Industry 4.0 technologies impact on supply chain sustainability.
\r\n\tThere are different types of multiple pregnancies: fraternal twins, identical twins, triplets, and higher-order multiples. Symptoms of multiple pregnancies are larger uterus than expected for the date in pregnancy, increased morning sickness, increased appetite, and excessive weight gain. In this book, we will examine the clinical aspects of multiple pregnancies and management. Also, we will examine the management of cases of twins including antenatal care, delivery, and postpartum.
",isbn:"978-1-80356-198-1",printIsbn:"978-1-80356-197-4",pdfIsbn:"978-1-80356-199-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"70396c6f5f2928c422c1eaf6d33c6269",bookSignature:"Prof. Hassan S Abduljabbar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11732.jpg",keywords:"Multiple Pregnancies, Twins, Physiology, Incidence, Epidemiology, Demographics, Predisposing Factors, Prenatal Diagnosis, Zygosity, Complications, Management of Birth, Antenatal Care",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 4th 2022",dateEndSecondStepPublish:"May 4th 2022",dateEndThirdStepPublish:"July 3rd 2022",dateEndFourthStepPublish:"September 21st 2022",dateEndFifthStepPublish:"November 20th 2022",remainingDaysToSecondStep:"16 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Professor of Obstetrics and Gynecology at King Abdulaziz University, Saudi Arabia, consultant, clinician, researcher, editor, and referee of many international scientific medical journals. Dr. Abduljabbar is president of the Saudi Society of Obstetrics and Gynecology and the president of the Federation of Arab Gynecology Obstetrics Societies. He has published more than seventy-five scientific articles and edited several books.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"68175",title:"Prof.",name:"Hassan",middleName:"S",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar",profilePictureURL:"https://mts.intechopen.com/storage/users/68175/images/system/68175.png",biography:"Hassan S. Abduljabbar, MD, FRCSC, American Board Diplomate, is a professor at the College of Medicine, King Abdulaziz\nUniversity, Saudi Arabia. He is also the president of the Saudi Society of Obstetrics and Gynecology and the Federation of Arab\nGynecology Obstetric Societies (FAGOS). He is a referee for\nmany international scientific journals. He is also an examiner for\ngraduate degrees as well as for the Saudi and Arab board exams.\nDr. Abduljabbar has published more than fifty articles and edited three books.",institutionString:"Dr. Erfan & Bagedo General Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"King Abdulaziz University",institutionURL:null,country:{name:"Saudi Arabia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"2013",title:"Steroids",subtitle:"Clinical Aspect",isOpenForSubmission:!1,hash:"31dfd32a77f71bc348d7922af48b8e62",slug:"steroids-clinical-aspect",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/2013.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"814",title:"Steroids",subtitle:"Basic Science",isOpenForSubmission:!1,hash:"74304f5d822f8f45d4b48a0e00ebd375",slug:"steroids-basic-science",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/814.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5937",title:"Obstetrics",subtitle:null,isOpenForSubmission:!1,hash:"092197b1191815505a23e7dd1c9edde6",slug:"obstetrics",bookSignature:"Hassan Salah Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/5937.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10485",title:"Fibroids",subtitle:null,isOpenForSubmission:!1,hash:"64ad14b1aba83e47fb100fa63e21533e",slug:"fibroids",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/10485.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7132",title:"Complications of Pregnancy",subtitle:null,isOpenForSubmission:!1,hash:"d2bdac8e99a71feab10bd0b9e1063bb9",slug:"complications-of-pregnancy",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/7132.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10721",title:"Preeclampsia",subtitle:null,isOpenForSubmission:!1,hash:"eb38592b7a656d02dd6b28c34e43de32",slug:"preeclampsia",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/10721.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7969",title:"Leiomyoma",subtitle:null,isOpenForSubmission:!1,hash:"659a9fef0f90168b2184c86af85d3a42",slug:"leiomyoma",bookSignature:"Hassan Abduljabbar",coverURL:"https://cdn.intechopen.com/books/images_new/7969.jpg",editedByType:"Edited by",editors:[{id:"68175",title:"Prof.",name:"Hassan",surname:"Abduljabbar",slug:"hassan-abduljabbar",fullName:"Hassan Abduljabbar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. 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Dr. Katsusaburo Yamagiwa, a Japanese pathologist, is famous for the experiment in which coal tar was applied to rabbit ears to induce carcinogenesis in 1915. He was also a candidate for the Nobel Prize in Medicine. The following year, his student Dr. Akira Fujinami was appointed to study carcinogenesis in Germany for 4 years. After returning to Japan, in 1900, he became the first professor at the Department of Pathology, Kyoto Imperial University Medical College. In 1905, he started studying chicken tumors, and as early as 1910, he established a chicken breast tumor transplant system. He had suggested the possibility of carcinogenesis by filterable pathogens, which were later called Fujinami sarcoma virus (FSV). He is also well known for the discovery of Japan schistosomiasis.
\nInterestingly, in the same year, Peyton Rous, who was studying at the Rockefeller laboratory in the United States, also established the avian sarcoma transplant system. In 1966, Rous received the Nobel Prize in Physiology and Medicine for the discovery of carcinogenic viruses. Hanafusa et al. elucidated the FSV gene structure and identified the similarity with the Rous sarcoma virus gene structure [1]. Both FSV and Rous sarcoma virus belong to the same alpha-retrovirus. FSV has the oncogene v-fps in its genome [2]. It also has long terminal repeats (LTRs) at the ends of the genome that stabilizes as parts of the host cell genome when inserted into host mesenchymal cells after reverse transcription. In addition to the host cell division, the viral genome also replicates during the DNA replication cycle. Tyrosine-protein kinase transforming protein Fps encoded by v-fps has the ability to induce transformation by promoting tyrosine phosphorylation of the PDGFbeta receptor [3, 4]. Thus, the Japanese scientists have greatly contributed to the field during the early days of oncology research.
