bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting Russian Economic Interests in Southern Africa
Authors: Kuznetsov A.
Published: November 2021

In this study Southern Africa refers to 10 countries: South Africa, Namibia, Botswana, Eswatini, Lesotho, Zimbabwe, Zambia, Malawi, Angola and Mozambique. The author states that this region can take an important place in the general policy of the economic turn of the Russian Federation to the Global South. The Soviet Union developed close ties with some countries, supporting them in their struggle for independence, but after the collapse of the USSR, our country “left the region”. Analysis of main features of modern Russian foreign trade in goods and services, as well as foreign direct investment, has shown that only South Africa and Angola are characterized by a diversified structure of bilateral economic relations, and quite favorable in terms of Russian exports of goods. However, even in South Africa and Angola, the dynamics of trade with Russia is unstable, Russian investment was made by a limited number of leading TNCs (mainly in raw materials). Imports from Angola are associated only with diamonds, which does not distinguish this country from Mozambique, Zimbabwe and Malawi, which mainly specialize in the supply of tobacco raw materials to Russia. Russian high-tech exports are primarily related to arms supplies, while a significant proportion of other high value-added goods are usually associated with small volumes of supplies (as in the case of Russia’s pharmaceutical exports to Angola). So far, Russian grain and mineral fertilizers are most in demand in Southern Africa. At the same time, almost all countries in the region have the potential to deepen cooperation with Russia. Russian companies that come to the region as investors will be able to significantly increase trade turnover and diversify its structure. The most significant investments have been made by Russian oil and gas TNCs and diamond mining giant ALROSA. However, Russian investors from other industries, as well as service companies, are also showing interest in Southern Africa. Acknowledgements. The article was prepared at IMEMO under the support of the Russian Science Foundation (project no. 17-78-20216).
“Islamic Factor” and Socio-Political Debate on Immigration in Modern France
Authors: Lapina N.
Published: November 2021

The article considers the place of Muslims in the socio-political life of modern France. The heterogeneity of the Muslim community, different trends within it, the attitude of French Muslims to religion and its place in life are shown. It is noted that in recent years, French Muslims, especially young ones, have become more religious and more often observe the norms of the Koran. There is a growing number of Muslims who believe that the French secular state must adapt to Islamic norms of life. Against this background, especially in connection with the terrorist attacks that have not stopped since 2015, French society is growing distrust of Muslims. Most of the French perceive Islam as a “threat to the Republic”. These sentiments are reflected in the socio-political discussion around issues related to immigration and the “Islamic factor”, which involves well-known French intellectuals, writers and scientists. In the discussion, the supporters of “happy globalization”, who believe that France will be saved by open borders (including President E. Macron and his followers), are opposed by “declinists”, who are afraid of “dissolving” France in the global world. Some advocate the recognition of communitarist movements, some defend the principles of French and/or Muslim identity, others defend multiculturalism, and yet others defend the Republican principles of “one nation” and the secular school. Recently, the discussion has included topics such as racism/anti-racism, the colonial past and anti-colonialism. The country approves a “cancel culture”, which came from the United States and is new to France. An intolerant “cancel culture” contributes to radicalization of the discussion. Another new phenomenon is “anti-white racism” in the French university environment, evident in the fact that meetings are held in universities, attending which is prohibited for “whites”. The peculiarity of the socio-political discussion today is that the number of its participants has increased dramatically. With the expansion of the circle of interested parties and the emergence of new platforms for discussion (social networks, messengers), it has acquired a new quality, and its tone is becoming more aggressive and irreconcilable.
Prediction Modeling of Household’s Preparedness of Natural Hazards Mitigation
Authors: Xia Chen , Hu Yuqing
Published: November 2021

Natural disasters are showing an increase in the magnitude, frequency, and geographic distribution. Studies have shown that individuals’ self-sufficiency, which largely depends on household preparedness, is very important for hazard mitigation in at least the first 72 hours following a disaster. However, for factors that influence a household’s disaster preparedness, though there are many studies trying to identify from different aspects, we still lack an integrative analysis on how these factors contribute to a household’s preparation. This paper aims to build a classification model to predict whether a household has prepared for a potential disaster based on their personal characteristics and the environment they located. We collect data from the Federal Emergency Management Agency’s National Household Survey in 2018 and train four classification models - logistic regression, decision trees, support vector machines, and multi-layer perceptron classifier models- to predict the impact of personal characteristics and the environment they located on household prepare for the potential natural disaster. Results show that the multi-layer perceptron classifier model outperforms others with the highest scoring on both recall (0.8531) and f1 measure (0.7386). In addition, feature selection results also show that among other factors, a household’s accessibility to disaster-related information is the most critical factor that impacts household disaster preparation. Though there is still room for further parameter optimization, the model gives a clue that we could support disaster management by gathering publicly accessible data.
Heated Tobacco Products Impair Cell Viability, Osteoblastic Differentiation, and Bone Fracture-Healing
Authors: Nishino Kazuya , Tamai Koji , Orita Kumi , Hashimoto Yusuke , Nakamura Hiroaki
Published: November 2021

Background:

The negative impact of cigarette smoking on bone union has been well documented. However, the impact of heated tobacco product (HTP) use on bone fracture-healing remains unclear. The present study investigated the effect of HTPs on preosteoblast viability, osteoblastic differentiation, and fracture-healing and compared the effects with those of conventional combustible cigarettes.

