bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Breast Cancer with a Combination of DNT and LAG3 Checkpoint Blockage and its Mechanism
Authors: Wang Miao , Wei Yuhan , Li Yingrui , Li Hongzhong , Jin Jiangtao , Lu Yuting , Li Qin
Published: December 2021

Background

The characteristics of the tumor immune microenvironment (TIME) are closely related to immunotherapy. Breast cancer is a highly heterogeneous tumor, and its TIME is still unclear.
Methods

We utilized mass cytometry to explore the immune cell heterogeneity in breast cancer. DNTs from healthy volunteers were enriched in vitro. Flow cytometry was used to detect the cell surface receptors of cancer cells and DNT cells. The correlation between immune checkpoints and the abundance of immune cells or prognosis of breast cancer was analyzed by the TCGA database. The mRNA expression of functional genes was performed by quantitative real-time PCR.
Results

We found that the frequencies of Granzyme B (GZMB)+CD8+T and GZMB+DNT cells in cancer tissues (CA) of breast cancer were lower than those in blood samples of patients (PB), and the frequencies of programmed cell death protein 1 (PD1)+CD8+T and PD1+DNT cells in CA were higher than those in PB. DNTs from healthy volunteers had the cytotoxicity on MDA-MB-231. LAG3Ab could upregulate the mRNA expression of IFNγ and perforin by increasing T-BET transcription to enhance cytotoxic effect of DNT cells in vitro.
Conclusion

Our study revealed the suppressive status of TIME in breast cancer and supported DNT cells had the potential to be applied as a novel adoptive cell therapy for TNBC either alone or combined with LAG3Ab.
BNIP3 Mediates the Different Adaptive Responses of Fibroblast-like Synovial Cells to Hypoxia in Patients With Osteoarthritis and Rheumatoid Arthritis
Authors: Ran Deng , Yan Wang , Yanhong Bu , Wu Hong
Published: December 2021

Background: Hypoxia is one of the important characteristics of synovial microenvironment in rheumatoid arthritis (RA), and it is very important in the process of synovial hyperplasia. Fibroblast-like synovial cells (FLSs) are relatively affected by hypoxia injury in cell survival, while FLSs from patients with RA (RA-FLSs) are particularly resistant to hypoxia-induced cell death. The purpose of this study was to evaluate whether FLSs in patients with osteoarthritis (OA) and RA-FLSs have the same adaptation to hypoxia. Methods: CCK-8, flow cytometry and BrdU were used to detect the proliferation of OA-FLSs and RA-FLSs under different oxygen concentrations. Apoptosis was detected by AV/PI, TUNEL and Western blot, mitophagy was observed by electron microscope and Western blot, mitochondrial state was detected by reactive oxygen species (ROS) and mitochondrial membrane potential by flow cytometry, BNIP3 and HIF-1α were detected by Western blot and RT-qPCR. The silencing of BNIP3 is achieved by stealth RNA system technology. Results: After hypoxia, the survival rate of OA-FLSs was reduced, and the proliferation activity of RA-FLSs was further increased. Hypoxia induced increased apoptosis and inhibited autophagy of OA-FLSs, but not in RA-FLSs. Hypoxia treatment led to a more lasting adaptive response. RA-FLSs showed a more significant increase in gene expression regulated by HIF-1α transcription. Interestingly, they showed higher BNIP3 expression than OA-FLSs, and showed stronger mitophagy and proliferation activities. The BNIP3 siRNA experiment in RA-FLSs confirmed the potential role of BNIP3 in the survival of FLSs. The inhibition of BNIP3 resulted in the decrease of cell proliferation and the decrease of mitophagy and the increase of apoptosis. Conclusion: In summary, RA-FLSs maintained redox balance through mitophagy to promote cell survival under hypoxia. The mitophagy of OA-FLSs was too little to maintain the redox balance of mitochondria, leading to apoptosis. The difference of mitophagy between OA-FLSs and RA-FLSs under hypoxia is mediated by the expression of BNIP3.
A Novel Portfolio Based on Interval-Valued Intuitionistic Fuzzy AHP with Improved Combination Weight Method and New Score Function
Authors: Deng Xue , Geng Fengting , Yang Jianxin
Published: December 2021

The classical Analytic Hierarchy Process (AHP) requires an exact value to compare the relative importance of two attributes, but experts often can not obtain an accurate assessment of every attribute in the decision-making process, there are always some uncertainty and hesitation. Compared with classical AHP, our new defined interval-valued intuitionistic fuzzy AHP has accurately descripted the vagueness and uncertainty. In decision matrix, the real numbers are substituted by fuzzy numbers. In addition, each expert will make different evaluations according to different experiences for each attribute in the subjective weighting method, which neglects objective factors and then generates some deviations in some cases. This paper provides two ways to make up for this disadvantage. On the one hand, by combining the interval-valued intuitionistic fuzzy AHP with entropy weight, an improved combination weighting method is proposed, which can overcome the limitations of unilateral weighted method only considering the objective or subjective factors. On the other hand, a new score function is presented by adjusting the parameters, which can overcome the invalidity of some existing score functions. In theory, some theorems and properties for the new score functions are given with strictly mathematical proof to validate its rationality and effectiveness. In application, a novel fuzzy portfolio is proposed based on the improved combination weighted method and new score function. A numerical example shows that these results of our new score function are consistent with those of most existing score functions, which verifies that our model is feasible and effective.
Eplerenone Reverses Age-Dependent Cardiac Fibrosis Through Downregulating Osteopontin
Authors: Malakootian Mahshid , Maleki Majid , Mohammadian Negar , Arabian Maedeh
Published: December 2021