\nRetroviral integration is a type of insertional mutagenesis. Integration processes are widely studied from biochemistry, and their molecular mechanisms are elucidated. Retrovirus-induced tumorigenesis is divided into two types. First, the retroviral genome carries the oncogene such as
The retroviral promoter and enhancer elements in LTRs originally promote the expression of retroviral genes such as
A common structure of the retroviral genome. Plus strand RNA is shown. R, terminal redundant sequence; U5, unique 5′ sequence; PBS, tRNA primer-binding site; gag, group-specific antigen encoding capsid protein MA (matrix), CA, capsid protein; NC, nucleocapsid; pro, protease; pol, polymerase including reverse transcriptase (RT) and integrase (IN) catalyzing integration; env, envelope glycoproteins; U3, unique 3′ sequence. U3, R, and U5 are duplicated at both ends of the DNA provirus genome in the host genome sequence to form the long terminal repeat (LTR). LTR is essential for the initiation of viral DNA syntheses by reverse transcription as well as the integration of proviral DNA and the regulation of viral gene expression.
To date, extensive research has been conducted on target motifs for retroviral insertion to better understand tumorigenesis, neuronal damage, aging, and immunodeficiency including acquired immunodeficiency syndrome (AIDS). Retroviral-host DNA interactions support specific host DNA structures [16, 17, 18, 19, 20, 21] but are less likely to be inserted into particular base sequences. Previous studies on human immunodeficiency virus (HIV)-1 insertion have shown that the insertion sites are distributed in 10-bp cycles on the nucleosome surface of the outward DNA major groove of chromatin [16, 22].
\nHPV is one of the most common viruses that infect more than half women once in life through sexual intercourse. It is a small DNA virus with approximately 8000 bp circular double-stranded DNA in its genome. The viral particle has icosahedral capsid structure as its outer shell. The virus has been known to be involved in the development of cervical, anal, and vaginal cancer and condyloma acuminatum. Many types of HPV are known, and high-risk HPV based on this cancer risk is concentrated in specific subgroups epidemiologically. In particular, types 16 and 18 have high carcinogenic risks of cervical intraepithelial neoplasia (CIN) and cancer. Type 16 has been detected in the Japanese 5-year-old girls [23]. High-risk group (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) causes bladder cancer and pharyngeal cancer in addition to vulvar and cervical cancer. Low-risk group (HPV2, 27, and 57) causes verruca vulgaris that develops in the hands and feet [24].
\nHPV genome has early genes (E1, E2, E4, E5, E6, and E7) and late genes encoding viral capsid proteins (L1 and L2). E6 and E7 are considered to be involved in carcinogenesis. E6 binds to a tumor-suppressor gene product p53 and degrades p53 through promoting the ubiquitination. It also contributes to carcinogenesis by reactivating telomerase reverse transcriptase (hTERT) and degrading proteins with PDZ domain [shared by—post-synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and Zonula occludens-1 protein (zo-1)]. E7 binds to the tumor suppressor gene pRb and contributes to carcinogenesis by releasing and activating the transcription factor E2F bound to pRb. It is also involved in carcinogenesis by interacting with cyclin-dependent kinase (Cdk) inhibitors p21 and p27 to evade cell cycle checkpoint mechanisms and apoptosis. However, in many cases, immortalization does not occur only by the actions of human cervix mucosal cells E6 and E7. In the well-known HeLa cell line, telomerase is activated, preventing the gradual shortening of telomeres in cell death.
\nHigh-risk HPV can be detected in more than 90% patients suffering from cervical cancer and dysplasia, which is a precancerous lesion, and in the vulva of 5% normal women. Although HPV is also integrated into the genome of host cells, its integration pattern has unique features. The E6 and E7 genes are retained in the provirus with frequent deletion mutations in E2 gene. Thus, the viral genome is also found to be truncated in the complex reaction of integration, but its carcinogenicity is rather enhanced. Low-grade dysplasia of the cervix and cervical intraepithelial neoplasia (CIN) is well known. These pathological changes are reversible and are known to spontaneously disappear within about 3 years. However, about 10% infected patients sustain the infection for more than 3 years, and cervical cancer occurs after several months to several decades in some of them. HPV genome is integrated into the host cell genome during the progression of CIN, and the progression becomes irreversible.
\nHPV-DNA typing tests have been conducted using real-time PCR, loop-mediated isothermal amplification (LAMP) [25, 26], invader, and hybridization methods. In recent years, the Clinichip method [27] combining LAMP is broadly available in advanced countries including Japan due to the ability to amplify genes at a constant temperature. The LAMP method is very specific because it uses four primers to recognize the six regions of the HPV genome. Nonspecific amplification does not occur because the amplification reaction depends on the order of the six regions of the HPV gene. In addition, since the amplification product constitutes the target gene sequence, the target gene can be detected immediately by the presence or absence of amplification.
\nIn an environment where electricity availability is limited, easy-to-use and durable reagents and equipment are desirable. In recent years, attempts have been made to spread virus testing as point-of-care tests (POCT) [28]. For some pathogens such as malarial parasite (
HBV has been identified as the pathogen that causes acute and chronic hepatitis B [29, 30]. HBV is a DNA hepatitis virus and has a double structure of an envelope and a core. In persistent infections, the HBV genome is often inserted into the hepatocyte genome and is not eliminated by the host’s immune system. Several studies on many common insertion sites have identified common integration sites in the HBV genome by full genome sequence of hepatocellular carcinoma [31]. The envelope protein of HBV covers the HBs antigen, and the core protein is called the HBc antigen. HBV DNA encodes HBs antigen, HBc antigen, X protein, and DNA polymerase. The HBe antigen is translated from the pre-C gene and the downstream HBc antigen. It is released into blood as a soluble protein during HBV virus growth and therefore considered a marker for the virus growth. In asymptomatic carriers positive for HBe antigen, the host immune system continuously reacts with HBV-infected hepatocytes, and biopsy reports show persistent lymphocyte infiltration in the portal vascular area of liver tissues. If the damage persists for a long time, remodeling of the hepatocytes occurs and progresses to cirrhosis with obvious fibrotic crosslinks. After all, when seroconversion occurs in HBV carriers negative for HBe antigen and positive for HBe antibody, the patient becomes an inactive carrier. HBV particles remain alive during periods of inactivity. Host immune system can attack infected hepatocytes, and hepatocyte regeneration may occur with genomic mutations, and the effects of the inserted HBV genome persist. Hepatocellular carcinoma can develop with persistent liver dysfunction associated with liver cirrhosis.