Methods:

Cigarette smoke extracts (CSEs) were generated from combustible cigarettes (cCSE) and HTPs (hCSE). CSE concentrations were standardized by assessing optical density. Preosteoblast (MC3T3-E1) cells were incubated with normal medium, cCSE, or hCSE. The cell viability was assessed via MTT assay. After osteoblastic differentiation of CSE-exposed cells, alkaline phosphatase (ALP) activity was assessed. To assess the in vivo effects of CSEs, a femoral midshaft osteotomy was performed in a rat model; thereafter, saline solution, cCSE, or hCSE was injected intraperitoneally, and bone union was assessed on the basis of micro-computed tomography (μCT) and biomechanical analysis 4 weeks later.

Results:

MC3T3-E1 cell viability was reduced in a time and concentration-dependent manner when treated with either cCSE or hCSE. ALP activity after osteoblastic differentiation of cCSE-treated cells was significantly lower than that of both untreated and hCSE-treated cells (mean and standard deviation, 452.4 ± 48.8 [untreated], 326.2 ± 26.2 [cCSE-treated], and 389.9 ± 26.6 [hCSE-treated] mol/L/min; p = 0.002). Moreover, the levels of osteoblastic differentiation in untreated and hCSE-treated cells differed significantly (p < 0.05). In vivo assessment of the femoral midshaft cortical region revealed that both cCSE and hCSE administration significantly decreased bone mineral content 4 weeks after surgery compared with levels observed in untreated animals (107.0 ± 11.9 [untreated], 94.5 ± 13.0 [cCSE-treated], and 89.0 ± 10.1 mg/cm3 [hCSE-treated]; p = 0.049). Additionally, cCSE and hCSE-exposed femora had significantly lower bone volumes than unexposed femora. Biomechanical analyses showed that both cCSE and hCSE administration significantly decreased femoral maximum load and elastic modulus (p = 0.015 and 0.019).

Conclusions:

HTP use impairs cell viability, osteoblastic differentiation, and bone fracture-healing at levels comparable with those associated with combustible cigarette use.

Clinical Relevance:

HTP use negatively affects bone fracture-healing to a degree similar to that of combustible cigarettes. Orthopaedic surgeons should recommend HTP smoking cessation to improve bone union.
The AOA: A Comprehensive House with Compassionate Leaders. Presidential Address to the AOA, June 15, 2020
Authors: Parsons Theodore W.
Published: November 2021

The American Orthopaedic Association (AOA) is the world’s oldest orthopaedic association and it has been responsible for the founding of many prominent organizations as well as The Journal of Bone & Joint Surgery. While the AOA has traditionally focused on academic orthopaedic leadership, the time has come to expand our horizons and look to include all orthopaedic leaders from the wide variety of leadership roles in which they currently serve.

Orthopaedic surgeons who demonstrate compassionate leadership will find that they create stronger, more successful teams. Compassionate leadership is a skill that can be learned, and investing the energy to develop this skill will have a profound impact on our success as orthopaedic surgeons and leaders.
Well Test Analysis for a Well in a Constant Pressure Square
Authors: Kumar Anil , Ramey H. J.
Published: November 2021

Very little information exists for analyzing well tests wherein a part of the drainage boundary is under pressure support from water influx or fluid injection. An idealization is the behavior of a well in the center of a square whose outer boundary remains at constant pressure. A study of this system indicated important differences from the behavior of a well in a closed outer boundary square, the conventional system. At infinite shut in, the constant- pressure boundary case well will reach the initial pressure of the system, rather than a mean pressure resulting from depletion. But it is possible to compute the mean pressure in the constant-pressure case at any time during shut in. Interpretative graphs for analyzing drawdown and buildup pressures are presented and discussed. This case is also of interest in analysis of well tests obtained from developed five-spot fluid injection patterns.

Introduction

Well-test analysis has become a widely used tool for reservoir engineers in the last twenty years. The initial theory was reported by Horner1 for unsteady flow of single phase fluids of small but constant compressibility to a well producing at a constant rate in -infinite and closed boundary reservoirs. Extension of the theory to the finite reservoir case involves specification of the outer boundary condition. The two most commonly observed conditions are: (1) no flow at the outer boundary corresponding to a closed or depletion reservoir, and (2) constant pressure at the outer boundary corresponding to complete water-drive.
Reconstitution of circularized nanodiscs using SpyCatcher-SpyTag
Authors: Zhang Shangwen , Ren Qian , Bao Huan
Published: November 2021

Circularized nanodiscs (cNDs) with diameters over 20 nm are useful tools for biochemical reconstitutions of membrane protein complexes1. However, the application of these large cNDs is limited by low yields and time-consuming procedures. To address this challenge, we herein present a protocol to ease the reconstitution of large cNDs using the SpyCatcher-SpyTag technology.
Collateral Predictors of Neovascularization After Indirect Revascularization in Adult Patients with Moyamoya Disease: A Single-Center Retrospective Study
Authors: Dai Kefang , Shi Zhiyong , Liu Xingju , Wang Rong , Zhang Yan , Zhang Dong
Published: November 2021

Objective.

The underlying factors of neovascularization after indirect bypass in the adult patients with moyamoya disease (MMD) remained unknow. The aim of this study was to explore potential predictors based on collateral characteristics for neovascularization after indirect bypass in adult MMD patients.
Methods.

