\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Dr. Tabbakh obtained advanced degrees from the University of Central Florida College of Optics and Photonics (CREOL-UCF), which is one of the top ten optics and photonics colleges in the United States.",institutionString:"King Abdulaziz City for Science and Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"King Abdulaziz City for Science and Technology",institutionURL:null,country:{name:"Saudi Arabia"}}},coeditorThree:{id:"293058",title:"Dr.",name:"Anish",middleName:null,surname:"Khan",slug:"anish-khan",fullName:"Anish Khan",profilePictureURL:"https://mts.intechopen.com/storage/users/293058/images/system/293058.JPG",biography:"Dr. Anish Khan is an assistant professor at the Center of Excellence for Advanced Materials Research (CEAMR), Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. He obtained a Ph.D. from Aligarh Muslim University, India, in 2010, and a postdoctoral degree in Electroanalytical Chemistry from the School of Chemical Sciences, University Sains Malaysia (USM), in 2010. Dr. Khan works in the fields of sensors, polymer composites, and organic-inorganic electrically conducting nanocomposites. He has more than 250 research articles, 80 book chapters, 50 edited books, and more than 20 international conferences/workshops to his credit. 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The accepted definition of ankylosis is the bony or fibrous tissue fusion between articular surfaces including the meniscus, glenoid fossa and condylar heads [3]. Consequently, jaw functions like the maximal incisal opening (MIO) and lateral excursive movements progressively decrease. This chapter describes the most important issues of early and late management of TMJ ankylosis in both children and adults.
Trauma to the TMJ has been cited as the most common underlying reason responsible for ankylosis; however, local infections (e.g. otitis media) and systemic disorders (e.g. rheumatoid arthritis) also can also cause unilateral or bilateral TMJ ankylosis in some cases [4-7]. By improving the immediate management protocol of condylar fracture and proper application of antibiotics to fully address ear infections, the prevalence of ankylosis has decreased significantly in recent years. In addition to the common etiologic factors of TMJ condylar ankylosis, some affected infants with unknown etiological factors have been reported in the literature (Figure 1 a-c) [8].
A 5-year-old girl with bilateral condylar ankylosis of unknown etiology (no history of trauma or infection). a) Extraoral facial photograph of the patient demonstrate the upper occlusal canting with the help of a tongue depressor, b) Intraoral photograph shows midline deviation, mandibular shift and increased overjet of the patient, c) three dimensional cone beam computer reconstruction of the patient demonstrates the facial asymmetry.
The pathogenesis of the TMJ ankylosis is described by a sequence of events. The increased intra-articular vascular supply at the traumatized joint develops fibrosis and ultimately excessive localized bone formation [4]. Most of the animal studies consider intra-capsular hematoma as the main underlying reason for development of the ankylotic mass following trauma. Observed hemorrhage contains different cellular pathways activated by bone morphogenic proteins (BMPs) and tumoral growth factors (TGFs) [9]. However, a study on human subjects, revealed that hematoma in the joint space does not always result in bony ankylosis [2]. This excessive bone mass does not have a neoplastic nature, but has the potential of continual growth [10]. The presence of abnormal bony mass may restrict mandibular movement, which subsequently may lead in loss of the functional matrix of bone and muscle interaction, and consequently result in growth failure [11]. Inadequately treated or excessive treatment of condylar fractures may lead to growth retardation or growth excess, respectively [3]. Therefore, the best treatment steps for post-traumatic ankylosis and resulting growth abnormality is prevention.
Maximum mouth opening in the presence of pain or without it is a clinical indicator of traumatized condyles [12]. In addition to routine extra and intraoral photographs, supplemental diagnostic records may be needed for complete diagnosis of each case. Towne’s projection, posteroanterior and cone beam CT (3D) radiographs are commonly used for this purpose (Figure 2 a, b).
a) Posteroanterior view of a condylar neck fracture, b) Coronal section of computer tomography scan of another adult patient with unilateral condylar fracture on the right side.