\nFor the diagnosis of hepatitis B, HBs antigen/antibody, HBc antibody, HBe antigen/antibody, and HBV DNA are detected, and HBV DNA polymerase activity is measured. HBs antigen is produced continuously in patients with HBV infection; thus, positive results for HBe antigen can diagnose current infection with HBV. Recently, the HBs antigen measurement system has become very sensitive, and infected people have been found to be positive for HBs. In addition to antigen or antibody detection method, viral DNA detection system (quantitative PCR, LAMP method) has been used for clinical tests. Liver fibrosis is seen as a precancerous stage of HBV and hepatitis C virus (HCV) infection. Liver biopsy and qualitative analysis of hyaluronic acid and type IV collagen in blood are well-known methods to evaluate liver fibrosis progress. Monitoring of glycolysis of serum M2BP (Macingo binding biomarker) is used to evaluate liver fibrotic stage [32]. Recent studies have suggested that the most common cause of nonexclusion of HBV is covalently closed circular DNA (cccDNA). When HBV infects hepatocytes, the incomplete duplex circular DNA genome becomes a complete duplex and is retained in the nucleus in the form of cccDNA. This HBV gene is the source of HBV replication. Since cccDNA is an extremely stable biochemical structure, it can be used as a monitoring marker after the infection. As the nucleic acid analog drug has little effect on reducing HBV cccDNA, a high risk of reactivation remains. If host immunity is suppressed, the reactivation occurs from this cccDNA as a starting transcriptional point. Therefore, elimination or suppression of reactivation will be central to future therapeutic strategies [33].
\nIn the clinical tests for HBV detection, the detection sensitivity of the enzyme-linked immunosorbent assay (ELISA) method for HBs antigen is higher than those of other tests. Each available method depends on the titer of the used antibody, and the sensitivity varies. In particular, the mutation in the gene encoding the envelope protein HBs antigen may cause false negative results. Many test kits increase sensitivity by using multiple monoclonal antibodies or a polyclonal antibody that has an affinity for multiple epitopes. In some cases, antibodies that recognize epitopes within the viral particle are used instead of surface proteins with many mutations. However, the high sensitivity of many kits may instead cause false positive results. Accordingly, actual early diagnosis requires careful evaluation of test results in combination with other clinical tests.
\nAnother important human carcinogenic virus is human T-cell leukemia virus type 1 (HTLV-1). This virus has the potential to cause adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy (HAM), and HTLV-1 uveitis (HU). These diseases develop in HTLV-1 carriers after prolonged latent infection. HTLV-1 carriers are particularly prevalent in southwest Japan, including Kyushu, Shikoku, and Okinawa. HTLV-1 was isolated and reported by Gallo R as the first human pathogenic retrovirus in 1980. Yorio Hinuma of Kyoto University in Japan precisely analyzed the genomic structure and identified the HTLV-1 [34]. HTLV-1 is a weakly infective virus particle, and cell-to-cell transmission is the main route of infection.
\nATL is a hematologic malignancy in which abnormal lymphocytes appear in peripheral blood and infiltrate various organs throughout the body. Kiyoshi Takatsuki of Kumamoto University in Japan and Taku Uchiyama of Kyoto University collected samples. In 1981, Hinuma identified HTLV-1 to be the causative virus of ATL; this was the first report on tumor-induced retrovirus in humans. Most infected cells are CD4 + CD25 + T cells. Viral receptors are thought to involve other proteins and heparan sulfate. HTLV-1 is an approximately spherical virus particle about 100 nm in diameter and has an envelope. It has an RNA genome composed of the genes common to retroviruses such as
Tax and HBZ may be the carcinogenic potentials of HTLV-1. Tax is a potent transactivator essential for the activation of the viral promoter 5′ LTR. After entering the cell by infection, the virus particle capsid is lost, and the HTLV-1 genomic RNA is reverse transcribed to form genomic duplex DNA. Thereafter, the integrase encoded by the viral genome and the DNA end forms a complex, which contacts the genomic DNA on the cell side, and inserts by catalytic reaction. The 5-base-long sequence of the targeted host cell genome is duplicated at both ends of the inserted viral genome in the insertion process. Tax, the transcript of TLV-1 regulatory gene tax, not only binds to the HTLV-1 promoter to promote viral transcription and expression but also interacts with cell-side transcription factors to activate host gene transcription activity. Therefore,
At present, in addition to the carcinogenesis by the proteins of these viruses themselves, attention has been focused on the activation of host genes at the insertion site. The integrated HTLV-1 provirus has the LTR [35] in both directions for the transcription. This sequence has many motifs that bind to transcription factors on the host and have strong promoter/enhancer activities. Therefore, there may be an increase in constitutive expression of the gene at the insertion site. Ogawa performed systematic genome analysis of ATL cells in 426 ATL patients and showed that genes interacting with Tax, T-cell receptor-NF-κB signal transduction, T-cell transport, and other T-cell-related pathways as well as genes related to immune surveillance are injured by the integration. Also, the expressions of VAV1, IRF4, and FYN related to lymphocyte maturation and signal transduction, chemokine receptors CCR4 and CCR7, and gene fusions (CTLA4-CD28 and ICOS-CD28) were enhanced in the infected cells [37]. Viral transcripts were mainly derived from the antisense strand. Also, the suppression of
To date, no chromosomal abnormality specific to HTLV-1 has been observed, and Southern blot or inverse PCR methods are used for diagnosis; however, in recent years, multiplex LAMP (RT-LAMP) using universal probe has been developed. The method detects both HIV and HTLV-1 RNA from the same sample [39]. HAS HTLV-1 analyzing system (HAS)-Flow method has also been proposed to evaluate the progression of ATL stage by applying flow cytometric analysis focusing on surface markers of infected immune cells [38].