The adult MMD patients treated by indirect bypass in a single-institution from August 2012 and January 2018 were retrospectively selected into our research. The collaterals based on cerebral angiography were classified into the following subtypes: intracerebral anastomosis, duro-cortical anastomosis, and leptomeningeal anastomosis. Neovascularization evaluation was based on Matsushima classification, with “good” collateral formation in level 2 and 3, and poor formation in level 0 and 1. Univariate and multivariate analyses were performed to identify neovascularization predictors after indirect bypass.
Results.

A total of 86 patients (97 hemispheres) (mean ± SD age 35.06 ± 15.09 years, range 18–61 years) were retrospectively included. Preoperative collateral circulation included intracerebral anastomosis in 49 (50.5%) cases, duro-cortical anastomosis in 19 (19.6%) cases, and leptomeningeal anastomosis in 29 (29.9%) cases, respectively. Postoperative good neovascularization was observed in 56 (57.7%) hemispheres. Multivariate analysis showed that intracerebral anastomosis (P<0.001, OR [95% CI] 2.984 [2.031-5.437]) was associated with favorable neovascularization, whereas older age (P<0.001, OR [95% CI] 0.827 [0.793-0.916]) and hemorrhagic onset (P<0.001, OR [95% CI] 0.138 [0.054–0.353]) were significantly associated with poor neovascularization. Hemispheres in the good neovascularization had lower modified Rankin scale score, and better long-term improvement than those in the poor neovascularization.
Conclusions.

Hemorrhagic onset and old age predict poor neovascularization after indirect bypass, while duro-cortical anastomosis and intracerebral anastomosis predict good neovascularization. Good neovascularization was associated with better long-term outcomes. The current study provides a basis for the selection of surgical procedure for MMD candidates.
Optimal Threshold of Urinary Albumin-to-Creatinine Ratio (UACR) for Predicting Long-Term Cardiovascular and Noncardiovascular Mortality
Authors: Yang Zhi-wen , Fu Yan-bin , Wei Xue-biao , Huang Jie-leng , Fu Bing-qi , Zhang Guan-rong , Yu Danqing
Published: November 2021

Background Traditional cutoff values of urinary albumin-to-creatinine ratio (UACR) for predicting mortality have recently been challenged. In this study, we investigated the optimal threshold of UACR for predicting long-term cardiovascular and noncardiovascular mortality in the general population.Methods Data for 25,302 adults were extracted from the National Health and Nutrition Examination Survey (2005–2014), with mortality status obtained by data matching with death certificates in the National Death Index until December 31, 2015. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of UACR for cardiovascular and noncardiovascular mortality. A Cox regression model was established to examine the association between UACR and cardiovascular and noncardiovascular mortality. X-tile was used to estimate the optimal cutoff of UACR.Results The UACR had acceptable predictive value for both cardiovascular (area under the ROC curve [AUC]=0.769, 95% confidence interval [CI]: 0.711–0.828) and noncardiovascular (AUC=0.722, 95% CI: 0.681–0.764) mortality. Excellent linearity was observed between log-transformed UACR and cardiovascular and noncardiovascular mortality. The optimal cutoff values were 16 and 30 mg/g for predicting long-term cardiovascular and noncardiovascular mortality, respectively. The adjusted hazard ratios of cardiovascular and noncardiovascular mortality for the high-risk group were 2.55 (95% CI: 2.03–3.22, P<0.001) and 1.94 (95% CI: 1.72–2.18, P<0.001), respectively.Conclusions Compared to the traditional cutoff value (30 mg/g), a UACR cutoff of 16 mg/g may be more sensitive for identifying patients at high risk for cardiovascular mortality in the general population.
Structural Equation Modeling and Management Role On The Control of Marek’s Disease Outbreaks in Amhara Region Ethiopia
Authors: Birhan Mastewal , Berhane Nega , Bitew Molalegne , Gelaye Esayas , Getachew Belayneh , Abayneh Takele
Published: November 2021

Background

Marek’s disease is a highly contagious and economically important oncogenic or paralytic viral disease of poultry and it is becoming a serious problem in the poultry industry of Ethiopia. A questionnaire was designed based on the framework to confirmed how the farm management is reduced the outback of the mark’s diseases. Each model construct was measured using a set of rating scale items (questions). A sample size of 200 farmers from different production systems were chosen for data collection. From the analysis, Cornbrash’s Alpha (coefficient of reliability) based on the average inter-item correlations were evaluated for each parameter. This structural equation model examines the relationship between risk factors (flock size, litter management, number of staff) and the risk of each farm (numbers of sick, drops in egg production, and the number of death).
Results

When litter management goes up by 1, the number of sick goes down by 37.575, the number of staff goes up by 1, the number of sick goes down by 7.63, litter management goes up by 1, the number of death goes down by 2.505, flock size goes up by 1, and the number of death goes down by 0.007.than the rest of the activities. The result of this structural equation modeling the finding indicates that the data fit the model well (Chi-square =0.201, root mean square error of approximation = 0.000, the comparative fit index = 1.00, the tucker-lewis coefficient = 1.496, Degrees of freedom =2) and the model was appropriated.
Conclusions

