosome-dependent iron supply during adaptation to KRAS–MAPK inhibition.

Significance:

Reduced c-MYC levels following MAPK pathway suppression facilitate the upregulation of autophagy and lysosome biogenesis. Increased autophagy–lysosome activity is required for increased ferritinophagy-mediated iron supply, which supports mitochondrial respiration under therapy stress. Disruption of ferritinophagy synergizes with KRAS–MAPK inhibition and blocks PDA growth, thus highlighting a key targetable metabolic dependency.

See related commentary by Jain and Amaravadi, p. 2023.

See related article by Santana-Codina et al., p. 2180.

This article is highlighted in the In This Issue feature, p. 2007
Successful Management of Severe Hyperhaemolysis with Combined Tocilizumab and Rituximab in Non-Transfusion-Dependent Thalassaemia: A Case Report
Authors: El Afifi Amal M. , Saeed Alia M. , Fekry Gihad H. , Mostafa Mariam A. , Elmetwally Reham A. , Hamed Inas M. , Hussein Aliaa N. , Hasanien Gomaa M.
Published: June 2022

Introduction: This is the fourth case reporting the administration of tocilizumab to control hyperhaemolysis. It was administered with rituximab to stop hyperhaemolysis refractory to frontline therapy. Hyperhaemolysis is a rare life-threatening subtype of delayed haemolytic transfusion reaction. Refractory cases pose a clinical challenge with no standard of care to date. Case Presentation: A 29-year-old lady with non-transfusion-dependent thalassaemia presented with refractory hyperhaemolysis necessitating the administration of rituximab. This was complicated with anaemic heart failure and altered sensorium exacerbated with further transfusions. A nadir haemoglobin of 2.1 g/dL was reached after the initiation of rituximab, and her condition was too critical to wait for the slow expected improvement. Hence, tocilizumab was given as a bridging therapy to block haemolysis till the delayed onset of radical treatment. Conclusion: Tocilizumab can be effectively combined with rituximab to stop hyperhaemolytic episode refractory to first-line treatment when a prompt response is needed.
Antenatal Magnesium Sulfate for Preterm Neuroprotection: A Single-Center Experience from Kuwait Tertiary NICU
Authors: Ayed Mariam , Ahmed Javed , More Kiran , Ayed Amal , Husain Hamid , AlQurashi Ammar , Alrajaan Najla
Published: June 2022

Objectives: The study aimed to evaluate the impact of antenatal exposure of magnesium sulfate (MgSO4) on short- and long-term outcomes in preterm neonates born less than 32 weeks gestation. Methods: Single-center retrospective cohort study of 229 neonates born between 24 and 32 weeks gestation was conducted from January 2018 through December 2018 in a level III neonatal care unit in Kuwait. Antenatal MgSO4 exposure was collected from the medical records, and the indication was for neuroprotection effect. Brain MRI was done on 212 neonates (median gestational age 36 weeks), and brain injury was assessed using the Miller’s score. Neurodevelopmental outcome was assessed by Bayley-III scales of infant development at 36 months corrected age (N = 146). The association of exposure to MgSO4 with brain injury and neurodevelopmental outcomes was examined using multivariable regression analysis adjusting for gestational age at MRI and variables with p value <0.05 on univariate analysis. Results: Among the 229 neonates, 47 received antenatal MgSO4. There were no differences between the groups in gestational age and birth weight. MgSO4 exposure was not associated with an increased risk of necrotizing enterocolitis, chronic lung disease, retinopathy of prematurity, and mortality. The incidence of cerebellar hemorrhage was significantly less in the MgSO4 group (0% vs. 16%, p value = 0.002). Neonates who received MgSO4 had lower risks of grade 3–4 intraventricular hemorrhage (IVH) adjusted OR 0.248 (95% CI: 0.092, 0.66), p = 0.006; moderate-severe white matter injury (WMI) adjusted odd ratio 0.208 (95% CI: 0.044, 0.96), p = 0.046; and grade 3–4 IVH and/or moderate-severe WMI adjusted OR 0.23 (95% CI: 0.06, 0.84), p = 0.027. Neurodevelopmental assessment at 36 months corrected age showed better motor (adjusted beta coefficient 1.08 [95% CI: 0.099, 2.06]; p = 0.031) and cognitive composite scores (adjusted beta coefficient 1.29 [95% CI: 0.36, 2.22]; p = 0.007) in the MgSO4 group. Conclusion: Antenatal exposure to MgSO4 in preterm neonates less than 32 weeks was independently associated with lower risks of brain injury and better motor and cognitive outcomes.
Interventions for the Prevention of Preterm Premature Rupture of Membranes: A Systematic Review and Meta-Analysis
Authors: El-Achi Vanessa , Aggarwal Sangita , Hyett Jon
Published: June 2022

