bluuebunny/crossref_metadata_2025 huggingface dataset:
Pluripotin facilitates the expansion of hematopoietic stem cells, but restricts the growth of fibroblasts and the proliferation of mesenchymal stem cells from the bone marrow
Authors: Turan Dilek Raife , Kocabas Fatih
Published: March 2021

Abstract

Hematopoietic stem/progenitor cell (HSPC) quiescence modulators play a key role in the modulation of HSPC numbers. Targeting HSPC modulators with small molecules could contribute to the cell cycle entry and expansion of HSPC. To this end, we have investigated the effect of two small molecules Pluripotin and CHIR-99021 on HSPC expansion. Both Pluripotin and CHIR-99021 have been shown to result in a 3-fold rise in the murine pool of HSPC in a dose-dependent compartment after 7 days of treatments. In addition, we investigated the influence of Pluripotin treatment on the ex vivo expansion of human umbilical cord blood and bone marrow mononuclear cells. In specific, Pluripotin treatment increased human CD34 + and ALDHbr HSPC content up to 3-fold compared to control. In addition, human CD133 + HSPC cell content was increased to 5-fold following treatment with Pluripotin. Intriguingly, we find that Pluripotin treatment inversely changes bone marrow-derived mesenchymal stem cell (MSC) proliferation and lowers fibroblast growth although there is no effect on adipose-derived MSCs. CHIR-99021 treatment did not have any effect in proliferation of MSCs or fibroblasts. In conclusion, Pluripotin-induced stem cell expansion is unique to HSPCs that can be used to expand HSPCs and reduce unwanted fibroblast or MSC growth in the primary ex vivo cultures.
Identification of DNA topoisomerase II-alpha as a regulatory target in hepatocellular carcinoma
Authors: Chen Changzhou , Zhao Haichao , Yang Chuanli , He Jiefeng , Zhao Haoliang
Published: March 2021

Background: Although DNA topoisomerase II-alpha (TOP2A) has been reported to be associated with tumour pathological processes, systematic research in hepatocellular carcinoma (HCC) prognosis remains scarce. Therefore, this study aimed to investigate the role of differential TOP2A expression in HCC.Results: Our findings revealed that TOP2A was significantly overexpressed in patients with HCC. Higher TOP2A expression is an independent risk factor for survival and prognosis. Subsequently, GO and KEGG pathway analyses showed TOP2A was mainly enriched in cell cycle, DNA replication, immunity, and metabolic-related pathway. We then conducted an integrated analysis of TOP2A, it showed specific relationship between TOP2A and immune-infiltrating cells in HCC. Furthermore, the latent function of query drugs in HCC was explored by integrating drug‑target, drug‑pathway and drug‑protein interactions.Conclusions: Mechanistically, we suggest that overexpression of TOP2A in patients with liver cancer can trigger an anti-tumour immune response by modulating the effective immune response and lymphocyte infiltration. Our findings suggest that TOP2A may play essential biological roles in HCC progression and represent potentially important candidate target in HCC therapy.
Differences in Host Immune Populations Between Rhesus Macaques and Cynomolgus Macaque Subspecies, in Relation to Susceptibility to Mycobacterium Tuberculosis Infection.
Authors: Sibley Laura , Daykin-Pont Owen , Sarfas Charlotte , Pascoe Jordan , Morrison Alexandra , White Andrew D. , Sharpe Sally
Published: March 2021

Rhesus (Macaca mulatta) and cynomolgus (Macaca fasicularis) macaques of distinct genetic origin are understood to vary in susceptibility to Mycobacterium tuberculosis, and therefore differences in their immune systems may account for the differences in disease control. Monocyte:lymphocyte (M:L) ratio has been identified as a risk factor for M. tuberculosis infection and is known to vary between macaque species. We aimed to characterise the constituent monocyte and lymphocyte populations between macaque species, and profile other major immune cell subsets including: CD4+ and CD8+ T-cells, NK-cells, B-cells, monocyte subsets and myeloid dendritic cells. We found immune cell subsets to vary significantly between macaque species. Frequencies of CD4+ and CD8+ T-cells and the CD4:CD8 ratio showed significant separation between species, while myeloid dendritic cells best associated macaque populations by M. tuberculosis susceptibility. A more comprehensive understanding of the immune parameters between macaque species may contribute to the identification of new biomarkers and correlates of protection.
Biomechanical effect of cage position combined with bilateral pedicle screw fixation in the osteoporotic lumbar spine of oblique lumbar interbody fusion: a finite element analysis
Authors: Qin Yichuan , Zhao Bin , Yuan Jie , Xu Chaojian , Su Junqiang , Hao Jiaqi , Lv Jie , Wang Yongfeng
Published: March 2021

