bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Guo Jing , Chen Hongdong , Zhang Xueqin , Lou Wenjiao , Zhang Pingna , Qiu Yuheng , Zhang Chao , Wang Yaoxian , Liu Wei Jing
Published: December 2021

Objective. Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta‐analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Methods. Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2‐hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment‐insulin resistance (HOMA‐IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL), along with inflammation factors such as C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Results. Forty‐six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = −0.73; 95% CI (−0.97, −0.51)), FPG (MD = −0.86, 95% CI (−1.10, −0.62)), and 2hPG (MD = −1.26, 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS (MD = −2.05, 95% CI (−2.62, −1.48)), HOMA‐IR (MD = −0.71, 95% CI (−1.03, −0.39)), and BMI (MD = −1.07, 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = −0.5, 95% CI (−0.61, −0.39)), TC (MD = 0.64, 95% CI (−0.78, −0.49)), and LDL (MD = 0.86, 95% CI (−1.06, −0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. Conclusion. There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.
No Evidence of Abnormal Expression of Beta-Catenin and Bcl-2 Proteins in Pilomatricoma as One Clinical Feature of Tetrasomy 9p Syndrome
Authors: Charalsawadi Chariyawan , Trongnit Sasipong , Jaruthamsophon Kanoot , Wirojanan Juthamas , Jaruratanasirikul Somchit , Nitiruangjaras Anupong , Limprasert Pornprot
Published: December 2021

Background. Little is currently known about the genetics of pilomatricoma. A number of studies have reported some evidence that this disease may have a genetic association with mutations of CTNNB1 gene or expression of the beta-catenin protein. In this study, we reviewed literatures involving 30 patients with various genetic syndromes that have been linked to pilomatricoma and found that somatic mutations of the CTNNB1 gene were reported in 67% of patients. Pilomatricoma has been reported in patients with chromosome 9 rearrangements, including 4 patients with tetrasomy 9p syndrome and one patient with partial trisomy 9. In addition to beta-catenin, the expression of bcl2 was observed in pilomatricoma. Objectives. To report an additional case of tetrasomy 9p syndrome with concurrent pilomatricoma and to examine whether abnormal protein expressions of the CTNNB1 and/or BCL2 genes were present. Methods. Cytogenetic analysis was carried out on peripheral blood, biopsied skin, and pilomatricoma tissue obtained from a patient with tetrasomy 9p syndrome. Immunohistochemical staining was performed on the pilomatricoma tissue, using beta-catenin and bcl2 monoclonal antibodies. Results. SNP microarray revealed nonmosaic gain of the short arm of chromosome 9. A nonmosaic isodicentric chromosome 9 was identified in the peripheral blood but this rearranged chromosome was detected in only 8.3% of the skin fibroblasts. Chromosomal abnormalities were not detected in the pilomatricoma nor expression of beta-catenin or bcl2 proteins in our patient. Conclusion. Pilomatricoma could be a new clinical feature associated with tetrasomy 9p syndrome; however, we found no evidence of tetrasomy 9p or abnormal beta-catenin or bcl2 proteins of the CTNNB1 and BCL2 genes in our pilomatricoma patient.
Survival Outcomes among Human Epidermal Growth Factor Receptor 2- (HER2-) Positive Breast Cancer Patients at Kenyatta National Hospital
Authors: Tuwei Gloria , Degu Amsalu
Published: December 2021

Introduction. HER2-positive breast cancer is associated with poor outcomes and higher mortality rates than other breast cancer subtypes. The advent of trastuzumab has significantly changed the natural history of HER2-positive breast cancer. However, it is not an affordable treatment option in sub-Saharan African countries. Because of the expense, most patients in our setting do not receive trastuzumab for the optimal control of their disease. Additionally, there is a lack of comprehensive data about the survival outcomes of HER2-positive breast cancer patients in our setting. The present study was aimed at determining the survival outcomes among HER2-positive breast cancer patients at the Oncology Department of Kenyatta National Hospital. Methods. A hospital-based retrospective cohort design was used to evaluate the survival outcomes among patients with HER2-positive breast cancer treated from 1st January 2015 to 31st December 2019 at Kenyatta National Hospital. A total of 50 eligible HER2-positive breast cancer patients were included in the study. In the predesigned data abstraction tool, data were collected by reviewing the medical records of the patients. The data were entered and analyzed using the Statistical Package for the Social Sciences version 27 software. The mean survival time was estimated using Kaplan-Meier survival analysis. Results. The mean age was

45.44
±
12.218

 years, with a majority (80%) of the patients being below 60 years. Most patients (64%) had advanced-stage disease. The median follow-up time for patients with curative stages of breast cancer was 41 months, while the median follow-up time for those with the advanced incurable disease was 8.5 months. The 4-year survival rate was 62.5% for those curable-stage HER2-positive breast cancer compared to 5.6% for those with metastatic disease at presentation. Conclusion. The 4-year survival rate for both early-stage and advanced-stage HER2-positive breast cancer in our setting is suboptimal when compared to existing outcome data from health care systems where trastuzumab is more widely available.
The Relationship between Red Cell Distribution Width and Residual SYNTAX Scores in ST-Segment Elevation Myocardial Infarction Patients after Percutaneous Coronary Intervention
Authors: Ling Yang , Wang Wei , Fu Cong , Fan Qun , Liu Jichun , Tang Shengxing
Published: December 2021