Background: The risk of cardiovascular disease dramatically increases with Ageing. Nowadays it is fully revealed that the fibrotic remodelling is the main cause of cardiac structural and functional changes related to the normal aging process, but the related signaling pathways and mechanisms are incompletely understood. Thus finding the new therapeutic approaches targeting cardiac fibrotic remodelling, may be necessary to develop preventive care in geriatric population against cardiovascular diseases. In this study, we evaluated the potential role of osteopontin (OPN) as novel mediators of age-dependent fibrotic pathways in heart as well as the effect of eplerenone on cardiac fibrosis reversal. Methods: Fischer-344 (F-344) rats has been used as three groups: young rats (2–3months old), aged rats (22-24 months old) without any treatment and aged rats treated with eplerenone (100 mg/kg/day) for 2 weeks. The expression level of OPN has been evaluated using real-time PCR and histological assessments were done to assess cardiac tissue fibrosis.Results: The expression level of OPN in aged rats was significantly higher than young rats and treatment with eplerenone significantly attenuated the level of OPN as well as cardiac fibrosis compare to untreated aged rats. Conclusion: Targeting cardiac fibroblast function with eplerenone could decrease expression of OPN marker and cause to reversal age-related cardiac fibrotic changes.
Separating Phages From Other Virus Families and Classifying the Different Phage Families By GI-Clusters
Authors: Jia Xingang , Han Qiuhong , Lu Zuhong
Published: December 2021

Background: Phages are the most abundant biological entities, but the commonly used clustering techniques are difficult to separate them from other virus families and classify the different phage families together.Results: This work uses GI-clusters to separate phages from other virus families and classify the different phage families, where GI-clusters are constructed by GI-features, GI-features are constructed by the togetherness with F-features, training data, MG-Euclidean and Icc-cluster algorithms, F-features are the frequencies of multiple-nucleotides that are generated from genomes of viruses, MG-Euclidean algorithm is able to put the nearest neighbors in the same mini-groups, and Icc-cluster algorithm put the distant samples to the different mini-clusters. For these viruses that the maximum element of their GI-features are in the same locations, they are put to the same GI-clusters, where the families of viruses in test data are identified by GI-clusters, and the families of GI-clusters are defined by viruses of training data.Conclusions: From analysis of 4 data sets that are constructed by the different family viruses, we demonstrate that GI-clusters are able to separate phages from other virus families, correctly classify the different phage families, and correctly predict the families of these unknown phages also.
Clinical Outcomes of Single-Step Transepithelial Photorefractive Keratectomy and Off-Flap Epipolis-Laser in Situ Keratomileusis in Moderate to High Myopia: 12-Month Follow-Up
Authors: Zhang Yunjie , Li Tiankun , Li Zhangliang , Dai Mali , Wang Qinmei , Xu Chenchen
Published: December 2021

Background

To compare the quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TPRK) and off-flap epipolis-laser in situ keratomileusis (Epi-LASIK) in moderate to high myopia.
Methods

In this prospective self-control study, we included patients with moderate to high myopia who were randomized to undergo TPRK in one eye and Epi-LASIK in the other eye. Twelve-month follow-up results for visual acuity, refraction, ocular high-order aberrations, contrast sensitivity, postoperative pain, epithelial healing, and haze grade were assessed.
Results

A total of 64 eyes (32 patients) were enrolled in the study. More eyes completed re-epithelialization in the TPRK group than in the Off-flap Epi-LASIK group 3–4 days postoperatively, while all eyes completed re-epithelialization by seven days. More eyes achieved a visual acuity (both UDVA and CDVA) of better than 20/20 in the TPRK group than in the Off-flap Epi-LASIK group. The ± 0.50 D predictability for correction of the spherical equivalent (SE) was higher in the eyes of the TPRK group (91%) than in those of the off-flap Epi-LASIK group (80%) 12 months after surgery. No significant differences in ocular aberrations, including coma, spherical, and trefoil, were found between the two groups at 12 months. There were also no significant differences in visual acuity, contrast sensitivity, pain, and haze grading between the two groups.
Conclusions

Both TPRK and off-flap Epi-LASIK are safe, effective, and predictable treatments for moderate to high myopia with comparable surgical outcomes.
Trial registration:

This study was retrospectively registered on ClinicalTrial.gov (NCT05060094, 17/09/2021).
Small Extracellular Vesicles Derived From Human Ipsc-Derived MSC Ameliorate Tendinopathy-Related Acute Pain Through Inhibiting Mast Cells Activation
Authors: Gao Renzhi , Ye Teng , Zhu Zhaochen , Li Qing , Zhang Juntao , Yuan Ji , Zhao Bizeng , Xie Zongping , Wang Yang
Published: December 2021

