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• W2917445900 abstract "Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz—in this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article by Greveling et al. (http://dx.doi.org/10.1016/j.jid.2016.06.014). Detailed answers and a list of relevant references are available following the Quiz Questions below. 1.What is your diagnosis?a.Melanocytic nevusb.Solar lentigoc.Lentigo malignad.Actinic keratosise.Seborrheic keratosis2.A suspicious, irregularly shaped, hyper-pigmented lesion on the cheek of a woman is biopsied. The histopathology results read Lentigo Maligna. Which of the following has the lowest cure rates?a.Mohs Micrographic Surgical Excisionb.Radiotherapyc.Imiquimodd.5- Fluorouracile.Cryotherapy3.Greveling et al. hypothesized four contributing factors to the underestimation in the number of cases of both Lentigo maligna (de Moraes et al., 2007de Moraes A.M. Pavarin L.B. Herreros F. de Aguiar Michelman F. Velho P.E. de Souza E.M. Cryosurgical treatment of lentigo maligna.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2007; 5: 477-480Google Scholar) and Lentigo maligna melanoma (LMM). Which of the following did the authors NOT give as a contributing factor?a.Cases of LMM that were registered without a previous diagnosis of LM were not included in the study.b.Excisions of LM lesions could have been done at a time before certain diagnostic criteria for LMM existed.c.Diagnosis of LM is challenging due to clinical presentation that can be subtle and varied.d.Only cases of LM that were histologically confirmed were included in the study.e.LM is typically treated in the Netherlands, decreasing the odds of it developing into LMM. See following pages for detailed answers. 1.What is your diagnosis? ANSWER: Lentigo maligna (third choice). The lesion in the picture represents lentigo Maligna—a type of melanoma in situ that has an estimated 5% lifetime risk of developing into lentigo maligna melanoma (McKenna et al., 2006McKenna J.K. Florell S.R. Goldman G.D. Bowen G.M. Lentigo maligna/lentigo maligna melanoma: current state of diagnosis and treatment.Dermatol Surg. 2006; 32: 493-504Crossref PubMed Scopus (171) Google Scholar; Read et al., 2016Read T. Noonan C. David M. Wagels M. Foote M. Schaider H. et al.A systematic review of non-surgical treatments for lentigo maligna.Journal of the European Academy of Dermatology and Venereology : JEADV. 2016; 30: 748-753Google Scholar). As opposed to lentigo maligna melanoma, in LM the proliferation of melanocytes are confined to the hair follicle or basal epidermis layer, making it an in situ melanoma (Reed and Shea, 2011Reed J.A. Shea C.R. Lentigo maligna: melanoma in situ on chronically sun-damaged skin.Archives of pathology & laboratory medicine. 2011; 135: 838-841PubMed Google Scholar). LM lesions typically appear on older patients on the head and neck as a pigmented and irregular lesion; also, LM is related to sun damage, appearing more often on those with fair skin (Reed and Shea, 2011Reed J.A. Shea C.R. Lentigo maligna: melanoma in situ on chronically sun-damaged skin.Archives of pathology & laboratory medicine. 2011; 135: 838-841PubMed Google Scholar; Hill and Gramp, 1999Hill D.C. Gramp A.A. Surgical treatment of lentigo maligna and lentigo maligna melanoma.The Australasian journal of dermatology. 1999; 40: 25-30Crossref PubMed Scopus (60) Google Scholar). The lesions appear as relatively large slow growing, smooth patches of skin with variable pigmentation (Reed and Shea, 2011Reed J.A. Shea C.R. Lentigo maligna: melanoma in situ on chronically sun-damaged skin.Archives of pathology & laboratory medicine. 2011; 135: 838-841PubMed Google Scholar). If an LM is suspected, biopsy should be performed. Because of the risk that LM can develop into Lentigo Maligna melanoma, it is typically surgically excised with clear margins (Hill and Gramp, 2011). In very elderly patients, an additional option is to forego surgical treatment and instead watch for changes and biopsy suspicious areas as they appear. Discussion of incorrect answers Melanocytic nevi (first choice), commonly referred to as moles, are common benign lesions caused by an increase in melanocytes (Suh and Bolognia, 2009Suh K.Y. Bolognia J.L. Signature nevi.J Am Acad Dermatol. 