Background: The influence of cage position on postoperative cage subsidence has been paid increasing attention. The best cage position in oblique lumbar interbody fusion (OLIF) is still unclear. This study aimed to evaluate the biomechanical effects of different cage positions with stand-alone (SA) methods and bilateral pedicle screw fixation (BPSF) in the osteoporotic lumbar spine after OLIF.Methods: A finite element (FE) model of an intact L3-L5 lumbar spine was constructed. After validation, an osteoporosis model (OP) was constructed by assigning osteoporotic material properties. SA models (SA1, SA2, SA3) and BPSF models (BPSF1, BPSF2, BPSF3) in which a cage was placed in the anterior, middle and posterior third of the L5 superior endplate (SEP) were constructed at the L4-L5 segment of the OP. The L4-L5 range of motion (ROM), the stress of the L5 SEP, the stress of the cage and the stress of fixation were compared among the different models.Results: According to the degree of ROM of L4-L5, the stress of the L5 SEP and the stress of the cage for most physiological motions, the SA and BPSF models were ranked as follows: SA2＜SA1＜SA3, BPSF2＜BPSF1＜BPSF3. In BPSF2, the stress of fixation was minimal in most motions. At the same cage position, the ROM of L4-L5, the stress of the L5 SEP and the stress of the cage in the BPSF models were significantly reduced compared with those in SA models; compared with SA2, BPSF2 had a maximum reduction of 83.24%, 70.71% and 73.52% in these parameters, respectively.Conclusions: Placing the cage in the middle third of the L5 SEP for OLIF could reduce the maximum stresses of the L5 SEP, the cage and the fixation, which may reduce the risk of postoperative cage subsidence, endplate collapse and fixation fracture in the osteoporotic lumbar spine. Compared with SA OLIF, BPSF could provide sufficient stability for the surgical segment and may reduce the incidence of the aforementioned complications.
Using Machine Learning to Characterize Atrial Fibrotic Substrate from Intracardiac Signals using a Hybrid in silico and in vivo Dataset
Authors: Sánchez Jorge , Luongo Giorgio , Nothstein Mark , Unger Laura , Saiz Javier , Trenor Beatriz , Luik Armin , Dössel Olaf , Loewe Axel
Published: March 2021

In patients with atrial fibrillation, intracardiac electrogram signal amplitude is known to decrease with increased structural tissue remodeling, referred to as fibrosis. In addition to the isolation of the pulmonary veins, fibrotic sites are considered a suitable target for catheter ablation. However, it remains an open challenge to find fibrotic areas and to differentiate their density and transmurality. This study aims to identify the volume fraction and transmurality of fibrosis in the atrial substrate. Simulated cardiac electrograms, combined with a generalized model of clinical noise, reproduce clinically measured signals. Our hybrid dataset approach combines in silico and clinical electrograms to train a decision tree classifier to characterize the fibrotic atrial substrate. This approach captures different in vivo dynamics of the electrical propagation reflected on healthy electrogram morphology and synergistically combines it with synthetic fibrotic electrograms from in silico experiments. The machine learning algorithm was tested on five patients and compared against clinical voltage maps as a proof of concept, distinguishing non-fibrotic from fibrotic tissue and characterizing the patient’s fibrotic tissue in terms of density and transmurality. The proposed approach can be used to overcome a single voltage cut-off value to identify fibrotic tissue and guide ablation targeting fibrotic areas.
Assessment of Knowledge, attitudes and practices concerning travel health among Hajj pilgrims (1439 H- 2018 G) at Prince Mohammad bin Abdulaziz International Airport in AL-Madina, Saudi Arabia
Authors: Abd-Ellatif Eman Elsayed , Alhomidan Lamya , Al-Assaf Lujain , AlGhamdi Lamees , Alharbi Alwaleed , Albeladi Omar , AlQusibri Asmaa , Rahman Shady Abd El , Almudarra Sami S.
Published: March 2021

BackgroundThe Kingdom of Saudi Arabia (KSA) hosts the Hajj pilgrimage, the largest annual mass gathering in the world. The Ministry of Health (MoH) of KSA issues requirements and recommendations for entry visas relevant to travelers visiting KSA during Hajj. These recommendations include vaccinations, health checks, and specific immunizations either at or prior to entry into KSA. We assessed Hajj pilgrims’ knowledge, attitude and practices regarding preventive, curative, hygienic and health promoting measures. Methods We administered a questionnaire to a cross-section of Hajj pilgrims(2018 G)traveling through Prince Mohammad bin Abdulaziz International Airport in Al-Madina, KSA. Variables collected included demographics, Hajj health preparations, and knowledge and attitudes towards travel-related health behaviors. Results Of 101 respondents, 20% were Saudi and 64%were male. Regarding travel profile, 75% were attending hajj for the first time. About half (52%) stayed in KSA for more than 2 weeks. Knowledge regarding travel heath of respondents was high: 82% scored as excellent and 11% scored as good. Positive attitude toward travel medicine was reported by 60% of participants; 56% of them sought pre-travel advice. Regarding health protection behaviors, 79%reported using protective measures against respiratory infections, 70%for insects, 95%for food and waterborne Diseases, 99%against heat-related conditions and 100%for injuries.Conclusion We found that less than half of participants obtained pre-travel advice, despite the health requirements for obtaining Hajj visas and the known health risks associated with attending Hajj. We identified a need for continued education and promotion of health prevention measures to ensure that Hajj pilgrims are able to have a safe and healthy experience in the Kingdom. This study may be a tool for a purposeful political will to empower countries to set up Hajj health programmes, which would be of great benefit and would go a long way to decrease mortality and morbidity, and associated burdens during Hajj.
Assessment of Microstructure and Mechanical Properties of Friction Stir Welded AA2014-O and AA2014-T6 Sheets
Authors: Muhammad Wali , Husain Wilayat , Tauqir Anjum , Wadood Abdul , Zaigham Hamid , Rehman Muhammad Atiq Ur
Published: March 2021