Background: Acute pain is the primary symptom of tendinopathy, and mast cells activation is a nonnegligible cause. Currently, safe and effective treatment for acute pain in tendinopathy is still lacking. This study was aimed to explore the analgesic effect of iPSC-derived mesenchymal stem cell-derived small extracellular vesicles (iMSC-sEVs) on acute pain and further investigate the underlying mechanisms in tendinopathy. Methods: A rat tendinopathy model was established and then treated with iMSC-sEVs or PBS for 4 weeks. The pathology of tendinopathy was accessed by H&E staining and immunohistochemical analysis 2 and 4 weeks after treatment. Then we measured pain-related behaviors 4 weeks after treatment. Double immunofluorescent staining on tendon sections for tryptase and PGP9.5 was conducted to assess whether iMSC-sEVs inhibit mast cells activation in tendinopathy. To further investigate the potential mechanism, RBL-2H3 cells were stimulated with substance P to mimic tendinopathy condition in vitro. The effect of iMSC-sEVs on inhibiting mast cells activation was measured by b-Hexosaminidase release assay, RT-qPCR, Toluidine blue staining and ELISA. RNA-seq was performed to analyze the related global changes and discover the underlying mechanism. Results: iMSC-sEVs effectively reduced inflammation, thereby alleviating acute pain in tendinopathy as reflected by histological analysis and pain-related behaviors. Moreover, iMSC-sEVs inhibited activated mast cell infiltration and interactions with nerve fibers in tendinopathy. In vitro study showed that the expression of proinflammatory cytokines and the degranulation of mast cells induced by substance P were reduced upon iMSC-sEVs treatment. Transcriptome analysis revealed that iMSC-sEVs treatment down-regulated the expression of genes involved in the HIF-1 signaling pathway.Conclusion: Overall, this study demonstrated that iMSC-sEVs relieved tendinopathy-related pain through inhibiting mast cells activation partly via the HIF-1 signaling pathway. These findings provide a novel treatment strategy for pain derived from tendinopathy and unravel the molecular mechanism underlying the application of iMSC-sEVs on mast cells.
COVID-19 Waves: Variant Dynamics and Control
Authors: Dutta Abhishek
Published: December 2021

The COVID-19 variants driven waves continue to try to nullify the success we achieved through efficacious vaccines, test and quarantine and social restrictions. This paper models the two major variants driven waves by two sets of susceptible-infected-quarantined-recovered-vaccinated-deceased coupled dynamics that is modulated by the three main interventions: vaccination, quarantine and restrictions. This SI2Q2R2VD system is used to demonstrate that the second major novel coronavirus wave in the US is caused by the delta variant and the corresponding rapid surge in infectious cases is driven by the unvaccinated pool of the populace. Next, a feedback control based planned vaccination strategy is derived and is shown to be able to suppress the surge in infections effectively.
Evaluation of the Impact of Maternal Training on Knowledge of Danger Signs in Sick Newborns and Health Seeking Behaviors Among Mothers in Enugu, South-east Nigeria- a Pre-and-post Interventional Study
Authors: Ekwochi Uchenna , Ndu Ikenna Kingsley , Nduagubam Obinna C , Chime Onyinye H , Amadi Ogechukwu F , Eneh Chizoma , Asinobi Isaac N , Osuorah Donatus Ignatius Chidiebere
Published: December 2021

Background: During the early weeks of life, the signs/symptoms of serious illness can be subtle, thus careful watching is crucial. The World health Organization has recognized nine “danger sign” which are closely associated with morbidity and mortality when not recognized early and given adequate care. This project was undertaken to assess mothers’ knowledge of these danger signs and health seeking behavior before and after training on newborn danger signs.Methodology: This community-based interventional study was carried amongst women in two rural communities of Enugu State. Participant’s knowledge of danger signs and care seeking behaviors were obtained using an interviewer administered questionnaire before and after training on the danger signs newborns using videos from the Integrated Management of Childhood Illnesses (IMCI). Pre- and post-training data were collated for analysis and comparison using SPSS version 20.Results: A total of 197 women were enrolled for the study. Among the socio-demographic indices examined, only the number of newborns nursed in the past significantly determined knowledge of danger signs in the sick newborn (P=0.032). Prior to the training, 47% of respondents could not recount offhand any danger sign compared to 1.5% after the training (P=0.001). Knowledge of up to 3 danger signs significantly increased after the training (P = 0.001) and participants who admitted seeking medical help within 24 hours of noticing any danger signs in newborn also significantly increased, (P= 0.043).Conclusion: Our study documented a strong impact of training of mothers on their knowledge of danger signs in the sick newborns and on their healthcare seeking behavior. Therefore, training and retraining of mothers and/or care givers could help improve newborn care and reduce overall infant mortality
Validation of an Online Calculator to Predict Short-term Postoperative Outcomes in Patients with Metastatic Brain Tumors
Authors: Kang Jennifer H. , Murphy Kelly Ryan , McCray Edwin , Ramirez Luis , Price Meghan , Dalton Tara E. , Peters Katherine B. , Desjardins Annick , Johnson Margaret O. , Friedman Allan H. , Cook Steven , Codd Patrick J. , Sampson John H. , Zomorodi Ali R. , Fecci Peter E. , Goodwin C. Rory
Published: December 2021