Due to the flexibility of bone, it is possible to open the mandible to some extent, particularly in unilateral ankylotic cases [13]. Long-standing TMJ ankylosis can result in functional loss and facial deformity of affected individuals. In growing patients (mostly under 15 years) lack of adequate growth at the condyles, which are the main growth centers of the mandible, forward and downward movement of the mandible does not occur [13]. This growth retardation can result in a distorted mandibular structure in all three dimensions, highlighted mostly on sagittal views. Furthermore, deepening of the antegonial notch following continuous subperiosteal bone formation at the angles may be seen in most of the affected. However, ankylosis in patients older than 15 years of age experience mild facial deformities concomitant with significant functional loss. Depending on the type of ankylosis (unilateral or bilateral) clinical features can vary.
In the case of unilateral ankylosis, the patient also develops a mandibular asymmetry and subdivision malocclusion [14]. Furthermore, in unilateral cases canting of the upper occlusal surface thought to be caused by compensatory vertical eruption of the posterior maxillary teeth ipsilateral to the restricted condyle is seen (Figure 3 a-c) . On the other hand, in bilateral ankylosis, more limited range of interincisal opening and absence of maxillary occlusal canting is observed. Patients with bilateral ankylosis develop retrognathia, short posterior facial height and openbite with possible upper airway obstruction and severely convex facial profile (Figure 4 a, b) [15].
A 3-year-old girl with unilateral condylar ankylosis following trauma at birth, a) on facial examination, the patient presented with facial asymmetry, shortened ramus height, jaw deviation and the chin was noticeably deviated to the left and the maxilla was canted downward on the right side. b) The mandibular border became flat and elongated on the unaffected side and round on the affected side. The asymmetry is usually the least at the cranial base area and becomes worse at the lower parts including the chin.
An 18-year-old girl with bilateral condylar ankylosis. a) Long term effect of bilateral condylar ankylosis in a growing adolescent, which result in limited mouth opening, micrognathia and absent neck chin angle. b) The profile view is helpful to assess anteroposterior and vertical facial imbalance as well as aid in the determination of etiology of the asymmetry. C) 3D CT scan.
Regaining normal range of mandibular movement should begin as soon as possible after trauma. Many clinicians recommended a few days [5-7] of no-intervention immediately after the injury. This phase allows resolution of pain and swelling of the TMJ before reestablishment of normal range of movement [16]. However, care must be taken not to overextend this phase regarding ankylosis development. Excellent compliance of the affected individuals with physiotherapy and functional appliances immediately after trauma is an essential part of future growth and development. Failure to achieve a high level of compliance to physiotherapy and application of intraoral appliances, increase the risk of future ankylosis, which would be more problematic for patients as time passes.
Prevention of the ankylosis of the traumatized condyles requires maintenance of the normal range of movement. In most cases, if the normal range of movement can be achieved, the TMJ will heal without any functional complication. When the patient is able to reach maximal opening, even in the presence of pain, the simplest prevention regimen would be insertion of a removable appliance, which guides the mandible into its correct position during closure. The design and fabrication of different types of removable appliances depends on the clinical situation of each patient, but commonly all are fabricated from a construction bite in which advances the mandible on the affected side more than the contralateral side in addition to concise maxillary and mandibular midlines. The major difficulty with construction bite is that the clinician must be able to guide the mandible to the proper position, rapidly and accurately. Different types of appliances and various combinations of components can be incorporated in these appliances to meet individual requirements. Depending on compliance and age of the affected child, we use four different techniques:
Two simple removable Hawley appliances attached together while the patient is in centric occlusion (CO) guiding the lower jaw to symmetric position (Figure 5).
Fixed functional appliance with the aid of cement luting agent on the primary molars bands for more secure retention (Figure 6-a).
Usage of bi-zygomatic suspension wires in more severe cases in the absence of patient compliance and inadequate intraoral retention of the appliance.
Interdental Kobayashi wires with guiding interarch elastics, in cases of excessive restricted mandibular movement, which do not permit the clinician to take an impression (Figure 6-b).
Two simple removable Hawley appliances attached together is the most common appliance used to guide the patient into symmetric position.
a) Fixed functional appliance with molar bands that can hold the mandible in its correct position full-time, b and c) Interdental Kobayashi wires and guiding interarch orthodontic elastics.