Introduction: Preterm prelabour rupture of membranes (PPRoM) is a significant cause of maternal and perinatal morbidity and mortality. The aim of this project was to identify interventions that reduce the prevalence of PPRoM. Methods: Search strategy included a systematic literature search of MEDLINE, EMBASE, PubMed, and Cochrane Library. The selection criteria included randomized control studies that compared a therapy to standard care (no therapy or placebo) in pregnancy and included PPRoM as an outcome. Risk of bias was assessed according to the Cochrane risk-of-bias tool for randomized trials. Odds ratios with 95% confidence intervals were calculated using random-effects models. Quality of evidence was assessed using the GRADE methodology. Results: Twenty-nine studies examining 10 interventions met the inclusion criteria. Therapies included docosahexaenoic acid (DHA), aspirin, rofecoxib, vitamin C alone and with vitamin E, folic acid (alone, with iron, with iron and zinc, within a multiple micronutrient supplement), zinc, calcium, copper, and treatment of bacterial vaginosis. There was no significant difference in the prevalence of PPRoM in the treatment groups compared to placebo, except for rofecoxib which showed an increased risk of PPRoM (RR 2.46, 95% CI 1.28–4.73; p = 0.007, 1 trial, 98 women; very low quality of evidence) and a multiple micronutrient supplement which showed a reduction in PPRoM (RR 0.40, 95% CI 0.19–0.84; p = 0.01, 1 trial, 1,671 women; very low quality of evidence). Conclusions: No interventions have been convincingly shown to reduce the prevalence of PPRoM. Given this is a common problem leading to significant morbidity and mortality, further research is required.
Evolving Mural Defects, Dilatation, and Biomechanical Dysfunction in Angiotensin II–Induced Thoracic Aortopathies
Authors: Weiss Dar , Long Aaron S. , Tellides George , Avril Stéphane , Humphrey Jay D. , Bersi Matthew R.
Published: June 2022

Background:

Thoracic aortopathy associates with extracellular matrix remodeling and altered biomechanical properties. We sought to quantify the natural history of thoracic aortopathy in a common mouse model and to correlate measures of wall remodeling such as aortic dilatation or localized mural defects with evolving microstructural composition and biomechanical properties of the wall.

Methods:

We combined a high-resolution multimodality imaging approach (panoramic digital image correlation and optical coherence tomography) with histopathologic examinations and biaxial mechanical testing to correlate spatially, for the first time, macroscopic mural defects and medial degeneration within the ascending aorta with local changes in aortic wall composition and mechanical properties.

Results:

Findings revealed strong correlations between local decreases in elastic energy storage and increases in circumferential material stiffness with increasing proximal aortic diameter and especially mural defect size. Mural defects tended to exhibit a pronounced biomechanical dysfunction that is driven by an altered organization of collagen and elastic fibers.

Conclusions:

While aneurysmal dilatation is often observed within particular segments of the aorta, dissection and rupture initiate as highly localized mechanical failures. We show that wall composition and material properties are compromised in regions of local mural defects, which further increases the dilatation and overall structural vulnerability of the wall. Identification of therapies focused on promoting robust collagen accumulation may protect the wall from these vulnerabilities and limit the incidence of dissection and rupture.
Serum L-Carnitine Levels Are Associated With First Stroke in Chinese Adults With Hypertension
Authors: Zhou Ziyi , Zhang Nan , Song Yun , Liu Lishun , Li Jianping , Zhang Yan , Huo Yong , Liu Xiangyi , Duan Yong , Wang Binyan , Zhang Hao , Guo Huiyuan , Qin Xianhui , Wang Xiaobin , Xu Xiping
Published: June 2022

Background:

This study aimed to evaluate the association of serum L-carnitine with first stroke and explore potential effect modifiers.

Methods:

This is a nested, case-control study drawn from the China Stroke Primary Prevention Trial among rural Chinese adults with hypertension, including 557 first stroke cases and 557 age-matched, sex-matched, treatment group–matched, and residence-matched controls. Serum L-carnitine was measured by liquid chromatography with tandem quadrupole mass spectrometry. Multiple conditional logistic regression models were used to evaluate the association between L-carnitine and first stroke.

