Neurologic Effects of SARS-CoV-2 Transmitted among Dogs.

SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2-infected dogs, particularly involving blood-brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2-associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.

Iridium(III)-Catalyzed C-H Cyclization of Sulfoximines with Diazo Meldrum's Acids for the Synthesis of Cyclic Sulfoximines.

Iridium(III)-catalyzed C-H cyclization of sulfoximines with diazo Meldrum's acid provided cyclic sulfoximines with a carbonyl group in good to excellent yields. These compounds were easily converted into unsubstituted and arylated sulfoximines. Moreover, the vinyl triflates obtained from the cyclic sulfoximines underwent palladium(II)-catalyzed cross-coupling reactions with a variety of aryl, arylalkynyl, and heteroatom (N and S) nucleophiles, affording a wide range of monosubstituted sulfoximines in high yields.

Differences of clinical characteristics and outcome in proven invasive Trichosporon infections caused by asahii and non-asahii species.

BACKGROUND: Trichosporon is an emerging yeast that causes invasive infections in immunocompromised patients experiencing prolonged hospitalisation, indwelling venous catheters and neutropenia. METHODS: This retrospective observational cohort study analysed invasive Trichosporon infections (ITIs) occurring between January 2005 and December 2022 at three tertiary hospitals and compared the clinical characteristics and prognostic factors of ITIs caused by Trichosporon asahii and non-T. asahii spp. After evaluating 1067 clinical isolates, we identified 46 patients with proven ITIs, defined as cases in which Trichosporon was isolated from blood, cerebrospinal fluid, or sterile tissues. RESULTS: The patients were separated into T. asahii and non-T. asahii groups containing 25 and 21 patients, respectively, all of which except one were immunocompromised. During this period, both the number of clinical isolates and patients with ITIs (mainly T. asahii) increased; whereas, cases involving non-T. asahii spp. decreased. Compared with the non-T. asahii group, the T. asahii group had more patients with multiple catheters (84% vs. 33%, p = .001) and those receiving renal replacement therapy (48% vs. 14%, p = .005). The all-cause 28-day mortality rate after ITI in the T. asahii group (44%) was significantly higher than in the non-T. asahii group (10%, Log-rank p = .014). The multivariate Cox regression model revealed that T. asahii (reference, non-T. asahii spp.; aHR = 4.3; 95% CI = 1.2-15.2, p = .024) and neutropenia for 5 days or more (aHR = 2.2, 95% CI = 1.5-3.6, p = .035) were independent factors in the 28-day mortality after ITI. CONCLUSION: The proven ITIs due to T. asahii produced more unfavourable outcomes compared with ITIs caused by non-T. asahii spp.

Co-Assembly of Colloids and Eumelanin Nanoparticles in Droplets for Structural Pigments with High Saturation.

Colloidal crystals have been used to develop structural colors. However, incoherent scattering causes the colors to turn whitish, reducing the color saturation. To overcome the problem, light-absorbing additives have been incorporated. Although various additives have been used, most of them are not compatible with a direct co-assembly with common colloids in aqueous suspensions. Here, the authors suggest eumelanin nanoparticles as a new additive to enhance the color chroma. Eumelanin nanoparticles are synthesized to have diameters of several nanometers by oxidative polymerization of precursors in basic solutions. The nanoparticles carry negative charges and do not weaken the electrostatic repulsion among same-charged polystyrene particles when they are added to aqueous suspensions. To prove the effectiveness of eumelanin as a saturation enhancer, the authors produce photonic balls through direct co-assembly of polystyrene and eumelanin using water-in-oil emulsion droplets, while varying the weight ratio of eumelanin to polystyrene. The high crystallinity of colloidal crystals is preserved for the ratio up to at least 1/50 as the eumelanin does not perturb the crystallization. The eumelanin effectively suppresses incoherent scattering while maintaining the strength of structural resonance at an optimum ratio, improving color chroma without compromising brightness.

Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP.