2009; 60: 508-514Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar). Nevi are either congenital or acquired, and are influenced by genetic factors and exposure to UV radiation (Suh and Bolognia, 2009Suh K.Y. Bolognia J.L. Signature nevi.J Am Acad Dermatol. 2009; 60: 508-514Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar). Nevi can occur on any part of the body and vary in shape, pigmentation, size, and surfacing, although they tend to be uniform in color and regular in shape. Because melanocytic nevi resemble early melanoma and people with more moles have a greater risk of developing melanoma, moles are often treated with caution ( Suh and Bolognia, 2009Suh K.Y. Bolognia J.L. Signature nevi.J Am Acad Dermatol. 2009; 60: 508-514Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar). Melanocytic nevi are typically not removed except for cosmetic reasons or if cancer is a concern. Solar lentigines (SL) (second choice) are typically well defined with moth-eaten borders caused by sun exposure. The brown pigment spots are benign and vary widely in size (Praetorius et al., 2014Praetorius C. Sturm R.A. Steingrimsson E. Sun-induced freckling: ephelides and solar lentigines.Pigment Cell Melanoma Res. 2014; 27: 339-350Google Scholar). SL most often occur on the arms, hands, and face in patients over 50 years old. Accumulated photodamage causes genetic changes that lead to SL (Praetorius et al., 2014Praetorius C. Sturm R.A. Steingrimsson E. Sun-induced freckling: ephelides and solar lentigines.Pigment Cell Melanoma Res. 2014; 27: 339-350Google Scholar). SL is characterized by hyperpigmentation in the basal layer and elongated epidermal ridges, which are thought to be caused by keratinocyte and melanocyte proliferation (Cario-Andre et al., 2004Cario-Andre M. Lepreux S. Pain C. Nizard C. Noblesse E. Taieb A. Perilesional vs. lesional skin changes in senile lentigo.J Cutan Pathol. 2004; 31: 441-447Crossref PubMed Scopus (46) Google Scholar). Actinic keratoses (AK)(fourth choice) are a rarely pigmented common pre-cancerous lesions that can evolve into squamous cell carcinoma (Costa et al., 2015Costa C. Scalvenzi M. Ayala F. Fabbrocini G. Monfrecola G. How to treat actinic keratosis? An update.J Dermatol Case Rep. 2015; 9: 29-35Crossref PubMed Scopus (50) Google Scholar). Older age, high levels of sun exposure, and immunosuppression are risk factors for developing AKs. AK lesions are typically dry, erythematous, and scaly; caused by the proliferation of keratinocytes (Warszawik-Hendzel et al., 2015Warszawik-Hendzel O. Olszewska M. Maj M. Rakowska A. Czuwara J. Rudnicka L. Non- invasive diagnostic techniques in the diagnosis of squamous cell carcinoma.J Dermatol Case Rep. 2015; 9: 89-97Google Scholar). The size of AK lesions is usually less than one centimeter, and the lesions can also form plaques with telangiectasias (Costa et al., 2015Costa C. Scalvenzi M. Ayala F. Fabbrocini G. Monfrecola G. How to treat actinic keratosis? An update.J Dermatol Case Rep. 2015; 9: 29-35Crossref PubMed Scopus (50) Google Scholar). Thick AKs usually appear on the hands and arms while thinner AKs typically form on the head and neck. Seborrheic keratoses (SK) (fifth choice) are skin lesions that arise from proliferation of keratinocytes. They require removal if they are irritating or bleeding. SK skin tumors can become darker, thicker, and larger with time, occasionally leading to cosmetic treatment (Jackson et al., 2015Jackson J.M. Alexis A. Berman B. Berson D.S. Taylor S. Weiss J.S. Current Understanding of Seborrheic Keratosis: Prevalence, Etiology, Clinical Presentation, Diagnosis, and Management.J Drugs Dermatol. 2015; 14: 1119-1125PubMed Google Scholar). SKs usually appear as a clearly demarcated plaque that can be raised or flat. Identifying features include milia-like cysts and comedo-like openings (Braun et al., 2002Braun R.P. Rabinovitz H.S. Krischer J. Kreusch J. Oliviero M. Naldi L. et al.Dermoscopy of pigmented seborrheic keratosis: a morphological study.Arch Dermatol. 