Despite the improvements, removable appliances are not a practical way to manage more severe situations that require extra manipulation of the TMJ fracture. A closed reduction often is useful to re-establish normal jaw function as a next step [17]. In fact, if the fractured condyle is still within the articular fossa, there is an opportunity to heal in a quite adequate functional position, only by maintaining the occlusion. This technique is preferred over open reduction due to high success rate, less complications and technical problems and also less remnant facial scars [18]. However, clinical decision on the most appropriate type of treatment must be made considering different individualized factors like patient age, medical history, risk of infection, and risk of chronic pain, risk of scarring or nerve injury, and also presence of other concomitant facial, mandibular or cranial fractures [19]. Conservative management of condylar fractures is still the preferred option, however, in rare cases of condylar displacement into the middle cranial fossa, or lateral extracapsular displacement of the fractured segment, open reduction is selected [17]. The advantages of open treatment for condylar fractures would be the possibility of restoring the anatomical position of the fragments and disc, and subsequently immediate functional movement of the jaw, which greatly avoids the development of ankylosis of the traumatized joint [20].
A 4-year-old boy was brought in approximately five hours after being hit on the left side of the face. He complained of pain on the left side (Figure 7 a). The impressions of upper and lower arch with limited jaw opening were performed and an attached upper and lower Hawley appliance was fabricated to guide the patient into correct closure (Figure 7 b). The condyle of the affected side healed and positive outcomes were maintained during a 1-year follow-up (Figure 7 c and\n\t\t\t\t\t\t\tFigure 8 a, b).
a) Pretreatment intraoral photograph shows inability of the patient to open the mouth. b) Removable appliance inserted for further guidance of the lower arch. c) Frontal facial view at the end of active treatment.
Same patient shown in
Sometimes adult patients suffer severe trauma to the condyles, particularly as a part of a catastrophic event [21]. Although, because of absence of required growth in later stages of life, this restricted condylar growth might not result in severe facial deformities, but it may result in limited mandibular function. Recent improvements in treatment techniques including advent of temporary anchorage devices (TAD) can help clinicians manage the other jaw fractures presenting with the traumatized condyles. In contrast to the traditional techniques like intermaxillary wire fixations, application of TADs does not restrict the range of normal functional movements. In addition, comparing their application in growing patients, TADs could be inserted in mature bony structures of the jaws without any additional risk regarding possible damage to un-erupted dental crypts. This approach removes the necessity of presence of enough remaining dentition to be used as guidance of jaw movements (Figure 9 a-c). With the help of these TADs and temporary light interarch elastics one can guide directional remodeling of traumatized condylar segments, in a manner similar to removable appliances [21].
a) Settling of the occlusion and guidance of proper healing procedure by means of TADs and light intermaxillary elastics in an adult patient, b) orthodontic brackets were bonded on teeth to correct the remaining dental malposition, c) final treatment result (From Tehranchi A: Rapid, conservative, multidisciplinary miniscrew-assisted approach for treatment of mandibular fractures following plane crash Dent Res J. 2013 Sep-Oct; 10: 678–684).
Treatment of TMJ ankylosis is an excellent example of an important principle in the timing of the treatment: because of devastating effects on future growth, presence of condylar ankylosis in growing patients is an indication for early treatment; in contrast, condylar ankylosis in adult patients must be treated considering the extent of functional limitation of mandibular movement. In many clinical situations pain is uncommon and limited range of opening is the first sign of condylar ankylosis, usually noticed by dental practitioners [22].
To date, various treatment approaches have been described to achieve successful management of ankylosis [23-24]; however no single treatment with uniformly successful results has been assigned for all cases [4, 25-26]. The optimum selection of an adequate technique depends directly on the details of clinical situation of the patients and is highlighted particularly in patients’ growing phase, since their consequent facial deformity could be significantly worsened during growth [27]. In the aforementioned patients, orthopedic treatment with functional appliances following surgical release of ankylosis is highly recommended.
Intra-operative view demonstrating gap arthroplasty technique.
