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BACKGROUND: Lake Bonney, which is divided into a west lobe (WLB) and an east lobe (ELB), is a perennially ice-covered lake located in the McMurdo Dry Valleys of Antarctica. Despite previous reports on the microbial community dynamics of ice-covered lakes in this region, there is a paucity of information on the relationship between microbial genomic diversity and associated nutrient cycling. Here, we applied gene- and genome-centric approaches to investigate the microbial ecology and reconstruct microbial metabolic potential along the depth gradient in Lake Bonney. RESULTS: Lake Bonney is strongly chemically stratified with three distinct redox zones, yielding different microbial niches. Our genome enabled approach revealed that in the sunlit and relatively freshwater epilimnion, oxygenic photosynthetic production by the cyanobacterium Pseudanabaena and a diversity of protists and microalgae may provide new organic carbon to the environment. CO-oxidizing bacteria, such as Acidimicrobiales, Nanopelagicales, and Burkholderiaceae were also prominent in the epilimnion and their ability to oxidize carbon monoxide to carbon dioxide may serve as a supplementary energy conservation strategy. In the more saline metalimnion of ELB, an accumulation of inorganic nitrogen and phosphorus supports photosynthesis despite relatively low light levels. Conversely, in WLB the release of organic rich subglacial discharge from Taylor Glacier into WLB would be implicated in the possible high abundance of heterotrophs supported by increased potential for glycolysis, beta-oxidation, and glycoside hydrolase and may contribute to the growth of iron reducers in the dark and extremely saline hypolimnion of WLB. The suboxic and subzero temperature zones beneath the metalimnia in both lobes supported microorganisms capable of utilizing reduced nitrogens and sulfurs as electron donors. Heterotrophs, including nitrate reducing sulfur oxidizing bacteria, such as Acidimicrobiales (MAG72) and Salinisphaeraceae (MAG109), and denitrifying bacteria, such as Gracilimonas (MAG7), Acidimicrobiales (MAG72) and Salinisphaeraceae (MAG109), dominated the hypolimnion of WLB, whereas the environmental harshness of the hypolimnion of ELB was supported by the relatively low in metabolic potential, as well as the abundance of halophile Halomonas and endospore-forming Virgibacillus. CONCLUSIONS: The vertical distribution of microbially driven C, N and S cycling genes/pathways in Lake Bonney reveals the importance of geochemical gradients to microbial diversity and biogeochemical cycles with the vertical water column.
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BACKGROUND: Pediatric inflammatory bowel disease (PIBD) affects different age groups and its incidence is increasing worldwide. However, there is a lack of research focusing on age subgroups in Asian countries. In this nationwide population-based study, we investigated the epidemiology of PIBD among different age subgroups in Korea. METHODS: We analyzed Korean health administration data from 2005 to 2016. Data were divided by age at diagnosis as follows: group 1, 0-1 years; group 2, 2-5 years; group 3, 6-9 years; group 4, 10-16 years. We analyzed the overall incidence, temporal changes, and regional differences by age subgroups, using Poisson regression analysis. RESULTS: From 2005 to 2016, 2734 inflammatory bowel disease (IBD) cases were diagnosed among patients under 17 years of age. In the overall population, the incidence rate of PIBD over the entire study period was 2.248/105 person-years (PY), significantly increasing from 1.173/105 PY in 2005-2007 to 3.267/105 PY in 2014-2016. The incidence rates in groups 1 and 2 remained unchanged, whereas those of groups 3 and 4 increased significantly. The same trend was observed when analyzed separately for Crohn's disease (CD) and ulcerative colitis (UC). The incidence rates of CD in groups 3 and 4 showed differences between metropolitan and non-metropolitan areas, whereas those in groups 1 and 2, and UC of all age subgroups showed no difference. CONCLUSIONS: The temporal trend and regional differences of PIBD differed among age subgroups, suggesting that genetic and environmental factors have varying impacts on IBD development across different subgroups.
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Enfermedades Inflamatorias del Intestino , Humanos , República de Corea/epidemiología , Niño , Adolescente , Incidencia , Masculino , Femenino , Preescolar , Lactante , Recién Nacido , Enfermedades Inflamatorias del Intestino/epidemiología , Distribución por Edad , Enfermedad de Crohn/epidemiología , Colitis Ulcerosa/epidemiologíaRESUMEN
Purpose: Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis. Methods: We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes. Results: Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively. Conclusion: This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.
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Purpose: To date, there is no region-specific guideline for pediatric endoscopy training. This study aimed to illustrate the current status of pediatric endoscopy training in Asia-Pacific region and identify opportunities for improvement. Methods: A cross-sectional survey, using a standardized electronic questionnaire, was conducted among medical schools in the Asia-Pacific region in January 2024. Results: A total of 57 medical centers in 12 countries offering formal Pediatric Gastroenterology training programs participated in this regional survey. More than 75% of the centers had an average case load of <10 cases per week for both diagnostic and therapeutic endoscopies. Only 36% of the study programs employed competency-based outcomes for program development, whereas nearly half (48%) used volume-based curricula. Foreign body retrieval, polypectomy, percutaneous endoscopic gastrostomy, and esophageal variceal hemostasis, that is, sclerotherapy or band ligation (endoscopic variceal sclerotherapy and endoscopic variceal ligation), comprised the top four priorities that the trainees should acquire in the autonomous stage (unconscious) of competence. Regarding the learning environment, only 31.5% provided formal hands-on workshops/simulation training. The direct observation of procedural skills was the most commonly used assessment method. The application of a quality assurance (QA) system in both educational and patient care (Pediatric Endoscopy Quality Improvement Network) aspects was present in only 28% and 17% of the centers, respectively. Conclusion: Compared with Western academic societies, the limited availability of cases remains a major concern. To close this gap, simulation and adult endoscopy training are essential. The implementation of reliable and valid assessment tools and QA systems can lead to significant development in future programs.