Therefore, it can be concluded that the model must give due attention to the risk factors such as flock size, litter management, number of staff which is different from the previous research result and this might be due to the fact that the effects of environmental factors are more on procurement and integration than the other farm risk factors.
En Bloc Resection of Right Renal Cell Carcinoma and Inferior Vena Cava with Tumor Thrombus: Is It Safe to Divide the Left Renal Vein?
Authors: Horodyski Laura , Gonzalez Javier , Tabbara Marina M. , Gaynor Jeffrey J. , Rodriguez-Cabero Maria , Herranz-Amo Felipe , Hernández Carlos , Shah Rushi , Ciancio Gaetano
Published: November 2021

Background
It has been suggested that IVC reconstruction of retroperitoneal tumors is not required when adequate collateral circulation is present, though transient rise in creatinine may occur post-operatively. There are no reports evaluating mid- and long-term effect on renal function in these patients. The purpose of this study is to assess whether resection of a right renal cell carcinoma and inferior vena cava with obstructing tumor thrombus is safe to perform without reconstructing the inferior vena cava with regard to long-term renal function.
Materials and Methods
A bi-institutional retrospective review was performed over an 18 year period, assessing patients with right renal cell carcinoma and obstructing level II-IV tumor thrombus.
Results
Twenty-two patients were included in the study. Median age was 62.5 (range 45-79) years old and 19 (86%) of the patients were male. One patient (5%) had a level II thrombus, 14 patients (64%) had a level III thrombus (IIIa n=3, IIIb n=6, IIIc n= 3, IIId n=2), and seven patients (32%) had a level IV thrombus. Intra-operatively, median estimated blood loss was 1.35 (range 0.2 – 25) L. The median length of hospital stay was 11 (range 5 – 50) days. Median preoperative creatinine was 1.20 (range 0.40 – 2.70) mg/dL and postoperatively, median creatinine was 1.3 (range 0.86 – 2.20) mg/dL. Median creatinine at 6 month and 12 months follow-up was 1.10 (range 0.5 – 1.6) and mg/dL 1.34 (range 0.6 – 2.0), respectively. Eight patients were lost to follow-up, and two died (one in the hospital, and the other three months post-operatively).
Conclusions
Resection of right renal cell carcinoma with inferior vena cava in the presence of an obstructing level II- IV tumor thrombus without reconstruction of the inferior vena cava appears not to have a significant adverse effect on long-term renal function.
Efficacy Evaluation and Prognosis Analysis of CT-Guided Radiofrequency Ablation for Non-Small Cell Lung Cancer
Authors: Pan Min , Xu Yufei , Jiang Xueqin , Ke Zhangyan , Ning Yajing , Han Xiaoyan , Jiang Zifeng , Zhu Yingying , Fang Lei , Zhang Yanbei , Fan Xiaoyun
Published: November 2021

Background: Lung cancer has a high morbidity and mortality, and has the highest incidence of all malignancies in men in China. In recent years, radiofrequency ablation (RFA) has become the fourth promising treatment for lung cancer.Method: We followed up patients with non-small cell lung cancer in the First Affiliated Hospital of Anhui Medical University to investigate the survival, complications and prognosis of RFA.Results: Among 34 patients, there were 25 men and nine women (age range 22–84 years; 64% aged 60–80 years. The mean diameter of lung lesions was 2.46±0.89 cm. The pathological types were adenocarcinoma (27/34, 79.41%) and squamous cell carcinoma (7/34, 20.59%). Half of the patients had reached stage IV at the time of the study. Sixteen patients had elevated carcinoembryonic antigen (CEA). Six patients did not receive any further treatment after RFA and nine received chemotherapy combined with targeted therapy. The median follow-up period was 18 (7.0–33.5) months. Complications of RFA were reported in 15 patients (44.12%) and the most common were pneumothorax and pleural effusion. The risk of complications was higher in smokers than in non-smokers (P<0.05). The median overall survival was 22 (2.58–41.42) months, and the overall survival rate was 69.78% (1 year), 59.10% (18 months) and 48.85% (2 years). The survival rate of patients with lung lesions diameter ≤2 cm was significantly higher than that of patients with lesion diameter >2 cm (P<0.05). The annual survival rate of patients with elevated serum CEA before RFA was significantly lower than that of patients with normal serum CEA (P<0.05). Patients with chemotherapy combined with tyrosine kinase inhibitors (TKIs) had significantly higher survival rates compared with patients with only chemotherapy or TKI/no treatment (P<0.05). Conclusion: CT-guided RFA is a safe and effective treatment for lung cancer. Small lesions and combined therapy can result in longer survival. Patients with serum increased CEA have poor survival.
DPEP1 Increases Drug Resistance in an ASCL2-Dependent Manner in Colon Cancer Cells and Correlates with Immune Cell Infiltration
Authors: Zeng Cheng , Shen Ying , Zhu Qi , Yang Chunxia , Wang Yue , Li Wenjing , Liu Jingsong , Dai Yuyang , Qi Guoping , Jin Jianhua , Liu Qian
Published: November 2021