In this study, friction stir welding of AA2014-O and AA2014-T6 aluminum alloy was performed at various welding speeds to evaluate the influence of temper conditions of base metal on the properties of the welded joints. The results showed strong influence of base metal temper conditions on the microstructural morphologies and mechanical behavior of the welded joints. In the 2014-O joints, different zones of weld joint were diffused into each other and there was no clear interface between them. In 2014-T6 joints, there was a distinct demarcation between the NZ, TMAZ, HAZ and base metal. The welded joints in 2014-O temper condition showed increase in hardness in the vicinity of weld center due to grain refinement whereas, in 2014-T6, softening occurred in the same region by the dissolution of strengthening precipitates. The mechanical properties of 2014-O joints were equivalent to the base metal showing a 100% weld efficiency with fracture located in the base metal, whereas 2014-T6 welds exhibited about 70% weld efficiency with fracture located at the NZ/TMAZ interface. All the samples in mechanical testing fractured at retreating side (RS) which exhibited heterogeneity in the mechanical properties of the welded joints. SEM fractographic analysis revealed a ductile fracture mode comprising of dimples in both temper conditions. The size and shape of the dimples was strongly dependent on base metal temper condition.
Fertility desire and associated factors among HIV positive women attending ART clinics, Afar region, northeast Ethiopia
Authors: Woldu Etsay , Ali Aydahis
Published: March 2021

BackgroundThe desire of human immune deficiency virus infected person to have children in the future has significant implication for the transmission of human immune deficiency virus to sexual partner and new born. However, fertility desire has given little attention and the uptake of PMTCT services is limited. Therefore, this study aimed to assess fertility desire and associated factors among HIV positive women attending ART clinics, Afar region, northeast EthiopiaMethodologyInstitution-based cross-sectional study was conducted on 402 HIV positive women attending ART clinic in selected Hospitals in Afar region. A systematic random sampling technique was employed to identify and enroll women. Logistic regression analysis was employed to identify the factors associated with fertility desire. Statistical association was measured and p-value < 0.05 was considered statistically significant.ResultIn this study a total of 391 HIV positive were participated with a response rate of 97.3%.The prevalence of fertility desire was 63.9 % (95 % CI, 59.1 %, 68.8 %). Young age between 15–24 (AOR = 11.98, 95% CI (4.04, 35.5) and 25–34 years (AOR = 2.93, 95% CI (1.46, 5.86), women who were not had live children (AOR = 5.1, 95% CI (1.31, 20.2) and women that had 1 or 2 live children (AOR = 2.7, 95% CI (1.39, 5.27), disclose sero status to their partner (AOR = 5.89, 95% CI (2.33, 14.9) were associated with increased odds of fertility desire. However, women who use contraceptive were associated with decreased odd of fertility desire (AOR = 0.11, 95%, CI (0.05, 0.22).ConclusionThis study showed that six in ten HIV positive women attending ART clinic were had fertility desire. Young age, not having live child, and having 1 or 2 live number of children, disclosing sero status to partner, and contraceptive use were predictors of fertility desire. Therefore, efforts should be made to increase fertility desire among young HIV positive women attending ART clinic. Moreover, awareness creation on the importance of disclosing sero status to partner is mandatory as it helps to increase fertility desire.
A fine-grained cell type deconvolution of bulk transcriptome from single-cell RNA-seq data reveals myeloid cells heterogeneity in lung adenocarcinomas
Authors: Wu Hao , Qin Jiale , Zhao Qiang , Lu Lu , Neculai Dante , Li Chen
Published: March 2021

Background

Tumor infiltrating myeloid cells (TIM) constitute a vital element of the tumor microenvironment. The cell-type heterogeneity of TIM has yet to be fully investigated.
Methods

We used a time saving approach to generate a single-cell reference matrix, allowing quantification of cell-type proportions and cell-type-specific gene abundances in bulk RNA-seq data.
Results

Two distinct clusters, MSC1 and MSC2 (MSC subtype) were newly identified in lung adenocarcinoma (LUAD) patients, both significantly associated with overall survival and immune blockade therapy responses. Twenty myeloid cell types were detected. Thirteen of these had distinct enrichment patterns between MSC1 and MSC2. LAMP3 + dendritic cells, being a mature and transportable subtype of dendritic cell which may migrate to lymph nodes, were noted as associated with non-responsiveness to immunotargeted therapy. High infiltration level of IFIT3 + neutrophils was strongly related to the response to immune targeted therapy and was seen to activate CD8 + T cells, partly through inflammasome activation. The infiltration levels of TIMP1 + macrophages and S100A8 + neutrophils were both significantly associated with poor prognosis. TIMP1 + macrophages were noted to recruit S100A8 + neutrophils via the CXCL5-CXCR2 axes and promote LUAD progression.
Conclusion

Altogether, we performed virtual micro-dissection of the bulk transcriptome at single-cell resolution and provided a promising TIM infiltration landscape that may shed new light on the development of immune therapy.
GBP1 Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Gastric Cancer
Authors: Feng Xiaoqiang , Zhang Zedan , Chen Qingke , Ye Chujin , Tan Tong , Tang Yanlin , Chen Hanzhong
Published: March 2021

