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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： md Entaz Bahar Hyun Joon Kim Deok Ryong Kim Department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(rafi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of rafi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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Research on Interpolation Method for Missing Electricity Consumption Data

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Computers, Materials & Continua 2024年第2期78卷 2575-2591页

作者： Junde Chen Jiajia Yuan Weirong Chen Adnan Zeb md Suzauddola Yaser A.Nanehkaran Department of Electronic Commerce Xiangtan UniversityXiangtan411105China School of Information Engineering Yancheng Teachers UniversityYancheng224000China Department of Information and Electrical Engineering Ningde Normal UniversityNingde352100China College of Engineering Southern University of Science and TechnologyShenzhen518005China School of Informatics Xiamen UniversityXiamen361005China

Missing value is one of the main factors that cause dirty *** high-quality data,there will be no reliable analysis results and precise ***,the data warehouse needs to integrate high-quality data *** the power system,the electricity consumption data of some large users cannot be normally collected resulting in missing data,which affects the calculation of power supply and eventually leads to a large error in the daily power line loss *** the problem of missing electricity consumption data,this study proposes a group method of data handling(GmdH)based data interpolation method in distribution power networks and applies it in the analysis of actually collected electricity ***,the dependent and independent variables are defined from the original data,and the upper and lower limits of missing values are determined according to prior knowledge or existing data *** missing data are randomly interpolated within the upper and lower ***,the GmdH network is established to obtain the optimal complexity model,which is used to predict the missing data to replace the last imputed electricity consumption *** last,this process is implemented iteratively until the missing values do not *** a relatively small noise level(α=0.25),the proposed approach achieves a maximum error of no more than 0.605%.Experimental findings demonstrate the efficacy and feasibility of the proposed approach,which realizes the transformation from incomplete data to complete ***,this proposed data interpolation approach provides a strong basis for the electricity theft diagnosis and metering fault analysis of electricity enterprises.

关键词： Data interpolation GmdH electricity consumption data distribution system

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Energy Harvesting in the Wake of An Inverted C-Shaped Bluff Body

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China Ocean Engineering 2024年第1期38卷 68-80页

作者： WANG Jun-lei LI Shen-fang md.Mahbub ALAM ZHU Hong-jun HU Guo-biao School of Mechanical and Power Engineering Zhengzhou UniversityZhengzhou 450000China Center for Turbulence Control Harbin Institute of Technology(Shenzhen)Shenzhen 518055China State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Southwest Petroleum UniversityChengdu 610500China Internet of Things Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China

This paper proposes a novel wake-induced vibration(WIV)-based energy harvesting system consisting of two bluff *** inverted C-shaped bluff body is stationary installed at the upstream position to generate an interference wake street,and a cylinder bluff body equipped with a transducer is elastically suspended at the downstream position to harness WIV *** hydrodynamics and energy harvesting(EH)performance of the proposed system are investigated via experimental *** reduced velocity(U*)ranging from 2 to 14(the corresponding Reynolds number ranging from 15100 to 106200)is considered in the present *** is found that the wake generated by the inverted C-shaped bluff body significantly affects the EH *** the opening angle(α)of the C-shaped bluff body increases the vibration amplitude of the downstream cylinder,thereby increasing the harvested *** the spacing(L)between two bluff bodies is two times the cylinder diameter(D),the wake-induced vibration(WIV)mode is observed,while the combined WIV and wake galloping(WG)mode occurs whenαis 150°,and L equals 3D or *** average drag coefficient becomes negative when L is 2D,3D,or *** carefully configuring a C-shaped bluff body,the wake generated by it can bring an augmenting effect on the vibration of the downstream EH *** example,the RMS power output of the proposed EH system reaches a maximum of 0.31 W at U*=8 and L=4D,which is 300%greater than that of its traditional ***,after a number of case stud-ies,it is identified that the proposed EH system can achieve the best performance whenαis 150°and L=2D.

