Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing

Background/Aims@#Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. @*Methods@#We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. @*Results@#In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. @*Conclusions@#We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Periodic Limb Movement Disorder and Mortality / 수면정신생리

Periodic limb movement disorder (PLMD) is a sleep-related movement disorder characterized by involuntary, rhythmic limb movements during sleep. While PLMD itself is not considered life-threatening, its association with certain underlying health conditions raises concerns about mortality risks. PLMD has been found to be associated with cardiovascular diseases such as hypertension and cardiovascular disease. The fragmented sleep caused by the repetitive limb movements and associated arousals may contribute to sympathetic activation, chronic sleep disruption, sleep deprivation, and subsequent cardiovascular problems, which can increase mortality risks. The comorbidities and health factors commonly associated with PLMD, such as obesity, diabetes, and chronic kidney disease, may also contribute to increased mortality risks. PLMD is often observed alongside other neurological disorders, including restless legs syndrome (RLS) and Parkinson's disease. The presence of PLMD in these conditions may exacerbate the underlying health issues and potentially contribute to higher mortality rates. Further research is needed to elucidate the specific mechanisms linking PLMD to mortality risks and to develop targeted interventions that address these risks.

Dietary Carotene Intake and Suicidal Ideation in Korean Females: Analysis of Data From the Korea National Health and Nutrition Examination Survey (2012, 2013, and 2015)

Objective@#The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression. @*Methods@#This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders. @*Results@#A total of 5,480 females aged 19–64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 μg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 μg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873–0.999). @*Conclusion@#These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.

The Factors Affecting Longitudinal Course of Posttraumatic Stress Disorder Symptoms in Sexual Assault Victims

Objective@#This study aimed to identify the factors affecting posttraumatic stress disorder (PTSD) symptom remission prospectively through a 1-year follow-up of sexual assault (SA) victims. @*Methods@#A total 65 female SA victims who visited the crisis intervention center were included. Self-administered questionnaires regarding PTSD symptoms and PTSD related prognostic factors were conducted at both recruitment (T1) and 1 year after recruitment (T2). The multivariate analyses were used to determine the significant predictors of PTSD remissionon-remission state 1 year after SA. @*Results@#In logistic regression analysis, both anxiety and secondary victimization were identified as significant factors explaining the results on PTSD remissionon-remission state at T2 (Beck’s Anxiety Inventory [BAI], p=0.003; Secondary Victimization Questionnaire, p=0.024). In a linear mixed analysis, both depression and anxiety were found to be significant variables leading to changes in Posttraumatic Diagnostic Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition from T1 to T2 (BAI, p<0.001; Center for Epidemiological Studies Depression Scale, p<0.001). @*Conclusion@#Depression, anxiety symptoms, and secondary victimization after SA were associated with PTSD symptom non-remission 1 year after SA.

Source Investigation and Control of Ralstonia mannitolilytica Bacteremia in a Neonatal Intensive Care Unit: A Case Report

A case of persistent Ralstonia mannitolilytica bacteremia in the neonatal intensive care unit prompted source investigation due to its rarity. After an extensive investigation, a contaminated ultrasonic nebulizer was identified as the source, and the infection was controlled by removing the source. This study emphasizes the importance of further investigations, even in single cases of rare pathogens.

Associations between Maternal sFlt-1/PlGF Ratio and Perinatal and Neonatal Outcomes in Newborns Born to Mothers with Preeclampsia

Purpose@#The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is considered a predictive marker of preeclampsia. However, the relationship between the sFlt-1/PlGF ratio and perinatal and neonatal outcomes remains unknown. This study aimed to determine the associations of the sFlt-1/PlGF ratio with perinatal and neonatal outcomes in newborns born to mothers with preeclampsia. @*Methods@#This retrospective cohort study reviewed singleton neonates born to mothers with preeclampsia who underwent testing for the sFlt-1/PlGF ratio. We investigated the relationship between maternal sFlt-1/PlGF ratios and gestational age (GA), birth weight (Bwt), Bwt z-score, morbidities, and mortality of neonates born to mothers tested for the sFlt-1/PlGF ratio. Maternal sFlt-1/PlGF ratios examined within 30 days before delivery were used for analysis. Neonatal morbidities and mortality were investigated only in preterm infants born earlier than 32 weeks GA. @*Results@#A total of 225 neonates were included, of which 163 (72.4%) were preterm infants. GA (R=– 0.577, p<0.001), Bwt (R=–0.713, p<0.001), and Bwt z-score (R=–0.608, p<0.001) exhibited significant negative correlations with the sFlt-1/PlGF ratios. Among the 50 preterm infants born earlier than 32 weeks GA, neonatal morbidities were not significantly associated with the sFlt-1/PlGF ratio after adjusting for GA and Bwt. @*Conclusion@#In mothers with preeclampsia, a higher sFlt-1/PlGF ratio was associated with the delivery of newborns with lower GA and lower Bwt. However, this ratio was not associated with increased morbidity or mortality in premature infants born earlier than 32 weeks GA.