\nAs experimental models of MLV integration, BXH2 [40], AKXD [41, 42, 43, 44], and SL/Kh [20, 45, 46, 47, 48, 49, 50, 51, 52] are well-known mouse strains into which endogenous provirus genomes have been inserted. The genome of an endogenous MLV, AKV [14], was integrated into
To study MLV genome insertion
Murine leukemia retrovirus (MLV) integration into oncogenes in SL/Kh lymphoma. In most cases of lymphoma, MLV integrations into more than one oncogenes, including Stat5a, c-myc, Fiz1, Hipk2, and others, are observed. It is not clear why the tumor cells are restricted to pre-B lymphoma phenotype. To date, genetic background dependent on
To date, such significantly selective insertion into the specific gene has not been known. When insertion further occurs in an oncogene (e.g.,
In AKXD and SL/Kh lymphoma genome,
Alternate palindrome sequence in
SL/Kh mouse has multiple copies of the endogenous virus, which produces viral particles and infects immature B-cell lineages suitable for tropism. Several common insertion sites such as Stat5a and Stat5b and well-known genes such as c-myc have been identified till date. Interestingly, many of these insertions occur upstream of the translational initiation site of the protein, so that many intact targeted proteins are produced. The fact that many insertions occur in such specific genes suggests that DNA structures such as palindromic sequences are targeted. However, insertions in a short 50-bp segment cannot have such secondary structure. MLV insertion was observed in almost the entire genome of this SL/Kh acute lymphocytic leukemia/lymphoma. The integration target segment is located just before the translation initiation origin of the Zfp521 gene, which was first reported as a retrovirus insertion sequence. As a result of the insertion, downstream Zfp521 gene is constitutively expressed, and the upregulation may be responsible for acute lymphocytic leukemia/lymphoma.
\nRecently, several cellular proteins including transcription regulatory factors and chromatin and RNA-binding proteins have been discovered as potential interaction partners for MLV integrase [67]. The bromodomain and extra-terminal domain (BET)-containing family of proteins (BRD2, BRD3, BRD4, and BRDT) act as cellular-binding partners of MLV integrase and preferentially bind to open chromatin regions that are enriched for transcription start sites, CpG islands, DNase I-hypersensitive sites, and proto-oncogenes [68, 69, 70, 71, 72, 73]. The BET family of proteins plays a critical role in regulating gene transcription through epigenetic interactions between dual bromodomains and acetylated lysines on histones H3 and H4 during cellular proliferation, cell cycle progression, and differentiation processes [8, 9].
The dual bromodomain protein of BRD2 promotes B-cell expansion and plays a critical role in the regulation of mitogenic response genes, particularly cyclin A, in B cells [15]. In addition, it has been shown that the inhibition of BRD4 leads to the suppression of germinal center B-cell differentiation and antibody responses through the down-regulation of nuclear factor-κBp65 activation and B-cell lymphoma 6 expression [16]. Hence, these BET proteins might broadly contribute to tumorigenesis in cooperation with MLV integration in spontaneous B-cell lymphoma development, and these findings likely provide novel standpoints of proto-oncogene function as well as a better understanding of MLV insertional mutagenesis [15, 17].
\nThe stable integration of retroviral vectors is suitable to deliver therapeutic genes into cells to correct genetic diseases. MLV-based retroviral vectors are one of the most frequently used gene delivery vehicles in gene therapy studies for primary immunodeficiencies such as adenosine deaminase deficiency-severe combined immunodeficiency [10, 18, 19]. However, a subset of patients developed serious adverse events including leukemia that could be attributed to the integration pattern and vector design [10, 18]. MLV-based retroviral vectors integrate in the vicinity of transcription start site through the interaction between the C-terminal tail of MLV integrase (amino acids 381–408) and the ET domain of BET family of proteins [18, 20]. To resolve side effects such as leukemia, BET-independent MLV vectors have been developed by truncation of the C-terminal tail of MLV integrase or the single W390A mutation [18, 20]. Most recently, next-generation BET-independent MLV vectors have been engineered with the addition of the chromodomain of Chromobox protein homolog 1 (CBX1) to MLV integrase_W390A. The MLV integrase_W390A-CBX1 efficiently targets integration away from traditional markers of MLV integration including gene regulatory elements [10]. These findings open new avenues to improve the biosafety of gammaretroviral vectors for gene therapy.
\nWe followed the history of viral carcinogenic research in this review. The topic of viral carcinogenesis mentioned here is a case where the viral genome is inserted into the host genome. Because the molecular mechanism of viral carcinogenesis has been elucidated, significant novel technical methods will be developed in the future.
\nClinical sequence analyzes gene changes occurring at diseased sites and provides information useful for diagnosis and treatment of diseases based on the results of gene mutations.
\nIn addition to the various nucleic acid analysis methods such as conventional PCR and LAMP, next-generation sequencing and other rapid technological innovation will aid in the measurement and analysis of numerous gene sequences in a short period. Furthermore, these technologies are expected to be used in the future to analyze infectious diseases such as cancer virus types, HPV high-risk groups, and virus insertion sites. Information on cancer virus infection will also be valuable for designing personalized drugs for cancer patients in the future.
