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      • Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

        ( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

      • KCI등재후보

        국내 의료기관의 항생제 사용 실태와 규제 시스템 조사

        방지환,송경호,박완범,김성한,조재현,김홍빈,김남중,오명돈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

        목적 : 이전 연구들에 따르면 아직까지 국내에서 불필요한 항생제 사용은 무시할 수 없는 수준이며, 특히, 수술환자들에 대한 예방적 항생제 투여가 문제로 지적되고 있다. 많은 병원에서 불필요한 항생제 처방을 제한하려는 노력을 하고 있지만 구체적인 현황에 대한 자료는 적은 실정이다. 이에 본 연구자 등은 국내 의료기관의 항생제 규제 시스템의 현황과 수술시 예방적 항생제 사용의 적정성을 알아보고자 한다. 재료 및 방법 : 전임 감염내과 전문의가 근무하는 의료기관 55곳에 대해 설문조사를 시행하였다. 설문의 내용은 적정한 항생제 사용을 유도하기 위한 정책 및 규제 프로그램, 실제 각 의료기관의 예방적 항생제 사용 현황 등으로 이루어져 있다. 결과 : 55개의 의료기관에 보낸 설문 중 44개가 회수되었다. 회신한 의료기관에서 항생제 처방 관리는 제한항생제 시스템을 가장 많이 이용하고 있었고(95.5%), 항생제에 대한 교육(79.5%), 전산시스템에서 관리(59.1%), 감염내과에 의뢰(54.5%), 항생제 사용 실적 검토(52.3%) 등의 순이었다. 대개의 병원에서 glycopeptides (100.0%), carbapenems (93.0%), quinupristin/dalfopristin 또는 linezolid(93.0%), 4세대 cephalosporin (74.4%), caspofungin 또는 voriconazole (62.8%), liposomal amphotericin B (60.5%) 등을 제한항생제로 분류하여 관리하고 있었다. 모든 의료기관에서 위절제술 및 유방절제술시에 불필요하게 예방적 항생제를 사용하고 있었다. 슬관절치환술의 경우 2세대 cephalosporin을 예방적으로 사용하는 경우가 가장 많았으며(30.2%), 관상동맥우회술의 경우 3세대 cephalosporin을 예방적으로 사용하는 경우가 가장 많았다(47.2%). 예방적 항생제의 투여 기간을 살펴보면 위절제술시 70.5%에서 4일을 초과하여 사용하고 있었고, 유방절제술시에는 63.6%에서, 슬관절치환술시에는 81.8%에서, 관동맥우회술시에는 81.1%에서 4일을 초과하여 장기간 예방적 항생제를 투여하고 있었다. 한편, 예방적 항생제 투여시 aminoglycoside계 항생제를 병용하는 경우도 많았다. 결론 : 아직까지 국내 의료기관에서 항생제 오남용을 막기 위한 노력이 더 필요할 것으로 생각되며, 특히 수술시 예방적 항생제의 올바른 투여에 많은 관심이 필요하다. Background : Previous studies in Korea showed that unnecessary antibiotic use could not be neglected, especially in prophylactic use. Currently many hospitals employ diverse antibiotic stewardship programs, but there are few studies on surveillance of such programs. So, we planned this study to evaluate current status of antimicrobial stewardship and adequacy of antimicrobial prophylaxis in surgery. Materials and Methods : We sent questionnaires about policy on antibiotic usage, control program for adequate antibiotic prescription, and actual status of prophylactic antibiotic usage to 55 infectious disease physicians in each hospital. Results : Of 55 contacted infectious diseases clinicians, 44 answered the questionnaire. Majority of hospitals employed restricted antimicrobial system (95.5%), education (79.5%), control by order communicating system (59.1%), consult to infectious disease physicians (59.1%), and review of cumulative antimicrobial usage (52.3%) to prevent inadequate antibiotic use. Glycopeptides were designated as a restricted antimicrobial agent in 100.0% of hospitals; carbapenems, 93.0%; quinupristin/ dalfopristin or linezolid, 93.0%; the 4th generation cephalosporins, 74.4%; caspofungin or voriconazole, 62.8%; liposomal amphotericin B, 60.5%, and so on. Unnecessary perioperative prophylactic antimicrobial agents were prescribed in gastrectomy and mastectomy in all the hospitals. The second generation cephalosporins and the third generation cephalosporins were the most commonly prescribed prophylactic antimicrobial agents in total knee replacement arthroplasty (TKRA) and coronary artery bypass graft surgery (CABG) respectively. In 70.5% of institutes they use prophylactic antimicrobial agents more than four days in gastrectomy; 63.6% in mastectomy; 81.8% in TKRA; 81.1% in CABG. Unnecessary combination of aminoglycosides with other antimicrobial agents for prophylactic use was another common problem. Conclusion : This study shows that more effort is required to diminish antimicrobial misuse or overuse, especially in prophylactic use for surgical patients.