Introduction: Estimating the risk of extended length of stay (LOS) or non-routine discharge disposition is helpful in surgical decision-making for patients with brain metastases (BM). In 2020, an online calculator was introduced by Khalafallah et al. that stratified the risk of patients with brain tumors based on poor surgical outcomes. We applied the calculator to our population of BM patients to determine its generalizability and validity. Methods: We included BM patients who underwent a cranial procedure between 2015 and 2018 at a single academic institution. Patient age, race, marital status, admission status, KPS score, and medical co-morbidities (5-point modified frailty index (mFI-5)) were included in the analysis. We calculated the areas under the Receiver Operating Characteristics (ROC) curves to determine the validity of the model proposed in predicting extended LOS (>7 days) and need for specialty care at discharge (non-routine discharge disposition). Results: We analyzed 244 patients (mean age 61.2 years (SD 11.1), 57.0% female, and 78.1% Caucasian). The areas under the ROC curves were 0.8427 and 0.8422 for extended LOS and non-routine discharge disposition, suggesting high accuracy of the models for these outcomes. However, the (mFI-5) was not a significant predictor of either outcome in our multivariate analyses. Conclusions: We validated Khalafallah et al.’s predictive models of extended LOS and non-routine discharge disposition in our patient population, which included a broader range of surgical procedures. Further investigation of this model could clarify how the type of neurosurgical procedure influences outcomes, the role of the mFI-5, and its overall generalizability.
miR-1301-3p is a Potential Prognostic Biomarker for Esophageal Carcinoma and Acts by Downregulating NBL1 Expression
Authors: Du Jianting , Xiao Li-rong , Xu Guobing , Zheng Bin , Chen Chun
Published: December 2021

The authors have requested that this preprint be removed from Research Square.
The Indian Ocean SST Link to Solar Induced Chlorophyll Fluorescence Over India During Early Summer Monsoon
Authors: Varghese Roma , Behera Swadhin K. , Behera Mukunda Dev
Published: December 2021

This is a maiden attempt to explore the influence of sea surface temperature (SST) variations in the tropical Indian Ocean on the gross primary productivity (GPP) of the terrestrial vegetation of India during the summer monsoon. We studied the productivity of the vegetation across India using solar-induced chlorophyll fluorescence (SIF) as a proxy. Our results demonstrated a strong negative SST–SIF relationship: the productivity decreases (increases) when the SST of the tropical Indian Ocean is higher (lower) than normal. This SST–SIF coupling observed during June can be explained through the atmospheric teleconnections. Positive SST anomalies weaken the land–ocean thermal gradient during the monsoon onset period, reduce the monsoon flow, and hence decrease the moisture transport from the ocean to the Indian mainland. The resultant water stress, along with the high air temperature, leads to a reduction in the GPP. Conversely, negative SST anomalies strengthen the monsoon and increase the availability of moisture for photosynthesis. There is scope for improving regional GPP forecasting studies using the observed SST–SIF relationships.
Preparation of a miR-155-activating Nucleic Acid Nanoflower to Study the Molecular Mechanism of miR-155 in Inflammation
Authors: Wang Wenxin , Geng Jie , Wu Xiaohan , Zhang Jianguang , Zheng Chenna , Rao Huachun , Xu Chaochen , Li Tianyu , Diao Yong , Yang Huiyong
Published: December 2021

BackgroundAt present, the molecular mechanisms underlying inflammation remain unclear. In recent years, research on inflammation has focused on stimulating cell inflammation by using external pathogens such as LPS or inflammatory factors. To investigate the molecular mechanism of inflammation from a new perspective, we designed a nucleic acid nanoflowers (NFs) complex to directly activate inflammatory genes to study the inflammatory response without the need for external microbial factors to trigger an inflammatory response. ResultsAn RNAa-type target gene-activated NF was designed. Human umbilical vein endothelial cells (HUVECs) were transfected with NFs carrying saRNAs to directly co-activate microRNA (miR)-155 and SHIP1 genes. Inflammatory gene and protein expression in the HUVECs were evaluated to assess whether miR-155 overexpression can trigger inflammation. After RNAa-type NFs were transferred into HUVECs, the expression of miR-155 and pro-inflammatory and cancer-related factors increased, anti-inflammatory factors were reduced, cell proliferation increased, and cell migration was promoted. IL-1β protein levels were decreased and SHIP1 expression was downregulated. When miR-155 and its target SHIP1 were both activated, the expression of both was unaltered, maintaining cell homeostasis. ConclusionMiR-155 and its target genes act as a molecular switch role in the development of inflammation.
Finishing of Micro-Aspheric Tungsten Carbide Mold Using Small Viscoelastic Tool
Authors: Zhu Xiangyou , Wang Han , Zhang Jiarong , Yao Honghui , Zhuo Shaomu , Yan Xiaoqiang , Deng Jiannan , Liang Lu , Cai Nian
Published: December 2021