Background: Dipeptidase 1 (DPEP1) is associated with several human cancers. However, its function in colon cancer remains unclear.Methods: DPEP1 expression was analyzed by TCGA and GTEx pancancer data. Survival analysis was performed using the R survival package to assess the prognostic value of the DPEP1 expression level in colon cancer. DPEP1 enrichment analysis was conducted by the clusterProfiler R software package. Correlation analysis, differential expression analysis, and Venn analysis were used to obtain key genes. Correlation of DPEP1 or ASCL2 expression with immune cell infiltration in colon cancer was performed by TIMER and GSCA databases. qRT-PCR, Western blot, Co-immunoprecipitation, dual luciferase reporter experiments, and immunohistochemistry were used to explore the correlation between DPEP1 and ASCL2. MTT was used to evaluate the role of DPEP1 in colon cancer drug resistance.Results: DPEP1 was overexpressed in various cancers, including colon cancer. High DPEP1 expression was negatively correlated with the disease-specific survival (DSS) and progression-free interval (PFI) but not significantly correlated with the overall survival (OS). Enrichment analysis showed that DPEP1 may be related to the Wnt signaling pathway and Hippo signaling pathway. Further analysis showed that DPEP1 and ASCL2 had a strong positive correlation, and both correlated with immune cell infiltration. Moreover, DPEP1 enhanced drug resistance in an ASCL2- dependent manner.Conclusions: Our findings revealed that DPEP1 enhanced drug resistance in an ASCL2-dependent manner and correlated with immune infiltration in colon cancer.
Bacterial Foraging Algorithm With Potential Field Guidance Mechanism
Authors: Li Zhiyuan , Wang Zhicheng
Published: November 2021

To address the problems of weak quorum sensing ability and slow convergence speed in bacterial foraging algorithm, a bacterial foraging algorithm with potential field guidance mechanism is proposed. The algorithm combines the sampling guidance mechanism in the artificial potential field algorithm to provide the optimization direction for each bacterium; The original swimming operation of bacterial foraging algorithm is used to realize the local optimization strategy, and the local dimension update is added after swimming, so that the search range of bacteria in chemotaxis operation is wider; In the elimination and dispersal operation of bacterial foraging algorithm, double Gaussian function is introduced to re initialize the location of bacteria, so as to better avoid the algorithm falling into local extremum and improve the optimization ability of the algorithm. The experimental results show that the improved bacterial foraging algorithm has better optimization ability than the basic bacterial foraging algorithm.
PI3K/AKT/mTOR Signaling Pathway Regulates MMP9 Gene Activation via Transcription Factor NF-κB in Mammary Epithelial Cells of Dairy Cows
Authors: Mao Yongjin , Su Chen , Yang Huilin , Zhao Feng , Qu Bo , Zhao Bing , Cui Yingjun
Published: November 2021

Background

Matrix metalloproteinase 9 (MMP9) plays a pivotal role in mammary ductal morphogenesis, angiogenesis, and glandular tissue architecture remodeling. However, the molecular mechanism of MMP9 expression in mammary epithelial cells of dairy cows remains unclear. The current study aimed to explore the underlying mechanism of MMP9 expression.
Results

In this study, to determine whether the PI3K/AKT/mTOR/NF-κB signaling pathway participates in the regulation of MMP9 expression, we treated mammary epithelial cells with specific pharmacological inhibitors of PI3K (LY294002), mTOR (Rapamycin), or NF-κB (Celastrol), respectively. Western blotting results indicated that LY294002, Rapamycin, and Celastrol markedly decreased MMP9 expression and P65 nuclear translocation. Furthermore, we found that NF-κB (P65) overexpression resulted in elevated expression of MMP9 protein and activation of MMP9 promoter. In addition, we observed that Celastrol markedly decreases P65-overexpression-induced MMP9 promoter activity. Moreover, the results of the promoter assay indicated that the core regulation sequence for MMP9 promoter activation may be located -80bp to -420bp downstream from the transcription start site.
Conclusions

These observations indicated that the PI3K/AKT/mTOR signaling pathway is involved in MMP9 expression by regulating MMP9 promoter activity via NF-κB in the mammary epithelial cells of dairy cows.
MyD88 in Hepatic Stellate Cells Promotes the Development of Alcoholic Fatty Liver via the AKT Pathway
Authors: Li Yukun , Wei Miaomiao , Yuan Qi , Liu Yu , Tian Tian , Hou Lingling , Zhang Jinhua
Published: November 2021

Myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in the TLRs signaling pathway, is expressed in various liver cells including hepatocytes, Kupffer cells and hepatic stellate cells (HSCs). However, the specific role of MyD88 in HSCs in alcoholic fatty liver (AFL) has not been well investigated. Here, to study the role of MyD88 in HSCs in the development of AFL and its related molecular mechanism, chronic-binge ethanol mice models were established in mice with specific MyD88 knockout in quiescent (MyD88GFAP−KO) and activated HSCs (MyD88SMA−KO), respectively. The results showed that the expression of MyD88 in HSCs was significantly increased in ethanol-induced liver tissues of wild-type mice. MyD88 deficiency in quiescent HSCs inhibited inflammation and lipogenesis, but in activated HSCs it only inhibited inflammation under the ethanol feeding condition. Further mechanism studies found that MyD88 promoted the osteopontin (OPN) secretion of HSCs, which further activated the AKT signaling pathway of hepatocytes and upregulated lipogenic gene expression to promote fat accumulation. In addition, OPN also promotes inflammation by activating p-STAT1. Thus, MyD88 may represent a potential candidate target for the prevention and targeted therapy in AFL, and MyD88 inhibitor can be also applied in inhibiting adipogenesis.
Electronic And Nonlinear Optical Features of Inorganic Ga12N12 Nanocage Decorated With Alkali Metals (Li, Na and K)
Authors: Jamshidi Azadeh , Biglari Zeinab
Published: November 2021