\nThis work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (no. 15H05721) and a Grant-in-Aid from the Scientific Research on Innovative Areas, MEXT, Japan (no. P2013-201).
\nThe authors declare no conflicts of interest.
\nHPV | human papilloma virus |
HBV | hepatitis B virus |
HTLV-1 | human T-cell leukemia virus type 1 |
MLV | murine leukemia virus |
Industry 4.0, often known as smart manufacturing, is built on information technology (IT)-driven industrial processes [1]. It combines smart factories and products with the Internet of Things [2, 3], with the goal of providing real-time information on production, machines, and component flow, and integrating this data to assist managers in making decisions, monitoring performance, and tracking parts and products.
Big data analytics (BDA) is the collecting of real-time data, the use of analytical tools, and the use of computer algorithms to derive relevant insights and patterns for better decision-making using data, text, audio, video [4]. Big Data 6Vs framework describe Volume, a very large amount of data; Velocity, the data are generated very quickly and must be processed in a very short time; Variety, a large number of structured and unstructured data types are processed; Value, the goal is to generate significant value for the organisation; Veracity, reliability of the processed data; and Variability, flexibility to adapt to new data formats by collecting, storing, and processing them. BDA aids in the achievement of long-term corporate success and competitive advantage [5].
Internet of Things (IoT) allows devices to communicate with one another without the need for human involvement [6]. The Internet of Things is based on a network of devices, each of which has its own unique identity to the computer system to which it is attached. IoT-controlled industrial systems are intelligent because they can accurately and efficiently operate all linked equipment from afar [7]. For example, big data has been utilised to enhance product development [8], SC demand forecasts [9], and green production strategies [8, 10].
Blockchain is a distributed data structure—a distributed ledger—in which the data is shared on a peer-to-peer network. The network members and nodes communicate and validate the data following a predefined protocol without a central authority. Distributed ledgers can be either decentralised, giving equal rights to all users or centralised, providing specific users with special rights.
Artificial intelligence (AI) is a field in computer science encompassing the development of systems capable of performing tasks that normally necessitate human intelligence. The science of making machines do things that would require intelligence if done by men. Three main functions are sensing and interacting, learning from the data and decision making.
Autonomous vehicles as more environmentally friendly automobiles are capable of sensing its navigation without human input, thus the costs, emission level and working time can be reduced dramatically. They can be used not only for long distances, but also for operational level of the supply chain.
Additive manufacturing (AM) begins with the creation of a three-dimensional digital model using computer-aided design software, followed by the formation of the finished object using a 3D printer [11]. AM helps to Industry 4.0 goals by generating personalised items in small batches and producing complex and lightweight designs with great precision [3].
Cloud manufacturing is a method of providing a shared network of manufacturing resources and capabilities through the internet by establishing a virtual and global environment. The logic of cloud manufacturing is service-based, which means providers and consumers interact to sell and acquire services such as product design, simulation, production, and assembly [12].
The Cloud computing (CC) is an Internet-based third-party service provider for data or database storage. The cloud is housed at a faraway location, not at the area where production takes place [12]. The CC has the advantages of lower operating costs, faster service, and simple accessibility [13].
Sustainability is a multi-dimensional concept incorporating economic, environmental, and social dimensions of business. Primary goal of any commercial enterprise is to make profit for long tern economic sustainability by balancing costs and revenues in sourcing, production and distribution of goods and services. Due to global pressure, climate change and pollution, environmental sustainability has taken centre stage in today’s business [14]. The focus is to minimise natural resources use, waste and pollution (air, water, land), and increased renewable energy use in production and distribution. Social sustainability includes working environment, employee morale and satisfaction, equity and social integration of communities. Industry 4.0 technologies (I4T) help manufacturing companies achieve long-term goals by reducing lead times, providing customised goods, improving product quality, improving the working environment, and employee morale [15]. Organisations have been compelled to adapt smart production systems which are more adaptable, intelligent, and agile, and allows to address the demands of a dynamic and global market [16].
Sustainable development is crucial necessity for the survival of humankind, which should integrate sustainable production and consumption [17]. Sustainability is three-dimensional concept encompassing economic, environmental and social (triple bottom line). Sustainable supply chain enables the management of material, information and capital flows as well as the cooperation among companies along the supply chain while taking goals from all three dimensions of sustainable development (economic, environmental and social) into account which are derived from customer and stakeholder requirements [18]. One of the key features of Industry 4.0 enabled by CPS, IoT, and big data analytics, is data accessibility and real-time information, which may help companies achieve low cost, high quality, low risk sharing, more flexible SC planning and effective decision making. Industry 4.0 allows for long-term purchase of more personalised items [19]. I40 opens up new and long-term commercial prospects by maximising resource efficiency, enhancing manufacturing flexibility, and reducing time to market [20]. IoT controlled industrial systems are clever as they can accurately and efficiently operate all linked equipment from afar [7]. Various I4T is shown to have a good influence on the organisations’ long-term success. However, there is a dearth of empirical evidence in the literature to substantiate the influence of I4T on sustainable operating practices in various industries [15]. I4T contribute to long-term operations management choices and new business models by connecting value chains through data collection and exchange [3, 21]. As a result, long-term operations management decisions help to establish a link between circular economy (CE) principles and Industry 4.0 concepts.