      • KCI등재

        3차 의료기관에 입원한 노숙환자에서 감염질환의 유병율

        함세운,남기석,노혜진,홍경득,황래석,방지환,신형식 대한감염학회 2007 감염과 화학요법 Vol.39 No.4

        목적 : 3차 의료기관에서 입원치료를 받았던 노숙자를 대상으로 감염성 질환의 유병율을 알아보고자 하였다. 재료 및 방법 : 2002년 1월부터 2004년 8월 사이에 국립의료원에서 입원 치료를 받았던 269명의 노숙자 환자들을 대상으로 의무기록을 조사하였다. 결과 : 연구 기간동안 입원치료를 받은 총 269명의 노숙자 환자 중 남자가 249명(92.9%), 여자가 19명(7.1%)이었다. 감염질환의 유병율은 B형 간염이 228명 중 15명(6.6%), C형 간염 113명 중 8명(7.1%), 결핵은 269명중 19명(7.1%), VDRL 양성인 경우는 234명 중 25명(10.7%), 항사람면역결핍바이러스항체 양성은 130명중 2명(1.5%)이었다. B형 간염표면항원에 대한 항체 형성자는 118명(51.7%), 항체 미형성자는 95명(41.7%)이었다. 결핵으로 진단된 19명 중 객담도말 및 배양검사와 조직검사로 확인된 경우가 14명, 균음성이나 임상적으로 의심되는 경우가 5명이었다. 간질환 및 관련된 합병증으로 입원한 환자 28명 중 B형 및 C형 간염바이러스에 관련된 경우는 5명(17.9%)에불과하였고 결핵은 19명중 13명(68.4%)이 폐결핵 및 림프절종대의 증상으로 입원치료를 받았다. 복합 감염의 경우는 총 9명이었는데 후천면역결핍증후군 환자였던 2명중 1명이 결핵에 이환되어 있으면서 VDRL 양성소견을 보였고 다른 1명이 HIV와 결핵의 동시감염이었다. 결론 : 노숙자 입원환자에서 결핵, C형 간염 및 매독의 유병율이 일반 인구에 비해 높았다. 노숙자환자를 담당하는 의료인력를 보호하고 환자의 감염질환 유무를 파악하기 위해 적절한 선별검사가 필요하며 감염질환의 확산을 방지하기 위한 정부의 적극적인 대책이 필요하다. Background : Despite the expected high prevalence of several infectious diseases among the homeless, a majority of them have not received screening test and early treatment. Materials and Methods : The subjects of this study were 269 homeless patients who had been hospitalized in the National Medical Center (Korea) between January 2002 and August 2004. Their medical histories and records were reviewed to analyze the prevalence and clinical characteristics of hepatitis B and C, syphilis, tuberculosis and HIV infection among them. Results : The entire 269 homeless patients being hospitalized during the period of this study consist of 249 male patients and 19 female patients. For the prevalence of infectious diseases, HBV was seen in 15 of 228 patients (6.6%); HCV in 8 of 113 patients (7.1%); VDRL positive in 25 of 234 patients (10.7 %); HIV antibody positive in 2 of 130 (1.5%); and tuberculosis in 19 of 269 (7.1%). The number of patients who had the antibody to hepatitis B was 118 (51.7%). Of 28 patients hospitalized with the chief complaints of liver diseases and/or their complications, the number of cases infected with hepatitis B and C viruses was only 5 (17.9%). On the other hand, for patients with tuberculosis, 13 of 19 cases (68.4%) were hospitalized with the chief complaints associated with symptoms of pulmonary tuberculosis or enlarged lymph nodes. The number of patients with multiple infectious diseases was 9 in total. Conclusion : As expected, the prevalence of some infectious diseases were higher among the homeless inpatients, than non-homeless population. Proper screening tests in order to determine the presence of any infectious diseases among the patients and protect involved medical staff are necessary. Further, the government should take proactive measures to prevent the spread of infectious diseases in the aspect of public health.