Objective. Residual SYNTAX score (rSS) values have been suggested to serve as an independent predictor of mortality in ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI). Prior work has also indicated that red cell distribution width (RDW) can predict the incidence of major adverse cardiac events (MACEs) in STEMI patients. As such, we sought to explore the relationship between RDW and rSS in STEMI patients that have undergone PCI. Methods. In total, 456 eligible patients were recruited for this study. Youden’s index was used to calculate the optimal RDW cut-off value, after which the relationship between RDW and rSS values was assessed through Spearman’s correlation analyses. Independent predictors of high rSS levels were then identified via multivariate logistic regression analysis. Results. Patients were separated into two groups based upon whether they exhibited high RDW levels (>13.9, Group 1) or low RDW levels (<13.9, Group 2). The average rSS value of patients in Group 2 was found to be significantly decreased compared to patients in Group 1 (

P
<
0.001

). RDW values were found to be positively correlated with rSS (

r
=
0.604

,

P
<
0.001

), and multivariate logistic regression analysis determined that high RDW levels were independently predictive of higher rSS (

OR
=
27.1

[14.8-51.7];

P
<
0.001

). Additionally, a nomogram incorporating RDW exhibited good calibration, discriminative capacity, and clinical utility. Conclusions. In summary, RDW is strongly correlated with rSS in STEMI patients following PCI, with high RDW levels serving as an independent predictor of high rSS in this patient population.
Enterprise Financial Risk Management Using Information Fusion Technology and Big Data Mining
Authors: Yue Huabo , Liao Haojie , Li Dong , Chen Ling
Published: December 2021

This paper aims to study enterprise Financial Risk Management (FRM) through Big Data Mining (BDM) and explore effective FRM solutions by introducing information fusion technology. Specifically, big data technology, Support Vector Machine (SVM), Logistic regression, and information fusion approaches are employedto study the enterprise financial risks in‐depth.Among them, the selection offinancial risk indexes has a great impact on the monitoring results of the SVM‐based FRM model; the Logistic regression‐based FRM model can efficientlyclassify financial risks; theinformation fusion‐based FRM model uses a fusion algorithm to fuse different information sources. The results show that the SVM‐based and Logistic regression‐based FRM models can manage and classify enterprise financial risks effectively in practice, with a classification accuracy of 90.22% and 90.88%, respectively; by comparison, the information fusion‐based FRM modelbeats SVM‐based and Logistic regression‐based FRM models by presenting a classification accuracy as high as 95.18%. Therefore, it is concluded that the information fusion‐based FRM is better than the SVM‐based and Logistic regression‐based models; it can integrate and calculate multiple enterprise financial risk data from different sources and obtain higher accuracy; besides, big data technology can provide important research methods for enterprise financial risk problems; SVM‐based FRM model and Logistic regression‐based FRM model can well classify enterprise financial risks, with relatively high accuracy.
How Is Gross Profit Margin Overestimated in China?
Authors: Shi Fulei , Huang Bingbing , Wu Chuanqi , Jin Liang
Published: December 2021

At present, the index of gross profit margin is overestimated in China. However, this problem has not attracted enough attention. This paper explores the theoretical limitations of the current revenue that lead to the overestimation of the gross profit margin. Then, we present the concept of revenue to correct the limitations of the current revenue. Moreover, we test the impact on the information content of gross profit margin under revenue caliber. The findings are as follows: (1) The current revenue includes some unrealized items such as in-price tax, so it is not completely consistent with the definition of revenue from the perspective of accounting, which will lead to the overestimation of gross profit margin. Therefore, the current revenue should exclude the in-price tax, bad debt loss, and cash discount in order to obtain the revenue. The gross profit margin based on the revenue can reflect the profitability of the company’s basic business more objectively. (2) The empirical test shows that the gross profit margin based on the revenue has higher information content compared with the gross profit margin based on the current revenue. (3) The current gross profit margin is overestimated by 1.36 percentage points because of the limitations of the current revenue.
Users’ Payment Intention considering Privacy Protection in Cloud Storage: An Evolutionary Game‐Theoretic Approach
Authors: Zheng Jianguo , Chen Jinming
Published: December 2021

To solve the current privacy leakage problems of cloud storage services, research on users’ payment intention for cloud storage services with privacy protection is extremely important for improving the sustainable development of cloud storage services. An evolutionary game model between cloud storage users and providers that considers privacy is constructed. Then, the model’s evolutionary stability strategies via solving the replication dynamic equations are analyzed. Finally, simulation experiments are carried out for verifying and demonstrating the influence of model parameters. The results show that the evolutionary stable strategies are mainly affected by the privacy protection profit growth coefficient of both parties, input costs, free‐riding gains, and other factors. If the profit growth coefficient is very small, users will not choose to pay and providers will not choose to actively protect user information. As the profit growth coefficient increases, both parties will promote the development of privacy protection with a higher probability. The results are beneficial for cloud storage providers to increase the number of paid users and thus to achieve the sustainable development of cloud storage service.
Semiconductor Quantum Dots (CdX, X = S, Te, Se) Modify Titanium Dioxide Nanoparticles for Photodynamic Inactivation of Leukemia HL60 Cancer Cells
Authors: Pan Qilin , Li Miaomiao , Xiao Mucang , He Yulu , Sun Guangyu , Xue Ting , Luo Youhuan , Chen Li , Ai Baoquan , Xiong Jianwen
Published: December 2021