The second category, interpositional arthroplasty addresses the main drawbacks of the first method, which is high recurrence rate [31]. In this technique, surgeons try to fill the gap with autogenous graft materials including skin, dermis, flap of temporal muscle, cartilage or even alloplastic materials like silastic (Figure 11 a-c). The placement of these materials prevents the recurrence possibility. TMJ reconstruction is the third treatment option commonly done by means of a costochondral graft. However, other autogenous graft sources like clavicular osteochondral graft, coronoid process graft or alloplastic condylar implants can be used to reconstruct the lost segments. Autogenous sources present donor site morbidity; however alloplastic grafts are procedures with significant disadvantages of implant fracture of foreign body reaction. Between autogenous sources, costochondral grafts represent the most variable growth behavior, particularly in growing children, as compared to coronoid process graft, which demonstrate more predictable growth behavior.
Interpositional arthroplasty of an ankylotic condyle by means of square-shaped silastic graft material, a) Selected alloplastic silastic-based graft material, b) Insertion of the alloplastic silastic material, c) final position of the alloplastic material filling up the entire space created by the gap arthroplasty.
Aggressive total resection of the ankylotic segment in the condylar TMJ region. Recently, complete excision of the bony mass has been questioned regarding the increasing probability of the recurrence rate [10]. The underlying postulation was that leaving the opposing bony cut surface of the condyles after complete excision increase the amount of clot formation on dead space, which ultimately results in the formation of dense fibrous bridges that impede future mandibular movement [32]. Partial osteotomy of the region with minimal clot formation has been cited as a more potent surgical approach [32].
Coronoidectomy on the affected side (ipsilateral) which usually elongates in long-standing ankylosis and prevents intra-operative maximal opening because of the restriction. The autogenous bone achieved by this step can be used as a source of graft material to re-establish the ramus height of the affected side.
If the above-mentioned procedures do not result in normal maximum opening (more than 35 mm) without excessive force, the opposite coronoid (contralateral) must also be removed.
Lining of the joint with temporalis fascia or the remaining disk [16]
Remnants of the meniscus can serve as a barrier to prevent direct bony contacts and further fusion between condylar heads and glenoid fossa. However, there is controversy in the literature regarding the main role of the disc on the development of ankylosis [7]. In many traumatized cases, it has been shown that the ankylosis can occur even in the presence of an intact meniscus in the joint space [33-34].
Reconstruction of the ramus segment with costochondral grafts in growing patients if possible using rigid fixation (Figure 12 a-c),
Intraoperative photographs of a patient with TMJ reconstruction treatment plan, a) extraoral access to the TMJ ankylotic mass through a preauricular excision, b) submandibular incision for placement of fixation plates over the costochondral graft, c) after aggressive excision of the ankylotic mass and fixation of the costochondral graft by means of fixation screws.
Intra-operative open bite creation on the affected side to permit settling of the bone graft, which should be maintained by a hybrid orthodontic appliance for 3-6 months (Figure 13 a) [35]. Simple removable functional appliance (Hybrid) with lingual and buccal shields on the affected side to encourage dental eruption and a bite block on the contralateral side to impede the eruption (Figure 13 b). In adult cases, however, considering the absence of passive dental eruption, the open bite should be managed by means of orthodontic brackets and light intermaxillary elastics (Figure 14 a, b).
a) A hybrid functional appliance consist of two set of shields (lingual and buccal) to facilitate dental eruption on the affected side and acrylic bite block to impede dental eruption on the opposite site, b) A hybrid functional appliance in place
a) Bonding of orthodontic brackets on the upper and lower arch to correct the openbite on the affected side; note the degree of anterior open bite, b) Intraoral photograph of the final occlusion (From Behnia H: A Textbook of Advanced Oral and Maxillofacial Surgery ISBN 978-953-51-1146-7. chapter 16, Distraction Osteogenesis; 2013).
Early mobilization with a short period of intermaxillary fixation (not more than 3 weeks),
Supportive adjunctive therapy including physiotherapy with strict follow up to prevent the re-ankylosis phenomena. This therapy disrupts and prevents adhesions and soft tissue contraction in the healing stage (Figure 15 a-c).
a-c) Adjunctive physiotherapy appliances that are used as aiding appliances during the physiotherapy phase.