Attenuating the expression of immediate early (IE) proteins is essential for controlling the lytic replication of human cytomegalovirus (HCMV). The human microRNAs (hsa-miRs), miR-200b-3p and miR-200c-3p, have been identified to bind the 3'-untranslated region (3'-UTR) of the mRNA encoding IE proteins. However, whether hsa-miRs can reduce IE72 expression and HCMV viral load or exhibit a crosstalk with the host cellular signaling machinery, most importantly the NF-κB cascade, has not been evaluated. In this study, argonaute-crosslinking and immunoprecipitation-seq revealed that miR-200b-3p and miR-200c-3p bind the 3'-UTR of UL123, which is a gene that encodes IE72. The binding of these miRNAs to the 3'-UTR of UL123 was verified in transfected cells stably expressing GFP. We used miR-200b-3p/miR-200c-3p mimics to counteract the downregulation of these miRNA after acute HCMV infection. This resulted in reduced IE72/IE86 expression and HCMV VL during lytic infection. We determined that IE72/IE86 alone can inhibit the phosphorylation of RelA/p65 at the Ser536 residue and that p-Ser536 RelA/p65 binds to the major IE promoter/enhancer (MIEP). The upregulation of miR-200b-3p and miR-200c-3p resulted in the phosphorylation of RelA/p65 at Ser536 through the downregulation of IE, and the binding of the resultant p-Ser536 RelA/p65 to MIEP resulted in a decreased production of pro-inflammatory cytokines. Overall, miR-200b-3p and miR-200c-3p-together with p-Ser536 RelA/p65-can prevent lytic HCMV replication during acute and latent infection.

Direct and Regioselective Palladium(II)-Catalyzed B(4)-H Monoacyloxylation and B(4,5)-H Diacetoxylation of o-Carborane Acids with Phenyliodonium Dicarboxylates.

A direct B(4)-H monoacyloxylation via a Pd-catalyzed regioselective B(4)-H activation of o-carborane acids with phenyliodonium dicarboxylates was developed, and a series of B(4)-H monoacyloxylated o-carboranes decorated with active groups were synthesized with moderate to good yields as well as excellent selectivity. In addition, a direct B(4,5)-H diacetoxylation from o-carborane acids with phenyliodonium diacetate was demonstrated.

Incidence rate of active tuberculosis in solid organ transplant recipients: Data from a nationwide population cohort in a high-endemic country.

BACKGROUND: The management of active tuberculosis (TB) in solid organ transplantation (SOT) recipients is challenging given the pharmacological interaction and the potential delays in diagnosis due to atypical presentation. The incidence rates (IRs) of post-SOT TB from the whole recipients' cohort in a high-endemic country have not been evaluated. METHODS: We established a SOT cohort (n = 15 598) and confirmed cases of TB between 2011 and 2015 from the Korean National Health Insurance Database using ICD-10 codes. After excluding 1302 and 180 SOT-recipients due to age (<18 years) and presence of pre-SOT TB and/or treatment for latent TB during wash-out period between 2006 and cohort entry, we analyzed 14 116 SOT recipients and 70 580 individuals with no history of SOT matched by age and sex. The hazard ratios (HRs) of IRs were adjusted for age, sex, low-income status, diabetes mellitus, chronic co-morbidities, and anti-TNF-α therapy. RESULTS: The IR of TB was significantly higher (adjusted HR [aHR]: 6.1, 95% confidence interval [CI]: 4.5-7.6) in SOT recipients (4.9/1000 person-years) than in non-SOT individuals (0.8/1000 person-years). Of the transplanted organs, the pancreas (pancreas alone and simultaneous pancreas-kidney) and lung had the highest IR (aHR: 16.3 [6.1-42.2] and 16.1 [5.9-43.8], respectively). The use of anti-thymocyte globulin and azathioprine was associated with a higher IR (aHR: 1.53 [1.01-2.43] and 3.92 [1.21-12.47], respectively), but basiliximab was associated with a lower IR (aHR: 0.67 [0.48-0.98]). CONCLUSION: The IR of TB in SOT recipients, especially in the pancreas and lung, was significantly higher than that in the non-SOT population.