Tungsten carbide is widely used as the material of replication mold to produce small aspheric optics, and the polishing process determines the precision of the mold. However, for micro-aspheric tungsten carbide mold, the existing polishing methods are difficult to realize the from error modification during the polishing because the polishing tool is always larger than small mold. Therefore, a polishing tool which using polyester fiber cloth to wrap small-size rigid ball is used in this paper. In order to predict the tool influence function (TIF) of this polishing tool, a series of theoretical analysis and experimental verification are carried out in this paper. Firstly, by analyzing the structural and viscoelastic characteristics of the fiber cloth, the pressure distribution in the polishing contact area is determined. And the polishing speed distribution is obtained by analyzing the kinematic movement of the polishing tool; Then, combined with Preston equation, the tool influence function is derived; Afterward, through a series of single point polishing experiments, it is verified that the volume error between the theoretical removal model and the experimental removal is less than 10.8%; Finally, the tool influence function is applied to the form error corrective polishing of small size symmetric aspheric tungsten carbide mold. After one form error corrective polishing, the PV value (Peak to Valley) of form error is decreased from 0.405um to 0.068um, which verifies the effectiveness of the polishing method of small size tungsten carbide mold in form error correction.
Seropositivity of Main Vector-Borne Pathogens in Dogs Across Europe
Authors: Miró Guadalupe , Wright Ian , Michael Helen , Burton Wade , Hegarty Evan , Rodón Jaume , Buch Jesse , Pantchev Niko , von Samson-Himmelstjerna Georg
Published: December 2021

Introduction: Canine Vector-borne disease (CVBD) has been an area of increasing interest in Europe over the last few decades, and there have been changes in the prevalence and distribution of many of these diseases. Monitoring CVBD infections in Europe is often done by individual countries, but aggregated data for the European countries are helpful to understand the distribution of CVBDs. Methods: We used an extensive retrospective database of results from point-of-care rapid enzyme-linked immunosorbent assay (ELISA) tests on dogs across Europe to identify distribution and seropositivity in animals tested for selected CVBDs (Anaplasma spp., Ehrlichia spp., Borrelia burgdorferi, Leishmania spp., and Dirofilaria immitis) from 2016 through 2020. Geographic distribution of positive tests and relative percent positive values were mapped by the Nomenclature of Territorial Units for Statistics classification for regions with sufficient test results for reporting.Results: A total of 404,617 samples corresponding with 1,134,648 canine results were available from dogs tested in 35 countries over the 5-year study period. Over this period the number of test results per year increased whereas test positivity decreased. Leishmania spp. had the largest increase in total test results from 25,000 results in 2016 to over 60,000 results in 2020. Test positivity for Leishmania spp. fell from 13.9% in 2016 to 9.4% in 2020. Test positivity fell for Anaplasma spp. (7.3% to 5.3%), Ehrlichia spp. (4.3% to 3.4%), and Borrelia burgdorferi (3.3% to 2.4%). D. immitis test positivity trended down with a high of 2.7% in 2016 and low of 1.8% in 2018. Leishmania spp. test positivity was highest in endemic areas and in several non-endemic countries with low numbers of test results. Co-positivity rates were significantly higher than expected for all pathogen test positive pairs except for Ehrlichia spp. with Borrelia burgdorferi and D. immitis with Borrelia burgdorferi.Conclusions: This study represents the largest data set on CVBD seropositivity in Europe to date. The increase in the number of test results and decreasing test positivity over the study period may reflect changes in testing behavior and increased screening of healthy animals. The Europe-wide mapping of CVBD provides expected test-positivity that can help inform veterinarians’ decisions on screening and improve prevention and identification of these important, sometimes zoonotic, diseases.
Compact And Scalable Large Vortex Array Generation Using Azocarbazole Polymer And Digital Hologram Printing Technique
Authors: Jessie Jackin Boaz , Masaki Shirai , Honoka Haginaka , Kinashi Kenji , Tsutsumi Naoto , Sakai Wataru
Published: December 2021

An integrated device capable of generating large number of multiplexed optical vortex beams with arbitrary topological charges is considered as one of the crucial requirement for driving information photonics forward. Here we report a simple method for simultaneous generation of 100 multiplexed optical vortex beams from a polymer film of size 1mm2 and thickness of 30µm. This is achieved through a combination of computer generated holography, digital hologram printing and photoisomeric polymers. When the fabricated sample is illuminated with a collimated laser beam, a predetermined vortex array with arbitrary topological charge is emitted. The polymer film easy to synthesise and exhibits good diffraction efficiency and long retention time.
The global prevalence of depression, anxiety, stress and insomnia among general population during COVID-19 pandemic: A systematic review and meta-analysis
Authors: Mahmud Sultan , Mohsin Md. , Dewan Md. Nayem , Muyeed Abdul
Published: December 2021

This study aimed to examine research findings related to depression, anxiety, stress, and insomnia during the COVID-19 pandemic. This study also explored periodic changes in the prevalence of depression, anxiety, stress, and insomnia among the general people during this pandemic. We performed a meta-analysis by searching articles from several sources (PubMed, MEDLINE, and GOOGLE SCHOLAR). We used the random-effects models, subgroup analysis, and heterogeneity test approaches. Results show that the prevalence of depression, stress, and insomnia increased during March to April 2020 (30.51%, 29.4%, and 25% respectively) compared to the study period before February 2020 (25.25%, 16.27%, and 22.63% respectively) and followed in May to June 2020 (16.47%, 5.1%, and 19.86 respectively). The prevalence of depression and anxiety from k= 30 studies was 28.18% (95% CI: 23.81-32.54), and 29.57% (95% CI: 24.67-34.47), respectively. And the prevalence of stress (k=13) was 25.18% (95% CI: 14.82 – 35.54) and the prevalence of insomnia (k=12) was 23.50% (95% CI: 16.44 – 30.57). These prevalence estimates during the pandemic are very high compared to normal times. Hence, the governments and policymakers should apply proven strategies and interventions to avoid psychological adversity and improve overall mental health during the COVID-19 pandemic.
Detection of Attacks in Pervasive Computing Using Gated Recurrent Unit Based on Bidirectional Weighted Feature Averaging
Authors: Rajasekaran P. , Magudeeswaran V
Published: December 2021