      • KCI등재후보

        석면폐증 1례

        이영수,장태원,유호대,정만홍,이용환,서지영,허 방,이재성 大韓産業醫學會 1999 대한직업환경의학회지 Vol.11 No.1

        Asbestosis is the disease of pulmonary fibrosis caused by the inhaled asbestos fibers, and could be diagnosed clinically, in the case of exposure history to asbestos is proved, by clinical symptoms of dyspnea or dry cough, physical examonation findings, and the radiographic features. But many othder inorganic dusts would show similar findings in the chest radiogram and sometimes the exposure history is obscure, so for the exact diagnosis of asbestosis lung biopsy is needed. In Korea, there have been some reports of survey in the workplace where asbestos is handled or of asbestos related diseases. This is a case report of asbestosis with accompanying pleural plaques, who had the occupational exposure to asbestos for 30 years and the consistent clinical, radiographic and pathological findings in the lung tissue obtained by the videoscope assisted thoracoscopic biopsy(VATS).

      • KCI등재후보

        국내 다기관에서 조사한 지역사회획득 메티실린내성 황색포도알균의 빈도와 임상적 특성

        송진수,최평균,송경호,조재현,김성한,방지환,이창섭,박경화,박경운,신수,최희정,김의석,김동민,이미숙,박완범,김남중,오명돈,김의종,김홍빈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

        목적 : 최근 전세계적으로 지역사회획득 메티실린내성 황색포도알균(community-associated methicillin-resistant Staphylococcus aureus, CA-MRSA)의 보고가 증가하고 있다. 하지만, 우리나라에서는 CA-MRSA 감염증에 대한 증례보고만 있을 뿐 아직까지 체계적인 연구결과가 없는 실정이다. 저자들은 국내에서 CA-MRSA의 빈도, 감염증의 임상적 양상, 분리된 균주의 항균제내성 양상을 조사하였다. 재료 및 방법 : 2005년 1월부터 2005년 6월까지 7개 병원에서 MRSA가 분리된 환자의 명단을 파악한 후 의무기록지와 건강보험심사평가원의 자료를 검토하였다. 외래나 응급실에서 혹은 입원 후 72시간 이내에 균주가 분리되고 MRSA 획득과 관련된 위험인자가 없는 경우 CA-MRSA로 정의하였으며, 분리된 균주의 임상적 의미에 따라 원인병원체(pathogen), 집락화(colonizer), 미결정(undetermined)으로 분류하였다. Penicillin과 oxacillin을 제외하고 3개 이상의 다른 계열 항균제에 내성이면 다제내성으로 정의하였다. 결과 : 연구기간동안 총 3,251주의 황색포도알균이 분리되었으며, 이 중 MRSA는 1,900주(58.4%)였다. MRSA 가운데 CA-MRSA는 114주(6.0%) 였으며, 이들이 분리된 부위는 귀(62주), 비뇨기계(14주), 피부 및 연부조직(11주), 호흡기계(10주), 혈액(3주) 등이었다. CA-MRSA 균주 가운데 집락균은 22주, 원인병원체는 22주였으며, 나머지 균주에 대해서는 그 임상적 의미를 결정할 수 없었다. 항균제 감수성 검사를 시행한 73균주 중 47주(64.4%)는 다제내성이었다. CA-MRSA 감염증 22예 중 피부 및 연부조직 감염(9예)과 중이염/외이도염(9예)이 가장 흔하였다. 침습적 감염증(invasive infection)은 4명(원발성 균혈증 3예, 감염성 관절염 1예)에서 확인되었지만, CA-MRSA 감염증으로 사망한 환자는 없었다. 결론 : 병원내 감염증에서는 MRSA가 심각한 문제이지만, 아직까지 지역사회 감염증에서 CA-MRSA는 흔하지 않았다. Background : Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. In Korea, little is known about the epidemiology and clinical features of community-associated MRSA (CA-MRSA). Material and Methods : Clinical microbiology laboratory databases of 7 hospitals were reviewed to identify the patients from whom MRSA was isolated during the period of January to July 2005. Only one isolate per patient was enrolled. In order to identify the risk factors of MRSA acquisition, the medical records and the Health Insurance Review Agency databases were reviewed. CA-MRSA was defined as MRSA isolated from patient without established risk factors. We analyzed patient demographics, underlying medical conditions, characteristics of infection, and antimicrobial susceptibility profiles. Results : Of total 3,251 S. aureus isolates, 1900 (58.4%) were MRSAs. Of the MRSA isolates, 114 (6.0%) were CA-MRSA. Of 114 CA-MRSA isolates, 22 (19.3%) were colonizers, 22 (19.3%) were pathogens, and the clinical significance of remaining 70 (61.4%) could not be determined. Median age of the 22 patients with CA-MRSA disease was 47 years. Nine patients had skin and soft tissue infections, 9 ear infections, 3 bacteremia, 1 septic arthritis. Seven patients had underlying medical disease. None died of the CA-MRSA infections. Of the 73 isolates of CA-MRSA, 47 (64.4%) were resistant to more than 3 classes of antibiotics besides β-lactams. Conclusion : Although MRSA is highly prevalent among hospital-associated S. aureus infection, CA-MRSA infections are not common.