2002; 138: 1556-1560Crossref PubMed Scopus (160) Google Scholar). Like solar lentigines, many SKs have moth-eaten borders.2.A suspicious, irregularly shaped, hyper-pigmented lesion on the cheek of a woman is biopsied. The histopathology results read Lentigo Maligna. Which of the following has the lowest cure rates? ANSWER: 5- Fluorouracil (fourth choice) Lentigo Maligna is a subset of Melanoma in situ, which consists of malignant cells but does not show invasive growth. Generally speaking, the Gold Standard and preferred treatment for Lentigo Maligna is surgery. Surgical excision with margins of 5-10mm is the recommendation for all types of Melanoma In Situ (MIS), including LM, according to several guidelines (Oncology NCCNCPGi; Bichakjian et al., 2011Bichakjian C.K. Halpern A.C. Johnson T.M. Foote Hood A. Grichnik J.M. Swetter S.M. et al.Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology.Journal of the American Academy of Dermatology. 2011; 65: 1032-1047Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar; Marsden et al., 2010Marsden J.R. Newton-Bishop J.A. Burrows L. Cook M. Corrie P.G. Cox N.H. et al.Revised U.K. guidelines for the management of cutaneous melanoma 2010.The British journal of dermatology. 2010; 163: 238-256Crossref PubMed Scopus (284) Google Scholar). However, in patients that are non-surgical candidates or for regions of the body where reconstruction is problematic, various modalities are available. Examples including tissue destruction techniques with cryotherapy, topical immune-modulator therapy with imiquimod, and radiotherapy have all been proven to be effective. 5- Fluorouracil or 5- FU (fourth choice), on the other hand, has not been proven to be effective in LM (Gaspar and Dawber, 1997Gaspar Z.S. Dawber R.P. Treatment of lentigo maligna.The Australasian journal of dermatology. 1997; 38 (quiz 7-8): 1-6Google Scholar). It is effective, however, in the treatment of several other in situ neoplasms of the skin. It is an established treatment for Actinic Keratosis (AK) since the 1960’s. Recommended dosing for this purpose is 5% twice daily for 2-4 weeks. It is also approved for treatment of basal cell carcinoma (BCC), but few studies support its efficacy (Micali et al., 2014Micali G. Lacarrubba F. Nasca M.R. Ferraro S. Schwartz R.A. Topical pharmacotherapy for skin cancer: part II. Clinical applications.Journal of the American Academy of Dermatology. 2014; 70 (e1-12; quiz 9912): 979Google Scholar). Discussion of Incorrect Answers Wide Local Excision (WLE), Staged Surgical Excision (SSE), and Mohs Micrographic Surgery (MMS) may all be used in the surgical treatment of LM (first choice). Currently, guidelines recommend that wide local surgical excision for any melanoma in situ (including LM) be between 5 and 10 mm, while wider margins such as 9 to 15 mm result in clearance rates of up to 94 percent. Some authors recommend dermatologists err on the side of caution in cases of LM, as there may be subclinical peripheral disease (McLeod et al., 2011McLeod M. Choudhary S. Giannakakis G. Nouri K. Surgical treatments for lentigo maligna: a review.Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2011; 37: 1210-1228Crossref PubMed Scopus (65) Google Scholar). As for SSE, this is any surgical procedure incorporating more than one stage of excision, with the next stage being determined by the histological findings of the last. MMS is a subcategory of SSE in which frozen sections are used for the histological analysis; its benefits are that virtually 100% of the tumor borders can be visualized, and only the smallest amount of tissue is excised. This surgical technique enjoys the added advantage of optimized cosmesis and functionality (McLeod et al., 2011McLeod M. Choudhary S. Giannakakis G. Nouri K. Surgical treatments for lentigo maligna: a review.Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2011; 37: 1210-1228Crossref PubMed Scopus (65) Google Scholar). Radiotherapy (second choice) may also be used in the treatment of LM. In a recent systematic review, ten studies were identified that evaluated radiotherapy in patients with LM. The complete response rates varied between 80–100% and recurrence rates were relatively low, with a maximum of 31.3%. Out of a total of 454 cases of LM, there were 52 recurrences and, therefore, a mean recurrence rate of 11.5% (Read et al., 2016Read T. Noonan C. David M. Wagels M. Foote M. Schaider H. et al.A systematic review of non-surgical treatments for lentigo maligna.Journal of the European Academy of Dermatology and Venereology : JEADV. 