Titanium dioxide nanoparticles (TiO2-NPs) are highly efficient photosensitizers in traditional photodynamic therapy (PDT). The particle size of TiO2-NPs is small, only about 20 nm. However, the demands of ultraviolet light (UV) excitation feature shallow tissue penetration depth and may lead to severe tissue photon damage. Thus, in this research, TiO2-NPs are modified with semiconductor quantum dots (QDs) CdX (X = S, Te, Se) in various methods, such as ultrasonic, hydrothermal, sol-gel, aqueous phase, and hydrolysis precipitation. The transmission electron microscopy (TEM) images show that the size of CdSe-TiO2 is ranging from 6 to 14 nm. The ultraviolet-visible (UV-Vis) spectrum demonstrates that the CdX (X = S, Te, Se) modification can successfully extend the absorption range of TiO2-NPs into a different visible light region. CdSe QDs have the narrowest band gap compared with CdX (X = S, Te, Se) QDs. Visible light-activated CdSe-TiO2 nanocomposite shows the highest PDT inactivation efficiency toward HL60 cells compared with CdX-TiO2. The photogenerated carrier separation efficiency of CdSe-TiO2 nanocomposite is the highest shown in a fluorescence spectrum (FS). Furthermore, when conjugated with folic acid (FA), the prepared FA-CdX-TiO2 (X = S, Se) exhibits excellent cancer-targeting ability during PDT treatment. Optimum PDT efficiency of FA-CdSe-TiO2 indicates that photocatalytic and targeting ability is much higher than pure TiO2 and CdSe-TiO2. Our results provided a detailed investigation on the PDT performance of CdX (X = S, Te, Se) modified TiO2 and may act as a guide for further design of highly targeted performance visible-light response TiO2-NPs.
Recognition of Ziziphus lotus through Aerial Imaging and Deep Transfer Learning Approach
Authors: Tufail Ahsan Bin , Ullah Inam , Khan Rahim , Ali Luqman , Yousaf Adnan , Rehman Ateeq Ur , Alhakami Wajdi , Hamam Habib , Cheikhrouhou Omar , Ma Yong-Kui
Published: December 2021

There is a growing demand for the detection of endangered plant species through machine learning approaches. Ziziphus lotus is an endangered deciduous plant species in the buckthorn family (Rhamnaceae) native to Southern Europe. Traditional methods such as object-based image analysis have achieved good recognition rates. However, they are slow and require high human intervention. Transfer learning-based methods have several applications for data analysis in a variety of Internet of Things systems. In this work, we have analyzed the potential of convolutional neural networks to recognize and detect the Ziziphus lotus plant in remote sensing images. We fine-tuned Inception version 3, Xception, and Inception ResNet version 2 architectures for binary classification into plant species class and bare soil and vegetation class. The achieved results are promising and effectively demonstrate the better performance of deep learning algorithms over their counterparts.
Surrounding Rock Stability Classification Method of Coal Roadway Based on In Situ Stress
Authors: Yang Yongjie , Huang Gang , Meng Lingren
Published: December 2021

In situ stress is one of the most important factors affecting surrounding rock stability classification of coal roadway. Most surrounding rock stability classification methods do not fully consider the influence of in situ stress. In this paper, the author applied a fuzzy clustering method to the classification of surrounding rock stability of coal roadway. Taking into account the complexity of the classification of surrounding rock, some factors such as the strength of surrounding rock, in situ stress, the main roof first weighting interval, the size of the chain pillar, and the immediate roof backfilled ratio are selected as the evaluation indexes. The weight coefficients of these evaluation indexes are determined by unary regression and multiple regression methods. Using fuzzy clustering and empirical evaluation method, the classification model of surrounding rock stability of coal roadway is proposed, which is applied to 37 coal roadways of Zibo Mining Group Ltd., China. The result is in good agreement with practical situation of surrounding rock, which proves that the fuzzy clustering method used to classify the surrounding rock in coal roadway is reasonable and effective. The present model has important guiding significance for reasonably determining the stability category of surrounding rock and supporting design of coal roadway.
Value of Peak Expiratory Flow Rate in Evaluating Cough Ability in Patients Undergoing Lung Surgery
Authors: Liu Gui-Xian , Su Jian-Hua , Wang Xin , He Jin-Tao
Published: December 2021