关键词： wake-induced vibration vortex-induced vibration galloping energy harvesting bluff body

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Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

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World Journal of Diabetes 2024年第5期15卷 853-866页

作者： md Abdul Alim Al-Bari Nicholas Peake Nabil Eid Department of Pharmacy University of RajshahiRajshahi 6205Bangladesh Biosciences and Chemistry and Biomolecular Research Centre Sheffield Hallam UniversitySheffield S11WBUnited Kingdom Department of Anatomy Division of Human BiologySchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor *** infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and ***[particularly type 2 DM(T2DM)]and TB have converged making their control even more *** contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive *** a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both *** are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and *** addition,autophagy may play a role in these ***,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double *** effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.

关键词： Diabetes mellitus Tuberculosis Coinfections Comorbidity Drug-drug interactions Autophagy Treatment challenges

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Development of small intestinal barrier function and underlying mechanism in Chinese indigenous and Duroc piglets during suckling and weaning periods

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Animal Nutrition 2024年第1期16卷 429-442页

作者： Sujuan Ding Yating Cheng md Abul Kalam Azad Qian Zhu Pan Huang Xiangfeng Kong CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China

This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning *** black(TB),Xiangcun black(XB),and Duroc(DR)piglets(10 litters per breed;half male and half female)were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1,10,21(weaned),and 24(3 d after weaning)d *** results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement.D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower(P<0.01)than that of DR piglets,as well as the ileal diamine oxidase level at 1 d *** expression level of mucin 1 was higher(P<0.05)in the ileum of TB and XB piglets than that of DR piglets,and it was the highest in the ileum of TB piglets at 21 d *** expression levels of mucin 2 and mucin 13 were higher(P<0.10)in TB and XB piglets than those of DR piglets at 21 d old,whereas mucin2 and mucin 13 in the ileum of TB and XB piglets were higher(P<0.05)than those of DR piglets at 24 d *** and XB piglets had a lower relative abundance of Escherichia_Shigella at 21 and 24 d old,but they had higher Streptococcus at 1 and 24 d old than DR piglets(P<0.01).Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation,steroid biosynthesis,and bile acid ***,these findings suggest that different pig breeds present differences in the development of the small intestinal barrier *** with DR piglets,TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after ***,intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.

关键词： Chinese indigenous piglet Duroc piglet Immune function Intestinal barrier function Weaning stress

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Complete separation of the urinary tract from proximal rectum during PSARP surgery: our experience with the novel technique

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World Journal of Pediatric Surgery 2024年第1期7卷 66-69页

作者： md Samiul Hasan md Nazmul Islam Refoyez Mahmud Umama Huq Ashrarur Rahman Pediatric Surgery Bangladesh Shishu Hospital and InstituteDhakaBangladesh

Anorectal malformation(ARM)is a frequently occurring surgical condition in neonates,with a prevalence of 1 in 4000 live births.'In boys with this anomaly,the rectum and urinary tract share a common wall for some distance,often ending up in fistulous *** goals of definite reconstruction are to separate the rectum from the urinary tract without injuring the urethra and mobilizing the rectum to the perineum within the muscle *** the rectum and the urinary tract is the most critical part of this operation and is associated with a significant risk of urinary tract injury.2-5 The original procedure described by Pena and Devries involves multiple stay sutures on the rectal mucosa just above the fistula,lifting the mucosa and continuing a submucosal dissection up to the prostate,where the entire thickness of the intestine can be separated from the urinary tract.

关键词： urinary rectum intestine

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Enhancing Telemarketing Success Using Ensemble-Based Online Machine Learning

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Big Data Mining and Analytics 2024年第2期7卷 294-314页

作者： Shahriar Kaisar md Mamunur Rashid Abdullahi Chowdhury Sakib Shahriar Shafin Joarder Kamruzzaman Abebe Diro Department of Information Systems and Business Analytics RMIT UniversityMelbourne 3000Australia School of Engineering and Technology Central Queensland UniversityRockhampton 4700Australia Faculty of Engineering Computer and Mathematical ScienceUniversity of AdelaideAdelaide 5005Australia Centre for Smart Analytics Federation University AustraliaBallarat 3350Australia School of Accounting Information Systems and Supply ChainRMIT UniversityMelbourne 3000Australia