Incidence of herpes zoster in adult solid organ transplant recipients: A meta-analysis and comprehensive review.

BACKGROUND: Chronic immunosuppressive therapy in solid organ transplant (SOT) recipients can trigger latent varicella zoster virus reactivation even in those with stable graft function. The inactivated herpes zoster (HZ) vaccine can be effective in preventing post-transplant HZ, which can cause severe neuralgia or disseminated disease. This meta-analysis aims to assess the incidences of HZ across transplant organs in SOT recipients. METHODS: We included 12 observational studies (6560 recipients) from a PubMed and EMBASE search of articles through October 2019 and collected data from single-center dating from January 2001 to December 2017 (3498 recipients). The pooled HZ incidence and its differences between subgroups were obtained from random-effect models and meta-analysis of variance tests using R package. RESULTS: The overall pooled crude incidence was 9.1% (95% confidence interval [CI], 7.6%-10.8%). The pooled incidence was similar between sexes but significantly different between transplanted organs (P < .001). Heart transplants (HT) (n = 644) have the highest pooled incidence with 15.2% (95% CI, 12.7%-18.2%), followed by lung transplants (LTX) (n = 780) with 11.0% (8.3%-14.4%). Kidney transplants (n = 5435) have the lowest incidence of 6.7 (5.1%-8.8%). The meta-regression analysis revealed that HZ development had a relationship with past graft rejection (P = .024). CONCLUSION: These data support the need for subunit HZ vaccination in SOT recipients with a high risk for HZ, especially HT and LTX recipients, without respect to the late post-transplant period.

The Incidence and Effect of Cytomegalovirus Disease on Mortality in Transplant Recipients and General Population: Real-world Nationwide Cohort Data.

Background: In addition to the conventional opportunistic infections in solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients, cytomegalovirus (CMV) infection is associated with various chronic inflammatory diseases or poor outcomes in non-immunocompromised critically ill patients. To evaluate the burden or outcome of CMV replication in non-transplant individuals, we compared the incidence rates (IRs) for CMV disease and all-cause mortality between SOT recipients, HSCT recipients, and non-transplant population. Methods: The SOT (N=16,368) and HSCT (N=10,206) cohorts between 2010 and 2015 were established using the WHO ICD-10 from the whole population-based large database of the Health Insurance Review & Assessment Service (HIRA). CMV cases, defined as symptomatic disease with isolation of virus, DNA, pp65 antigen, and pathology except CMV syndrome, were extracted with the unique codes for relief of medical costs of HIRA in the same dataset. Cox's proportional hazard regression analyses and log-rank test in the Kaplan-Meier curves were performed to compare all-cause mortality between the three groups. Results: The CMV IRs adjusted by age and sex were significantly higher in the SOT (adjusted IR [95% confidence intervals], 33.1 [28.8-38.0] per 1,000 person-years) and HSCT recipients (5.1 [4.6-6.1] per 1,000 person-years) than in the whole population (0.58 [0.49-0.67] per 100,000 person-years). However, SOT recipients with CMV (18/283, 6.4%) had significantly lower all-cause mortality than non-transplant individuals with CMV (207/1,258, 16.5%) (adjusted hazard ratio [95% CI], 0.42 [0.25-0.67], log-rank P < 0.001). Conclusion: These data suggest that CMV disease in patients without transplants is associated with poor outcomes.

De Novo Genotypic Heterogeneity in the UL56 Region in Cytomegalovirus-Infected Tissues: Implications for Primary Letermovir Resistance.