Introduction. Postoperative ineffective cough is easy to occur after thoracic surgery, and it is also a risk factor for postoperative pulmonary complications (PPCs). Objectives. To explore the value of peak expiratory flow rate (PEF) in evaluating cough ability in patients undergoing lung surgery and evaluate the effectiveness of chest wall compression during the expiratory phase by PEF. Methods. From September 2020 to May 2021, the researchers collected the data of patients who underwent lung surgery. Eventually, 153 patients who met the criteria were included, 102 cases were included in the effective cough group and 51 cases were included in the ineffective cough group. The receiver working curve (ROC curve) was used to analyze whether PEF could evaluate cough ability. At the same time, the researchers collected the pulmonary function data of the first 30 patients of the ineffective cough group while compressing the chest wall during the expiratory phase to evaluate the effectiveness of chest wall compression. Results. The area under the curve (AUC) of postoperative PEF to evaluate the postoperative cough ability was 0.955 (95% CI: 0.927–0.983,

P
<
0.001

). The values of PEF (127.17 ± 34.72 L/min vs. 100.70 ± 29.98 L/min,

P
<
0.001

, 95% CI: 18.34–34.59) and FEV1 (0.72 (0.68–0.97) L vs. 0.64 (0.56–0.82) L,

P
<
0.001

) measured while compressing the chest wall were higher than those without compression. Conclusions. PEF can be used as a quantitative indicator of cough ability. Chest wall compression could improve cough ability for patients who have ineffective cough.
A Decision-Making Model for Self-Driving Vehicles Based on Overtaking Frequency
Authors: Huang Mengyuan , Li Shiwu , Guo Mengzhu , Han Lihong
Published: December 2021

The driving state of a self-driving vehicle represents an important component in the self-driving decision system. To ensure the safe and efficient driving state of a self-driving vehicle, the driving state of the self-driving vehicle needs to be evaluated quantitatively. In this paper, a driving state assessment method for the decision system of self-driving vehicles is proposed. First, a self-driving vehicle and surrounding vehicles are compared in terms of the overtaking frequency (OTF), and an OTF-based driving state evaluation algorithm is proposed considering the future driving efficiency. Next, a decision model based on the deep deterministic policy gradient (DDPG) algorithm and the proposed method is designed, and the driving state assessment method is integrated with the existing time-to-collision (TTC) and minimum safe distance. In addition, the reward function and multiple driving scenarios are designed so that the most efficient driving strategy at the current moment can be determined by optimal search under the condition of ensuring safety. Finally, the proposed decision model is verified by simulations in four three-lane highway scenarios. The simulation results show that the proposed decision model that integrates the self-driving vehicle driving state assessment method can help self-driving vehicles to drive safely and to maintain good maneuverability.
Status and Challenges on Design and Implementation of Camber Morphing Mechanisms
Authors: Majid Tuba , Jo Bruce W.
Published: December 2021

This paper presents state-of-the-art technologies of camber morphing mechanisms from the perspectives of design and implementation. Wing morphing technologies are aimed at making the aircraft more energy or aerodynamically efficient during flight by actively adjusting the wing shape, but their mechanism designs and implementation aspects are often overlooked from practical sense in many technical articles. Thus, it is of our interest that we thoroughly investigate morphing mechanisms and their nature of design principles and methodologies from the implementation and test flight aspects, navigate the trends, and evaluate progress for researchers’ methodology selection that possibly turns to design and build stages. This paper categorizes the camber morphing mechanisms from a wide collection of literature on morphing wings and their mechanisms, and the defined classifications are based on mechanism’s design features and synthesis methodology, i.e., by the tools and methods used to solve the design problem. The categories are (1) structure-based, (2) material-based, and (3) hybrid. Most of the structure-based camber morphing mechanisms have distinctive structural features; however, the material-based camber morphing mechanisms make use of material properties and tools to enhance the elastic nature of its structures. Lastly, the hybrid morphing mechanisms are a combination of both the aforementioned categories. In summary, this review provides researchers in the field of morphing mechanisms and wings with choices of materials, actuators, internal and external structure design for wings, and overarching process and design methodologies for implementation with futuristic and practical aspects of flight performance and applications. Moreover, through this critical review of morphing mechanism, selective design criteria for appropriate morphing mechanisms are discussed.
Identification of Metabolism-Related Genes Influencing Prognosis of Multiple Myeloma Patients
Authors: Wang Rui , Bu Wenxuan , Yang Yang
Published: December 2021

Multiple myeloma (MM) is the second most commonly diagnosed hematological malignancy. Understanding the basic mechanisms of the metabolism in MM may lead to new therapies that benefit patients. We collected the gene expression profile data of GSE39754 and performed differential analysis. Furthermore, identify the candidate genes that affect the prognosis of the differentially expressed genes (DEGs) related to the metabolism. Enrichment analysis is used to identify the biological effects of candidate genes. Perform coexpression analysis on the verified DEGs. In addition, the candidate genes are used to cluster MM into different subtypes through consistent clustering. Use LASSO regression analysis to identify key genes, and use Cox regression analysis to evaluate the prognostic effects of key genes. Evaluation of immune cell infiltration in MM is by CIBERSORT. We identified 2821 DEGs, of which 348 genes were metabolic-related prognostic genes and were considered candidate genes. Enrichment analysis revealed that the candidate genes are mainly related to the proteasome, purine metabolism, and cysteine and methionine metabolism signaling pathways. According to the consensus clustering method, we identified the two subtypes of group 1 and group 2 that affect the prognosis of MM patients. Using the LASSO model, we have identified 10 key genes. The prognosis of the high-risk group identified by Cox regression analysis is worse than that of the low-risk group. Among them, PKLR has a greater impact on the prognosis of MM, and the prognosis of MM patients is poor when the expression is high. In addition, the level of immune cell infiltration in the high-risk group is higher than that in the low-risk group. In the summary, metabolism-related genes significantly affect the prognosis of MM patients through the metabolic process of MM patients. PKLR may be a prognostic risk factor for MM patients.
Synthesis, DFT Analysis, and Evaluation of Antibacterial and Antioxidant Activities of Sulfathiazole Derivatives Combined with In Silico Molecular Docking and ADMET Predictions
Authors: Samuel Yoseph , Garg Ankita , Mulugeta Endale
Published: December 2021

Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72–81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (E. coli and P. aeruginosa) and two Gram-positive bacterial strains (S. pyogenes and S. aureus) by disk diffusion method. Among synthesized compounds, compound 11a showed potent inhibitory activity against Gram-negative, E. coli with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound 11a showed the strongest activity with IC50 values of 1.655 μg/mL. The synthesized compounds were evaluated for their in silico molecular docking analysis using S. aureus gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from −7.8 to −10.0 kcal/mol with 2XCT and −7.5 to −9.7 with 1DNU. Compound 11a showed very good binding score −9.7 kcal/mol with both of the proteins and had promising alignment with in vitro results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6–31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.
Effect of Metformin on Anthropometric Measurements and Hormonal and Biochemical Profile in Patients with Prediabetes
Authors: Safiah Mustafa , Hyassat Dana , Khader Yousef , Farahid Oraib , Batieha Anwar , El-Khateeb Mohammed , Ajlouni Kamel
Published: December 2021

Objectives. Metformin is the most widely preferred first-line oral antidiabetic agent that results in clear benefits in blood sugar regulation and diabetes-related complications. This study is aimed at assessing the effect of metformin on anthropometric, hormonal, and biochemical parameters in patients with prediabetes or insulin resistance. Methods. A prepoststudy was conducted among 52 patients with prediabetes or insulin resistance who met the inclusion criteria. Weight, body mass index (BMI), and waist circumference were measured before and 12 months after metformin treatment. Serum concentrations of sex steroids, gonadotropins, and lipids were also assessed. Homeostasis model assessment (HOMA) index and quantitative sensitivity check (QUICKI) index scores were calculated before metformin treatment and after 12 months of use. Results. After 12 months of metformin treatment, female patients had significant reduction in weight, BMI, and waist circumference after adjusting for age. Metformin use for 12 months resulted in significant reduction in mean fasting blood glucose and HbA1c in females only. Total cholesterol decreased significantly among men only and serum HDL-C showed a significant rise among females only. Serum LDL-C and triglycerides did not change significantly in females and males. Our study did now significant changes in ACTH and cortisol levels in both females and males after metformin treatment. Metformin use resulted in significant increase in luteinizing hormone (LH) and progesterone levels in males, while it was associated with significant increase in prolactin, follicular stimulating hormone (FSH), and dehydroepiandrostenedione-sulphate (DHEA-S) levels and significant decrease in total testosterone level in females. Conclusion. Metformin treatment in females with prediabetes reduces BMI, waist circumference, fasting blood glucose, and HbA1c. The changes in the studied parameters differed significantly according to sex.
Optimization of Subsurface Smart Irrigation System for Sandy Soils of Arid Climate
Authors: Farooq Qazi U. , Naqash Muhammad T. , Ahmed Abdelkader T. , Khawaja Bilal A.
Published: December 2021

The Arabian Peninsula is an arid zone with a hot desert climate and severe water scarcity. The low humidity, elevated ambient temperatures, and high evaporation rates in the region deemed conventional surface irrigation unsustainable. The IoT-based subsurface smart irrigation systems can be essentially developed for these regions to avoid surface evaporation losses. In this research, the sandy soil conditions of western Saudi Arabia have been considered in numerical simulations to evaluate the performance of a subsurface smart irrigation system. The influence zone of saturation generated by subsurface diffusers in the target root region has been analysed for two different types of sandy soils. The simulation results generated by the COMSOL Multiphysics program reveal that the subsurface smart irrigation system can be effectively applied to simultaneously manage the target root zone at the ideal saturated conditions and prevent surface evaporation losses.
Ensemble of EfficientNets for the Diagnosis of Tuberculosis
Authors: Oloko-Oba Mustapha , Viriri Serestina
Published: December 2021