Results:

The mean level of serum L-carnitine in the stroke population was 4.7 μg/mL, which was significantly lower than that of the control group (5.7 μg/mL). When L-carnitine was assessed as quintiles, compared with the reference group (quintile 1, <3.3 μg/mL), the odds of stroke were 0.62 (95% CI, 0.39–1.00) in quintile 2, 0.66 (95% CI, 0.40–1.10) in quintile 3, 0.47 (95% CI, 0.28–0.81) in quintile 4, and 0.50 (95% CI, 0.30–0.84) in quintile 5. The trend test was significant (
P
=0.01). When quintiles 2 to 5 were combined, the adjusted odds ratio of first stroke was 0.58 (95% CI, 0.38–0.87) compared with quintile 1. Similar associations were found for ischemic stroke and hemorrhagic stroke. In subgroup analysis, a significant L-carnitine–stroke association was only observed in the normal folate group (
P
interaction, 0.039) and in the
MTHFR
CC genotype group (
P
interaction, 0.047).

Conclusions:

In this study of rural Chinese adults with hypertension, serum L-carnitine had an inverse but nonlinear association with first stroke. Folate status and the
MTHFR
C677T variant were significant effect modifiers of the association.
Single-Cell Transcriptome Analysis of the Circle of Willis in a Mouse Cerebral Aneurysm Model
Authors: Martinez Alejandra N. , Tortelote Giovane G. , Pascale Crissey L. , McCormack Isabella G. , Nordham Kristen D. , Suder Natalie J. , Couldwell Mitchell W. , Dumont Aaron S.
Published: June 2022

Background:

The circle of Willis (CoW) is the most common location for aneurysms to form in humans. Although the major cell types of the intracranial vasculature are well known, the heterogeneity and relative contributions of the different cells in healthy and aneurysmal vessels have not been well characterized. Here, we present the first comprehensive analysis of the lineage heterogeneity and altered transcriptomic profiles of vascular cells from healthy and aneurysmal mouse CoW using single-cell RNA sequencing.

Methods:

Cerebral aneurysms (CAs) were induced in adult male mice using an elastase model. Single-cell RNA sequencing was then performed on CoW samples obtained from animals that either had aneurysms form or rupture 14 days post-induction. Sham-operated animals served as controls.

Results:

Unbiased clustering analysis of the transcriptional profiles from >3900 CoW cells identified 19 clusters representing ten cell lineages: vascular smooth muscle cells, endothelial cells fibroblasts, pericytes and immune cells (macrophages, T and B lymphocytes, dendritic cells, mast cells, and neutrophils). The 5 vascular smooth muscle cell subpopulations had distinct transcriptional profiles and were classified as proliferative, stress-induced senescent, quiescent, inflammatory-like, or hyperproliferative. The transcriptional signature of the metabolic pathways of ATP generation was found to be downregulated in 2 major vascular smooth muscle cell clusters when CA was induced. Aneurysm induction led to significant expansion of the total macrophage population, and this expansion was further increased with rupture. Both inflammatory and resolution-phase macrophages were identified, and a massive spike of neutrophils was seen with CA rupture. Additionally, the neutrophil-to-lymphocyte ratio (NLR), which originated from CA induction mirrored what happens in humans.

Conclusions:

Our data identify CA disease-relevant transcriptional signatures of vascular cells in the CoW and is searchable via a web-based R/shiny interface.
Assessing (and Making Sense of) Severity
Authors: Cakal Ergun
Published: June 2022

The element of severity remains core to the definition and interpretation of torture under international law. It has long represented a source of confusion and obfuscation for the legally-oriented anti-torture professional, whether academic, advocate or adjudicator. Its character as decisive differentiator, setting torture apart from cruelty, inhumanity and degradation, remains problematically entrenched and contested. It is a legal construct not finding its origins in the scholarship on pain, and evades precise measurement – as pain is socio-culturally constructed, relative and subjective. Accepting the prevailing complexity and addressing the perennial ambiguity, this article aims to offer some clarifications towards conceptualising and contextualising, and thereby better specifying and applying, torture’s core.
Redescription of the Caucasian endemic Diamesa caucasica Kownacki et Kownacka (Diptera: Chironomidae: Diamesinae)
Authors: MAKARCHENKO EUGENYI A. , SEMENCHENKO ALEXANDER A. , PALATOV DMITRY M.
Published: June 2022