2016; 30: 748-753Google Scholar). One study showed a mean recurrence time of 61 months, emphasizing that clinical recurrence might occur after long latency periods. While this treatment may not be as successful as surgery, it is a fair substitute ( Read et al., 2016Read T. Noonan C. David M. Wagels M. Foote M. Schaider H. et al.A systematic review of non-surgical treatments for lentigo maligna.Journal of the European Academy of Dermatology and Venereology : JEADV. 2016; 30: 748-753Google Scholar). Reported adverse effects include pigment change, telangiectasia, erythema, chronic radiodermatitis, and even skin cancer; but for the most part, radiotherapy is safe and well tolerated (Read et al., 2016Read T. Noonan C. David M. Wagels M. Foote M. Schaider H. et al.A systematic review of non-surgical treatments for lentigo maligna.Journal of the European Academy of Dermatology and Venereology : JEADV. 2016; 30: 748-753Google Scholar; Suter, 2015Suter L. Radation Treatment and Radiation Reactions in Dermatology.in: Panizzon R.G.S,.M.H. Side Effects of Radiation Treatment. Springer-Verlag, Berlin Heidelberg2015Google Scholar). Imiquimod (third choice) is a topical immune-modulator compound which both stimulates the immune system and inhibits angiogenesis. This contributes to its clinical efficacy against different types of dermatologic conditions including genital warts, actinic keratosis, basal-cell carcinoma, squamous-cell carcinoma, and Lentigo Maligna (de Moraes et al., 2007de Moraes A.M. Pavarin L.B. Herreros F. de Aguiar Michelman F. Velho P.E. de Souza E.M. Cryosurgical treatment of lentigo maligna.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2007; 5: 477-480Google Scholar; Hengge and Schaller, 2004Hengge U.R. Schaller J. SUccessful treatment of invasive squamous cell carcinoma using topical imiquimod.Archives of Dermatology. 2004; 140: 404-406Google Scholar). In a recent review, Imiquimod cream offered a 76% histologic, and 78% clinical clearance rate for LM. Both cumulative dose and treatment intensity affected tumor clearance, with greater than 60 total applications, or greater than five applications per week, being associated with a higher likelihood of histologic clearance (Mora et al., 2015Mora A.N. Karia P.S. Nguyen B.M. A quantitative systematic review of the efficacy of imiquimod monotherapy for lentigo maligna and an analysis of factors that affect tumor clearance.Journal of the American Academy of Dermatology. 2015; 73: 205-212Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar). In another study by Kai et al, of all patients successfully treated with topical Imiquimod therapy, none (0%) recurred within a 5 year follow-up time frame (Kai et al., 2016Kai A.C. Richards T. Coleman A. Mallipeddi R. Barlow R. Craythorne E.E. Five-year recurrence rate of lentigo maligna after treatment with imiquimod.British Journal of Dermatology. 2016; 174: 165-168Crossref Scopus (34) Google Scholar). Cryotherapy (fifth choice) involves applying a cold agent, such as liquid nitrogen, to the surface of the skin, which acts to remove heat from the region, and is also thought to be effective management for LM. Melanocytes are known to be destroyed by temperatures ranging from -4°C to -7°C (McLeod et al., 2011McLeod M. Choudhary S. Giannakakis G. Nouri K. Surgical treatments for lentigo maligna: a review.Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2011; 37: 1210-1228Crossref PubMed Scopus (65) Google Scholar). In a recent study, patients were treated with two freeze-thaw cycles of liquid nitrogen in a single sitting. The lesions resolved clinically in every case, with no recurrence or metastasis detected during the mean follow-up time of 75.5 months. Some patients do develop hypopigmented scars (de Moraes et al., 2007de Moraes A.M. Pavarin L.B. Herreros F. de Aguiar Michelman F. Velho P.E. de Souza E.M. Cryosurgical treatment of lentigo maligna.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2007; 5: 477-480Google Scholar). Previous studies evaluating the usefulness of cryotherapy report clinical clearance rates of 60% or higher (Kuflik and Gage, 1994Kuflik E.G. Gage A.A. Cryosurgery for lentigo maligna.Journal of the American Academy of Dermatology. 1994; 31: 75-78Abstract Full Text PDF PubMed Scopus (71) Google Scholar; Bohler-Sommeregger et al., 1992Bohler-Sommeregger K. Schuller-Petrovic S. Neumann R. Muller E. Cryosurgery of lentigo maligna.Plastic and reconstructive surgery. 