The effect of alkali metals (Li, Na and K) interaction on the nonlinear optical response (NLO) of Ga12N12 nanocage has been performed using density functional theory (DFT) calculations. The results show that the exo-M@Ga12N12 structures are energetically favorable with negative interaction energies in the range of ‒1.50 to ‒2.28 eV. The electronic properties of decorated structures are strongly sensitive to interaction with the alkali metals. The HOMO-LUMO gap of Ga12N12 is reduced by about 70% due to the decoration with alkali metals. It is obtained that the adsorption of alkali metals over the tetragonal ring of Ga12N12 nanocage remarkably enhances the first hyperpolarizability up to 6.5×104 au. The results display that decorating Ga12N12 nanocage with alkali metals can be introduced it as a novel inorganic nanomaterial with significant NLO properties.
Mapping the Spatiotemporal Diversity of Precipitation in Iran
Authors: Jamshidi Zahra , Samani Nozar
Published: November 2021

Despite located in a semi-arid and arid part of the world, Iran enjoys a very diverse climate. As a result, water availability in different regions of the country is in a veil of ambiguity. To have a better insight, we investigate the spatiotemporal diversity of precipitation over the country by analyzing the 33-years long monthly precipitation time series (1983-2016) at 461 measuring rain-gauge stations. Cluster Analysis (CA) both hierarchical and non-hierarchical clustering approaches and Principal Component Analysis (PCA) was used to determine the homogeneous precipitation zones at three macro, meso, and micro-scales. First, the country is divided into six precipitation macro-regions using CA. Each region shows a unique mean annual hyetograph and is influenced by a particular air moisture mass entering the country. Then, the six regions were divided into 10 regions of meso-resolution through Hierarchical clustering (HC) and K-Means Clustering. Finally, an optimal number of 24 micro-zones is established that reflect a comprehensive precipitation map over the country, employing PCA, Hierarchical clustering, and K-Means Clustering. The annual hyetograph of each zone showed a unique pattern and distribution with a varying magnitude of monthly precipitation compared to others. The long-term (i.e., 33-years) mean annual rainfall in each region and zone is calculated, and the monthly and annual-precipitation water availability in the country is estimated. The result gives an accurate insight into the amount of precipitation that is expected to fall in each zone during each month of the year, that may be used as the reference for the prediction of the dry and wet seasons and years and also for the allocation of the harvested precipitation water to different consumptive sectors. The result shows that the Hierarchical clustering and PCA have significant classification performance in meso and micro- climatological zoning. Also, it was observed that there are significant similarities between the PCA and Hierarchical clustering (Ward’s method-Pearson correlation) results in micro-climatological zoning.
Diagnostic Performance of Deep LearnIng AlgoriThm for Analysis of Computed Tomography Myocardial PerfusION
Authors: Muscogiuri Giuseppe , Chiesa Mattia , Baggiano Andrea , Spadafora Pierino , De Santis Rossella , Guglielmo Marco , Scafuri Stefano , Fusini Laura , Mushtaq Saima , Conte Edoardo , Annoni Andrea , Formenti Alberto , Mancini Maria Elisabetta , Ricci Francesca , Ariano Francesco Paolo , Spiritigliozzi Luigi , Babbaro Mario , Mollace Rocco , Maragna Riccardo , Giacari Carlo Maria , Andreini Daniele , Guaricci Andrea Igoren , Colombo Gualtiero I. , Rabbat Mark G. , Pepi Mauro , Sardanelli Francesco , Pontone Gianluca
Published: November 2021

Purpose: Artificial intelligence could play a key role in cardiac imaging analysis. To evaluate the diagnostic accuracy of a deep learning (DL) algorithm predicting hemodynamically significant coronary artery disease (CAD) by using a rest dataset of myocardial computed tomography perfusion (CTP) as compared to invasive evaluation. Methods: One hundred and twelve consecutive symptomatic patients scheduled for clinically indicated invasive coronary angiography (ICA) underwent CCTA plus static stress CTP and ICA with invasive fractional flow reserve (FFR) for stenoses ranging between 30% and 80%. Subsequently, a DL algorithm for the prediction of significant CAD by using the rest dataset (CTP-DLrest) and stress dataset (CTP-DLstress) was developed. The diagnostic accuracy for identification of significant CAD using CCTA, CCTA+CTPStress, CCTA+CTP-DLrest, and CCTA+CTP-DLstress were measured and compared. The time of analysis for CTPStress, CTP-DLrest and CTP-DLStress were recorded. Results: Patient-specific sensitivity, specificity, NPV, PPV, accuracy and area under the curve (AUC) of CCTA alone and CCTA+CTPStress were 100%, 33%, 100%, 54%, 63%, 67% and 86%, 89%, 89%, 86%, 88%, 87%, respectively. Patient-specific sensitivity, specificity, NPV, PPV, accuracy and AUC of CCTA+DLrest and CCTA+DLstress were 100%, 72%, 100%, 74%, 84%, 96% and 93%, 83%, 94%, 81%,88%,98%, respectively. All CCTA+CTPStress, CCTA+CTP-DLRest and CCTA+CTP-DLStress significantly improved detection of hemodynamically significant CAD (p<0.01).Time of CTP-DL was significantly lower as compared to human analysis (39.2±3.2 vs. 379.6±68.0 seconds, p<0.001).Conclusion: Evaluation of myocardial ischemia using a DL approach on rest CTP datasets is feasible and accurate. This approach may be a useful gatekeeper prior to CTPStress.
The K Nearest Neighbor Algorithm for Imputation of Missing Longitudinal Prenatal Alcohol Data
Authors: Sania Ayesha , Pini Nicolò , Nelson Morgan E. , Myers Michael M. , Shuffrey Lauren C. , Lucchini Maristella , Elliott Amy J. , Odendaal Hein J. , Fifer William P.
Published: November 2021