BACKGROUND: Letermovir, an inhibitor of unique long (UL)56-encoded cytomegalovirus (CMV)-terminase, shows prophylactic effects with low-grade adverse events in hematopoietic stem cell transplant recipients. Despite few case reports on acquired letermovir resistance, the frequency of de novo amino acid (A.A.) changes encoded by UL56 in CMV-infected tissues is unclear. METHODS: We analyzed CMV UL56 sequences between the conserved region IV and variable region I in 175 formalin-fixed, paraffin-embedded tissues obtained from 147 patients showing positive CMV immunochemical staining between November 2012 and October 2016. Nucleotides 552-1330 of the open reading frame of UL56 were amplified with 5 primers and sequenced by a dideoxy fluorescence-based cycle. RESULTS: Six (3.4%) tissues from 4 (2.7%) patients harbored A.A. substitutions. There were no known potent resistant mutations. However, we found C325Y in 2 tissues from 1 patient, along with other mutations. Four novel A.A. changes, which have not been observed in previous in vitro experiments, were identified (T244I, S301T, G312V, and M434I). Most (9 of 11, 81.8%) of the A.A. changes occurred between the codons 301 and 325 present between the conserved regions V and VI. CONCLUSIONS: The treatment difficulties associated with letermovir resistance in a clinical setting need to be verified before its widespread use.

Iridium-Catalyzed Cyclative Indenylation and Dienylation through Sequential B(4)-C Bond Formation, Cyclization, and Elimination from o-Carboranes and Propargyl Alcohols.

Described herein is the first iridium-catalyzed cyclative indenylation through sequential B(4)-C and intramolecular C-C bond formation from o-carboranes and propargyl alcohols, leading to the formation of B(4)-indenylated o-carboranes with excellent regioselectivity via direct B-H activation. Moreover, the iridium-catalyzed regioselective 1,3-dienylation has been accessed through sequential B-H activation, dehydration, and decarboxylation, producing B(4)-dienylated o-carboranes.

COVID-19: A global transplant perspective on successfully navigating a pandemic.

The COVID-19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID-19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health-care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID-19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant-related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.

Deoxygenative Amination of Azine-N-oxides with Acyl Azides via [3 + 2] Cycloaddition.

A transition-metal-free deoxygenative C-H amination reaction of azine-N-oxides with acyl azides is described. The initial formation of an isocyanate from the starting acyl azide via a Curtius rearrangement can trigger a [3 + 2] dipolar cycloaddition of polar N-oxide fragments to generate the aminated azine derivative. The applicability of this method is highlighted by the late-stage and sequential amination reactions of complex bioactive compounds, including quinidine and fasudil. Moreover, the direct transformation of aminated azines into various bioactive N-heterocycles illustrates the significance of this newly developed protocol.

Phthalazinone-Assisted C-H Amidation Using Dioxazolones Under Rh(III) Catalysis.

The preparation of phthalazinone derivatives is pivotal for their utilization as pharmaceutical agents and other entities. Herein, we report the phthalazinone-assisted carbon-nitrogen bond forming reaction using dioxazolones as robust amidation sources under Rh(III) catalysis. The broad functional group tolerance and complete site-selectivity are observed. Notably, a series of transformations of synthesized compounds into biologically relevant N-heterocycles demonstrates the applicability of the developed methodology.

Expansion of Azulenes as Nonbenzenoid Aromatic Compounds for C-H Activation: Rhodium- and Iridium-Catalyzed Oxidative Cyclization of Azulene Carboxylic Acids with Alkynes for the Synthesis of Azulenolactones and Benzoazulenes.

Rhodium-catalyzed oxidative [4 + 2] cyclization reactions through the C-H activation of azulene carboxylic acids as nonbenzenoid aromatic compounds with symmetrical and unsymmetrical alkynes were developed under aerobic conditions, which produced azulenolactone derivatives with a wide substrate scope and excellent functional group tolerance. Interestingly, azulenic acids in reaction with alkynes underwent iridium-catalyzed [2 + 2 + 2] cyclization accompanied by decarboxylation to afford tetra(aryl)-substituted benzoazulene derivatives. The reactivity order for C-H activation reaction is greater toward azulene-6-carboxylic acid, azulene-1-carboxylic acid, and azulene-2-carboxylic acid. For the first time, the expansion of azulenes having directing group as nonbenzenoid aromatic compounds for C-H activation was successful, indicating that nonbenzenoid aromatic compounds can be used as good substrates for the C-H activation reaction. Therefore, the research area of C-H activation will certainly expand to nonbenzenoid aromatic compounds in future.