Additional corrective surgery at the later stages when growth is completed
Recurrence of ankylosis and restricted mandibular movement are the most common complications after surgical management of the ankylotic mass. Following surgical protocol and also adequate compliance with postoperative adjunctive therapy might prevent these complications [31]. The final postoperative result is dependent directly on the selected surgical procedure, surgical technique, and attention to postsurgical physiotherapy.
A 5-year-old girl with a history of left condylar trauma at age 2, with progressive facial asymmetry and deviation of the dental midlines due to left condylar ankylosis (Figure 16 a). There was no history of any other congenital malformation or childhood illness. On clinical examination her jaw deviated slightly to the left on closure and showed limited right lateral excursion. The ankylotic mass of the left condyle was demonstrated clearly on the MRI (Figure 16 b). An autogenous costochondral graft to reconstruct the left condyle had been done at age 5, which left an intraoperative open bite on the left side (Figure 16 c, d). A removable functional hybrid appliance was provided for the patient immediately after surgery to maintain the graft in a suitable position and let the posterior teeth on contralateral side erupt. This appliance opened the bite on the left side and brought the chin to the midline (Figure 16 e). The patient cooperated very well in the postsurgical phase with removable appliance and functional exercises of the jaws. One year after the orthodontic phase, the patient demonstrated an acceptable occlusion and facial symmetry (Figure 16 f).
a) Facial view of a 5 year-old boy, b) MRI before any orthodontic intervention, c) postoperative openbite immediately after surgery to free the ankylotic condyle, d) Insertion of a hybrid functional appliance for differential dental eruption, e) occlusion of the patient. The remarkable improvement from unilateral condylar ankylosis and subsequent normal symmetric growth of facial structure was achieved. The functional appliance was also worn at night during the growth period. f) Final facial view
Patients with a history of persistent ankylosis usually demonstrate significant facial asymmetry. In addition to previously described surgery to release the ankylotic mass, these patients usually should undergo a second procedure to compensate developed facial asymmetries. This second procedure can range from a conservative genioplasty to orthognathic surgery of both jaws. Recently, distraction osteogenesis has become popular as another possible treatment option for the second phase [36]. However, precise monitoring of the distraction direction is an important consideration during this procedure. The final result of the distraction osteogenesis must be maintained via help of other functional appliances in growing patients [37]. Other adjunctive cosmetic surgical techniques like fat injection also can be applied to compensate the remaining asymmetry of the face [30].
A case with unilateral distraction osteogenesis after receiving costochondral graft. Lateral cephalometry of the patient before (left) and after (right) distractor insertion.
A 21-year-old male with a history of trauma at age 9, presented severe mandibular deficiency, micrognathia with restricted excursive and protrusive mandibular movement secondary to bilateral condylar ankylosis (Figure 18 a). The dental history of the patient revealed that, he had previously undergone an autogenous costochondral graft after bilateral condylectomy one year later, but re-ankylosis occurred. This whole procedure was repeated again one year after failure; however it did not fully address the patient’s problem.
a) Pre-distraction facial and intraoral appearance. Significant mandibular deficiency is apparent. b) Circumferential osteotomies were made at the body of the right and left ramus and then custom-made unidirectional extraoral distractors were fixed in place. The mandible was advanced by 7 mm. The posterior open bite was created at the right side as a result of mandibular lengthening. Orthodontic triangle elastics were used concomitant with fixed orthodontic appliance to manage the posterior right open bite. c) Frontal facial view after debonding.
Although significant complications in the postoperative phase subsequent to surgery are not dramatic, it varies from mild pain to more serious persisting pain with restricted jaw movement and re-ankylosis. These unexpected adverse events and complications after surgery are mostly divided into two broad categories; those related to re-ankylosis and those related to the overgrowth of the cartilaginous autograft [38].