      • Experimental-Parametric Study on Residual Water During Vacuum Drying of Spent Nuclear Fuel Canisters

        Ji Hwan Lim,Kyoung-Sik Bang,Kyung-Wook Shin,Nam-Hee Lee,Seung-Hwan Yu 한국방사성폐기물학회 2023 한국방사성폐기물학회 학술논문요약집 Vol.21 No.2

        The saturation of wet storage facilities constructed and operated within nuclear power plant sites has magnified the significance of research concerning the dry storage of spent nuclear fuel. Not only do wet storage facilities incur higher operational and maintenance costs compared to dry storage facilities, but long-term storage of metal-clad fuel assemblies submerged in aqueous tanks is deemed unsuitable. Consequently, dry storage is anticipated to gain prominence in the future. Nevertheless, it is widely acknowledged that quantitatively assessing the residual water content remains elusive even when employing the apparatus and procedures utilized in the existing dry storage processes. The presence of residual water can only be inferred from damage or structural alterations to the spent nuclear fuel during its dry storage, making precise prediction of this element crucial, as it can be a significant contributor to potential deformations and deterioration. The aforementioned challenges compound the issue of retrievability, as substantial complexities emerge when attempting to retrieve spent nuclear fuel for permanent disposal in the future. Consequently, our research team has established a laboratory-scale vacuum drying facility to investigate the sensitivity of various parameters, including canister volume, pump capacity, water surface area, and water temperature, which can exert thermohydraulic influences on residual water content. Moreover, we have conducted dimensional analysis to quantify the thermohydraulic effects of these parameters and express them as dimensionless numbers. These analytical approaches will subsequently be integrated into predictive models for residual water content, which will be further developed and validated at pilot or full-scale levels. Furthermore, our research team is actively engaged in experimental investigations aimed at fine-tuning the duration of the pressure-holding phase while optimizing the evaporation process under conditions designed to avert the formation of ice caused by abrupt temperature fluctuations. Given that the canister is constructed from acrylic material, we are able to identify, from a phenomenological perspective, the specific juncture at which the boiling phenomenon becomes manifest during the vacuum drying process.

      • A case of eruptive penile syringoma

        ( Chul Hwan Bang ),( Seung Ah Yoo ),( Yeong Ho Kim ),( Jae Yeon Ryu ),( Hyun Ji Lee ),( Ju Hee Han ),( Young Min Park ),( Jun Young Lee ),( Ji Hyun Lee ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

        A 12-year old boy presented with asymptomatic, multiple, 0.1 cm-sized, yellowish to brownish papules on the penile shaft for several years. The lesions appeared suddenly and there was no history of any trauma, injection or underlying disorder. A punch biopsy of representative lesions on the penis was performed. Histopathological examination revealed many tadpole-shaped cords of epithelial cells and small ducts in the dermis. The diagnosis of syringoma was made by the given clinical and histopathological findings. The patient denied any further procedure for those lesions. Syringomas are common benign eccrine neoplasms. Classic syringoma occurs more frequently in young adult women. Eruptive syringoma is a rare variant and the age of onset ranges from 3 to 50 years. Eruptive syringoma is the term for multiple lesions that occur synchronously in any part of the body. The most common site for syringoma is the eyelid. On the other hand, penile syringoma is extremely rare. Until now, there have been several cases of penile syringoma reported, but eruptive penile syringoma is rarely seen. Herein, we report a case of eruptive penile syringoma.