Ru(II)-Catalyzed C-H Hydroxyalkylation and Mitsunobu Cyclization of N-Aryl Phthalazinones.

Ruthenium(II)-catalyzed C(sp2)-H functionalization of N-aryl phthalazinones with a range of aldehydes and activated ketone is described. Initial formation of hydroxyalkylated phthalazinones and subsequent Mitsunobu cyclization provided facile access to biologically relevant indazolophthalazinones. The utility of this method is highlighted by synthetic transformations into a series of potentially bioactive scaffolds.

Association between cytomegalovirus end-organ diseases and moderate-to-severe dementia: a population-based cohort study.

BACKGROUND: The association between cytomegalovirus (CMV) and dementia remains controversial. Previous studies have suggested that CMV serostatus, as assessed by serum immunoglobulin G, plays a role in neurodegeneration with cognitive impairment. We aimed to evaluate the association between CMV tissue-invasive end-organ diseases and moderate-to-severe dementia. METHODS: The ICD 10th revision codes from the National Health Insurance Database covering the entire population of the Republic of Korea were used to classify patients into exposed (n = 687, age ≥ 40 years, with CMV disease) and unexposed (n = 3435, without CMV disease) groups, matched by age and sex at a 1:5 ratio of exposed: unexposed. All non-HIV-1-infected subjects selected during 2010-2014 with a washout period of the previous 4 years were followed up until December 2016 to identify newly diagnosed cases of moderate-to-severe dementia. RESULTS: Multivariate regression model (M3) adjusted for age, sex, low income, body mass index, transplantation status, malignant neoplasms, end-stage renal disease on dialysis, type 2 diabetes mellitus, hypertension, and dyslipidaemia showed a significantly higher incidence of dementia (odds ratio: 1.9; 95% confidence interval: 1.2-2.8) in the exposed group than that in the unexposed group. The risk of vascular dementia (2.9, 1.1-7.5) was higher than that of Alzheimer's disease (1.6, 1.0-2.6) in the exposed group in M3. In M3, patients aged 40-59 years with CMV diseases had a significantly higher risk of all kinds of dementia than those aged 60-79 and ≥ 80 years (11.7, 2.5-49.4 vs. 1.8, 1.1-3.2 vs. 1.3, 0.5-2.8; P = 0.025). CONCLUSIONS: CMV diseases may be associated with the risk of moderate-to-severe dementia.

Stenting as a bridge to surgery for extra-colonic malignancy induced colorectal obstruction: preliminary experience.

BACKGROUND: The majority of colonic obstructions result from colorectal cancer. However, malignancies of extra-colonic origin can also disrupt colorectal patency, and the efficacy of self-expanding metal stents (SEMS) insertion as a bridge to surgery in these patients are still in debate. The aim of this study is to evaluate the efficacy of endoscopic stenting as a bridge to surgery (BTS) for extra-colonic malignancy (ECM)-induced colonic obstruction. METHODS: Thirty-three patients with colonic obstruction due to ECM who received self-expanding metal stents (SEMS) insertion at a single academic tertiary medical center between 2004 and 2015 were included. The purpose of SEMS insertion was determined based on whether the patient's medical records indicated any surgical plans before SEMS insertion. Technical success was defined as a patent SEMS covering the entire length of the obstruction. Bridging success was defined as elective surgical procedures after the first SEMS insertion. RESULTS: Among the 33 patients who underwent SEMS insertion for colorectal obstruction due to ECM, nine underwent SEMS as a BTS. Technical success was achieved in 100% (9/9). Seven patients underwent elective surgery after successful decompression with the first SEMS, and the bridging success rate was 77.8% (7/9). Two patients needed secondary stent insertion before elective surgery. However, none of them required emergent surgery. No major complications occurred, including death related to colorectal endoscopic procedures, perforation, or bleeding. CONCLUSION: SEMS insertion as a BTS is a good treatment option to avoid emergent surgery in patients with colonic obstruction caused by extra-colonic malignancy.