In the literature, there are two main reasons for re-ankylosis after surgical release including inadequate resection of the ankylotic mass intraoperatively and also, absence of patient compliance regarding post-operative jaw exercises [39-40]. The higher rate of reported re-ankylosis in children comparing to adults may be due to poor compliance to aggressive post-operative physiotherapy [4]. Complete diagnostic assessment of the ankylotic area, based on preoperative imaging examinations, is necessary to determine the extent of bony fusion and the length of the coronoid process on both sides [38]. The extent of bony fusion in both sagittal and coronal planes should be studied carefully to prevent any serious complication of facial nerve and maxillary artery injuries. Adequate mouth opening must be checked intraoperatively as a clinical indicator of successful surgery. Further ipsilateral or contralateral coronoidectomy with or without soft tissue release may need to be performed to achieve required mouth opening [38]. Growth behavior of inserted grafts including under and overgrowth may also present some complications in later stages of treatment. The role of jaw mobility exercises at home and at physiotherapy in prevention of re-ankylosis cannot be over-emphasized in children or adults. The preventive approach should be strict adhesion to surgical protocol and post-operative physiotherapy requirements, monitored by both the orthodontist and surgeon (Figure 19).
a) Panoramic radiograph of re-ankylosis after previous costochondral grafting b) 3D CT showing complete bony ankylosis of the right condyle.
However, if the re-ankylosis occurs, the best option for its management depends directly on the type of ankylosis. Bony re-ankylosis needs additional surgical procedures. Fibrosis re-ankylosis may be managed by means of progressive jaw mobility exercises that can be delivered through different approaches. Some removable appliances may help clinicians overcome this problem (Figure 20 a-d). If the patient cannot comply with these techniques, the surgeon should help them by initiating physiotherapy under local anesthesia.
A 5-year-old with bilateral condylar ankylosis following a traumatic event. He underwent a surgical procedure to release the ankylotic condyles, which involved bilateral coronoidectomy also, a) Restricted opening secondary to re-ankylosis, b) Intraoral appliance consisting of labial pads, and acrylic posterior bite plates that incorporate two vertical-direction screws, c) The patient was asked to open the screw once a day, d) Because of the fibrosis type of ankylosis, the patient was able to open his mouth significantly more after treatment.
A 29-year-old man was seen for treatment of severe facial asymmetry secondary to right condylar overgrowth (Figure 21 a-e). There was a history of TMJ ankylosis of the right condyle at age 3. Three years later, the patient underwent an autogenous costochondral graft to reconstruct the right mandibular condyle. The condylar structure was composed of the cartilage part of rib graft. As reported by the patient, the condylar overgrowth initiated approximately four years after graft surgery, when he was 10 years old, which lead to a marked facial asymmetry. On clinical examination there was chin deviation and midline divergence (mandibular dental midline shift). On functional evaluation of the patient, there was a significant restriction on full range of anterior and transverse jaw motion, with deviation upon opening. The treatment plan was to remove the condylar overgrowth through a preauricular incision (Figure 21 f, g). Postoperative facial photography and panoramic view showed significant improvement in facial symmetry at 18 month follow up (Figure 21 h-k).
Male aged 29 years, a,b) severe facial asymmetry secondary to right condylar overgrowth is apparent, c-e) 3D computed tomography, posteroanterior and panoramic radiographs of the patient before surgical procedure, f) intra-operative view of the right condylar overgrowth mass, g) excess part of overgrowth of the condyle. h,i) postoperative clinical appearance of the patient after surgical removal of condylar overgrowth mass, j,k) Final posteroanterior and panoramic radiographs of the patient following 18 months follow up.
The authors thank staff of Orthodontic, Pediatric and Oral and Maxillofacial Surgery departments for general support and treatment procedures of the presented cases.