Background: The guanylate-binding protein 1 (GBP1) belongs to the member of GTPase dynamin superfamily and plays a major role as tumor suppressor or tumorigen in cancers, such as colon cancer, ovarian cancer, melanoma, and head and neck squamous cell carcinoma. However, the relationship between GBP1 and gastric cancer (GC) remains scanty. Methods: GBP1 mRNA expression in different types of tumors and their corresponding adjacent normal tissues were evaluated via exploring Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) database, while the protein expression was detected by The Human Protein Atlas (HPA). The relationship between the clinical characteristics and outcome of gastric cancer patients was examined through Kaplan–Meier plotter tool. The correlations between GBP1 and tumor immune infiltrates were evaluated via TIMER and TISIDB. Additionally, the relationship between GBP1 expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.Results: GBP1 expression was significantly higher in GC compared with corresponding normal tissues. High GBP1 expression in GC associated with better overall survival (OS HR=0.53, P=5.2e-09) and progression-free survival (PFS HR=0.49, P=1.90e-06). Moreover, its expression level was positively correlated with different clinical characteristics, such as sex, TNM stage, and Lauren classification. With a comprehensive analysis of three immune-related databases, TIMER, GEPIA, and TISIDB, we found GBP1 not only showed a strong correlation with tumor-infiltrating CD8+ T cells, Th1 cells, but also with Tregs, exhausted T cells, M2 macrophage, monocytes. Furthermore, GBP1 was significantly associated with IFN-γ, granzyme B, perforin, FasL and CXCL9, CXCL10, and CXCL11. Conclusion: This study provides the first evidence that GBP1 is a key gene that correlates with the prognosis and associated with various tumor-infiltrated immune cells in gastric cancer patients. In conclusion, GBP1 may act as a potent prognostic biomarker for predicting cancer progression and a sign of tumor-immune infiltration in GC.
Mesenchymal Stem Cells-derived Exosomes as Probable Triggers of Radiation-induced Heart Disease
Authors: Luo Lan , Yan Chen , Fuchi Naoki , Kodama Yukinobu , Zhang Xu , Shinji Goto , Kiyonori Miura , Sasaki Hitoshi , Li Tao-Sheng
Published: March 2021

Background: Radiation-induced heart disease have been reported, but the mechanisms remain unclear. Mesenchymal stem cells (MSCs), also resident in heart are highly susceptible to radiation. We examined the hypothesis that altered secretion of exosomes from MSCs as the triggers of radiation-induced heart disease. Methods: By exposing human placental tissue-derived MSCs to 5 Gy γ-rays, we will then isolate exosomes from the culture medium 48h later and use to evaluate the quantity and quality changes of exosomes from MSCs after radiation exposures. The biological effects of exosomes from irradiated MSCs on HUVEC and H9c2 cells were also examined. Results: Although the amount and size distribution of exosomes did not differ between the non-irradiated and irradiated MSCs, miRNA sequences indicated many up- or down-regulated miRNAs in irradiated MSCs-exosomes. In vitro experiments using HUVEC and H9c2 cells showed that irradiated MSCs-exosomes significantly decreased cell proliferation, but increased cell apoptosis and DNA damage. Moreover, irradiated MSCs-exosomes impaired the tube formation of HUVEC cells and induced calcium overload of H9c2 cells. Conclusions: Exosomes released from irradiated MSCs shows an altered miRNA profiling and harmful effect to damage heart cells, which provides new insight on the mechanism of radiation-related heart disease risks.
Aberrant Expression of Fgl-1 and Lag-3 in Adenomyosis
Authors: Sun Wenjing , Qin Xiaoyan , Yuan Guangxi , Li Na , Liang Junhui , Li Chunyan , Li Changzhong , Li Mingjiang , Zhao Xingbo , Zhang Hui
Published: March 2021

Background: The presence of ectopic functional endometrial glands and stroma in the myometrium of the uterine cavity is considered as adenomyosis. Various inflammatory, vascular and mechanical factors are involved in the symptoms and evolution of this pathology. Lymphocyte-activation gene 3 (Lag-3) is an immune inhibitory receptor and fibrinogen-like protein 1 (Fgl-1) is a major functional ligand of Lag-3. The binding of Lag-3 and Fgl-1 leads to inhibition of T-cell immunity, which is an important target of immunotherapy. The objective of this study was to evaluate the expression of Lag-3 and Fgl-1 in normal endometrium and adenomyosis.Methods: The expression of the Lag-3 and Fgl-1 in normal endometrium (proliferative phase: n=15; secretory phase: n=15) and adenomyotic endometrium (proliferative phase: n=15; secretory phase: n=15) were determined using immunohistochemistry and immunofluorescence analysis.Results: In normal and adnomyotic endometrium, no significant difference of Fgl-1 expression was noted between proliferative and secretory phases. Compared with normal endometrium, eutopic and ectopic endometrium of adenomyosis showed increased expression of Fgl-1. Lag-3 was almost negative in endometrial glands of normal and adenomyosis. Compared with normal endometrium, Lag-3 positive T-lymphocytes were more common in the stroma of adenomyosis.Conclusions: Our data suggest that aberrant expression of Lag-3 and Fgl-1 is present in the eutopic and ectopic endometrium of adenomyosis. We conclude that Lag-3/Fgl-1 signaling may be involved in the pathogenesis and development of adenomyosis.
A Spread Model of COVID-19 With Some Strict Anti-epidemic Measures
Authors: Yang Bo , Yu Zhenhua , Cai Yuanli
Published: March 2021