The search for a more sustainable production and consumption system is so important now that the United Nations Organisation (UNO) has made it one of their most important social goals for long-term development [22]. The ultimate goal of implementing sustainability into production is to take the industry to a world-class level of sustainable manufacturing [23]. Moghaddam et al. [24] developed several reference designs for sustainable smart I40 factories to dealt with the production of environmentally friendly products. Nascimento et al. [25] proposed a circular economy (CE) business model using I4T for recycling garbage. Kiel et al. [26] classified Internet of Things (IoT) issues and benefits that centred on the long-term value creation. Waibel et al. [20] investigated the effects of smart production systems in terms of resource efficiency and sustainability. Zambon et al. [27] proposed an Agriculture 4.0 through the virtualization of the Agro-food chain. Ding [28] conducted a literature review to identify the barriers of incorporating sustainability into the pharmaceutical SC and proposed I40 application in SC known as Pharma 4.0. Bag et al. [29] developed a framework incorporating thirteen enablers I40 affecting SC sustainability. Tsai and Lu [30] developed a I40 based production planning and control framework using a carbon price. Ghadimi et al. [31] suggested a multiagent system to automatically analyse and choose suppliers that contribute to sustainable SC. Belaud et al. [32] developed agriculture 4.0 by integrating I40 into a SC and waste valorization using big data to improve sustainability management. Sensing, smart, and sustainable technologies were identified as crucial aspects of future sustainable goods [33]. Bibaud-Alves et al. [34] used I4T to establish a relationship between the development process of new goods, digital transformation, and sustainable development. Paravizo et al. [35] offered a conceptual framework using I40 for developing gamified apps that focus on sustainable manufacturing. Kamble et al. [15] reviewed 85 articles on I40 and established a sustainable industry 4.0 framework. Stock et al. [36] carried out qualitative assessment of I40 that enables ecological and social sustainable development. Hidayatno et al. [37] proposed a conceptual model to assess the effect I40 technology on sustainable energy in Indonesian industries. Bonilla et al. [38] used multiple development scenarios to assess the impact and challenges of I40 implementation on long-term sustainable development. Man and Strandhagen [21] presented I40 and sustainability adoption into various business operations. Luthra and Mangla [39] conducted a literature analysis and categorised eighteen I40 implementation challenges of sustainable SC into four categories: organisational, strategical, legal, and ethical. Ardanza et al. [40] demonstrated a human–machine interface using I40 that enable operators to be more productive and safer. Meng et al. [41] carried out literature review on sustainability and energy efficiency in smart factories, their interaction, benefits and issues. Chaim et al. [42] examined the feasibility of using key performance indicators (KPIs) to assess sustainability in I40 virtual learning environment. Kamble et al. [43] analysed the barriers of I40 adoption in manufacturing industry.
Manavalan and Jayakrishna [44] examined the IoT application for a sustainable SC and suggested software to organise material resources in businesses. Birkel et al. [45] proposed a risk framework using I40 for sustainable manufacturing in SMEs using a long-term strategy. Jabbour et al. [46] identified eleven critical success factors for implementing I40 and environmentally sustainable manufacturing and proposed an integrated framework for future research. Kamble et al. [15] investigated the barriers to I40 adoption in Indian manufacturing and analysed their driving and dependence relationship. Monteleone et al. [47] suggested a water management conceptual model in agricultural 4.0. [48, 49] carried out empirical study of 234 manufacturing firms in Pakistan to investigate the effect of I40 on green practices in manufacturing and logistics, which have substantial effect on sustainability of the firms.
Chalmeta and Santos-deLeón [50] carried out literature review on I40, big data and sustainable SC. Mastos et al. [51] provided IoT application for scrap metal waste management. Strandhagen et al. [52] proposed I40 solutions to shipbuilding supply chains sustainability challenges in a case company. Yadav et al. [53] identified 22 I40 and CE based solutions measures to overcome 28 sustainable SC challenges in an automotive industry using BWM-ELECTRE.
Belhadi et al. [54] carried out empirical study by collecting data from 306 organisations in Europe, Asia and Africa to explore the role of digital business transformation, organisational ambidexterity and circular business models on the relationship between I40 capabilities and sustainable performance. Fatorachian and Kazemi [55] conducted exploratory research based on inductive reasoning and systems theory to explore the impact of I4T on SC performance in terms of integration, information sharing and transparency, processes improvement in procurement, production, inventory management and retailing through digitisation, automation, and analytical capabilities. Kumar et al. [56] analysed critical success factors for I40 implementation in circular SC. Kumar et al. [57] studied the barriers of integrating I40 and CE in the agriculture SC using ISM-ANP and concluded that government policies, support and incentives is major barrier. Kusi-Sarpong et al. [58] adopted I40 initiatives for sustainable supplier selection in circular SC. Mastos et al. [59] used I40 technologies to redesign SC for circular economy with key identified benefits of improved availability of personnel and fleet resources, and SC traceability through the full visibility and automation. Mubarik et al. [60] collected data from 154 electrical and electronics Malaysian firms and found that I40 application impact SC mapping and visibility. Sharma et al. [61] found in the study that the environmental and social factors were the highest-ranked drivers while organisational and environmental dimensions as the highly ranked barriers of I40 adoption with the sustainability context in multi-tier manufacturing SC. Umar et al. [48, 49] studied the effect of I40 on sustainable operations and green SC practices.
Industry 4.0 technologies are intended to play a key role in guiding industrial and social organisations toward long-term sustainability [46]. I4T makes it easier to achieve a high level of process integration, which improves organisational performance across three aspects of sustainability [15]. Braccini and Margherita [62] explored the impact of I40 adoption in a case study of a ceramics manufacturing firm and found that product quality and productivity improvement, energy monitoring and consumption reduction, safe work environment and job satisfaction for workers. Birkel and Muller [63] provided a literature review on potential of I40 on SC triple bottom line of sustainability in planning, sourcing, logistics and recycling logistics. Digital and smart manufacturing processes, machines and devices are likely to offer advantages of manufacturing productivity, resource efficiency, and waste reduction [64].