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Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood.
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Colestasis Intrahepática , Colestasis , Citrulinemia , Gastroenterología , Enfermedades del Recién Nacido , Transportadores de Anión Orgánico , Adolescente , Niño , Humanos , Lactante , Recién Nacido , Colestasis/diagnóstico , Colestasis/etiología , Colestasis/terapia , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/etiología , Colestasis Intrahepática/terapia , Citrulinemia/complicaciones , Citrulinemia/diagnóstico , Citrulinemia/genética , Proteínas de Transporte de Membrana Mitocondrial/genética , Mutación , Transportadores de Anión Orgánico/genéticaRESUMEN
Recurrence of progressive familial intrahepatic cholestasis (PFIC) type II poses challenges during postoperative liver transplant care. Posttransplant patients with PFIC type II risk developing recurrent cholestasis with normal gamma-glutamyl transferase activity, which mimics the original bile salt export pump (BSEP) protein deficiency and is related to a form of immunoglobulin G antibody (anti-BSEP)-mediated rejection. Bortezomib effectively induces apoptosis of actively antibody-producing plasma cells that may have a role in antibody-mediated rejection. In this case, we used bortezomib to treat PFIC type II recurrence after liver transplantation in a child.
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X-linked inhibitor of apoptosis protein (XIAP) deficiency causes refractory inflammatory bowel disease. The XIAP protein plays a pivotal role in the pro-inflammatory response through the nucleotide-binding oligomerization domain-containing signaling pathway that is important in mucosal homeostasis. We analyzed the molecular mechanism of non-synonymous pathogenic variants (PVs) of XIAP BIR2 domain. We generated N-terminally green fluorescent protein-tagged XIAP constructs of representative non-synonymous PVs. Co-immunoprecipitation and fluorescence cross-correlation spectroscopy showed that wild-type XIAP and RIP2 preferentially interacted in live cells, whereas all non-synonymous PV XIAPs failed to interact properly with RIP2. Structural analysis showed that various structural changes by mutations, such as hydrophobic core collapse, Zn-finger loss, and spatial rearrangement, destabilized the two loop structures (174-182 and 205-215) that critically interact with RIP2. Subsequently, it caused a failure of RIP2 ubiquitination and loss of protein deficiency by the auto-ubiquitination of all XIAP mutants. These findings could enhance our understanding of the role of XIAP mutations in XIAP-deficient inflammatory bowel disease and may benefit future therapeutic strategies.
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Enfermedades Inflamatorias del Intestino , Proteína Inhibidora de la Apoptosis Ligada a X , Humanos , Proteínas Fluorescentes Verdes , Homeostasis , Enfermedades Inflamatorias del Intestino/genética , Proteína Inhibidora de la Apoptosis Ligada a X/genéticaRESUMEN
Background and Aims: Biliary atresia is a rare and devastating bile duct disease that occurs during the neonatal period. Timely identification and prompt surgical intervention is critical for improving the outcome. The aim of the study was to develop a new machine learning-based prediction model for the detection of biliary atresia. Methods: Neonates aged <100 days with cholestasis at least once were retrospectively screened in 2 tertiary referral hospitals between 2015 and 2020. Simple demographic data, routine laboratory indices, and imaging findings of ultrasonography and hepatobiliary scintigraphy were used as features in the multivariate analysis. The extreme gradient boosting (XGBoost) framework was used to develop prediction models according to the diagnostic steps. Results: Among 1605 enrolled neonates with all-cause cholestasis, 145 (9%) were included as having biliary atresia. Direct bilirubin, gamma-glutamyl transpeptidase, abdominal sonography, and hepatobiliary scan were the most impactful features in prediction models. The Step II XGBoost model, consisting of nonimaging inputs, showed excellent discriminatory performance (area under the curve = 0.97). The Step III and IV XGBoost models showed near-perfect performances (area under the curve = 0.998 and 0.999, respectively). In external validation (n = 912 with 118 [12.9%] biliary atresia), XGBoost-based prediction models consistently showed acceptable performances. Utilizing shapley additive explanation values also provided visualized insight and explanation of the contribution of features in detecting biliary atresia. The models were integrated into a web-based diagnostic tool for case-level application. Conclusion: We introduced a new machine learning-based prediction model for detecting biliary atresia in the largest cohorts of neonatal cholestasis.
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Acinetobacter baumannii, a strictly aerobic, non-fermentative, Gram-negative coccobacillary rod-shaped bacterium, is an opportunistic pathogen in humans. We recently isolated a multidrug-resistant A. baumannii strain KBN10P02143 from the pus sample drawn from a surgical patient in South Korea. We report the complete genome of this strain, which consists of 4,139,396 bp (G + C content, 39.08%) with 3,868 protein-coding genes, 73 tRNAs and six rRNA operons. Identification of the genes related to multidrug resistance from this genome and the discovery of a novel conjugative plasmid will increase our understanding of the pathogenicity associated with this species.