In the era of information technology, the new types of cyber-attacks affect the performance of the network, which is very risky and cannot be restored quickly. In pervasive computing, there are more chances for such types of attacks since the personal data of the user is closely connected to the social environment. The research is performed using SNMP-MIB dataset, and feature selection are made by using the Enhanced Salp Swarm Optimization to select the optimal features to identify the attacks by using wrapper techniques. Then, various types of attacks are appropriately distinguished with proposed classifier Gated Recurrent Unit Neural Network based on Bidirectional Weighted Feature Averaging for high detection rate and accuracy. The value of performance metrics obtained from the proposed method outperforms the existing methods in terms of 99.9% accuracy, 99.8% in precision and detection rate is 99% in classifying different types of attacks.
The Hierarchical Organization of Syntax
Authors: Ravandi Babak , Concu Valentina
Published: December 2021

Hierarchies are the backbones of complex systems and their analysis allows for a deeper understanding of their structure and how they evolve. We consider languages to be also complex adaptive systems. Hence, we analyzed the hierarchical organization of historical syntactic networks from German that were created from a corpus of texts from the 11th to 17th centuries. We tracked the emergence of syntactic structures in these networks and mapped them to specific communicative needs. We named these emerging structures communicative hierarchies. We hypothesise that the communicative needs of speakers are the organizational force of syntax. We propose that the emergence of these multiple communicative hierarchies is what shapes syntax, and that these hierarchies are the prerequisite to the Zipf's law. The emergence of communicative hierarchies indicates that the objective of language evolution is not only to increase the efficiency of transferring information. Language is also evolving to increase our capacity to communicate more sophisticated abstractions as we advance as a species.
Short chain fatty acids reduces OPCs loss by inhibiting activation of astrocytes via SGK1/IL-6 signaling pathway
Authors: Gao Yanmin , Xie Di , Wang Yang , Niu Lei , Jiang Hua
Published: December 2021

Short chain fatty acids (SCFAs) are known to be actively involved in neurological disease, but their roles in hypoxic-ischemic brain injury (HIBI) is unclear. This study established a rat model of HIBI, then measured the changes in IL-6 and NLRP3, proliferation and apoptosis indicators of oligodendrocyte precursor cells (OPCs). The mechanism of SCFAs on astrocytes were also investigated. To further explore the mechanism, astrocytes were treated with hypoxia in vitro and OPCs were treated with IL-6. The results showed that SCFAs significantly alleviated the activation of astrocyte and loss of OPCs induced by HIBI. SCFAs pretreatment was associated with the following: (1) downregulation of NLRP3, IL-6, CCL2, and IP-10; (2) was no effect on proliferation of OPCs; (3) amelioration of the abnormal expression of Bax and Bcl-2; and (4) regulation of IL-6 expression via SGK1 related pathway in astrocytes. Our findings revealed that SCFAs alleviated loss of OPCs through regulating the astrocytes activation by SGK1/IL-6 signaling pathway.
Improved convergence results for the Nelder-Mead simplex method in low dimensional spaces
Authors: Aurél
Published: December 2021

We prove two results on the convergence of the Nelder-Mead simplex method. Both theorems prove the convergence of the simplex vertices to a common limit point. The first result is an improved variant of the convergence theorems of [7] and [8], while the second one proves the convergence with probability 1.
Gene Updater: A Streamlit web tool that autocorrects and updates for Excel misidentified gene names
Authors: Koh Clara WT , Ooi Justin SG , Joly Gabrielle LC , Chan Kuan Rong
Published: December 2021

Background

Opening and processing gene expression data files in Excel runs into the inadvertent risk of converting gene names to dates. A plausible solution is to update these genes and dates to the new approved gene names as recommended by the HUGO Gene Nomenclature Committee (HGNC).
Results

We found that molecular pathways related to cell division, exocytosis, cilium assembly, protein ubiquitination and nitric oxide biosynthesis are most affected by this Excel auto-conversion. To circumvent this issue, we developed a web tool, Gene Updater, with Streamlit that can convert old gene names and dates back into the new gene names recommended by HGNC. The running instance of the web tool is accessible at: https://share.streamlit.io/kuanrongchan/date-to-gene-converter/main/date_gene_tool.py
Conclusions

Gene Updater can convert old gene names and dates back into the updated gene names, which are more resilient to Excel auto-conversion. We envision this tool to facilitate the sharing of gene expression datasets across multiple analytics platforms.
Stochastic Numerical Investigations for a Food Web System of Prey-Predation, Competition and Commensalism
Authors: Sabir Zulqurnain , N Seshagiri Rao , K Kalyani
Published: December 2021