Background — Missing data are a source of bias in epidemiologic studies. This is problematic in alcohol research where data missingness is linked to drinking behavior. Methods — The Safe Passage study was a prospective investigation of prenatal drinking and fetal/infant outcomes (n=11,083). Daily alcohol consumption for last reported drinking day and 30 days prior was recorded using Timeline Follow-back method. Of 3.2 million person-days, data were missing for 0.36 million. We imputed missing data using a machine learning algorithm; “k-Nearest Neighbor” (k-NN). k-NN imputes missing values for a participant using data of participants closest to it. Imputed values were weighted for the distances from nearest neighbors and matched for day of week. Validation was done on 500 iterations after randomly deleting data for 5-15 consecutive days. Results — Data from 5 nearest neighbors and segments of 55 days provided imputed values with least imputation error. After deleting data segments from with no missing days from first trimester, there was no difference between actual and predicted values for 64% of deleted segments. For 31% of the segments, imputed data were within +/-1 drink/day of the actual. Conclusions — k-NN can be used to impute missing data from longitudinal studies of alcohol during pregnancy with high accuracy.
Metadichol®, a Novel Nano Lipid Formulation that Inhibits SARS-COV-2 and a Multitude of Pathological Viruses in vitro
Authors: Raghavan Palayakotai
Published: November 2021

Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus envelope and the host cell plasma membrane as a critical mechanism of infection. Metadichol®, a nano lipid emulsion of long chain alcohols, has been demonstrated as a strong candidate that inhibits the proliferation of SARS-CoV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce viral infectivity, including that of coronaviruses (such as SARS-CoV-2) by modifying their lipid-dependent attachment mechanism to human host cells. The receptor ACE2 mediates the entry of SARS-CoV-2 into the host cells, whereas the serine protease TMPRSS2 primes the viral S protein. In this study, Metadichol® was found to be 270 times more potent an inhibitor of TMPRSS2 (EC50 = 96 ng/ml) than Camostat mesylate (EC50 = 26000 ng/mL). Additionally, it inhibits ACE with an EC50 of 71 ng/mL, but very weak inhibitor of ACE2 at an EC50 of 31 µg/ml. Furthermore, the live viral assay performed in Caco-2 cells revealed that Metadichol® inhibits SARS-CoV-2 replication at an EC90 of 0.16 µg/ml. Moreover, Metadichol® had an EC90 of 0.00037 µM, making it 2081 and 3371 times more potent than Remdesivir (EC50 = 0.77 µM) and chloroquine (EC50 = 1.14 µM), respectively.
Universe: the dynamics of the minimum and maximum expansion states
Authors: Petrakis Sócrates
Published: November 2021

Two hypotheses stand out in describing the evolution of the Universe. The predominant one predicts that the current expansion began at a certain instant and will not preserve any variation of energy that performs work; apparent flat Universe (Ω = 1) is advocated by relativistic calculations and observational data, with an end or thermal death at its maximum expansion (3D Space). The other hypothesis considers that the Universe is cyclical (always alternating phases of expansion and contraction). This proposal aims to demonstrate that both hypotheses can be correct by not being distinct, but complementary. Supported by the immutability of physical laws, analyses of concepts such as space, mass, energy, gravity, spin, and entropy define an exclusive presence of 1D Space in the minimum and maximum expansion states of the Universe. With our 3D Space Universe created and existing between these extreme states, every dynamic is outlined and completes the usual relativity. The concept of complete rest energy (1D Space) was able to be applied, demonstrating that the complete evolution of the Universe is spatially dynamic in a perpetual time dimension, always recreating our Universe.
A Linear Dynamical Perspective on Epidemiology: Interplay Between Early COVID-19 Outbreak and Human Mobility
Authors: Mustavee Shakib , Agarwal Shaurya , Das Suddhasattwa , Enyioha Chinwendu
Published: November 2021

This paper investigates the impact of human activity and mobility (HAM) in the spreading dynamics of an epidemic. Specifically, it explores the interconnections between HAM and its effect on the early spread of the COVID-19 virus. During the early stages of the pandemic, effective reproduction numbers exhibited a high correlation with human mobility patterns, leading to a hypothesis that the HAM system can be studied as a coupled system with disease spread dynamics. This study applies the generalized Koopman framework with control inputs to determine the nonlinear disease spread dynamics and the input-output characteristics as a locally linear controlled dynamical system. The approach solely relies on the snapshots of spatiotemporal data and does not require any knowledge of the system’s physical laws. We exploit the Koopman operator framework by utilizing the Hankel Dynamic Mode Decomposition with Control (HDMDc) algorithm to obtain a linear disease spread model incorporating human mobility as a control input. The study demonstrated that the proposed methodology could capture the impact of local mobility on the early dynamics of the ongoing global pandemic. The obtained locally linear model can accurately forecast the number of new infections for various prediction windows ranging from two to four weeks. The study corroborates a leader-follower relationship between mobility and disease spread dynam-
Collectivism in a Replication Network of Minimal Nucleobase Sequences
Authors: Vela-Gallego Sonia , Pardo-Botero Zulay , Moya-Álamo Cristian , Escosura Andrés de la
Published: November 2021