On the economic front, I4T makes a significant contribution to value creation, production flexibility, and product customization, which lead to higher consumer satisfaction [3]. Automation and digitisation capabilities of I40 help manufacturers achieve shorter lead times, cheaper manufacturing costs, and higher quality [11, 65]. I4T helps in raw material inventory reduction and efficient capacity utilisation [66]. The data offered by cloud manufacturing and IoT may be used to alter the design, production, and logistics choices of sustainable operations management [46]. IoT applications enable the reuse of resources in a remanufacturing process. The data generated by IoT sensors is evaluated using a mathematical model in order to lower expenses and dynamically manage limited resources [67]. Blockchain capabilities can support sustainable supply chains, which can help reduce the product recall and rework, and trace actual footprint of products; and reduce fraud [68]. Dev et al. [69] adopted agent-based modelling and decision trees to facilitate inventory and supply chain reconfiguration issues of a mobile phone supply chain. The information gathered by I40 may be used to improve product life cycle and industry’s economic performance. Using Additive manufacturing (AM) and IoT together can help create a more sustainable manufacturing process by increasing resource efficiency and reducing recovery procedures [70]. Big data technology can influence the SC methods in terms of eco-efficiency and long-term performance. Esmaeilian et al. [71] reviewed capabilities of Blockchain as enabler for the successful implementation of sustainability and circular economy concepts under four main categories of (i) promoting green behaviour through designing specialised tokens, (ii) enhancing the visibility of product lifecycle, (iii) increasing systems efficiency and decreasing development and operational costs, and (iv) enhancing corporate performance reporting and sustainability monitoring capabilities. Digital supply chain may offer benefits of higher operational efficiency, ad-hoc dynamic planning, collaborative planning, collaborative product design, marketing effectiveness, financial flow, and deeper customer integration [72]. CPS, IoT, and big data analytics, enable a flexible supply chain planning and effective decision making, which may help to achieve high quality with low cost and risk in sustainable purchasing [19].
In terms of the environment, real-time data acquired from various value chain partners assists organisations in effectively allocating industrial resources such as materials, energy, water, and products [3, 46]. I4T also support reduced greenhouse gas emissions [73], energy consumption [74], reduced fuel consumption as a result of improved transportation and logistics planning; and the use of advanced tracking and monitoring systems [75]. The Big data offers predictive analytics that improve environmental and social sustainability [76, 77]. The inclusion of sensors in goods enables performance monitoring such as tracking maintenance requirements-allowing businesses to deliver high-quality service to clients on a proactive basis. Further, organisations may invest in extending product life spans by using the 3Rs (reduce, re-use, and recycle) and monitoring items throughout customer usage. Cloud manufacturing and IoT can gather data from processes and things, such as machinery, allowing for the faults detection that might result in waste. Managers may also monitor and regulate the performance of operations based on production and resource consumption criteria, such as energy usage; the use of sensors would allow them to intervene in processes, even during component/product manufacturing. Machine efficiency might also be monitored in real time in order to schedule maintenance and avoid wasting resources [46]. Blockchain offers visibility, transparency, relationship management, and smart contracting which in turn offers environmental as well as economic benefits and plays a positive role in circular economy [78]. Abdella et al. [79] proposed machine learning using a set of environmental, social and governance criteria to predict sustainability performance across the supply chain. The revolution of autonomous vehicles can provide several benefits particularly in transportation part of the supply chain to reduce the damaged products. Automated guided vehicles (AGV) help in efficient materials handling operations improving the environmental and social sustainability. Krueger et al., [80] analysed possibilities of shared autonomous vehicles implementation implemented in a logistic cluster in public transport industry to improve utilisation of assets and reduce environment effect. Additive manufacturing result in less material being used and requires recycling of tiny amounts of trash due to mobility of 3D printers [70]. The usage of AM also helps to improve the sustainability of a manufacturing process by lowering the materials use and energy consumption. I40 help in energy monitoring that will result into increased energy efficiency and lower CO2 emissions [81]. AM and IoT can aid in improving reverse logistics operations, such as tracking and tracing end of use and end of life items and monitoring recycling activities to pave the way for a long-term route toward circular manufacturing [82]. Cloud technology allows for the capture, exchange, and sharing of dynamic life-cycle data, as well as SC partnerships for environmental footprint assessment [83]. Cloud-based service platform can help in improved decision-making and thereby minimise greenhouse gas emissions in the transportation and logistics industries [84]. Big data analytics in process control, for example, might help in pollution control and natural resource management [85]. Cyber-physical systems aid in production without generating waste or consuming unnecessary resources; the IoT enables mass customization and production that meets demand without producing excess inventory; cloud manufacturing enables controlled resource consumption (e.g., raw materials, energy, water); and additive manufacturing proactively maintains products, saves energy, and reduces waste from defective products [2, 20, 86]. By designing goods based on precise consumption data, cyber-physical systems improve customer satisfaction. As a result, using the 5Rs technique (reduce, repair, re-use, recycle, and remanufacture) [86, 87], it is feasible to develop goods with longer life spans. CPS and IoT aid in the planning of energy and carbon-efficient logistics routes, as well as assisting suppliers in managing their own performance in terms of production planning, delivery quality and reliability, and environmental compliance via remote monitoring [88]. In smart factory, communication efficiency, transparency, surveillance, and control will minimise downtime, waste, defect, and risk across production processes [89].
On the social front, I4T provides a plethora of options for employees to learn new technology, boosting morale and motivation [73, 74]. I4T provides employees with a better and safe working environment [15]. AI and data analytics can help in personalised career development programs based on the behaviour, experience, skills, personality, and learning patterns of each employee [90]. I4T will create new jobs in area of informatics, mechatronics, process engineering, and system integration [91]. Industry 4.0 technologies impact on supply chain sustainability is summarised in Table 1. Industry 4.0 sustainability benefits are shown in Table 2.
Industry 4.0 Technology Features | ||
---|---|---|
Automation | Integration | Modularity |
Real-time capability | Flexibility | Interoperability |
Virtualisation | Decentralisation | Data quality and availability |
Servitisation | Product and service customisation | Transparency |
⇩ | ||
Process and Production efficiency | Material and Resource use reduction | Worker’s productivity improvement |
Cost effectiveness | Energy Consumption reduction | Working condition improvement |
Quality improvement | Water Consumption reduction | Worker’s Health and safety improvement |
Scalability | Waste reduction | Equity |
Profit Margin improvement | Air pollution and GHG emission reduction | |
Reverse logistics reduction |
Industry 4.0 technologies impact on supply chain sustainability.