Employing Levenberg-Marquardt backpropagation(LMB) neural network, the system of three species nonlinear equations are illuminated by designing an integrated numerical computing-based plot. The proposed dynamical system comprises of two competing species which are growing logistically in nature and, the third species is predating with Holling type II functional response mode on second species and also acts host for the first prey species. Besides, the prey species protect themselves to refuge high predation. The designed LMB neural network has been used to exhibits the solutions of the dynamical frame work. In each case of the species, a reference dataset of the planned LMB neural network is initiated in comparison of Adam numerical program. The approximate results of the food web system are displayed within the training, confirmation and testing strategies to redesign the neural network to minimize the mean square error (MSE) function employing the designed LMB. The investigations depend on the corresponding achievements and the examinations based on MSE out comes, correlation, regression and error histograms signify the proficiency, rightness as well as the potency of the suggested LMB neural network conspire.
Conspicuity and imaging features of breast cancers on digital breast tomosynthesis according to molecular profile
Authors: Manse Léa , Boisserie-Lacroix Martine , Brouste Véronique , Depetiteville Marie-Pierre , Mesurolle Benoît , Chamming's Foucauld
Published: December 2021

Objective
To describe BI-RADS features and evaluate conspicuity of breast cancer on digital breast tomosynthesis (DBT) according to their molecular profile.
Materials and method
Institutional review board was obtained for this retrospective study. Consecutive patients with histologically proven breast cancers who underwent digital breast tomosynthesis (DBT) with 2D synthetic mammography (SM) and digital mammography (DM) at the time of diagnosis were included. Morphological features and conspicuity of cancers on DM, SM and DBT were evaluated in consensus by two breast radiologists. Imaging features were compared across molecular subtypes (luminal, triple negative (TN) and HER2+) using Fisher’s exact test and between DBT and SM and DM using McNemar’s test. Conspicuity was compared between DBT and SM and DM using Wilcoxon matched pairs test and between each molecular subtype using the Wilcoxon test.
Results
One hundred and eleven consecutive patients were included. On DBT, TN cancers more frequently presented as masses with microlobulated margins (P = 0.04) while HER2 + cancers were more often associated with microcalcifications (P = 0.02). Greater conspicuity on DBT in comparison to DM was observed for cancers with low Ki67 (P = .015), less aggressive tumours (P = .005), positive ER (P = 0.005), positive PR (P = .005) or negative HER2 (P = .024), and for luminal molecular profiles (P = 0.012) while no difference was observed between the two techniques for TN (P = .73) and HER+ (P = .79) tumours.
Conclusion
DBT reveals specific features of breast cancers according to their molecular characteristics. In comparison with DM, DBT improves conspicuity of luminal subtype cancers and tumours demonstrating less aggressive features on pathology.
Exploiting Synthetic Lethal Network for Precision Treatment of Clear Cell Renal Cell Carcinoma
Authors: Liu Zhicheng , Lin Dongxu , Zhang Linmeng , Yang Chen , Guo Bin , Xia Feng , Li Yan , Chen Danyang , Wang Cun , Xiao Zhenyu , Chen Zhong , Leng Chao
Published: December 2021

Background

The emerging of targeted therapies has revolutionized the treatment modalities of advanced clear cell renal cell carcinoma (ccRCC) over the past fifteen years. However, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles of ccRCC cohorts were exploited for conducting an integrative analysis.
Method

Based on synthetic lethality (SL), a concept that simultaneous losses of two genes cause cell death while a single loss does not, we sought to develop a computational pipeline to infer potential SL partners of ccRCC. Drug response prediction were received from three pharmacological databases to select agents which are likely to be effective in precisely treating patients with target gene mutation.
Results

We developed a credible method to identify SL pairs and determined a list of 72 candidate pairs which might be utilized to selectively eliminate tumors with genetic aberrations through SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medicine targets for patients with BAP1 mutations. After mapping these target genes to comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potential in BAP1 mutant tumors.
Conclusion

Overall, our findings provide insight into the overview of ccRCC mutation patterns and offer novel opportunities for improving individualized cancer treatment.
Strategic Roadmap in Five Priority Development Areas of the Republic of Uzbekistan in 2017–2021: Strategizing of Socio-Economic Processes
Authors: Mirzieeva Caida
Published: December 2021

In 2021, Uzbekistan finishes the implementation of the Strategic Roadmap for the development of the country in five socio-economic priority areas. The strategy proved to be a valuable experience in short-, medium-, and long-term strategizing at the national, regional, and industrial levels. The Strategic Roadmap can serve as a model for other post-Soviet countries because it is an excellent example of how to use potential capabilities and competitive advantages to modernize all socio-economic processes.
Progress on legal and practical aspects on water reuse with emphasis on drinking water – an overview
Authors: Santos Ana Silvia Pereira , Pachawo Vimbai , Melo Marilia Carvalho , Vieira José Manuel Pereira
Published: December 2021

The present study highlights the evolution, progress and prospects of future practices of water reuse in the world. The objective was to produce a comprehensive timeline on the global evolution and progress of water reuse. This was achieved through the analysis of the state of the art on the subject. The present study is a qualitative research, where three aspects have been considered to highlight the global evolution of water reuse: i) Regulations, Standards, Criteria or Guidelines (RSCG); ii) Indirect Potable Reuse Projects (IPR); and iii) Direct Potable Reuse Projects (DPR). The study focused on both legal and practical aspects of water reuse and considered three timelines in the context of RSCG, IPR and DPR: 29 RSCG instruments, institutionalized from 1918 to 2020, where only four instruments were solely dedicated to drinking water reuse; 10 IPR projects; five DPR projects. To achieve good, effective results, the regulatory framework must support the objectives of a structured water reuse policy in addition to guaranteeing legitimacy and maintaining public confidence. Integrated water and wastewater management, based on technological and scientific advances, has become a relevant aspect for implementation of more adequate measures by decision makers to address future global water challenges.
IoT-based performance analysis of hybrid solar heater-double slope solar still
Authors: Benghanem M. , Mellit A. , Emad M.
Published: December 2021