1992; 90 (discussion 41-4): 436-440Google Scholar).3.Greveling et al. hypothesized four contributing factors to the underestimation in the number of cases of both Lentigo maligna (de Moraes et al., 2007de Moraes A.M. Pavarin L.B. Herreros F. de Aguiar Michelman F. Velho P.E. de Souza E.M. Cryosurgical treatment of lentigo maligna.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2007; 5: 477-480Google Scholar) and Lentigo maligna melanoma (LMM). Which of the following did the authors NOT give as a contributing factor? ANSWER: Diagnosis of LM is challenging due to clinical presentation that can be subtle and varied (third choice). Kasprzak et al. stated that diagnosis of Lentigo maligna is challenging due to clinical presentation that can be subtle and varied. Early diagnosis is then achieved via dermoscopy, Wood’s lamp examination, and/or confocal microscopy. The most definitive method for determining the presence of Lentigo maligna is to do a histological analysis (Kasprzak and Xu, 2015Kasprzak J.M. Xu Y.G. Diagnosis and management of lentigo maligna: a review.Drugs Context. 2015; 4: 212281Crossref PubMed Scopus (50) Google Scholar). Additional research suggests that histological analysis for Lentigo maligna can still be challenging if the histological sample includes atypical melanocytes, which are often present in sun damaged skin (McKenna et al, 2016). These are a few of the reasons it can be challenging to correctly diagnose Lentigo maligna. However, challenges due to diagnosis are not mentioned by Greveling et al. as contributing factors to the underestimation of cases. Discussion of Incorrect Answers The authors maintained some exclusion criteria for selecting the clinical data to be included in the study. One of the exclusion criteria was to remove diagnoses of LMM that were not preceded by a diagnosis of LM (Greveling et al., 2016Greveling K. Wakkee M. Nijsten T. van den Bos R.R. Hollestein L.M. Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989 - 2013.J Invest Dermatol. 2016; Google Scholar). Since this (first choice) was a contributing factor to the underestimation of cases, it is considered an incorrect answer. The authors hypothesized that excision and removal of LM lesions could have led to an underestimation in cases of both LM and LMM. This is because LM lesions could have been removed as a precaution, limiting the chance that LM would develop into LMM. Additionally, the authors hypothesized that LMM lesions could have been removed at a time when they would have been diagnosed as LM due to certain diagnostic criteria (Greveling et al., 2016Greveling K. Wakkee M. Nijsten T. van den Bos R.R. Hollestein L.M. Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989 - 2013.J Invest Dermatol. 2016; Google Scholar). Thus making the (second choice) an incorrect answer. Given the complexity of diagnosing LM, as mentioned by Kasprzak et al and McKenna et al, the authors decided to limit the clinical data to patients that had an LM diagnosis confirmed by histological analysis. One of the limitations mentioned in the study was the lack of information on LM that was not histologically confirmed, which could have altered the overall picture when it came to overestimation or underestimation of LM and subsequent LMM risk (Greveling et al., 2016Greveling K. Wakkee M. Nijsten T. van den Bos R.R. Hollestein L.M. Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989 - 2013.J Invest Dermatol. 2016; Google Scholar). Since the authors included confirmation from histological analysis as a contributing factor to the underestimation of overall cases, it makes this (fourth choice) an incorrect answer. Given that cases of LM are typically treated in the Netherlands, this decreases the risk of progression of LM into LMM ( Greveling et al., 2016Greveling K. Wakkee M. Nijsten T. van den Bos R.R. Hollestein L.M. Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989 - 2013.J Invest Dermatol. 2016; Google Scholar). The authors deemed the treatment of LM as a contributing factor directly relating to the reduction in overall cases of LMM, thus making the (fifth choice) an incorrect answer. Download .pdf (.02 MB) Help with pdf files Quiz and brief explanation of correct answers Download .pdf (.12 MB) Help with pdf files Detailed discussion of all quiz answers" @default.
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• W2917445900 title "Cells to Surgery Quiz: October 2016" @default.
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