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Ametaj, Afshin Hosseini, John F. Odhiambo, Summera Iqbal, Sumeet Sharma, Qilan Deng, Tran H. Lam, Umar Farooq, Qendrim Zebeli and Suzanna M. Dunn",authors:[{id:"35129",title:"Prof.",name:"Burim",middleName:null,surname:"Ametaj",slug:"burim-ametaj",fullName:"Burim Ametaj"},{id:"49239",title:"Prof.",name:"Qendrim",middleName:null,surname:"Zebeli",slug:"qendrim-zebeli",fullName:"Qendrim Zebeli"},{id:"49242",title:"MSc",name:"Sarah",middleName:null,surname:"Terrill",slug:"sarah-terrill",fullName:"Sarah Terrill"}]},{id:"46263",doi:"10.5772/57507",title:"HLA-E, HLA-F and HLA-G — The Non-Classical Side of the MHC Cluster",slug:"hla-e-hla-f-and-hla-g-the-non-classical-side-of-the-mhc-cluster",totalDownloads:2460,totalCrossrefCites:11,totalDimensionsCites:17,abstract:null,book:{id:"3824",slug:"hla-and-associated-important-diseases",title:"HLA and Associated Important Diseases",fullTitle:"HLA and Associated Important Diseases"},signatures:"Iris Foroni, Ana Rita Couto, Bruno Filipe Bettencourt, Margarida\nSantos, Manuela Lima and Jácome Bruges-Armas",authors:[{id:"68881",title:"Dr.",name:"Jacome",middleName:null,surname:"Bruges-Armas",slug:"jacome-bruges-armas",fullName:"Jacome Bruges-Armas"},{id:"81144",title:"Dr.",name:"Ana Rita",middleName:null,surname:"Couto Rendeiro",slug:"ana-rita-couto-rendeiro",fullName:"Ana Rita Couto Rendeiro"},{id:"81147",title:"Prof.",name:"Manuela",middleName:null,surname:"Lima",slug:"manuela-lima",fullName:"Manuela Lima"},{id:"82501",title:"Ph.D.",name:"Bruno Filipe",middleName:null,surname:"Bettencourt",slug:"bruno-filipe-bettencourt",fullName:"Bruno Filipe Bettencourt"},{id:"170238",title:"Dr.",name:"Iris",middleName:null,surname:"Foroni",slug:"iris-foroni",fullName:"Iris Foroni"},{id:"170824",title:"Dr.",name:"Margarida",middleName:null,surname:"Santos",slug:"margarida-santos",fullName:"Margarida Santos"}]}],mostDownloadedChaptersLast30Days:[{id:"65210",title:"Introductory Chapter: Concept of Human Leukocyte Antigen (HLA)",slug:"introductory-chapter-concept-of-human-leukocyte-antigen-hla-",totalDownloads:2722,totalCrossrefCites:2,totalDimensionsCites:5,abstract:null,book:{id:"7140",slug:"human-leukocyte-antigen-hla-",title:"Human Leukocyte Antigen (HLA)",fullTitle:"Human Leukocyte Antigen (HLA)"},signatures:"Batool Mutar Mahdi",authors:[{id:"77656",title:"Dr.",name:"Batool Mutar",middleName:null,surname:"Mahdi",slug:"batool-mutar-mahdi",fullName:"Batool Mutar Mahdi"}]},{id:"21456",title:"Haptoglobin and Hemopexin in Heme Detoxification and Iron Recycling",slug:"haptoglobin-and-hemopexin-in-heme-detoxification-and-iron-recycling",totalDownloads:4111,totalCrossrefCites:5,totalDimensionsCites:20,abstract:null,book:{id:"234",slug:"acute-phase-proteins-regulation-and-functions-of-acute-phase-proteins",title:"Acute Phase Proteins",fullTitle:"Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins"},signatures:"Deborah Chiabrando, Francesca Vinchi, Veronica Fiorito and Emanuela Tolosano",authors:[{id:"30837",title:"Prof.",name:"Emanuela",middleName:null,surname:"Tolosano",slug:"emanuela-tolosano",fullName:"Emanuela Tolosano"},{id:"48270",title:"Dr.",name:"Deborah",middleName:null,surname:"Chiabrando",slug:"deborah-chiabrando",fullName:"Deborah Chiabrando"},{id:"48271",title:"Dr.",name:"Francesca",middleName:null,surname:"Vinchi",slug:"francesca-vinchi",fullName:"Francesca Vinchi"},{id:"48272",title:"Dr.",name:"Veronica",middleName:null,surname:"Fiorito",slug:"veronica-fiorito",fullName:"Veronica Fiorito"}]},{id:"46315",title:"In Phase HLA Genotyping by Next Generation Sequencing — A Comparison Between Two Massively Parallel Sequencing Bench-Top Systems, the Roche GS Junior and Ion Torrent