Sustainability Benefits | Herrmann et al. [74] | Peng et al. [84] | Despeisse et al. [70] | Hofmann and Rüsch [88] | Waibel et al. [20] | Zhao et al. [85] | Keil et al. [26] | Fatorachian and Kazemi [92] | Ghobakhloo [93] | Jabbour et al. [46] | Kamble et al. [15] | Luthra & Mangla [39] | Muller et al. [94] | Stock et al. [36] | Stone et al. [90] | Tortorella and Fettermann [64] | Ghobakhloo & Fathi [91] | Braccini & Margherita [62] | Saberi et al. [68] | Dev et al. [82] | Garcia-Muina et al. [95] | Khan et al. [78] | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Lead time reduction | x | ||||||||||||||||||||||
Customer specific planning | x | x | |||||||||||||||||||||
Autonomous supplier selection and procurement | x | x | |||||||||||||||||||||
Improved supply chain resilience | x | ||||||||||||||||||||||
Downtime prediction | x | x | |||||||||||||||||||||
Aligned production and logistics | c | x | x | x | |||||||||||||||||||
Logistics process efficiency | x | x | x | ||||||||||||||||||||
Faster delivery | x | x | x | ||||||||||||||||||||
Order accuracy | x | ||||||||||||||||||||||
Recycling cost reduction | x | x | |||||||||||||||||||||
Repair and maintenance efficiency | x | x | |||||||||||||||||||||
Resource consumption reduction | x | x | x | ||||||||||||||||||||
Energy consumption reduction | x | x | x | ||||||||||||||||||||
Sustainable Process optimisation | x | ||||||||||||||||||||||
Environmental monitoring easier | x | ||||||||||||||||||||||
Physical prototyping reduction | x | ||||||||||||||||||||||
Scrap reduction | x | x | |||||||||||||||||||||
Transport optimisation | x | ||||||||||||||||||||||
Transparency | x | ||||||||||||||||||||||
Tracking and tracing of recycling | x | x | x | x | x | x | |||||||||||||||||
GHG emission reduction | x | x | |||||||||||||||||||||
Safe working environment | x | x | x | ||||||||||||||||||||
Reduction of hazardous tasks and stress | x | x | x | ||||||||||||||||||||
Learning and training improved | x | x | |||||||||||||||||||||
Hazardous recycling process reduction | x | x |
Industry 4.0 sustainability benefits.
Industry 4.0 technologies such as AI, ML, IoT, Big data, Block chain technology, VR, AR, CPS, Industrial Autonomous Robotics, Cloud computing etc. are being adopted in manufacturing and supply chain throughout the world but slowly. Researchers and professional managers believe that I40 offers integration, interoperability, real-time capability, quality data, modularity, decentralisation, product customisation, servitisation, collaboration, transparency and virtualisation, which may positively impact sustainability. On economic dimension, I4T adoption in supply chain will improve supply chain efficiency, quality, resilience, customer specific planning, production and logistics alignment, on-time delivery, order accuracy, downtime prediction, and repair and maintenance, supplier selection and procurement, and reduce lead time. Economic sustainability will reduce cost and improve profitability. I40 acts environment friendly as its adoption will lead to reduction of raw materials and resources, energy consumption, GHG emission, scrap and waste, physical prototyping, transparency, tracking and traceability. It will enhance sustainability processes and transportation and environmental monitoring. Regarding social sustainability dimension, I4T can offer safe working environment and flexibility, reduce stress and hazardous tasks, and improve learning and development. It is not free from challenges. Human activities such as inventory tracking, quality control, and even product distribution may be performed by Industrial robots, automated vehicles, and intelligent machines and there would be loss of jobs [96]. At the same time, it will provide opportunity for new jobs in I4T. Most of the studies are theoretical. Hence, it needs to be supported by qualitative and case studies.
Data collection and monitoring, information sharing, tracking, decision-making, and coordination between organisational areas and SC partners are technical and organisational factors that could influence the integration of Industry 4.0 and environmentally sustainable SC decision-making. This paper argues for an integrated approach to the issues that Industry 4.0 technologies may unleash the full potential of ecologically sustainable SC. The impact of Industry 4.0 technologies in economic dimension of triple bottom line is efficiency, flexibility, productivity and quality, which will enhance economic performance. On the environmental dimension, better resources utilisation, more quantity production, reduction of waste and energy will result into environmental performance. Finally on societal dimension, better labour utilisation and safe working conditions due to digitalisation and automation. The goal of this paper is to highlight the convergence of two important subjects; Industry 4.0 and sustainable SC with triple bottom line considerations. These two aspects have mostly been investigated separately. Industry 4.0 has the potential to increase ecologically sustainable production, distribution and consumption by allowing for the creation of green products, green manufacturing processes, and green SCM in ways that have never been possible before. On the other hand, the synergy between Industry 4.0 and ecologically sustainable production and distribution is contingent on a number of important success factors. Industry 4.0 adoption is faces few challenges. I4T need to be connected continuously and massive data centres will increase energy consumption. Therefore, it is necessary to balance energy savings and additional energy requirement in I40 adoption. I40 device replacement may also create additional waste. In recycling, sharing information about product by manufacturer, product use and transparency is also a matter of concern that needs to be addressed. Initial high investment and return also need to be studied. Major limitation of the study is the theoretical aspect. It is suggested that these theoretical research propositions be further explored, either through qualitative research or further investigated using quantitative methodology.
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\n\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
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\n\nRead more about Open Access in Horizon 2020 here.
\n\nWhich scientific publication to choose?
\n\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
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