Tuberculosis (TB) remains a life‐threatening disease and is one of the leading causes of mortality in developing regions due to poverty and inadequate medical resources. Tuberculosis is medicable, but it necessitates early diagnosis through reliable screening techniques. Chest X‐ray is a recommended screening procedure for identifying pulmonary abnormalities. Still, this recommendation is not enough without experienced radiologists to interpret the screening results, which forms part of the problems in rural communities. Consequently, various computer‐aided diagnostic systems have been developed for the automatic detection of tuberculosis. However, their sensitivity and accuracy are still significant challenges that require constant improvement due to the severity of the disease. Hence, this study explores the application of a leading state‐of‐the‐art convolutional neural network (EfficientNets) model for the classification of tuberculosis. Precisely, five variants of EfficientNets were fine‐tuned and implemented on two prominent and publicly available chest X‐ray datasets (Montgomery and Shenzhen). The experiments performed show that EfficientNet‐B4 achieved the best accuracy of 92.33% and 94.35% on both datasets. These results were then improved through Ensemble learning and reached 97.44%. The performance recorded in this study portrays the efficiency of fine‐tuning EfficientNets on medical imaging classification through Ensemble.
The Quest to Define and Target Cellular Senescence in Cancer
Authors: Wang Boshi , Demaria Marco
Published: December 2021

Cellular senescence represents a double-edged sword in cancer and its therapy. On one side, senescence-associated growth arrest and immunomodulatory properties exert potent antimalignant functions. On the other side, senescence bypass and secretory phenotype are associated with tumor progression and relapse. Recent studies have demonstrated the enormous potential to combine pro- to antisenescence interventions as a new anticancer approach. However, the heterogeneity of senescence-associated features makes definition and targeting of therapy-induced senescent cells a challenging task. Here, we describe these challenges and discuss how to exploit senescence-associated features to improve treatment efficacy and tolerability.
Coiled-Coil Domain: Uncoiling Tumor Suppression by BRCA1
Authors: Mishra Arun P. , Sahu Sounak , Sharan Shyam K.
Published: December 2021

The coiled-coil domain of BRCA1 is essential for its interaction with partner and localizer of BRCA2 (PALB2). In mice, loss of this interaction is known to result in Fanconi anemia–associated phenotypes. In a study published in this issue of Cancer Research, Pulver and colleagues from the Jonkers lab have generated a mouse model with a leucine to proline change in codon 1363 in the coiled-coil domain of BRCA1 (Brca1LP), which disrupts its binding with PALB2. Unlike the previously reported viable coiled-coil defective mice, homozygous Brca1LP/LP mutant mice die during embryogenesis. The authors examined the role of the BRCA1/PALB2 interaction on mammary tumorigenesis and reported increased incidence of mammary tumors that are carcinosarcomas or sarcomatoids, unlike the adenocarcinomas that are characteristic mammary tumor types associated with loss of Brca1 and Trp53 in mice. The findings reveal the relevance of the coiled-coil domain in mammary tumor suppression by BRCA1.

See related article by Pulver et al., p. 6171
RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors
Authors: Roulston Anne , Zimmermann Michal , Papp Robert , Skeldon Alexander , Pellerin Charles , Dumas-Bérube Émilie , Dumais Valerie , Dorich Stéphane , Fader Lee D. , Fournier Sara , Li Li , Leclaire Marie-Eve , Yin Shou Yun , Chefson Amandine , Alam Hunain , Yang William , Fugère-Desjardins Chloe , Vignini-Hammond Sabrina , Skorey Kathryn , Mulani Amina , Rimkunas Victoria , Veloso Artur , Hamel Martine , Stocco Rino , Mamane Yael , Li Zuomei , Young Jordan T.F. , Zinda Michael , Black W. Cameron
Published: December 2021

Ataxia telangiectasia and Rad3-related (ATR) kinase protects genome integrity during DNA replication. RP-3500 is a novel, orally bioavailable clinical-stage ATR kinase inhibitor (NCT04497116). RP-3500 is highly potent with IC50 values of 1.0 and 0.33 nmol/L in biochemical and cell-based assays, respectively. RP-3500 is highly selective for ATR with 30-fold selectivity over mammalian target of rapamycin (mTOR) and more than 2,000-fold selectivity over ataxia telangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK), and phosphatidylinositol 3-kinase alpha (PI3Kα) kinases. In vivo, RP-3500 treatment results in potent single-agent efficacy and/or tumor regression in multiple xenograft models at minimum effective doses (MED) of 5 to 7 mg/kg once daily. Pharmacodynamic assessments validate target engagement, with dose-proportional tumor inhibition of phosphorylated checkpoint kinase 1 (pCHK1) (IC80 = 18.6 nmol/L) and induction of phosphorylated H2A.X variant histone (γH2AX), phosphorylated DNA-PK catalytic subunit (pDNA-PKcs), and phosphorylated KRAB-associated protein 1 (pKAP1). RP-3500 exposure at MED indicates that circulating free plasma levels above the in vivo tumor IC80 for 10 to 12 hours are sufficient for efficacy on a continuous schedule. However, short-duration intermittent (weekly 3 days on/4 days off) dosing schedules as monotherapy or given concomitantly with reduced doses of olaparib or niraparib, maximize tumor growth inhibition while minimizing the impact on red blood cell depletion, emphasizing the reversible nature of erythroid toxicity with RP-3500 and demonstrating superior efficacy compared with sequential treatment. These results provide a strong preclinical rationale to support ongoing clinical investigation of the novel ATR inhibitor, RP-3500, on an intermittent schedule as a monotherapy and in combination with PARP inhibitors as a potential means of maximizing clinical benefit.
NKG7 Is a T-cell–Intrinsic Therapeutic Target for Improving Antitumor Cytotoxicity and Cancer Immunotherapy
Authors: Wen Ti , Barham Whitney , Li Ying , Zhang Henan , Gicobi Joanina K. , Hirdler Jacob B. , Liu Xin , Ham Hyoungjun , Peterson Martinez Kodi E. , Lucien Fabrice , Lavoie Roxane R. , Li Hu , Correia Cristina , Monie Dileep D. , An Zesheng , Harrington Susan M. , Wu Xiaosheng , Guo Ruifeng , Dronca Roxana S. , Mansfield Aaron S. , Yan Yiyi , Markovic Svetomir N. , Park Sean S. , Sun Jie , Qin Hong , Liu Minetta C. , Vasmatzis George , Billadeau Daniel D. , Dong Haidong
Published: December 2021