      • Therapeutic effect of topical galectin-9 application in atopic dermatitis animal model

        ( Hyun Ji Lee ),( Ji Young Pak ),( Ji Hyun Lee ),( Ju Hee Han ),( Chul Hwan Bang ),( Jun Young Lee ),( Young Min Park ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

        Background: Galectin-9 is a protein that interacts with galactose (β-galactoside) and acts as a potent chemoattractant for eosinophils. This protein alters the T-cell balance by negatively regulating T-helper (Th) 1 and Th17 cells, resulting in Th2 polarization. Objectives: The purpose of this study is to examine the therapeutic effect of galectin-9 for atopic dermatitis (AD) animal model. Methods: NC / Nga mice (female, 14 weeks old) were sensitized with 1% 2,4-dinitrochlorobenzene (DNCB) twice a week. After sensitization, the mice were challenged with 0.4% DNCB for 1 week, and then simultaneously treated with various concentrations of galectin-9 three times a week for 3 weeks. A total of 35 mice were divided into 7 groups according to the following topical treatment modalities; non-treated, 0.4% DNCB only, vehicle (20% poloxamer 407 in PBS), 0.003%, 0.03% and 0.3% galectin-9, and 0.03% tacrolimus. Results: Ear thickness of all topically galectin-9 treated groups was significantly reduced compared with the DNCB only group (P < 0.001). Among sGal-9 treated groups only 0.3% group had a significant difference compared to the vehicle group (P < 0.01). Conclusion: These results suggest that topical application of galectin-9 may be one candidate for the treatment of AD.

      • [P078] A case of zosteriform primary cutaneous anaplastic CD30+ large-cell lymphoma showing spontaneous regression after skin biopsy

        ( Chul Hwan Bang ),( Hyun Ji Lee ),( Hyun-min Seo ),( Young Min Park ),( Jun Young Lee ),( Ji Hyun Lee ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1

        Primary cutaneous anaplastic large cell lymphoma (PCALCL) is CD30 positive lymphoproliferative disorder, presenting as solitary or localized nodules, papules or plaques without evidence of systemic involvement. Although the clinical appearance varies over a wide morphological spectrum, its mimicking herpes zoster is rare. PCALCL usually experience favorable prognosis and spontaneous regression occurs in 20-25% of patients. Herein, we report a case of zosteriform PCALCL showing spontaneous regression after skin biopsy. A 79-year-old man presented 8-month history of asymptomatic, crusted, zosteriform grouped papules and plaques on the left upper back. He was treated with antiviral medication for herpes zoster 8 months ago, which was not improved and consulted to us. Histopathological examination revealed a non-epidermotropic pan-dermal cellular infiltration through the dermis. The infiltrated cells were composed predominantly large atypical lymphoid cells. Immunohistochemically, atypical lymphoid cells were positive for CD3, CD4, and CD30, while negative for CD8, CD20 and ALK. Imaging study showed no systemic involvement other than skin lesion and peripheral blood and bone marrow aspiration smear revealed no atypical lymphocytes. From these findings, we diagnosed PCALCL on the left upper back. After the skin biopsy, spontaneous partial regression was observed without any treatment within 2 months.

      • A novel tissue culture method using 3D bioprinting of melanoma acquired from patient derived xenograft model

        ( Chul Hwan Bang ),( Yun-mi Jeong ),( Hae Eun Park ),( Jin Woo Park ),( Ga Hee Jeong ),( Min Ji Park ),( Yunjae Lee ),( Songwan Jin ),( Ji Hyun Lee ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

        Background: Although advances have been made in in vitro technologies of culturing cells, there is limitation that microenvironment in which cells are cultured is not same as that in human skin, making it difficult to predict therapeutic response. Using 3D bioprinting in in vitro melanoma tissue culture would provide environments more similar to the physiologic conditions, realizing personalized medicine. Objectives: We investigated whether melanoma acquired from patient-derived xenograft model (PDX) is well maintained and proliferated when tissue culture is performed in 3D bioprinited skin. Methods: The melanoma acquired from PDX was sectioned into 0.2-cm diameter and 0.1-cm height. They were cultured on 3D bioprinted collagen, dermis, and full-thickness skin, and the size change and cell viability of melanoma tissues were measured. Immunohistostaining and western blotting for cell markers of melanoma were performed. Results: The novel tissue culture model was well maintained until the 21st day. There was no significant change in diameter or height and cell viability. New melanoma nests proliferation was observed both grossly and microscopically at the 21st day. The characteristic findings of melanoma were well observed with immunohistostaining and western blotting. These results were best seen in the melanoma tissue culture with 3D bioprinted dermis group. Conclusion: Melanoma tissue culture with 3D bioprinted skin may be a novel method for melanoma culture and in vitro model of melanoma.

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