Telemarketing is a well-established marketing approach to offering products and services to prospective *** effectiveness of such an approach,however,is highly dependent on the selection of the appropriate consumer base,as reaching uninterested customers will induce annoyance and consume costly enterprise resources in vain while missing interested *** introduction of business intelligence and machine learning models can positively influence the decision-making process by predicting the potential customer base,and the existing literature in this direction shows promising ***,the selection of influential features and the construction of effective learning models for improved performance remain a ***,from the modelling perspective,the class imbalance nature of the training data,where samples with unsuccessful outcomes highly outnumber successful ones,further compounds the problem by creating biased and inaccurate ***,customer preferences are likely to change over time due to various reasons,and/or a fresh group of customers may be targeted for a new product or service,necessitating model retraining which is not addressed at all in existing works.A major challenge in model retraining is maintaining a balance between stability(retaining older knowledge)and plasticity(being receptive to new information).To address the above issues,this paper proposes an ensemble machine learning model with feature selection and oversampling techniques to identify potential customers more accurately.A novel online learning method is proposed for model retraining when new samples are available over *** newly introduced method equips the proposed approach to deal with dynamic data,leading to improved readiness of the proposed model for practical adoption,and is a highly useful addition to the *** experiments with real-world data show that the proposed approach achieves excellent results in all cases(e.g.,98.6

关键词： machine learning online learning oversampling telemarketing imbalanced dataset ensemble model

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Japanese Sign Language Recognition by Combining Joint Skeleton-Based Handcrafted and Pixel-Based Deep Learning Features with Machine Learning Classification

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 2605-2625页

作者： Jungpil Shin md.Al Mehedi Hasan Abu Saleh Musa Miah Kota Suzuki Koki Hirooka School of Computer Science and Engineering The University of AizuAizuwakamatsu965-8580Japan Department of Computer Science&Engineering Rajshahi University of Engineering&TechnologyRajshahi6204Bangladesh

Sign language recognition is vital for enhancing communication accessibility among the Deaf and hard-of-hearing *** Japan,approximately 360,000 individualswith hearing and speech disabilities rely on Japanese Sign Language(JSL)for ***,existing JSL recognition systems have faced significant performance limitations due to inherent *** response to these challenges,we present a novel JSL recognition system that employs a strategic fusion approach,combining joint skeleton-based handcrafted features and pixel-based deep learning *** system incorporates two distinct streams:the first stream extracts crucial handcrafted features,emphasizing the capture of hand and body movements within JSL ***,a deep learning-based transfer learning stream captures hierarchical representations of JSL gestures in the second ***,we concatenated the critical information of the first stream and the hierarchy of the second stream features to produce the multiple levels of the fusion features,aiming to create a comprehensive representation of the JSL *** reducing the dimensionality of the feature,a feature selection approach and a kernel-based support vector machine(SVM)were used for the *** assess the effectiveness of our approach,we conducted extensive experiments on our Lab JSL dataset and a publicly available Arabic sign language(ArSL)*** results unequivocally demonstrate that our fusion approach significantly enhances JSL recognition accuracy and robustness compared to individual feature sets or traditional recognition methods.

关键词： Japanese Sign Language(JSL) hand gesture recognition geometric feature distance feature angle feature GoogleNet

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 265-271页

作者： Yuen Keat Gan Shiivaa Manjare Birapadian Muhammad Irfan Abdul Jalal Norshamsiah md Din Department of Ophthalmology Faculty of MedicineUniversiti Kebangsaan MalaysiaKuala Lumpur 56000Malaysia UKM Molecular Biology Institute Universiti Kebangsaan MalaysiaKuala Lumpur 56000Malaysia Hospital Canselor Tuanku Muhriz Jalan Yaacob LatifBandar Tun RazakKuala Lumpur 56000Malaysia