Remote monitoring of solar still systems is an interesting step for performance analysis and supervision. In this article, a monitoring system is developed and integrated to a solar still system. The parameters considered (such as air temperatures, relative humidity, etc) have been posted on a webpage via the Internet of Things (IoT) technique. For this, the ThingSpeak platform of MathWorks is used. The results demonstrate that ground water after desalination has practically the same chemical parameter values as mineral water (Nestle) and ordinary home drinking water. It has also been confirmed that by adding a solar preheater, the process of evaporation of saline water has been accelerated, which permits improvement of the efficiency of the proposed prototype.
Research into the Status of Special Administrative Regions in China
Authors: Symaniuk N. , Tomberg O. , Zhang X.
Published: December 2021

This article analyzes the legal status of special administrative regions in China. This type of territorial unit occupies a special place and has a specific legal status, which is especially noticeable in relations with the central authorities. The authors focus on the historical prerequisites for the formation of such a legal status and analyze the current situation. A special feature of this study is the research methodology, since a comprehensive analysis requires the use of a mixed research method. The conclusions reached by the authors can be used to formulate a new form of government.
Violence Against Women in Russia and Brazil: International and Domestic Responses
Authors: Nelaeva G.
Published: December 2021

The problem of domestic violence and violence against women, despite being an age-old phenomenon, came to the fore of public debate relatively late. It entered the agenda of intergovernmental organizations in the 1990s, but became the subject of international litigation only in the 2000s and 2010s. While this belated response of the international community can be associated with the inadequate conceptualization of the problem and insufficient data, it also has to do with the ongoing public/private dichotomy that became especially pronounced in the recent years when various conservative groups increasingly question the necessity of specific laws and policies aimed at eliminating this kind of crime. In this article, I briefly trace the developments concerning women’s rights, and, particularly, domestic violence and violence against women in international law. Then, based on the analysis of international and regional court decisions, I try to see how and whether these decisions contributed to the domestic developments in the field of combatting this phenomenon in Russia and Brazil. It is also important to examine how COVID-19 pandemic impacted the narratives of violence and how the international community should respond to the challenge of protecting the most vulnerable members of the society in the conditions of health emergency.
EFFECT OF 14-DAY HEAD UP BEDREST ON ORTHOSTATIC TOLERANCE IN HUMANS
Authors:   Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Katuntsev V.P. , Sukhostavtseva T.V. ,   Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Baranov M.V. ,   Federal Research and Clinical Center of Federal Medical Biological Agency of Russia, Moscow, Kotov A.N. ,   Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Puchkova A.A. ,   Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Tarasenkov G.G. ,   Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Nosovsky А.М. ,   Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow
Published: December 2021

Effect of 14-day head up bedrest (HUBR) on the human orthostatic tolerance studied with participation of 23 essentially healthy male subjects at the age of 18 to 35 years. HUBR with the head-end tilted up at +9.6º was to imitate physiological effects of the lunar gravity. Orthostatic tolerance was tested on the day prior to and immediately after HUBR completion with subjects tilted up to +70° for 20 min maximum. The parameters registered before, during and after the tilt test included blood pressure, ECG and heart rate. In comparison with the baseline testing, HUBR reduced the number of completed tests and increased the number (10 vs. 4) of tests terminated for the reason of precollapse (p < 0.05). The group mean time of OS test tolerance decreased by 3.8 minutes (p < 0.01) and time interval between the test onset and precollapse decreased by 4.7 minutes (p = 0.055). For the most part, orthostatic disorders following HUBR were described as a vasodepressor type hypotension collapse with high activity of the chronotropic function of the heart. Several cases of vagus-mediated HR slowing pointed to a sharp decline of the sympathetic nervous activity which is an important mechanism of hemodynamics regulation in changed postural conditions.
EFFECT OF ATTENUATED MAGNETIC FIELD ON DEVELOPMENT OF THE LIVER AND SPLEEN IN EMBRYONIC JAPANESE QUAIL
Authors:   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow, Pineguin S.A. , Dadasheva O.A. ,   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow, Mednikova E.I. ,   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow, Grushina O.A. ,   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow, Spassky A.V. ,   Lomonosov Moscow State University, Skobeltsyn Institute of Nuclear Physics, Lebedev V.M. ,   Lomonosov Moscow State University, Skobeltsyn Institute of Nuclear Physics, Ionov S.V. ,   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow, Gurieva T.S. ,   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow, Sychev V.N. ,   Institute of Biomedical Problem of Russian Academy of Sciences, Moscow
Published: December 2021

Expectation of remote space missions and long-term stay and work on the Moon with the magnetic field 1,000 times weaker than on Earth sets the researchers the formidable task to investigate effects of the hypomagnetic environment on living organisms. The paper reports data about the liver and spleen development in Japanese quail embryos of various age exposed in a modeled lunar magnetic field. Retardation of hemopoiesis was observed as in the first generation embryos (F1), so in sequential embryo generations developed in the ordinary magnetic environment (F2).