In the absence of specific drugs and vaccines, the best way to control the spread of COVID-19 is to adopt and diligently implement effective and strict anti-epidemic measures. In this paper, a mathematical spread model is proposed based on strict epidemic prevention measures and the known spreading characteristics of COVID-19. The equilibriums and the basic regenerative number of the model are widely analyzed. As a validation, the model is used to simulate the spread of COVID-19 in Hubei Province of China for a period of time. The model parameters are estimated and the model is validated by the actual data related to COVID-19 in Hubei. Simulation results show that themodel can accurately describe the spread dynamics of COVID-19. Sensitivity analysis of the parameters is also done to provide the basis for formulating prevention and control measures.
Experimental Study on the Thermal Characteristics of Urban Mockups With Different Paved Streets
Authors: Qin Yinghong , Wei Peiyuan , Wang Junsong , TAN Kanghao
Published: March 2021

Pavements in urban area absorb more sunlight due to the canyon-like geomorphology of the urban geometry, and store more heat due to the great thermal bulk properties of concrete. Heat released from pavements warms up the urban air, contributing to the urban heat island. Recently, the uses of cool pavements to reduce the pavement temperature as an urban heat island mitigation have gained momentum. Understanding the temperature and solar insolation of a pavement in an urban area is important to adopt the right cool pavement option for the right place. This study measured the temperature of paved streets in an urban mockup for four days in summer. It is found that east-west (EW) streets are the hottest place in an urban area, followed by the intersection, and finally the south-north (SN) street; and that increasing the pavements albedo reduces the pavement temperature effectively. The dark grey pavement in open space is hotter than those in an urban canyon. The heat storage in the building blocks keeps the pavement warmer more than 2oC at nightime. The EW street is exposed to solar insolation for long hours, so it is suitable for preferentially developing of reflective cool pavements.
Modeling Moisture Redistribution of Pulse Drip Irrigation Systems by Soil and System Parameters: New Regression-based Approaches
Authors: Karimi Bakhtiar , Karimi Nazir , Shiri Jalal , Sanikhani Hadi
Published: March 2021

One of the strategies for increasing water use efficiency and reducing deep percolation drip irrigation systems is considering the patterns of moisture redistribution after cut-offing the irrigation process. An experimental study was conducted in the present research to evaluate the moisture redistribution process under surface and subsurface pulse drip irrigation systems and developing new regression-based methodologies for estimating moisture redistribution dimensions using both the soil and system parameters together. A physical model was made and the experiments were performed on three different types of soil texture (light, medium, and heavy) with three emitter flow rates (2, 4, and 6 lit/hr) in three emitter installation depths (0, 15, and 30 cm). The experiments were conducted for both continuous (CI) and pulse (PI) irrigation modes. The results showed that significant amounts of wetting dimensions and wetted area of the moisture bulb are related to post-cut-offing stage. Then, using the nonlinear regression analysis, several models were proposed to estimate the horizontal and vertical redistribution pattern as well as the wetted area (upper and lower parts of the emitter). The comparison of the measured and the stimulated values indicated that the non-linear regression models simulated the parameters associated with redistribution, accurately.
Spatial frameworks for prioritization of agricultural research and development
Authors: Edreira Juan Rattalino , Andrade Jose , Cassman Kenneth , Ittersum Martin van , Loon Marloes van , Grassini Patricio
Published: March 2021

Food security interventions and policies need reliable estimates of actual crop production and the scope to enhance production on existing cropland. We assess the performance of two widely used “top-down” gridded frameworks (GAEZ and AgMIP) versus an alternative “bottom-up” approach that estimates extra production potential locally, for a number of representative sites, and then upscales the results to larger spatial scales (GYGA). Our results show that estimates from top-down frameworks are alarmingly unlikely, with estimated potential production being lower than current production at some locations. The consequences of using these coarse estimates to predict food security are illustrated by an example from sub-Saharan Africa. Our study shows that current foresights on food security, land use, and climate change and associate priority setting on AR&D based on yield potential and yield gaps derived from top-down approaches are subject to a high degree of uncertainty and would benefit from incorporating estimates from bottom-up approaches.
TN14003 attenuates cartilage degeneration by targeted blocking of the SDF-1/CXCR4 signaling pathway in knee osteoarthritis
Authors: Li Yanlin , Wang Kun , He Chuan , Wang Guoliang , Cai Guofeng , Yang Xianguang , Song En , Han Rui
Published: March 2021