Induction of liver transplant immune tolerance in an outbred rat strain model using tacrolimus / 한국실험동물학회지

Background@#Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model. @*Results@#To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver. @*Conclusions@#Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.

Generative Adversarial Network-Based Image Conversion Among Different Computed Tomography Protocols and Vendors: Effects on Accuracy and Variability in Quantifying Regional Disease Patterns of Interstitial Lung Disease

Objective@#To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. @*Materials and Methods@#This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1–7 according to acquisition conditions. CT images in groups 2–7 were converted into the target CT sty le (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. @*Results@#Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2–7 improved after CT conversion (original vs. converted: 0.63vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists’ scores were significantly higher (P < 0.001) and less variable on converted CT. @*Conclusion@#CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

The Difference between Serum Vitamin D Level and Depressive Symptoms in Korean Adult Women before and after Menopause: The 5th (2010–2012) Korean National Health and Nutrition Examination Survey

Background@#The relationship between serum vitamin D levels and depressive symptoms has not been consistent in previous studies in Korean women. Menopause is known to be related to depression and vitamin D. @*Methods@#This study included 11,573 women from the 5th Korea National Health and Nutrition Examination Survey. Serum vitamin D levels were divided into four groups according to quartiles, and depressive symptoms were collected into two groups. Multiple logistic regression analysis was conducted in each group of women before and after menopause. @*Results@#Compared with the highest vitamin D group, the lowest vitamin D group did not show significant differences in all females (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.78-1.22). In premenopausal women, compared to the first quartile, ORs were presented in the second quartile (OR, 0.75; 95% CI, 0.53-1.07), third quartile (OR, 0.70; 95% CI, 0.49-1.00) and fourth quartile (OR, 0.62; 95% CI, 0.43-0.92) respectively, and they were statistically significant (P=0.016). In postmenopausal women, compared to the first quartile, ORs were presented in the second quartile (OR, 1.06; 95% CI, 0.78-1.44), third quartile (OR, 1.18; 95% CI, 0.87-1.61), and fourth quartile (OR, 1.27; 95% CI, 0.98-1.66) respectively; however, they were not statistically significant (P=0.057). @*Conclusions@#Depression symptoms increased with a decrease in serum vitamin D in premenopausal women, but the opposite trend was observed in postmenopausal women. In future studies, if the relationship between blood vitamin D and depression is studied, the menopausal status of women can be used as an important criterion.

A study on the effect of denture cleaning utilizing active micro-locomotion of diatom complex / 대한치과재료학회지

This study compared the effectiveness of self-propelling diatom microbubblers to clean dental appliances with commercial denture cleaning agents according to the Ministry of Food and Drug Safety’s guidelines. The microbubbler is made by doping diatoms with MnO2 nanosheets that can decompose hydrogen peroxide to generate oxygen bubbles. Artificial saliva is prepared in accordance with the criteria presented by the American Dental Association, dispensed, and dried in 96 well plates. Experimental groups include 10-15% NaOCl (positive control), distilled water (negative control), diatom microbubbler A (Aulacoseira, MnO2-polydopamine (PDA)-A), diatom microbubbler M (Melosira nummuloids, MnO2-sugar (S)-M), Polident (GlaxoSmithKline, Dungarvan, Ireland), Dentfix-forte (Helago-Phama GmbH&Co, Parchim, Germany). After washing, absorbance (OD 600) was measured. If the absorbance was 70% or higher, the condition was determined to have “cleaning power potency,”Statistical significance was evaluated by one-way ANOVA and Bonferroni correction to compare cleaning effects among groups (p<0.05).The average cleaning rates were 93.8±1.0% in NaOCl (positive control) and 79.1±1.5% in distilled water (negative control).With the diatom microbubbler A, the average cleaning rate was 79.8±4.5% in the 3% H 2O 2 2 mg/mL, 64.7±5.5% in 6% H 2O 2 2 mg/mL, and 81.9±7.9% in 6% H 2O 2 4 mg/mL. The diatom microbubbler M group showed average cleaning rates of 88.5±3.6% in 3% H2O2 2 mg/mL, 75.8±4.0% in 6% H2O2 2 mg/mL, and 84.5±4.5% in 6% H2O2 4 mg/mL. Finally, conventional denture cleaning agents showed average cleaning rates of 88.2±1.2% in Polident and 83.3±3.0% in Dentfix-forte. The positive control group had significant differences from all experimental groups, but the negative control group showed significant differences only in A2 and A3, M1 and M2, M3, Polident, and Dentfix-forte (F=190.141, p<0.001). Among all groups except the positive control group, MnO2 -S-M mixed with 3% H2O2 2 mg/mL showed the highest cleaning rate. As the results of this study show, diatom complexes exhibit cleaning effects compatible with conventional denture cleaning agents. Further studies need to be conducted to narrow down the specific optimal conditions of diatom microbubblers and maximize the cleaning effect.