PGM",slug:"in-phase-hla-genotyping-by-next-generation-sequencing-a-comparison-between-two-massively-parallel-se",totalDownloads:4475,totalCrossrefCites:1,totalDimensionsCites:7,abstract:null,book:{id:"3824",slug:"hla-and-associated-important-diseases",title:"HLA and Associated Important Diseases",fullTitle:"HLA and Associated Important Diseases"},signatures:"Jerzy K. Kulski, Shingo Suzuki, Yuki Ozaki, Shigeki Mitsunaga,\nHidetoshi Inoko and Takashi Shiina",authors:[{id:"169295",title:"Dr.",name:"Jerzy",middleName:"Kazimierz",surname:"Kulski",slug:"jerzy-kulski",fullName:"Jerzy Kulski"},{id:"170241",title:"Dr.",name:"Shingo",middleName:null,surname:"Suzuki",slug:"shingo-suzuki",fullName:"Shingo Suzuki"},{id:"170242",title:"Dr.",name:"Yuki",middleName:null,surname:"Ozaki",slug:"yuki-ozaki",fullName:"Yuki Ozaki"},{id:"170243",title:"Dr.",name:"Shigeki",middleName:null,surname:"Mitsunaga",slug:"shigeki-mitsunaga",fullName:"Shigeki Mitsunaga"},{id:"170244",title:"Prof.",name:"Hidetoshi",middleName:null,surname:"Inoko",slug:"hidetoshi-inoko",fullName:"Hidetoshi Inoko"},{id:"170245",title:"Prof.",name:"Takashi",middleName:null,surname:"Shiina",slug:"takashi-shiina",fullName:"Takashi Shiina"}]},{id:"66411",title:"TNFR2 and Regulatory T Cells: Potential Immune Checkpoint Target in Cancer Immunotherapy",slug:"tnfr2-and-regulatory-t-cells-potential-immune-checkpoint-target-in-cancer-immunotherapy",totalDownloads:961,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"TNF has both proinflammatory and antiinflammatory effects. It binds to two structurally related but functionally distinct receptors TNFR1 and TNFR2. Unlike TNFR1 that is ubiquitously expressed, TNFR2 expression is more limited to myeloid and lymphoid cell lineages including a fraction of regulatory T cells (Treg). In general, TNFR1 is responsible for TNF-mediated cell apoptosis and death, and mostly induces proinflammatory reactions. However, TNFR2 mainly leads to functions related to cell survival and immune suppression. Treg play an indispensable role in maintaining immunological self-tolerance and restraining excessive immune reactions deleterious to the host. Impaired Treg-mediated immune regulation has been observed in various autoimmune diseases as well as in cancers. Therefore, Treg might provide an ideal therapeutic target for diseases where the immune balance is impaired and could benefit from the regulation of Treg properties. TNFR2 is highly expressed on Treg in mice and in humans, and TNFR2+ Treg reveal the most potent suppressive capacity. TNF-TNFR2 ligation benefits Treg proliferation, although the effect on Treg suppressive function remains controversial. Here, we will describe in detail the TNF-mediated regulation of Treg and the potential clinical applications in cancer immunotherapy as well as in autoimmune diseases, with the focus on human Treg subsets.",book:{id:"7853",slug:"cytokines",title:"Cytokines",fullTitle:"Cytokines"},signatures:"Xuehui He and Xinhui Wang",authors:[{id:"284559",title:"Dr.",name:"Xuehui",middleName:null,surname:"He",slug:"xuehui-he",fullName:"Xuehui He"},{id:"296531",title:"Dr.",name:"Xinhui",middleName:null,surname:"Wang",slug:"xinhui-wang",fullName:"Xinhui Wang"}]},{id:"46259",title:"HLA in Gastrointestinal Inflammatory Disorders",slug:"hla-in-gastrointestinal-inflammatory-disorders",totalDownloads:1997,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"3824",slug:"hla-and-associated-important-diseases",title:"HLA and Associated Important Diseases",fullTitle:"HLA and Associated Important Diseases"},signatures:"M.I. Torres, T. Palomeque and P. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"May 26th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!1,editor:null,editorTwo:null,editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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