In order to investigate the effect of TN14003 and its mechanism on cartilage degeneration in vitro and in vivo. P1 chondrocytes isolated from cartilage tissues of OA patients who underwent total knee arthroplasty were randomly assigned to blank control group, TN14003 group, T140 group, and AMD3100 group in vitro. Each group cells were cultured for 1, 2, 4, 6, 8, 10 days. Cell morphology were observed under inverted phase-contrast microscope and examined using MTT assay, flow cytometry, ELISA (MMPs in the chondrocyte medium) and quantitative real-time PCR (mRNA expressions of Col II and ACAN). Moreover, 96 male Hartley guinea pigs with spontaneous OA were randomly assigned to examine the effect of TN14003, T140, and AMD3100 in vivo. After 12 weeks, guinea pigs were sacrificed, the knee articular cartilage histopathology was analyzed. No difference in morphology, proliferation rate and apoptosis among four groups (P > 0.05). The content of MMP-3 and MMP-13, mRNA expression levels of ACAN and Col II were significantly lower in TN14003 group compared with other groups (P < 0.05). TN14003 had stronger effect in decreasing cartilage degeneration compared with T140 and AMD3100 in vivo. TN14003 could effective targeted to prevention and treatment of OA.
Hyperspectral Characterization and Chlorophyll Content Inversion Study of Reclaimed Vegetation in Rare Earth Mines
Authors: Li Hengkai , Xu Feng , Zhou Beibei , Wei Zhian
Published: March 2021

Taking the Lingbei rare earth mining area in Dingnan county of Jiangxi Province as the research object of the reclaimed vegetation, the original spectrum, derivative spectrum and the continuum removed spectrum of the reclaimed vegetation were detected. The spectral characteristics and variation regularity of the typical reclaimed vegetation were analyzed, the correlation between chlorophyll content and spectral characteristic index of reclaimed vegetation was analyzed, and the sensitive spectral parameters were extracted. Partial Least Squares Algorithm, Back Propagation Neural Network Algorithm and Sparse Autoencoder Network Algorithm were selected to construct the estimation model of chlorophyll content, and compare the accuracy. The results show that; The vegetation spectrum of rare earth mine reclamation has the spectral characteristics of higher reflectance in visible region, red shift of green peak and red valley, blue shift of “red edge”, with less spectral variation in bamboo willow; Variability in the sensitive spectral parameters extracted from different vegetation; Sparse Autoencoder network algorithm is the optimal estimation model (R2 value of three vegetation is 0.9117,0.7418 and 0.9815 respectively). In the case of the small sample, it has higher estimation precision and universality for different reclaimed vegetation.
Explainable artificial intelligence for predicting remission in patients with rheumatoid arthritis treated with biologics
Authors: Koo Bon San , Eun Seongho , Shin Kichul , Yoon Hyemin , Hong Chaelin , Kim Do-Hoon , Hong Seokchan , Kim Yong-Gil , Lee Chang-Keun , Yoo Bin , Oh Ji Seon
Published: March 2021

Background: We developed a model to predict remissions in patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify important clinical features associated with remission using explainable artificial intelligence (XAI).Methods: We gathered the follow-up data of 1204 patients treated with bDMARDs (etanercept, adalimumab, golimumab, infliximab, abatacept, and tocilizumab) from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. Remission was predicted at one-year follow-up using baseline clinical data obtained at the time of enrollment. Machine learning methods (e.g., lasso, ridge, support vector machine, random forest, and XGBoost) were used for the predictions. The Shapley additive explanation (SHAP) value was used for interpretability of the predictions.Results: The ranges for accuracy and area under the receiver operating characteristic of the newly developed machine learning model for predicting remission were 52.8%–72.9% and 0.511–0.694, respectively. The Shapley plot in XAI showed that the impacts of the variables on predicting remission differed for each bDMARD. The most important features were age for adalimumab, rheumatoid factor for etanercept, erythrocyte sedimentation rate for infliximab and golimumab, disease duration for abatacept, and C-reactive protein for tocilizumab, with mean SHAP values of -0.250, -0.234, -0.514, -0.227, -0.804, and 0.135, respectively.Conclusions: Our proposed machine learning model successfully identified clinical features that were predictive of remission in each of the bDMARDs. This approach may be useful for improving treatment outcomes by identifying clinical information related to remissions in patients with rheumatoid arthritis.
Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS
Authors: Prieto-Alhambra Daniel , Kostka Kristin , Duarte-Salles Talita , Prats-Uribe Albert , Sena Anthony , Pistillo Andrea , Khalid Sara , Lai Lana , Golozar Asieh , Alshammari Thamir M , Dawoud Dalia , Nyberg Fredrik , Wilcox Adam , Andryc Alan , Williams Andrew , Ostropolets Anna , Areia Carlos , Jung Chi Young , Harle Christopher , Reich Christian , Blacketer Clair , Morales Daniel , Dorr David A. , Burn Edward , Roel Elena , Tan Eng Hooi , Minty Evan , DeFalco Frank , de Maeztu Gabriel , Lipori Gigi , Alghoul Heba , Zhu Hong , Thomas Jason , Bian Jiang , Park Jimyung , Roldán Jordi Martínez , Posada Jose , Banda Juan M , Horcajada Juan P , Kohler Julianna , Shah Karishma , Natarajan Karthik , Lynch Kristine , Liu Li , Schilling Lisa , Recalde Martina , Spotnitz Matthew , Gong Mengchun , Matheny Michael , Valveny Neus , Weiskopf Nicole , Shah Nigam , Alser Osaid , Casajust Paula , Park Rae Woong , Schuff Robert , Seager Sarah , DuVall Scott , You Seng Chan , Song Seokyoung , Fernández-Bertolín Sergio , Fortin Stephen , Magoc Tanja , Falconer Thomas , Subbian Vignesh , Huser Vojtech , Ahmed Waheed-Ul-Rahman , Carter William , Guan Yin , Galvan Yankuic , He Xing , Rijnbeek Peter , Hripcsak George , Ryan Patrick , Suchard Marc
Published: March 2021