AIM:To report the outcome of Baerveldt glaucoma implant(BGI)with Supramid©ripcord use in neovascular glaucoma(NVG).METHODS:We retrospectively evaluated the surgical outcome of the BGI with Supramid©3/0 ripcord stent in patients with *** tube ligation or venting slits were *** was removed after 3mo if the target intraocular pressure(IOP)was not *** success was defined as IOP≤21 mm Hg with(qualified success)or without IOP-lowering medications(complete success).RESULTS:Twenty-six eyes from 24 patients were included in the *** median duration of follow-up was 4[interquartile range(IQR)=1-5]y,ranging from 0.5 to *** decreased by a mean of 24.2 mm Hg(59.7%);from a mean of 40.5±12.6 mm Hg at baseline to 16.3±11.9 mm Hg,P≤*** number of glaucoma medications reduced from a median of 5(IQR=5-6)to 1(IQR=0-2,P≤0.001)at the final *** success rates were 88.0%at 1y,34.8%at 3y,66.7%at 4y,and 50%at *** phase(HP)in the first 3mo occurred in 15/26 eyes(57.7%)with a mean IOP of 31.1 mm ***:BGI with Supramid©ripcord stent gives close to 90%of the overall survival rate at the final follow-up without significant early ***,early HP is still a challenge.

关键词： neovascular glaucoma Supramid ripcord stent Baerveldt glaucoma implant

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Genome-Wide Analysis for Yield-Related Agronomic and Biochemical Traits of Chinese and Bangladeshi Grass Pea Genotypes Using SSR Markers

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Phyton-International Journal of Experimental Botany 2024年第8期93卷 1781-1804页

作者： md.Mosiur Rahman md.Ruhul Quddus Quanle Xu Muhammad Malek Hossain Rong Liu Mengwei Li Xin Yan Guan Li Yishan Ji Chenyu Wang Ashutosh Sarker Tao Yang Xuxiao Zong md.Monoar Hossain Saleh Alfarraj Mohammad Javed Ansari Sagar Maitra Akbar Hossain Institute of Crop Sciences Chinese Academy of Agricultural Sciences(CAAS)Beijing100081China Pulses Research Center Bangladesh Agricultural Research Institute(BARI)Gazipur1701Bangladesh Hybrid Rice Division Bangladesh Rice Research Institute(BRRI)Gazipur1701Bangladesh Northwest Agriculture&Forestry University Yangling712199China International Center for Agricultural Research in the Dry Areas(ICARDA) New Delhi110012India Wheat Breeding Division Bangladesh Wheat and Maize Research InstituteDinajpur5200Bangladesh Zoology Department College of ScienceKing Saud UniversityRiyadh11451Saudi Arabia Department of Botany Hindu College Moradabad(Mahatma Jyotiba Phule Rohilkhand UniversityBareilly)Moradabad244001India Department of Agronomy and Agroforestry Centurion University of Technology and ManagementOdisha761211India Soil Science Division Bangladesh Wheat and Maize Research InstituteDinajpur5200Bangladesh

Grass pea(Lathyrus sativus L.)is an imperative food crop cultured in dryland agricultural *** is a vital source of dietary protein to millions of populaces living in low-income countries in South-East Asia and *** study highlights the improvement of genomic properties and their application in marker-trait relationships for 17 yield-related characters in 400 grass pea genotypes from China and *** characters were assessed via 56 polymorphic markers using general linear model(GLM)(P+G+Q)and mixed linear model(MLM)(P+G+Q+K)in the tassel software based on the linkage disequilibrium and population structure *** structure analysis showed two major groups and one admixed group in the *** significant loci pairs of linkage disequilibrium(LD)mean value(D′)was 0.479.A total of 99 and 61 marker-trait associations in GLM and MLM models allied to the 17 traits were accepted at a 5%level of *** these markers,21 markers were associated with more than one trait;12 marker-trait associations passed the Bonferroni correction *** models found six markers C41936,C39067,C34100,C47146,C47638,and C43047 significantly associated with days to maturity,flower color,plant height,and seed per pod were detected in the Hebei and Liaoyang location(p≤0.01),and the interpretation rate(R^(2)value)11.2%to 43.6%.Conferring to the consequences,the association analysis methodology may operative system for quantitative,qualitative,and biochemical traits related to gene position mapping and support breeders in improving novel approaches for advancing the grass pea quality.

关键词： Grass pea dryland agriculture genome-wide association yield contributing traits SSR markers

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