Temperament and Character Associated With Resilience in Patients With Bipolar Disorder / 생물치료정신의학

Objectives@#The aim of this study was to investigate temperament and character associated with resilience in patients with bipolar disorder (BD). @*Methods@#A total of 55 outpatients diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and 55 healthy controls matched by age and sex with the BD group were recruited.All participants completed the Connor-Davidson Resilience Scale (CD-RISC) and Temperament and Character Inventory (TCI). Multiple linear regression analysis was performed by controlling for age, length of education, age of onset, number of depressive episodes, and number of hospitalizations to determine factors related to resilience. In addition, multiple regression analysis was performed using the interaction term to investigate whether temperament and character associated with resilience differed between the two groups. @*Results@#Patients with BD showed higher harm avoidance (p<0.001) and lower self-directedness (p<0.001) among the TCI dimensions compared to the control group. In multiple regression analysis, harm avoidance (β=-0.274, p=0.025) and self-directedness (β=0.431, p=0.002) were associated with resilience in patients with BD, while harm avoidance (β=-0.411, p=0.008), persistence (β=0.244, p=0.031), and cooperativeness (β=0.264, p=0.037) were associated with resilience in the control group. Self-directedness had a different relationship with resilience between the two groups (β=0.212, p=0.001). @*Conclusions@#The findings suggest that BD patients’ particular temperament and character are associated with resilience.Furthermore, temperament and character related to resilience differed between the BD group and the control group.

Choroidal Vascularity Index and Treatment Outcomes in Branch Retinal Vein Occlusion Patients with Macular Edema

Purpose@#To explore the association between the visual and anatomical outcomes and the choroidal vascularity index (CVI) post-intravitreal injection in patients with macular edema associated with branch retinal vein occlusion (BRVO). @*Methods@#We conducted a retrospective review of medical records of 50 patients (27 eyes treated with anti-vascular endothelial growth factor and 23 eyes treated with a dexamethasone implant) with BRVO and macular edema who underwent intravitreal injections from January 2017 to October 2020. We measured the central macular thickness (CMT), subfoveal choroidal thickness, and CVI of the BRVO eyes and the fellow eyes using optical coherence tomography and then analyzed the correlation between these measurements and visual and anatomical outcomes. @*Results@#After six months of treatment, the best corrected visual acuity improved, and CMT decreased. Multiple linear regression analysis revealed that factors associated with best corrected visual acuity improvement at six months were fellow eye CVI (standardized β = 0.346, p = 0.008), ellipsoid zone integrity (standardized β = 0.398, p = 0.001), and initial best corrected visual acuity (standardized β = 0.590, p < 0.001). Initial CMT (standardized β = 0.563, p < 0.001) was the only factor associated with the decrease in CMT at six months. @*Conclusions@#In cases of severe macular edema, accurate evaluation of choroidal vessels can be challenging due to shadowing. We discovered that a larger CVI in the fellow eye was associated with greater visual improvement in patients with BRVO and macular edema. CVI could be a prognostic factor for predicting treatment outcomes in BRVO patients, suggesting that the choroidal vascular status may play a role in the pathophysiology of BRVO.

Association Between Depressed Mood Changes and Physical Activity Among Adolescents Post COVID-19 Pandemic

Objectives@#Following the coronavirus disease 2019 (COVID-19) pandemic, adolescents have experienced decreased physical activity and a decline in mental health. This study analyzed the association between changes in depressed mood after the COVID-19 pandemic and physical activity among adolescents. @*Methods@#The analysis was based on the results of the 17th Youth Health Behavior Online Survey conducted in 2021, which included 54848 middle and high school students in South Korea. Information on physical activity included low-intensity physical activity lasting >60 min/day, high-intensity physical activity, and strength training exercises. A logistic regression analysis was performed to evaluate the association between physical activity and changes in depression after the COVID-19 pandemic. @*Results@#After adjusting for sociodemographic characteristics and previous depression, adolescents who performed strength training exercises more than once per week had a 0.95-fold lower risk (odds ratio [OR]=0.948, 95% confidence interval [CI]=0.905–0.994, p= 0.027) of increasing depression after the COVID-19 pandemic, while the risk of decreasing depression increased by 1.22-fold (OR=1.215, 95% CI=1.131–1.305, p60 min/day and high-intensity physical activity. @*Conclusion@#Strength-training exercises are significantly associated with the prevention of depression among adolescents following the COVID-19 pandemic.

Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience

Objective@#: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. @*Methods@#: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. @*Results@#: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. @*Conclusion@#: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea

Background@#Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. @*Methods@#This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. @*Results@#At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. @*Conclusion@#These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Corrective Surgery Using Virtual Surgical Simulation and a Three-Dimensional Printed Osteotomy Guide: A Case Report / 대한족부족관절학회지

A 74-year-old female patient, who underwent surgery for a left distal tibiofibular fracture 40 years earlier, visited the hospital with an ankle varus deformity due to malunion. The patient complained of discomfort while walking due to the ankle and hindfoot varus deformity but did not complain of ankle pain. Therefore, correction using supramalleolar osteotomy was planned, and through virtual surgical simulation, it was predicted that a correction angle of 24° and an osteotomy gap open of 12 mm would be necessary. An osteotomy guide and an osteotomy gap block were made using three-dimensional (3D) printing to perform the osteotomy and correct the deformity according to the predicted goal. One year after surgery, it was observed that the ankle varus was corrected according to the surgical simulation, and the patient was able to walk comfortably. Thus, for correction of deformity, virtual surgical simulation and a 3D-printed osteotomy guide can be used to predict the target value for correction. This is useful for increasing the accuracy of correction of the deformity.

Cholesterol side-chain cleavage enzyme deficiency caused by a novel homozygous variant in P450 sidechain cleavage enzyme gene (CYP11A1) in a 46,XX Korean girl

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother.Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

A streamlined pipeline based on HmmUFOtu for microbial community profiling using 16S rRNA amplicon sequencing

Microbial community profiling using 16S rRNA amplicon sequencing allows for taxonomic characterization of diverse microorganisms. While amplicon sequence variant (ASV) methods are increasingly favored for their fine-grained resolution of sequence variants, they often discard substantial portions of sequencing reads during quality control, particularly in datasets with large number samples. We present a streamlined pipeline that integrates FastP for read trimming, HmmUFOtu for operational taxonomic units (OTU) clustering, Vsearch for chimera checking, and Kraken2 for taxonomic assignment. To assess the pipeline’s performance, we reprocessed two published stool datasets of normal Korean populations: one with 890 and the other with 1,462 independent samples. In the first dataset, HmmUFOtu retained 93.2% of over 104 million read pairs after quality trimming, discarding chimeric or unclassifiable reads, while DADA2, a commonly used ASV method, retained only 44.6% of the reads. Nonetheless, both methods yielded qualitatively similar β-diversity plots. For the second dataset, HmmUFOtu retained 89.2% of read pairs, while DADA2 retained a mere 18.4% of the reads. HmmUFOtu, being a closed-reference clustering method, facilitates merging separately processed datasets, with shared OTUs between the two datasets exhibiting a correlation coefficient of 0.92 in total abundance (log scale). While the first two dimensions of the β-diversity plot exhibited a cohesive mixture of the two datasets, the third dimension revealed the presence of a batch effect. Our comparative evaluation of ASV and OTU methods within this streamlined pipeline provides valuable insights into their performance when processing large-scale microbial 16S rRNA amplicon sequencing data. The strengths of HmmUFOtu and its potential for dataset merging are highlighted.

Current Status and Key Issues of Data Management in Tertiary Hospitals: A Case Study of Seoul National University Hospital / 대한의료정보학회지

Objectives@#In the era of the Fourth Industrial Revolution, where an ecosystem is being developed to enhance the quality of healthcare services by applying information and communication technologies, systematic and sustainable data management is essential for medical institutions. In this study, we assessed the data management status and emerging concerns of three medical institutions, while also examining future directions for seamless data management. @*Methods@#To evaluate the data management status, we examined data types, capacities, infrastructure, backup methods, and related organizations. We also discussed challenges, such as resource and infrastructure issues, problems related to government regulations, and considerations for future data management. @*Results@#Hospitals are grappling with the increasing data storage space and a shortage of management personnel due to costs and project termination, which necessitates countermeasures and support. Data management regulations on the destruction or maintenance of medical records are needed, and institutional consideration for secondary utilization such as long-term treatment or research is required. Government-level guidelines for facilitating hospital data sharing and mobile patient services should be developed. Additionally, hospital executives at the organizational level need to make efforts to facilitate the clinical validation of artificial intelligence software. @*Conclusions@#This analysis of the current status and emerging issues of data management reveals potential solutions and sets the stage for future organizational and policy directions. If medical big data is systematically managed, accumulated over time, and strategically monetized, it has the potential to create new value.

Effects of Particulate Matter Exposure on the Eustachian Tube and Middle Ear Mucosa of Rats

Objectives@#. Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. @*Methods@#. Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). @*Results@#. In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). @*Conclusion@#. The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.