Background: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response [1,2]. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) [3] Characterizing Health Associated Risks, and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Methods: We conducted a descriptive cohort study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub [4]. Findings: We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice.
On the role of natural multidecadal oscillations on global warming and its hiatus
Authors: Pal Mayukha , Panigrahi Prasanta K
Published: March 2021

In this study, we investigate the role of the multidecadal oscillation patterns in the global temperature in the global warming hiatus. We analyze the global instrumental temperature records and multiple tree-ring temperature reconstruction records using wavelet transforms and register the presence of a multidecadal cycle of approximately 55-75 years. The hiatus and post-hiatus rise in temperature arises from the declining phase of the multidecadal oscillation which temporally compensates the rising phase. The unusual rise in the temperature after the hiatus is possibly explained by the positive uprising phase of this natural cycle. The origin of the global warming debate has been partly ascribed to faulty calculations or biased judgments. However, in these studies, little emphasis has been given to the possible presence of multidecadal oscillation patterns in the global temperature, which may lead to such an effect. Our result demonstrates that, phase of this cycle has accidentally played an important role in fueling the global warming debate. Therefore, while assessing any future climate changes, such possibilities should be accounted.
Genome-wide investigation and expression profiling of polyphenol oxidase (PPO) family genes uncover likely functions in organ development and stress responses in populus trichocarpa
Authors: He Fang , Shi Yu-Jie , Zhao Qian , Zhao Kuang-Ji , Cui Xing-Lei , Chen Liang-Hua , Yang Han-Bo , Zhang Fan , Mi Jia-Xuan , Huang Jin-Liang , Wan Xue-Qin
Published: March 2021

Background: Trees such as Populus are planted extensively for reforestation and afforestation. However, their successful establishment greatly depends upon ambient environmental conditions and their relative resistance to abiotic as well as biotic stress. Polyphenol oxidase (PPO) is a ubiquitous metalloproteinase in plants, which plays crucial roles in plant resistance against biotic and abiotic stresses. Although the whole genome sequence of populus trichocarpa has long been published, little is known about the PPO genes in Populus, especially those related to drought stress, mechanical damage, insect feeding and hormone response at the whole genome level. Results: In the recent research, a genome-wide analysis of the Poplar PPOs family was finished and 18 PtrPPOs gene were identified. Then, bioinformatics and qRT-PCR were applied to analyze the gene structure, phylogeny, chromosomal localization, gene replication, Cis-elements, expression patterns of PtrPPOs. Sequence analysis revealed that 2/3 of the PtrPPO genes not contained introns. Phylogenetic analysis revealed that all PPOs gene were split into 11 subfamilies, and woody plants differentiated a large number of PPO genes. 18 PtrPPOs gene were disproportionally apportioned on 19 chromosomes, and the number of three pairs of segmented replication genes and four tandem repeat genomes were detected in poplars. Cis-acting element analysis identified a large number elements of growth and development, secondary metabolism process, and stress-related elements on the promoters of different PPO members. Furthermore, PtrPPO genes were expressed preferably in young plant tissues and fruits. In addition, some PtrPPOs could be significantly induced by PEG, ABA and JA, thus revealing their potential role in regulating stress response. Conclusions: Comprehensive analysis is helpful to select candidate PPO genes for the follow-up study of the biological function, and molecular genetic progress of stress resistance in forest trees provides genetic resources.
First report of Mesocriconema sphaerocephalum (Taylor, 1936) Loof, 1989 associated with wild grass in Botswana
Authors: Shokoohi Ebrahim
Published: March 2021

During a survey on the biodiversity of plant-parasitic nematodes of natural areas in Botswana, Mesocriconema sphaerocephalum was discovered around the rhizosphere of the wild grass. The nematodes were extracted using the tray method and then fixed according to the available protocols. The morphological characters fit well with the M. sphaerocephalum. Besides, molecular aspects using 18S and 28S rDNA were studied. The phylogenetic analysis of 18S and 28S rDNA placed the examined population with other populations of M. sphaerocephalum in a group. According to the knowledge, this is the first report of M. spaherocephalum from Botswana.
Integrative taxonomy, distribution, and host associations of Geocenamus brevidens and Quinisulcius capitatus from southern Alberta, Canada
Authors: Munawar Maria , Yevtushenko Dmytro P. , Castillo Pablo
Published: March 2021

Two stunt nematode species, Geocenamus brevidens and Quinisulcius capitatus, were recovered from the potato growing regions of southern Alberta, described and characterized based on integrative taxonomy. Morphometrics, distribution, and host associations of both species are discussed. The Canadian populations of both species displayed minor variations in morphometrical characteristics (viz., slightly longer bodies and tails) from the original descriptions. The populations of G. brevidens and Q. capitatus species examined in this study are proposed as standard and reference populations for each respective species until topotype specimens become available and molecularly characterized. Phylogenetic analyses, based on partial 18S, 28S, and ITS sequences, placed both species with related stunt nematode species. The present study updates the taxonomic records of G. brevidens and Q. capitatus from a new location, southern Alberta, Canada, and will aid in the decision whether these stunt nematodes should be included in nematode management programs.
Network Coding with Multimedia Transmission and Cognitive Networking: An Implementation based on Software-Defined Radio
Authors: Thi Thuy Quynh Tran , Khac Hoang Ngo , Van Ly Nguyen , Linh Trung Nguyen , Quoc Tuan Nguyen , Bastug Ejder , Azarian Sylvain , Vu Ha Le , Nguyen Quoc Bao Vo , Xuan Nam Tran , Debbah Merouane , Duhamel Pierre
Published: March 2021