A major challenge for understanding the origins of life is to explore how replication networks can engage in an evolutionary process. Herein, we shed light on this problem by implementing a network constituted by two different types of extremely simple biological components: the amino acid cysteine and the canonical nucleobases adenine and thymine, connected through amide bonds to the cysteine amino group and oxidation of its thiol into three possible disulfides. Supramolecular and kinetic analyses revealed that both self- and mutual interactions between such dinucleobase compounds drive their assembly and replication pathways. Those pathways involving sequence complementarity led to enhanced replication rates, suggesting a potential bias for selection. The interplay of synergistic dynamics and competition between replicators was then simulated in an open reactor with experimental kinetic data, showing the selective amplification of different species depending on the initial mixture composition. Overall, this network configuration can favor a collective adaptability to changes in the availability of feedstock molecules, with disulfide exchange reactions serving as 'wires' that connect the different individual auto- and cross-catalytic pathways.
Metformin Intake Suppresses The Degree of Liver Metastasis From Colorectal Cancer In Diabetic Patients But Does Not Improve Their Prognosis
Authors: Saito Akira , Kitayama Joji , Horie Hisanaga , Koinuma Koji , Ohzawa Hideyuki , Yamaguchi Hironori , Kawahira Hiroshi , Mimura Toshiki , Lefor Alan Kawarai , Sata Naohiro
Published: November 2021

Background: Metformin reduces the risk of, and mortality from, colorectal cancer in patients with diabetes mellitus. However, the effect of metformin on patients with stage IV disease is unknown. In the present study we reviewed the clinical features and outcomes of patients with diabetes mellitus and stage IV colorectal cancer (M1, liver metastases) treated with or without metformin.Methods: The 202 patients with colorectal cancer and macroscopic liver metastasis who were treated in the Department of Surgery or Department of Clinical Oncology at Jichi Medical University Hospital from January 2006 through June 2019 were surveyed treatment of diabetes, clinical and pathological factor and prognosis of these patients. Results: We retrospectively examined the effect of metformin use on outcomes in 32 patients with liver metastases from colorectal cancer. Hepatic metastases were stage H1 in 8/8 patients taking metformin and stage H2-3 in 17/24 non-users. Of 22 patients who underwent colectomy, colorectal tumors were pT4 in 5 metformin users, and pT2-3 in 10/17 non-users. The mean survival of metformin users and non-users was equal (28.0 mo vs 29.3 mo, p>.05). No significant difference was detected when survival was compared between 6 metformin users and 19 non-users who received systemic chemotherapy. Conclusion: These results suggest that metformin has less potent anti-tumor effects in patients with advanced stage disease. Metformin for the treatment of patients with metastatic colorectal cancer requires further study.
The Impact of Exogenous Tetrodotoxin on the piRNAs and mRNAs Profiles of Gonads in Pufferfish Takifugu Flavidus
Authors: He Xue , Wu Hexing , Ye Yaping , Gong Xiaolin , Bao Baolong
Published: November 2021

Tetrodotoxin (TTX) is a deadly neurotoxin and usually accumulates in large amounts in the ovaries but is non-toxic or low toxic in the testis of pufferfish. The molecular mechanism underlying sexual dimorphism of TTX accumulation in gonads is complex and unclear. Piwi/piRNA complexes are essential for germline specification, gametogenesis, and gonadal development, they also demonstrate sexual dimorphism in teleosts. Hence, the present study investigated the expression of piRNAs and mRNAs by transcriptomics in cultured pufferfish Takifugu flavidus after intramuscular administration of exogenous TTX. The results showed 80 piRNAs were down-regulated and 223 genes were up-regulated in the ovary after TTX administration. By contrast, 286 piRNAs were down-regulated and 445 genes were up-regulated after TTX administration in testis. Functional and pathway analyses indicated that the TTX up-regulated genes were enriched in the Wnt, ErbB and GnRH signaling pathways in ovary, while were enriched in the oocyte meiosis, estrogenesis biosynthesis and cell apoptosis-related pathways in testis. Interestingly, these genes were also the potential target genes of TTX downregulated piRNAs. Amhr2 and cyp19a were also identified as sex-related genes, involved in TTX administration. These results showed a certain level of consistency with the enrichment pathway analysis, which indicated that the TTX could affect the expression of sex-related genes, and work as an inhibitor for the testicular meiosis, but as a promoting factor for ovary development through piRNAs in pufferfish. In addition, TUNEL staining showed that significant apoptosis was detected in the TTX treated testis, and the role of the cell apoptotic pathway was further confirmed. Overall, this research will contribute to an understanding of the piwi function in TTX sexual dimorphism accumulation in pufferfish and provide a basis for further studies.