Diamesa caucasica Kownacki et Kownacka was described from the watercourses of the Terek River basin flowing down from the high mountain glaciers of the Caucasus (alt. 2000–2700 m a.s.l.), namely from the Chkheri River (Ortsveri Glacier), the Suatisi River (Savitisi Glacier) and the Mnaisidon River (Mna Glacier) in Georgia (Kownacki & Kownacka 1973). So far, no other finds of this species have been recorded in the Caucasus and other mountainous regions of Europe. Apparently, D. caucasica is endemic to the Caucasus and its distribution probably does not go beyond the glacial streams of the Terek River basin. This assumption is confirmed by the finds of adult males of this species made by Dmitry Palatov in 2018–2022 in the rivers at an altitude 1402–1980 m a.s.l., originating in the Mostocete, Tanantsete, Skazsky and Tseysky glaciers of North Ossetia and which also belong to the Terek River basin.
Entropy Generation of Electrothermal Nanofluid Flow Between Two Permeable Walls Under Injection Process
Authors: Mukherjee S. , Shit G. C. , Vajravelu K.
Published: June 2022

This paper aims to study the electroosmotic nanofluid flow and heat transfer phenomena in a microchannel with porous walls by paying due attention to the interaction of the injected fluid velocity and the net charge density in the base fluid on the development of zeta potential and
electroosmotic slip velocity. The novelty of this study is to obtain the integral expression for electroosmotic slip velocity which is found to converge to Smoluchowski velocity when the injected fluid velocity is low and porous permeability of channel wall becomes negligible. Under a weak
electric field condition, the enhancement of pressure gradient is found to increase the normalized temperature and decrease the normalized nanoparticle concentration. The bulk nanofluid temperature is found to follow an almost quadratic relationship with applied pressure gradient. Additionally,
in the absence of injection velocity, we observed a new expression for Soret number as a ratio of the cross sectional nanoparticle concentration to Joule heating parameter. Finally, a comparative study on the total entropy generation is carried out to minimize the loss of thermal energy due
to irreversible physical mechanisms such as heat transfer, viscous dissipation and Joule heating effects that take place during the fluid flow process in a microchannel. It is thereby observed that the total entropy generation follows a quadratic relation with the Joule heating parameter in
the absence of both injection and viscous dissipation. The increment in diffusive Reynolds number reduces EDL thickness near the upper channel bed. With an increment in the applied pressure gradient, the normalized temperature increases whereas the normalized nanoparticle concentration reduces.
Micro Ribonucleic Acid Combined with Nanoparticles in Molecular Diagnosis of Depression
Authors: Zhao Lanhui , Ou Qiaoling , Zheng Peixing , Cheng Jiehua , Yuan Xiaoxia , Wang Demin
Published: June 2022

This study was aimed to investigate the application of micro ribonucleic acid (miRNA) combined with nanographene particles in molecular diagnosis of depression. After the sheet-shaped graphene oxide was mixed with a solvent to form a solution, it was atomized at high temperature to
form droplets and extract nanographene oxide, which was applied to an electrochemical sensor. 90 patients with depression were selected as the research objects and they were randomly divided into control group and experimental group, patients from the two groups received the miRNA molecular
diagnosis and the miRNA molecular diagnosis combined with nanographene electrochemical sensor dopamine detection method, respectively. As a result, the diagnostic sensitivity (82.4%), specificity (90.3%), and accurate index (71.3%) of patients from the experimental group were higher obviously
than those of the control group (54.3%, 72.8%, and 55.6%) (P <0.05). The expression levels of MiR-92b-5p and MiR-19a-3p in patients with depression were higher markedly than the levels of the normal population (P <0.05). The detection rates of mild depression, moderate
depression, and severe depression in patients from the experimental group were 97.3%, 96.5%, and 91.2%, which were higher greatly than the rates of the control group (84.3%, 85.4%, and 83.2%) (P <0.05). Besides, the false positive rate (11.2%) and false negative rate (5.6%) of patients
from the experimental group were sharply lower than the rates of the control group (31.5% and 16.4%) (P <0.05). In short, miRNA combined with nanographene electrochemical sensors could accurately diagnose depression with high accuracy and sensitivity, which could be applied in the
clinical diagnosis.