Network coding (NC) is considered a breakthrough to improve throughput, robustness, and security of wireless networks. Although the theoretical aspects of NC have been extensively investigated, there have been only few experiments with pure NC schematics. This paper presents an implementation of NC under a two-way relay model and extends it to two non-straightforward scenarios: (i) multimedia transmission with layered coding and multiple-description coding, and (ii) cognitive radio with Vandermonde frequency division multiplexing (VFDM). The implementation is in real time and based on software-defined radio (SDR). The experimental results show that, by combining NC and source coding, we can control the quality of the received multimedia content in an on-demand manner. Whereas in the VFDM-based cognitive radio, the quality of the received content in the primary receiver is low (due to imperfect channel estimation) yet retrievable. Our implementation results serve as a proof for the practicability of network coding in relevant applications.
Effect of Tannin-Rich Extract of Chasmanthera dependens on Piroxicam-induced Liver Damage in Male Wistar Rats
Authors: Abiola Tijani Stephanie , David Olori Ogaraya , Olatunde Farombi Ebenezer
Published: March 2021

Background: Piroxicam is one of the nonsteroidal anti-inflammatory drugs used as antipyretic, analgesic and anti-inflammatory drug often used for the relief of nonspecific fever condition and in arthritis. This study investigated the protective potential of tannin-rich extract of Chasmanthera dependens (TRECDS) against piroxicam-induced hepatotoxicity in male Wistar rats.Materials and Methods: Thirty two rats were divided into four groups. Group 1 received normal saline and served as the control group, group 2 were given 20 mg/kg piroxicam only, while groups 3 and 4 were given 20 mg/kg piroxicam with the addition of 200 and 400 mg/kg of tannin-rich extract of Chasmanthera dependens, respectively. All rats were treated orally once daily for ten days.Results: Administration of piroxicam caused liver atrophy demonstrated by significant rise in serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), glucose-6-phosphate dehydrogenase (G6PDH) levels of albumin (ALB), bilirubin (BIL), total cholesterol (TCHOL), triglyceride (TRIGS) and low-density lipoprotein (LDL). Piroxicam also decreased high-density lipoprotein (HDL) level, enzymatic and nonenzymatic antioxidant levels significantly (p>0.05) with attendant increase in oxidative stress indices in the liver of rats compared with control group. Histological assessment reveled severe damaged to the liver of rats. However, co-administration with TRECDS reversed these observations as evidenced in the histological results.Conclusion: The findings of this study showed that exposure of rats to piroxicam provoked damage to the liver via oxidative damage and TRECDS has the potential of ameliorating the damage.Keywords: hepatotoxicity, piroxicam, Chasmanthera dependens, oxidative stress
Expression, Rapid Purification and Functional Analysis of DnaK from Rhodococcus ruber
Authors: Fan Xin , Yuan Yuan , Zhang Fan , Ai Lei , Wu Zhonghao , Peng Ren
Published: March 2021

Background:

Heat shock proteins (HSPs) represent a group of important proteins which
are produced by all kinds of organisms especially under stressful conditions. DnaK, an Hsp70 homolog
in prokaryotes, has indispensable roles when microbes was confronted with stress conditions.
However, few data on DnaK from Rhodococcus sp. were available in the literature. In a previous
study, we reported that toluene and phenol stress gave rise to a 29.87-fold and 3.93-fold increase
for the expression of DnaK from R. ruber SD3, respectively. Thus, we deduced DnaK was
in correlation with the organic solvent tolerance of R. ruber SD3.

Objective:

To elucidate the role of DnaK in the organic solvent tolerance of R. ruber SD3, expression,
purification and functional analysis of Dnak from R. ruber SD3 were performed in the present
paper.

Methods:

In this article, DnaK from R. ruber SD3 was heterologously expressed in E. coli
BL21(DE3) and purified by affinity chromatography. Functional analysis of DnaK was performed
using determination of kinetics, docking, assay of chaperone activity and microbial growth.

Results:

The recombinant DnaK was rapidly purified by affinity chromatography with the purification
fold of 1.9 and the recovery rate of 57.9%. Km, Vmax and Kcat for Dnak from R. ruber SD3
were 80.8 μM, 58.1 nmol/min and 374.3 S-1, respectively. The recombinant protein formed trimer
in vitro, with the calculated molecular weight of 214 kDa. According to in-silico analysis, DnaK interacted
with other molecular chaperones and some important proteins in the metabolism. The specific
activity of catalase in the presence of recombinant DnaK was 1.85 times or 2.00 times that in
the presence of BSA or Tris-HCl buffer after exposure to 54 °C for 1h. E. coli transformant with
pET28-dnak showed higher growth than E. coli transformant with pET28 at 43°C and in the presence
of phenol, respectively.

Conclusion:

The biochemical properties and the interaction analysis of DnaK from R. ruber SD3
deepened our understanding of DnaK function. DnaK played an important role in microbial growth
when R. ruber was subjected to various stress such as heating and organic solvent.