Positive conversion of interferon-γ release assay in patients with rheumatic diseases treated with biologics.

The objective of this study is to investigate whether the type of biologics (TNFi or others) or type of rheumatic diseases (RA or AS) influence the conversion rate of initially negative tuberculosis (TB) screening test results. A total of 119 patients with RA or AS who had negative baseline interferon-γ release assay (IGRA) results assessed by QuantiFERON-TB Gold in tube (QTF-GIT) were included. All patients received biologic agents, and rescreening with QTF-GIT was performed after a median of 25.9 months from the baseline test. Clinical characteristics and IFN-γ levels were compared between converters and non-converters. Logistic regression analysis was performed to identify factors associated with positive conversion. IGRA conversion was found in 14 of 119 patients (11.8%). The converters were older (53.4 ± 14.2 vs 44.4 ± 15.5 years, p = 0.040), had higher baseline TB-specific IFN-γ responses (0.105 [0.018-0.205] vs 0.010 [0.000-0.035] IU/ml, p = 0.001) and higher incidence of active TB (14.3% vs 0.0%, p = 0.013). The number of patients with RA or AS was 9 (64.3%) or 5 (35.7%) in converters, and 45 (42.9%) or 60 (57.1%) in non-converters. In terms of use of biologics, TNFi of monoclonal antibody form was less commonly used in the converters (p = 0.024). In the logistic regression analysis, type of disease and type of biologics used were not associated with IGRA conversion, whereas baseline TB-specific IFN-γ response was significantly associated with IGRA conversion (OR 1.083, 95% CI 1.019-1.151, p = 0.011). Serial monitoring of LTBI with IGRA retesting is needed during biologic treatment, regardless of the type of rheumatic diseases or type biologics used.

Human cytomegalovirus seroprevalence and titres in solid organ transplant recipients and transplant donors in Seoul, South Korea.

BACKGROUND: Human cytomegalovirus (HCMV) can cause poor outcomes in solid organ transplant (SOT) recipients; moreover, it is associated with cardiovascular diseases (CVD) in the general population. Accordingly, anti-HCMV immunoglobulin G (IgG) seroepidemiology may be useful in identifying the risk of post-SOT HCMV infection or disease as well as immunosenescence or CVD. However, HCMV seroprevalence and titre have not been fully evaluated with regard to age distribution or compared between SOT recipients and healthy individuals in South Korea. METHODS: We retrospectively retrieved all unduplicated anti-HCMV IgG results of individuals aged > 1 year evaluated between July 2006 and November 2017 at Severance Hospital in Seoul. The cohort, excluding haematopoietic stem cell transplant recipients and subjects with equivocal values, included 2184 SOT recipients and 3015 healthy transplant donors. All IgG results in the SOT recipients were measured during the pre-transplant period. RESULTS: The overall IgG seroprevalence and titres were significantly higher among SOT recipients than among healthy donors (98.7% vs. 88.6%, p < 0.001, and 64.7 ± 44.3 vs. 49.8 ± 20.6 arbitrary units/mL, p < 0.001, respectively). The lowest seropositive rate in the SOT group was observed in recipients aged between 11 and 15 years (70.6%). The frequency of seropositivity among adults aged ≥41 years increased to ≥90% in SOT recipients and healthy donors. Age was independently associated with higher HCMV seroprevalence (41-60 years, OR, 76.4, 95% CI, 24.5-238.9, p < 0.001; ≥ 61 years, OR, 4.4, 95% CI, 1.3-14.9, p < 0.001, compared to ≤40 years). The healthy donor group had an independently low HCMV seropositive rate (OR, 0.1, 95% CI, 0.1-0.2, p < 0.001). CONCLUSIONS: HCMV seropositivity was the lowest among school-aged children and adolescents. IgG testing revealed an intermediate serostatus risk of post-transplant HCMV infection and disease for most adult SOT recipients in South Korea.