Cytotoxic CD8+ T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. By evaluating human CD8+ T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function. Single-cell RNA-sequencing analysis of peripheral CD8+ T cells from patients treated with anti–PD-1 therapy showed that cells from nonresponders exhibited decreased expression of the cytolytic granule-associated molecule natural killer cell granule protein-7 (NKG7). Functional assays revealed that reduced NKG7 expression altered cytolytic granule number, trafficking, and calcium release, resulting in decreased CD8+ T-cell–mediated killing of tumor cells. Transfection of T cells with NKG7 mRNA was sufficient to improve the tumor-cell killing ability of human T cells isolated from nonresponders and increase their response to anti–PD-1 or anti–PD-L1 therapy in vitro. NKG7 mRNA therapy also improved the antitumor activity of murine tumor antigen–specific CD8+ T cells in an in vivo model of adoptive cell therapy. Finally, we showed that the transcription factor ETS1 played a role in regulating NKG7 expression. Together, our results identify NKG7 as a necessary component for the cytotoxic function of CD8+ T cells and establish NKG7 as a T-cell–intrinsic therapeutic target for enhancing cancer immunotherapy.

See related article by Li et al., p. 154.
Pulling the Strings of the Tumor Microenvironment
Authors: Burrello Claudia , de Visser Karin E.
Published: December 2021

Macrophages are in the spotlight of cancer immunotherapy research because they exert a wide spectrum of protumorigenic functions. In this issue, Pfirschke and colleagues report that macrophage targeting pulls the strings of the tumor microenvironment, ultimately leading to a coordinated antitumorigenic immune reaction in a lung carcinoma mouse model.

See related article by Pfirschke et al., p. 40. (4).
Application of 16 G Biopsy Needle in Transperineal Template-Guided Prostate Biopsy
Authors: Ding Xue-fei , Luan Yang , Xia An-le , Zhu Liang-yong , Xiao Qin , Chen Ji , Chen Hao-peng , Han Yue-xing , Liu Zhong
Published: December 2021

Background: The aim of this study was to evaluate the clinical value of 16 G biopsy needle in transperineal template-guided prostate biopsy (TTPB), compared with 18 G biopsy needle. Methods: The patients who underwent TTPB from August 2020 to February 2021 were randomized into 2 groups using a random number table. The control group (n = 65) and the observation group (n = 58) performed biopsy with 18 G (Bard MC l820) and 16 G (Bard MC l616) biopsy needles, respectively. Positive rate of biopsy, Gleason score, complications, and pain score were statistically analyzed. Results: The age, prostate volume, PSA, and the number of cores were comparable between the 2 groups. The positive rate of biopsy in the observation group was 68.9% (40/58), meanwhile the control group was 46.2% (30/65). There was statistical difference between the 2 groups (p = 0.011). Gleason score of the observation group (8 [7–9]) was higher than that of the control group (8 [6–9]) (p = 0.038). There was no significant difference in pain score and complications including hematuria, hematospermia, perineal hematoma, infection, and urinary retention between the 2 groups (p > 0.05). Conclusions: 16 G biopsy needle significantly improved the positive rates and accurately evaluate the nature of lesions, meanwhile did not increase the incidence of complications compared with 18 G biopsy needle.
Surgery in Autoimmune Pancreatitis
Authors: Nikolic Sara , Ghorbani Poya , Pozzi Mucelli Raffaella , Ghazi Sam , Baldaque-Silva Francisco , Del Chiaro Marco , Sparrelid Ernesto , Verbeke Caroline S. , Löhr J.-Matthias , Vujasinovic Miroslav
Published: December 2021

Introduction: Autoimmune pancreatitis (AIP) is a disease that may mimic malignant pancreatic lesions both in terms of symptomatology and imaging appearance. The aim of the present study is to analyze experiences of surgery in patients with AIP in one of the largest European cohorts. Patients and Methods: We performed a single-center retrospective study of patients diagnosed with AIP at the Department of Abdominal Diseases at Karolinska University Hospital in Stockholm, Sweden, between January 2001 and October 2020. Results: There were 159 patients diagnosed with AIP, and among them, 35 (22.0%) patients had surgery: 20 (57.1%) males and 15 (42.9%) females; median age at surgery was 59 years (range 37–81). Median follow-up period after surgery was 50 months (range 1–235). AIP type 1 was diagnosed in 28 (80%) patients and AIP type 2 in 7 (20%) patients. Malignant and premalignant lesions were diagnosed in 8 (22.9%) patients for whom AIP was not the primary differential diagnosis, but in all cases, it was described as a simultaneous finding and recorded in retrospective analysis in histological reports of surgical specimens. Conclusions: Diagnosis of AIP is not always straightforward, and in some cases, it is not easy to differentiate it from the malignancy. Surgery is generally not indicated for AIP but might be considered in patients when suspicion of malignant/premalignant lesions cannot be excluded after complete diagnostic workup.
A expressão das emoções no homem e nos animais, de Charles Darwin: algumas considerações
Authors: Castilho Fernando Moreno
Published: December 2021

Como é sabido, a obra mais conhecida de Charles Robert Darwin (1809-1882) é o Origin of species (1859) que teve seis edições. Contudo, ele publicou também outras obras, dentre elas, The expression of the emotions in man and animals (1872). Nesta obra, ele tratou de aspectos comportamentais de antepassados primitivos do homem e outros animais, segundo os mecanismos evolutivos propostos no Origin of species (1859). O objetivo do presente artigo é discutir sobre alguns aspectos relacionados à mesma. Nesse sentido, comentaremos brevemente sobre seu conteúdo, traduções, edições e alguns desdobramentos posteriores. Este estudo levou à conclusão de que The expression of the emotions in man and animals foi relevante no conjunto de obras de Darwin, considerando a grande quantidade de impressões e traduções para os diferentes idiomas dessa obra. Além disso, levando em conta a repercussão das ideias nela contidas em estudos posteriores como aqueles feitos por Konrad Lorenz (1903-1989) e Nikolaas Tinbergen (1907-1988) e suas contribuições para a emergência da disciplina Etologia, voltada ao estudo do comportamento animal, na década de 1960.
Revisitando a história da genética clássica: dos caracteres unitários ao gene (1900-1926)
Authors: Durigan Larissa Nunes , Martins Lilian Al-Chueyr Pereira
Published: December 2021

O presente artigo se refere ao período da chamada genética clássica. Seu objetivo é discutir sobre as concepções e terminologia aplicadas ao material hereditário entre 1900 (“redescoberta” do trabalho de Mendel) e a publicação do livro The theory of the gene (1926) de Thomas Hunt Morgan (1866-1945), procurando averiguar se houve mudanças em relação a esses aspectos durante o período. O foco de nossa análise são as contribuições de dois grupos: o grupo britânico liderado por William Bateson (1861-1926) e o grupo norte-americano, liderado por Morgan. No período estudado, a terminologia foi mudando de “fator”, “caracteres”, “caracteres-unitários” e “gene”, que foi adotado a partir de 1926. Apesar de Bateson e Morgan considerarem que os agentes hereditários estivessem nas células germinativas, desconheciam sua composição. Esta pesquisa mostrou que durante o estabelecimento de uma nova área de estudo vão ocorrendo modificações em relação à terminologia empregada bem como à conotação dos termos, até que haja um consenso por parte da comunidade científica que os adote.
A natureza humana e o altruísmo em Sociobiology: the new synthesis de Edward Wilson
Authors: Pinho Tomás  Antonio Freire de
Published: December 2021

O conceito de natureza humana é alvo de discussão entre especialistas das ciências humanas e naturais. Um marco incontornável do debate é o livro Sociobiology: the new synthesis de Edward Wilson e sua interpretação darwinista do comportamento humano. O presente artigo investiga os principais instrumentos teóricos e conhecimentos científicos usados pelo autor para realizar esse tipo de interpretação. Defendemos que, ao fazê-lo, Wilson almeja dialogar com especialistas de outras áreas e “biologizar” as humanidades. Exploraremos em particular como o autor explica a natureza humana a partir do dilema altruísmo-egoísmo. Identificamos que a análise de Wilson sobre o comportamento humano assume a forma de premissas e inferências envolvendo a ubiquidade, a origem genética, a adaptação e o tratamento matemático.
Quatro atos para ler e agir: a obra de teatro na perspectiva de ensino dos (multi)letramentos
Authors: Marega Larissa Minuesa Pontes , Vinha Everton Luis Paulino , Aquino Zilda Gaspar de Oliveira
Published: December 2021

Neste artigo, propomos proceder à correlação de teorias do ensino de literatura e dos multiletramentos, a partir de atividades em torno de uma obra teatral. Contextualizamos este estudo no bojo das discussões que analisam e que justificam a presença do livro na escola. A partir deste preâmbulo, buscamos embasamento teórico voltado ao letramento literário, à concepção de texto dramático e à multimodalidade. Metodologicamente, apresentamos a produção de uma sequência de ensino da leitura do texto A megera domada, de William Shakespeare, para o ano final do ensino fundamental. Os resultados apontam para a importância de procedermos a reflexões em torno do ensino de literatura, especificamente, da obra de teatro, sob uma perspectiva de leitura integral e multimodal, tendo em vista que estas podem promover a ampliação dos saberes e das competências aí implicadas.